15th Annual Las Vegas Dermatology Seminar: Scientific Abstract

The Cosmopolitan Hotel, Las Vegas, Nevada

October 30-November 1, 2014

PA-01: A pooled analysis of major adverse cardiovascular events (MACE) data from 10 phase 2 and 3 clinical trials in psoriasis subjects treated with secukinumab

Leonardi CL,1 Mehta NN,2 Lebwohl M,3 Cooper S,4 Fox T5
1Saint Louis University Health Sciences Center, St. Louis, Missouri, USA.
2National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA.
3Mount Sinai Hospital, New York, New York, USA.
4Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA (former employee).
5Novartis Pharma AG, Basel, Switzerland.

BACKGROUND: Psoriasis is associated with cardiovascular risk and an increased frequency of major adverse cardiovascular events (MACE).1 Secukinumab, a fully human anti–interleukin-17A monoclonal antibody, demonstrated rapid, robust, and sustained efficacy with an acceptable safety profile up to 52 weeks in clinical studies of subjects with moderate-to-severe plaque psoriasis.
OBJECTIVE: Here, we report the safety analysis of data pooled from secukinumab trials that assessed the incidence of cardiovascular safety.
METHODS: We evaluated pooled data from 10 randomized, double-blind, phase 2 and 3 studies. Subjects were treated with subcutaneous secukinumab 300 mg (n = 1410; 1178 subject-years of exposure) or 150 mg (n = 1395; 1142 subject-years of exposure), etanercept 50 mg (n = 323; active comparator; 294 subject-years of exposure), or placebo (n = 793; 201 subject-years of exposure) for up to 52 weeks.
RESULTS: Overall, 13 MACE were reported, with an incidence per 100 subject-years of: secukinumab 300 mg, 0.51 (6 cases); secukinumab 150 mg, 0.44 (5 cases); etanercept, 0.34 (1 case); placebo, 0.50 (1 case). No dose dependence was evident. To verify potential MACE, an independent, blinded Cardiovascular and Cerebrovascular Safety Adjudication Committee was established. Two cases (1 for secukinumab 300 mg [myocardial infarction]; 1 for 150 mg [moyamoya disease]) did not meet prespecified adjudication criteria (the 300 mg dose level event initially reported as a myocardial infarction was reclassified as an electrocardiographic abnormality). The exposure-adjusted rate of confirmed incident MACE was thus 0.42 for secukinumab 300 mg and 0.35 for 150 mg. All confirmed MACE incidence occurred in subjects with prior/active cardiovascular disease or risk factors. Risk difference between secukinumab and placebo was calculated through meta-analysis across placebo-controlled studies (all phase 2 and four phase 3 studies). Meta-analyses showed that there was no difference in risk of developing MACE between secukinumab and placebo during the placebo-controlled induction periods.
LIMITATIONS: Data for etanercept is available from only one phase 3 study. Placebo data were mostly from the first 12 weeks of treatment. Mode of administration varied between studies, and range of doses tested was broad (intravenous doses of 3 to 30 mg/kg and subcutaneous doses of 25 to 300 mg).
CONCLUSION: MACE incidence, regardless of the outcomes based on prespecified adjudication criteria, was infrequent and comparable among each secukinumab dose level, etanercept, and placebo.
CORRESPONDING AUTHOR: Craig L. Leonardi, Saint Louis University Health Sciences Center, 1034 S. Brentwood Blvd, Suite 600, St. Louis, MO 63117. E-mail: [email protected] centralderm.com.
CONFLICTS: Dr Leonardi reports personal fees (honoraria) from Abbvie for his services as speaker and consultant. He reports personal fees (honoraria) from Amgen, Dermira, Janssen, Boehringer-Ingelheim, Eli-Lilly, LEO Pharmaceuticals, Sandoz, UCB, and Pfizer for his services as consultant. He reports other (fee for service) from Abbvie, Amgen, Anacor, Celgene, Coherus, Eli Liily, Galderma, Janssen, Merck, Pfizer, Sandoz, Stiefel, LEO Pharmaceuticals, Novartis, and Tolmar for his work as investigator, outside the submitted work. Dr Mehta has nothing to disclose. Dr Lebwohl reports personal fees from Novartis, during the conduct of the study; personal fees from Abbott, grants and personal fees from Amgen, personal fees from Anacor Pharmaceuticals, Inc, personal fees from BioLineRX, Ltd, grants and personal fees from Celgene Corporation, personal fees from Columbia laboratories, Inc, personal fees from Coronado Biosciences, other from Dermipsor, personal fees from Eli Lilly & Co., personal fees from Galderma, personal fees from GlaxoSmithKline-Stiefel, grants and personal fees from Janssen Ortho Biotech, grants and personal fees from LEO Pharmaceuticals, personal fees from Maruho Co., Ltd, personal fees from Meda Pharmaceuticals, personal fees from Pfizer, grants and personal fees from Ranbaxy, personal fees from Thesan Pharmaceuticals, personal fees from Valeant, other from AbGenomics, other from Clinuvel, outside the submitted work. Dr Cooper reports personal fees from Novartis, during the conduct of the study. Dr Fox reports personal fees from Novartis, during the conduct of the study.
FUNDING/SUPPORT: The study was sponsored by Novartis Pharma AG, Basel, Switzerland.
1 Armstrong EJ, Harskamp CT, Armstrong AW. Psoriasis and major adverse cardiovascular events: a systematic review and meta-analysis of observational studies. J Am Heart Assoc. 2013;2(2):e000062.

PA-02: AN2728, a new boron-based topical anti-inflammatory agent, inhibits phosphodiesterase4 (PDE4)

Freund Y, Dong C, Virtucio-Frates C, Rock F, Mak Y, Zhou Y, Zane L, MD, Jarnagin K
Anacor Pharmaceuticals, Inc, Palo Alto, California, USA.
BACKGROUND: AN2728 is a boron-based topical anti-inflammatory agent currently being investigated in phase 3 clinical trials for the treatment of mild-to-moderate atopic dermatitis.
OBJECTIVE: The objectives of the studies described herein were to further characterize the mechanism of action of AN2728.
METHODS: The methodology used to characterize the mechanism of action of AN2728 included enzyme kinetic assays, phosphodiesterase-4 (PDE-4) subtype inhibition studies, protein crystallography, and an analysis of cytokine inhibition in peripheral blood mononuclear cells. In addition, to investigate reactivity against other targets, AN2728 was tested against 50 receptors and ligand-gated ion channels for inhibition at 10 µM.
RESULTS: AN2728 competes with cAMP to inhibit the PDE4B1-catalytic domain with a Ki of 173 ± 26 nM; thus AN2728 interacts at the enzyme active site. The X-ray structure of PDE4B-catalytic domain with AN2728, and its structural relative, AN2898, reveals that the boron atom interacts with the bimetal center and occupies a position in the catalytic site similar to that of the phosphate of cAMP. AN2728 has good affinity across the PDE4 gene products, A, B, C, and D. Its selective affinity for PDE4 is 4-to 10-fold greater than its affinity for PDE1, PDE2, PDE3A, PDE6, or PDE7B. It is inactive on PDE3B, PDE5, PDE7A1, and PDE8-11. The activity of AN2728 results in an increase in intracellular cAMP and activation of PKA, followed by phosphorylation and negative regulation of transcription factors of various cytokines. In the analysis of AN2728 binding to 50 receptors and ligand-gated ion channels, inhibition was less than 25% for all of the receptors tested; thus, AN2728 is specific for PDE4.
LIMITATIONS: This study is limited by its in vitro, exploratory nature; future studies will further define the mechanism of action of AN2728.
CONCLUSION: The novel boron-containing compound, AN2728, exerts its anti-inflammatory effect by inhibition of PDE4, one of 11 subtypes of the enzymes which catalyze the breakdown of cyclic nucleotides to their inactive monophosphates (in the case of PDE4, cAMP to AMP). Through inhibition of cAMP-dependent PDE4 activity, AN2728 inhibits the production of specific cytokines with a pattern that is notably similar to that of other established PDE4 inhibitors and distinctly different from those of a glucocorticoid and a calcineurin inhibitor.
CORRESPONDING AUTHOR: Lee Zane, MD, Anacor Pharmaceuticals, Inc, 1020 East Meadow Circle, Palo Alto, CA 94303-4230. E-mail: [email protected]
CONFLICTS: All authors are employees and stockholders of Anacor Pharmaceuticals, Inc.

PA-03: Analysis by novel microperfusion method confirms higher levels of IL-17A and B-defensin-2 in psoriasis lesional skin compared with nonlesional skin

Loesche C,1 Bruin G,1 Valentin MA,1 Polus F,1 Sinner F2
1Novartis Pharma AG, Novartis Institutes for BioMedical Research, Basel, Switzerland.
2JOANNEUM RESEARCH, Institute for Biomedicine and Health Sciences, Medical University, Department of Internal Medicine, Graz, Austria.

BACKGROUND: Secukinumab, a selective fully human anti-IL-17A monoclonal antibody, has shown proven efficacy in the treatment of moderate-to-severe plaque psoriasis. Clinical evidence in psoriasis suggests that IL-17A plays an important role in disease pathogenesis.1 However, our understanding of the contribution of IL-17 to psoriasis skin pathophysiology remains limited.
OBJECTIVE: Here we sought to characterize IL-17 subtype proteins as well as pathway relevant biomarkers, such as ß-defensin-2, in the skin of healthy volunteers and in psoriasis patients before and after a single dose of secukinumab using the novel open flow microperfusion (OFM) methodology.
METHODS: In this single-center, open-label, exploratory study, 8 healthy volunteers and 8 psoriasis patients received a single dose of 300 mg s.c. secukinumab. At baseline, 1, and 2 weeks later, skin catheters were placed in healthy skin or nonlesional and lesional skin from patients to collect a perfusate of dermal interstitial fluid (dISF) for up to 15 h continuous sampling time. Relevant pathway and disease markers were analyzed in dISF and in skin biopsies.
RESULTS: Baseline IL-17A protein in lesional skin of psoriasis patients was significantly higher (geometric mean: 1.46 pg/mL) than in nonlesional skin or in skin of healthy volunteers (0.12 and <0.096 pg/mL, respectively). In addition, baseline serum levels of IL-17A were significantly higher in psoriasis patients compared with healthy volunteers. In contrast, IL-17F protein levels did not differ significantly in lesional and nonlesional skin. Further, circulating IL-17F levels did not decrease significantly after treatment with secukinumab. Consistent with our IL-17A observations, baseline ß-defensin-2 levels in lesional skin (410 pg/mL) were significantly higher compared with nonlesional skin and skin of healthy volunteers (62.2 and <32.5 pg/mL, respectively). Both skin and serum levels of ß-defensin-2 decreased rapidly after treatment. In psoriasis patients, single-dose treatment with secukinumab resulted in a significant decrease of PASI score from baseline to end of study.
LIMITATIONS: The study population of this exploratory study was small.
CONCLUSION: Using OFM, the differential expression of IL-17A protein could be confirmed in psoriasis lesional skin while IL-17F levels were not different in diseased and unaffected tissue and were not impacted by secukinumab treatment. A single dose of secukinumab was able to induce a significant decrease in clinical efficacy endpoints as well as pathway-relevant biomarkers.
CORRESPONDING AUTHOR: Christian Loesch, Novartis Pharma AG, Novartis Institutes for Biomed, Research, Postfach, Basel, Switzerland CH-4002. E-mail: [email protected].
CONFLICTS: Dr Loesche reports personal fees from Novartis (Employee), during the conduct of the study. Dr Bruin reports other from Novartis (Employee), during the conduct of the study. Dr Valentin reports personal fees from Novartis (Employee), during the conduct of the study. Dr Polus reports other from Novartis (Employee), during the conduct of the study. Dr Sinner has nothing to disclose.
FUNDING/SUPPORT: The study was sponsored by Novartis Pharma AG, Basel, Switzerland.
1Langley RG, Elewski BE, Lebwohl M, et al; ERASURE Study Group; FIXTURE Study Group. N Engl J Med. 2014 ;371(4):326-338.

PA-04: Apremilast in moderate-to-severe plaque psoriasis: 32-week results in patients with nail, scalp, and palmoplantar involvement (ESTEEM 2)

Crowley J,1 Cather J,2 Gooderham M,3 Sebastian M,4 Girolomoni G,5 Ferrandiz C,6 Hu C,7 Stevens RM,7 Day RM,7 Beylot-Barry M,8
1Bakersfield Dermatology, Bakersfield, California, USA.
2Modern Research Associates, Dallas, Texas, USA.
3SKiN Centre for Dermatology, Peterborough, Ontario, Canada.
4Gemeinschaftspraxis Mahlow, Mahlow, Germany.
5University of Verona, Verona, Italy.
6Hospital Germans Trias i Pujol, Barcelona, Spain.
7Celgene Corporation, Warren, New Jersey, USA.
8Hôpital Haut Lévêque, CHU Bordeaux, France.

BACKGROUND: Apremilast, an oral phosphodiesterase 4 inhibitor, works intracellularly to regulate inflammatory mediators. The ESTEEM 2 trial evaluated apremilast efficacy in patients with difficult-to-treat nail, scalp, and palmoplantar psoriasis.
OBJECTIVE: The objective of this presentation is to report the results of apremilast efficacy for patients with difficult-to-treat nail, scalp, and palmoplantar psoriasis over 32 weeks of the ESTEEM 2 phase 3, randomized, placebo-controlled study.
METHODS: Patients with moderate-to-severe plaque psoriasis (Psoriasis Area and Severity Index [PASI] ≥12, body surface area [BSA] ≥10%, static Physician Global Assessment [sPGA] ≥3) were randomized 1:2 to placebo (PBO) or APR 30 mg BID (APR). At Week 16, PBO patients switched to APR through Week 32. At Week 32, patients treated with APR at baseline who achieved ≥50% reduction from baseline in PASI score (PASI-50) were randomized (1:1, blinded) to continue APR or receive PBO. Upon loss of 50% of PASI improvement obtained at Week 32, patients who had been rerandomized to PBO resumed APR. Nail, scalp, and palmoplantar psoriasis were assessed based on the Nail Psoriasis Severity Index (NAPSI), Scalp Physician Global Assessment (ScPGA), and Palmoplantar Physician Global Assessment (PPPGA).
RESULTS: The full analysis set included 411 patients (PBO: n = 137; APR: n = 274) (mean PASI score: 19.3; mean BSA: 26.2%; prior systemic therapy and/or phototherapy: 64.2%). At Week 16, significantly more patients receiving APR achieved PASI-75 (28.8%) and PASI-50 (55.5%) vs PBO (5.8% and 19.7%, respectively; P < .0001). At Week 16, among patients with NAPSI ≥ 1 (n = 266), ScPGA ≥ 3 (n = 269), or PPPGA ≥ 3 (n = 42) at baseline, APR demonstrated significantly greater response rates vs placebo for psoriasis affecting nails, scalp, and palmoplantar areas. Significantly more patients receiving APR achieved NAPSI-50 (44.6%) vs PBO (18.7%; P < .0001) and the mean percent change from baseline in NAPSI score was 29.0% for APR vs 7.1% (P = .0052). Scalp and palmoplantar responses at Week 16 were 40.9% (ScPGA 0-1) vs 17.2% for PBO (P < .0001) and 65.4% (PPPGA 0-1) vs 31.3% for PBO (P = .0315). Among patients initially randomized to APR and maintained on APR through Week 32, nail psoriasis was further improved at Week 32 (-60.0%, mean % change in NAPSI; 55.4% of patients achieved NAPSI-50). Scalp and palmoplantar responses at Week 32 were 32.4% (ScPGA 0-1) and 53.8% (PPPGA 0-1). Improvements were observed at Week 32 in PBO patients who switched to APR at Week 16. The most common adverse events (AEs) were nausea, diarrhea, nasopharyngitis, upper respiratory tract infection, tension headache, headache, and vomiting. Most AEs were mild to moderate in severity, and discontinuation rates due to AEs were low and similar between treatment groups (PBO: 5.1%; APR: 5.5%) during Weeks 0 to 16.
LIMITATIONS: Study limited to 52 weeks. The placebo controlled period ended at week 16, therefore the 32-week data includes an open label period and lacks a control group.
CONCLUSION: APR significantly reduced the severity of moderate-to-severe plaque psoriasis, including nail, scalp, and palmoplantar psoriasis, at Week 16, and improvements were observed up to Week 32. APR was generally well tolerated.
CORRESPONDING AUTHOR: Jeffrey Crowley, MD, Bakersfield Dermatology, 5101 Commerce Dr, Suite 101, Bakersfield, CA 93099. E-mail: [email protected].
CONFLICTS: Dr Crowley reports personal fees from Celgene Corporation during the conduct of the study, and personal fees from AbbVie Pharmaceuticals, Amgen, AstraZeneca, Janssen Pharmaceuticals Inc, Merck, Pfizer Inc, and Regeneron outside the submitted work. Dr Cather reports personal fees from Celgene Corporation during the conduct of the study, and personal fees from Amgen, Celgene Corporation, Galderma Laboratories, Merck, Novartis, Pfizer Inc, AbbVie Pharmaceuticals, Janssen OrthoBiotech, and Medac outside the submitted work. Dr Gooderham reports personal fees from Celgene Corporation during the conduct of the study, and personal fees from AbbVie Pharmaceuticals, Actelion Pharmaceuticals Ltd, Allergan, Amgen, Astellas, Celgene Corporation, Dermira, Dr Reddy's Laboratories, Galderma Laboratories, Janssen Pharmaceutical, Kythera, Kyowa Hakko Kirin Pharma, LEO Pharma, Eli Lilly, Merck, Novartis, Pfizer Inc, Regeneron, and Takeda outside the submitted work. Dr Sebastian reports personal fees from Celgene Corporation during the conduct of the study. Dr Girolomoni reports personal fees from Celgene Corporation during the conduct of the study, and personal fees from AbbVie Pharmaceuticals, Actelion Pharmaceuticals Ltd, Almirall, Amgen, Bioderma, Boehringer Ingelheim, Celgene Corporation, Dompé, Galderma Laboratories, GSK, Janssen Pharmaceuticals Inc, L'Oreal, LEO Pharma, Eli Lilly, Maruho, Merck-Serono, MSD, Novartis, Otsuka, and Pfizer outside the submitted work. Dr Ferrandiz reports personal fees from Celgene Corporation during the conduct of the study, and personal fees from AbbVie Pharmaceuticals, Celgene Corporation, Janssen Pharmaceuticals Inc, and Novartis outside the submitted work. C Hu reports personal fees from Celgene Corporation during the conduct of the study. Dr Stevens is an employee of Celgene Corporation. Dr Day is an employee of Celgene Corporation. Dr Beylot-Barry reports personal fees from Celgene Corporation during the conduct of the study, and personal fees from AbbVie Pharmaceuticals, Amgen, Celgene Corporation, Janssen-Cilag, MSD, Novartis, and Pfizer Inc outside the submitted work.

PA-05: Assessment of neutropenia with secukinumab in subjects with moderate-to-severe plaque psoriasis: a pooled analysis from 10 clinical studies

Griffiths CEM,1 Prinz J,2 Güttner A,3 Cooper S4
1University of Manchester, Manchester, United Kingdom.
2Ludwig-Maximilians-University, Munich, Germany.
3Novartis Pharma AG, Basel, Switzerland.
4Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.

BACKGROUND: Secukinumab, a fully human anti–interleukin-17A monoclonal antibody, has demonstrated rapid, robust, and sustained efficacy with an acceptable safety up to 52 weeks in moderate-to-severe plaque psoriasis. Evidence suggests that Th17/IL-17 signaling plays a role in the homeostasis of neutrophil granulopoiesis.1
OBJECTIVE: Here, we assessed incidence and severity of neutropenia of data pooled from secukinumab trials.
METHODS: This pooled analysis included 10 randomized, double-blind, placebo-controlled, multicenter, phase 2 and 3 studies. Subjects were treated with subcutaneous secukinumab 300 mg (n = 1410; 1178 subject-years of exposure) or 150 mg (n = 1395; 1142 subject-years of exposure), etanercept 50 mg (n = 323; active comparator; 294 subject-years of exposure) or placebo (n = 793; 201 subject-years of exposure) for ≤ 52 weeks. Neutropenia was assessed postbaseline by analyzing neutrophil count as a laboratory parameter. Subjects were stratified by neutropenia grade based on common terminology criteria for adverse events: grade 1, <lower limit of normal to 1500/mm3; grade 2, <1500 to 1000/ mm3; grade 3, <1000 to 500/mm3; grade 4, <500/mm3.
RESULTS: During the induction period (baseline to Week 12), Grade 1 or 2 neutropenia incidence reported was 7.3% (n = 84) and 1.4% (n = 16) in 300 mg, 6.8% (n = 78) and 1.8% (n = 21) in 150 mg, 2.3% (n = 18) and 0.3% (n = 2) in placebo, and 9.4% (n = 29) and 3.2% (n = 10) in etanercept. Grade 3 neutropenia incidence reported was 0.3% (n = 3, 300 mg), 0.2% (n = 2, 150 mg), 0.1% (n = 1, placebo), and 0% (etanercept). There was one case of Grade 4 neutropenia (0.3%) with etanercept. For the entire treatment period (to Week 52), Grade 1 or 2 neutropenia incidence reported was 10.5% (n = 145) and 2.4% (n = 34) in 300 mg, 11.2% (n = 153) and 2.8% (n = 38) in 150 mg, 2.6% (n = 20) and 0.3% (n = 2) in placebo, and 17.1% (n = 53), 6.0% (n = 19) in etanercept. Grade 3 neutropenia occurred in 0.5% of subjects (n = 18) receiving secukinumab; most cases (15/18) did not show a temporal relationship with infection; 3 cases had mild-to-moderate, nonserious infections which were rhinitis, upper respiratory tract infection and cystitis. No dose-effect of secukinumab on neutropenia was observed. The exposure-adjusted incidence rate per 100 subject-years of neutropenia overall (reported as adverse event) was higher for etanercept (1.4) versus secukinumab 300 mg (0.6), 150 mg (0.8), and placebo (0).
LIMITATIONS: Data for etanercept were available from only one phase 3 study. Placebo data were mostly from the first 12 weeks of treatment. Mode of administration varied between studies, and a broad range of doses were tested.
CONCLUSION: Neutropenia was reported infrequently in subjects treated with secukinumab or etanercept; these cases were generally mild and transient.
CORRESPONDING AUTHOR: Christopher E.M. Griffiths, University of Manchester, Dermatology Centre, Hope Hospital, University of Manchester, Manchester M6 8HD, United Kingdom. E-mail: [email protected]. ac.uk.
CONFLICTS: Dr Griffiths reports grants and personal fees from Novartis, during the conduct of the study; grants and personal fees from Abbvie, grants and personal fees from Janssen-Cilag, grants and personal fees from Leo, grants and personal fees from MSD, grants and personal fees from Pfizer, grants and personal fees from Trident, grants and personal fees from GSK, outside the submitted work. Dr Prinz reports personal fees from Biogen-Idec, personal fees from Novartis, personal fees from Wyeth, personal fees from Pfizer, personal fees from Merk-Serono, personal fees from Essex pharma, personal fees from MSD, personal fees from Galderma, personal fees from Centocor, personal fees from Abbott, personal fees from Janssen-Cilag/Janssen-Orthofor, during the conduct of the study. Dr Güttner reports personal fees from Novartis, during the conduct of the study. Dr Cooper reports personal fees from Novartis, during the conduct of the study.
FUNDING/ SUPPORT: The study was sponsored by Novartis Pharma AG, Basel, Switzerland.
1. Krstic A, Mojsilovic S, Jovcic G, Bugarski D. The potential of interleukin-17 to mediate hematopoietic response. Immunol Res. 2012;52(12):34–41.

PA-06: Difference in patient reported psoriasis health-related quality of life between patients rated as 'clear' versus 'almost clear' based on physician global assessment

Bushnell DM,1 Feldman S,2 Viswanathan HN,3 Martin ML,1 Wade SW,4 Scanlon M,1 Yang W,3 Pinto L,3 Kircik L,5 Klekotka P3
1Health Research Associates Inc, Seattle, Washington, USA.
2Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
3Amgen, Inc, Thousand Oaks, California, USA.
4Wade Outcomes Research and Consulting, Salt Lake City, Utah, USA.
5Physicians Skin Care, PLLC and DermResearch, PLLC, Louisville, Kentucky, USA.

BACKGROUND: The static Physician's Global Assessment (sPGA, ranging from 0 [clear of disease] to 5 [very severe disease]) is a traditional assessment tool for measuring psoriasis severity with treatment success defined as achieving a sPGA of 0 (clear) or 1 (almost clear). Differences in self-perceived health-related quality of life (HRQoL) among patients with sPGA 0 and those with sPGA 1 are not well characterized.
OBJECTIVE: To compare HRQoL between sPGA 0 and sPGA 1 using the Dermatology Life Quality Index (DLQI), a patient-reported measure of HRQoL.
METHODS: A cross-sectional, observational study was conducted in adult patients with moderate-to-severe psoriasis receiving a biologic. Patients completed the 10-item paper version of the DLQI at the study visit. Each item is scored on a 4-point response scale (0-3) and item scores are summed to yield a total score (0-30). Higher scores indicate greater impairment of HRQoL. DLQI 0 or 1 indicate no impairment in HRQoL. Physician-reported sPGA was collected at the same visit. Two-by-two cross-tabulations, with Pearson chi-square and mean square contingency statistics, were used to compare sPGA 0 and sPGA 1 based on DLQI score thresholds (DLQI = 0 vs DLQI >0 and DLQI = 0 or 1 vs DLQI > 1). Age and gender were used as covariates in all analyses.
RESULTS: 230 subjects were included in the analysis. The mean age was 48 (range: 18 to 83) years; 46% were female and 86.5% were white. The average PASI score among sPGA 0 patients (N = 79) and sPGA 1 patients (N = 151) was 0.009 and 1.666, respectively (P < .001). Of the subjects with sPGA 0, 91.1% reported a DLQI = 0 or 1 (no impairment on HRQoL) compared to 48.3% of subjects with sPGA 1(χ2 = 40.8, P < .0001; phi = 0.421, P < .0001). Of the subjects with sPGA 0, 78.5% reported a DLQI = 0 compared to 23.8% of subjects with sPGA 1(χ2 = 63.3, P < .0001; phi = 0.525, P < .0001).
LIMITATIONS: The number of subjects enrolled across the 18 sites varied from 1 to 56 per site, potentially limiting the generalizability of the study findings.
CONCLUSION: A significantly higher proportion of subjects with complete skin clearance (sPGA 0, "Clear") reported no impairment at all on HRQoL compared to subjects who achieved "almost clear" (sPGA 1) status. Complete clearance of psoriasis provides a meaningfully greater degree of treatment success for patients than does almost clearing the condition.
CORRESPONDING AUTHOR: Sally Wade, Wade Outcomes Research and Consulting, 358 South 700 East, Suite B-432, Salt Lake City, UT, 84103. E-mail: [email protected].
CONFLICTS: Dr Bushnell is an employee of HRA, Inc which received funding from Amgen to conduct the study. Dr Feldman has received consulting fees from Amgen. Drs Viswanathan, Martin, Scanlon, and Yang have no conflicts to report. Dr Wade has received consulting fees for assistance in designing and implementing the study from Amgen, Inc Dr Kircik is a remunerated speaker for Abbott Laboratories, Allergan, Inc, Amgen, Inc, Assos Pharma, Astellas Pharma US, Inc, CollaGenex, Connetics Corporation, Dermik Laboratories, Embil Pharmaceuticals, Galderma Laboratories, LP, Genentech, Inc, Innocutis, Innovail, Johnson & Johnson, Leo, L'Oreal, 3M, Onset, OrthoNeutrogena, PharmaDerm, Serono (Merck Serono International SA), SkinMedica, Inc, Stiefel Laboratories, Inc, Triax, UCB, Valeant Pharmaceuticals Intl., and Warner-Chilcott; is a remunerated consultant for Allergan, Inc, Amgen, Inc, Anacor Pharmaceuticals, Colbar, CollaGenex, Connetics Corporation, Galderma Laboratories, LP, Genentech, Inc, Intendis, Johnson & Johnson, Laboratory Skin Care Inc, Leo, Medical International Technologies, Merck, Merz, Novartis AG, OrthoNeutrogena, Promius, PuraCap, SkinMedica, Inc, Stiefel Laboratories, Inc, UCB, Valeant Pharmaceuticals Intl., and ZAGE; is a remunerated advisory board member for Allergan, Inc, Anacor Pharmaceuticals, Biogen-Idec, Colbar, Celgene, Connetics Corporation, EOS, Ferndale Laboratories, LP, Galderma Laboratories, LP, Genentech, Inc, Intendis, Innocutis, Johnson & Johnson, Nano Bio, OrthoNeutrogena, Promius, SkinMedica, Inc, Stiefel Laboratories, Inc, Valeant Pharmaceuticals Intl., and Warner-Chilcott; is a remunerated investigator for Allergan, Inc, and QLT, Inc; has received research grant support as an investigator for Acambis, Amgen, Inc, Anacor Pharmaceuticals, Astellas Pharma US, Inc, Asubio, Berlex Laboratories (Bayer HealthCare Pharmaceuticals), Biolife, Biopelle, Breckinridge Pharma, Celgene, Centocor, Inc, CollaGenex, Combinatrix, Connetics Corporation, Coria, Dow Pharmaceutical Sciences, Inc, Dusa, Eli Lily, Ferndale Laboratories, LP, Galderma Laboratories, LP, Genentech, Inc, GlaxoSmithKline, PLC, Health Point, LTD, Intendis, Johnson & Johnson, Leo, L'Oreal, 3M, Maruho, Medical International Technologies, Merck, Medicis Pharmaceutical Corp, Nano Bio, Novartis AG, Noven Pharmaceuticals, Nucryst Pharmaceuticals Corp, Obagi, Onset, OrthoNeutrogena, Promius, PharmaDerm, Pfizer, Quatrix, SkinMedica, Inc, Stiefel Laboratories, Inc, TolerRx, UCB, Valeant Pharmaceuticals Intl, Warner-Chilcott, and XenoPort; and is a stock shareholder in Johnson & Johnson. Drs Pinto and Klekotka are employees and shareholders of Amgen, Inc.
FUNDING/SUPPORT: This work was sponsored by Amgen, Inc.

PA-07: Disconnect between radiographic progression and skin or arthritic outcomes in psoriatic arthritis patients treated with adalimumab

Mease, P,1 Ritchlin C,2 Rubant S,3 Varothai N,4 Hojnik M,5 Okun M,4 Gottlieb A6
1Swedish Medical Center and University of Washington, Seattle, Washington, USA.
2University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
3AbbVie Deutschland GmbH & CoKG, Wiesbaden, Germany.
4AbbVie Inc, North Chicago, Illinois, USA.
5AbbVie s.r.o., Ljubljana, Slovenia.
6Tufts Medical Center, Boston, Massachusetts, USA.

BACKGROUND: ADEPT was a 24-week, randomized, controlled trial where patients (pts) with active psoriatic arthritis (PsA) received adalimumab (ADA, n = 153) or placebo (PBO, n = 162), stratified by extent of psoriasis (≥3% BSA, 45%). ADA treatment reduced disease activity and radiographic progression, as assessed by ACR20 response at week 12 (ADA, 58%; PBO, 14%) and change in modified Total Sharp Score (ΔmTSS) from baseline (BL) to week 24. In pts with rheumatoid arthritis (RA), inhibition of radiographic progression can occur independently of clinical symptom improvements following anti-TNF treatment.
OBJECTIVE: This post hoc analysis explored the relationship between skin or arthritic clinical response and radiographic progression in pts with active PsA in ADEPT.
METHODS: Disease activity was monitored by ACR20 and PASI50 response at week 24; radiographic progression was defined as ΔmTSS >0.25.
RESULTS: 64/144 ADA pts and 62/152 PBO pts with evaluable BL and week 24 radiographs had BSA involvement ≥3% at BL. Radiographic progression occurred at a lower frequency following ADA treatment; through week 24, 83.3% (120/144) of ADA-treated pts and 60.5% (92/152) of PBO pts had no radiographic progression (P < .001). Regardless of therapy, ACR20 response was associated with a numerically lower likelihood of radiographic progression. In ADA-treated pts, radiographic progression was detected in 12.8% (11/86) of ACR20 responders vs 22.4% (13/58) of ACR20 nonresponders (P = .128), and in the PBO group, radiographic progression was detected in 24.0% (6/25) of ACR20 responders vs 42.5% (54/127) of ACR-20 nonresponders (P = .083). PASI50 response was also associated with a lower likelihood of radiographic progression. In ADA-treated pts, radiographic progression was detected in 11.8% (6/51) of PASI50 responders vs 38.5% (5/13) of PASI50 nonresponders (P = .037), and in the PBO group, radiographic progression was detected in 0% (0/8) of PASI50 responders vs 46.3% (25/54) of PASI50 nonresponders (P = .017).
CONCLUSIONS: Radiographic progression was lower in pts with active PsA treated with ADA compared with PBO. Pts treated with ADA or PBO who achieved skin or arthritic improvement were unlikely to have radiographic progression. ADA treatment was associated with a lower likelihood of radiographic progression even in pts without a good clinical response at week 24. As in RA, a disconnect can occur between radiographic progression and disease activity in PsA pts treated with ADA.
CONFLICTS: Dr Mease has served as a consultant and a speaker for AbbVie; he has also received research/educational grants from AbbVie. Dr Ritchlin has served as a consultant for Amgen, AbbVie, Janssen, Lilly, and UCB; he has also received research/educational grants from Amgen, Janssen, and UCB. S. Drs Rubant, Varothai, and Okun , and M. Hojnik are AbbVie employees and may own AbbVie stock and/or stock options. Dr Gottlieb has served as a consultant to or on advisory boards for AbbVie; she has also received research/educational grants (paid to Tufts Medical Center) from AbbVie.
CORRESPONDING AUTHOR: Martin Okun, AbbVie Inc, 1 North Waukegan Road, Dept NJ44, Bldg. AP4-2, North Chicago, IL 60064. E-mail: [email protected].
AUTHOR CONTRIBUTIONS: The authors and AbbVie scientists designed the study and analyzed and interpreted the data. All authors contributed to the development of the content; all authors and AbbVie reviewed and approved the presentation; the authors maintained control over the final content.
FUNDING/SUPPORT: AbbVie funded the research and medical writing support.
ADDITIONAL CONTRIBUTIONS: Medical writing support was provided by Jennifer Han, MS, of Complete Publication Solutions, LLC, Horsham, Pennsylvania.

PA-08: Drug exposure limitations of oral methotrexate (MTX) at doses >15 mgs may be overcome by using a subcutaneous MTX auto-injector

Schiff MH,1 Jaffe J,2 Freundlich B3
1University of Colorado, Denver, Colorado, USA.
2Antares Pharma, Inc, Ewing, New Jersey, USA.
3University of Pennsylvania, Philadelphia, Pennsylvania, USA.

BACKGROUND: Methotrexate (MTX) is an effective treatment for severe psoriasis, although absorption saturability limitations compromise the bioavailability (BA) of oral MTX. While parenteral MTX may provide greater MTX BA this method of administration is infrequently used in clinical practice, likely because of a lack of familiarity and availability, and the challenges of self-injection. To facilitate the self-administration of parenteral MTX, a single-use subcutaneous (SC) MTX auto-injector (MTXAI) was developed with 10-, 15-, 20-, and 25-mg fixed doses.
OBJECTIVE: The purpose of this study was to compare the relative BA of MTX delivered by the MTXAI with that of oral MTX at each of the 4 doses and to examine the safety and tolerability of the MTXAI.
METHODS: In this 12-week, open-label, crossover study, 49 adults with rheumatoid arthritis who had been receiving MTX for at least 3 months were given a random sequence of 3 MTX treatments of equal dose: oral MTX, MTXAI delivered to the thigh, and MTXAI delivered to the abdomen. Each patient was assigned a dose from the 4 available MTXAI doses, based on the individual's current MTX dose and disease status. Pharmacokinetic (PK) blood samples were collected pre dose and at 13 time points from 0.25 to 12 hours post dose, and were analyzed by liquid chromatography-mass spectrometry. PK measures obtained included AUC, Cmax, and Tmax. Ratios for dose-normalized parameters were calculated.
RESULTS: Mean patient age was 61 years, mean body mass index was 30.7 kg/m2, mean disease duration was 13 years, and 63% of patients were female. MTXAI thigh and MTXAI abdomen PK measures were similar, although the BA of oral MTX was consistently lower than that of MTXAI thigh at each dose. Oral MTX BA plateaued at 15 mg, whereas the MTXAI BA had no plateau, resulting in higher exposure than comparable oral doses. The relative BA (AUC of MTXAI vs oral MTX) at 10, 15, 20, and 25 mg was 121%, 114%, 131%, and 141%, respectively. The ratios of the dose-normalized AUC (0 -24 h) and Cmax of MTXAI vs oral MTX were 127.61 (90% CI: 122.30 -133.15) and 94.88 (90% CI: 87.95 -102.37), respectively. Few adverse events (AEs) were reported with the MTXAI; observed AEs were transient, manageable, and required no medical treatment. Two serious AEs were considered unrelated to treatment, including a death from a myocardial infarction in a 79-year-old man with a prior cardiac history. Oral MTX and MTXAI were otherwise generally safe and well tolerated.
CONCLUSIONS: SC MTX delivered by auto-injector has a linear absorption compared with oral MTX, which plateaued at doses higher than 15 mg. Patients receiving oral MTX with an inadequate clinical response may benefit from higher drug exposure levels by switching to SC MTX via MTXAI. This study confirms existing findings that higher systemic exposure to MTX is not associated with increased rates of AEs.
CORRESPONDING AUTHOR: Michael Schiff, MD, University of Colorado, 5400 South Monaco Street, Englewood, CO 80111. E-mail: [email protected].
CONFLICTS: Dr Schiff reports personal fees from Antares Pharma, Inc, outside the submitted work. Dr Jaffee is an employee of Antares Pharma, Inc. Dr Freundlich has received consulting fees from Antares Pharma, Inc, Bristol-Myers Squibb, and Celgene; Dr Freundlich is a shareholder of Pfizer.

PA-09: Evaluating the economic burden of psoriasis in the United States

Vanderpuye-Orgle J,1 Shrestha A,1 Sexton A,1 Chan D,1 Zhao Y,2 Lu J,2 Tran MH,2 Seabury S3
1Precision Health Economics, Los Angeles, California, USA.
2Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
3University of Southern California, Los Angeles, California, USA.

BACKGROUND: Psoriasis can have a significant economic impact on patients. However, the total economic burden to the overall economy has not been fully quantified in the United States (US).
OBJECTIVE: To assess the burden of psoriasis on the US economy, including direct medical costs and other indirect nonmedical costs incurred by adult patients.
METHODS: A systematic literature review was conducted to extract relevant estimates for prevalence, incremental medical costs, productivity loss, and reductions in health-related quality of life (HRQoL) associated with psoriasis. The most recent prevalence estimates were used to calculate the psoriasis population in that year. To estimate the population in 2013, we applied incidence rates and their growth rates to predict the population in each subsequent year, taking into account mortality rates. Incremental costs were calculated using estimates from studies that compared medical costs for a control group and a psoriasis group. Productivity loss was estimated using recent measures of presenteeism, absenteeism, and unemployment, which, taken together, measured productivity lost while at work, while absent from work, and while unable to be employed. Finally, using studies with Short Form Health Survey 12 (SF-12) scores for both psoriasis patients and a control group, we estimated psoriasis-related reductions in HRQoL and calculated quality-adjusted life year (QALY) values based on prepublished weights for both groups.
RESULTS: 91 peer-reviewed articles were used to estimate the total economic burden. The estimated psoriasis prevalence at the beginning of 2013 was about 7.4 million people. Overall, psoriasis patients incurred higher annual medical costs compared to the nonpsoriasis patients (with per-patient incremental costs of $929 and $423 for outpatient and inpatient care, respectively; $925 for pharmacy services; and $24 for emergency care). Total annual productivity losses were in excess of $14 billion. Using a conservative QALY value ($40,000), psoriasis resulted in a $2,148 reduction in HRQoL per patient, annually. In aggregate these estimates suggest a total US burden of psoriasis of $46.5 billion in 2013, with approximately two-thirds attributable to reduced productivity and HRQoL.
LIMITATIONS: This study was constrained by the scope of the existing research. In particular, the literature examining psoriasis patients under the age of 18 was very sparse. Thus, this study focused only on adults ages 18 and over. Similarly, there was a dearth of information on indirect burden components such as disability, social stigma, and caregiver burden, which made it impossible to impute dollar values for these components.
CONCLUSION: With increasing fiscal pressure in the US, the substantial burden of psoriasis may place additional strain on limited resources.
CORRESPONDING AUTHOR: Yang Zhao, PhD, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936-1080. E-mail: [email protected].
CONFLICTS: Drs Vanderpuye-Orgle, Shrestha, Sexton, and Seabury and D. Chan are current or former associates (as employees or paid consultants) of Precision Health Economics. Dr Zhao is an employee of Novartis Pharmaceuticals Corporation. J Lu and MH Tran were employees of Novartis Pharmaceuticals Corporation at the time of the study.
FUNDING/SUPPORT: Precision Health economics conducted this study with sponsorship support from Novartis Pharmaceuticals Corporation.

PA-10: Evaluation of symptoms in patients of Razi Dermatology Hospital with a diagnosis of acrodermatitis enteropathica

Beigi PKM,1,2,4,5 Seirafi H,1 Farnaghi F,1 Niyyati SS3,4,5
1Department of Dermatology, Tehran University of Medical Sciences, Tehran, Iran.
2Division of Reproductive and Developmental Sciences, Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada.
3Department of Biological Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
4Northwest Marine Medical Clinic, North Vancouver, British Columbia, Canada.
5Father Charity Society, Vancouver, British Columbia, Canada.

BACKGROUND: Acrodermatitis Enteropathica (AE) is an inherited autosomal recessive disorder caused by a mutation in the gene coding for the hZip4 Zn transporter, which affects intestinal zinc absorption and metabolism and causes reduction of all body zinc levels, including blood serum. First described by Brandt in 1936, AE remains however largely misdiagnosed and it is often fatal if not diagnosed and treated promptly during infancy.
OBJECTIVE: To determine the symptoms and blood zinc level ranges of said patients and determine the relationship between the two.
METHODS: The article is presented as a retrospective cross sectional study. This study surveyed 27 infant patients with severe zinc deficiency that is suggestive of AE, who were referred to Razi Hospital's Dermatology Center in Tehran, Iran during the years 1999 to 2004. Multivariate analyses were used to determine significantly present symptoms (P < .05).
RESULTS: The symptoms of this disorder, which were found to be statistically significant, can be listed as perioral, perinasal, BACKGROUND: perigenital, and perirectal lesions, acral lesions and lesions on fingers, hands, elbow and feet, diarrhea and stomach ache, diffused alopecia, and neurological symptoms like fatigue, moodiness, irritability, photophobia, and anorexia. On the contrary, symptoms such as periorbital lesions, lesions on toes, vomiting, and focal alopecia were determined to be insignificant and should no longer be regarded as symptoms of AE.
LIMITATIONS: Since this study was done in 2004 and we were focusing on the dematological aspect of the disorder we did not use genetics mapping as a way of diagnosis.
CONCLUSION: The significant symptoms of this disorder were identified through this study.
CORRESPONDING AUTHOR: Pooya Khan Mohammad Beigi, NWM Medical Clinic, 1881 Marine Drive, North Vancouver, BC, V7P1V5, Canada. E-mail: [email protected].
CONFLICTS: The authors have no conflicts to report.

PA-11: Field Cancerization using optical coherence tomography and handheld confocal microscopy pre- and post-treatment with ingenol mebutate 0.015% gel

Markowitz O,1,2,3 Feldman E,1,2,3 Schwartz M,1,2,3 Kalowitz A,1,2,3 Bienenfeld A,1,2,3 Siegel DM1,2
1SUNY Downstate Medical Center, Brooklyn, New York, USA.
2NY Harbor Healthcare System, Brooklyn, New York, USA.
3Mount Sinai Medical Center, New York, New York, USA.

BACKGROUND: Optical coherence tomography (OCT) and reflectance confocal microscopy are noninvasive imaging tools that enable deeper skin visualization. Field cancerization is described as a biological process in which large areas of cells at a tissue surface or within an organ are affected by carcinogenic alterations. The process arises from exposure to an injurious environment, often over a lengthy period. Field therapy treats not only the individual cancer but all of the surrounding damaged cells that could lead to further cancers and/or recurrence.
OBJECTIVE: The purpose of this study was to find evidence for field cancerization with the use of fourier domain OCT and the handheld confocal microscope on actinically damaged skin of the face.
METHODS: 30 patients with a minimum of 7 nonhyperkeratotic actinic keratoses were recruited. A total of 3 actinic keratoses along with adjacent sub-clinical skin were scanned in both a 25 cm2 treated and a nontreated area. A biopsy of an additional clinically suspicious actinic keratosis and its adjacent normal-appearing skin was taken and compared by blindly evaluation to both a handheld confocal scan as well as an OCT scan.
RESULTS: The accuracy of the devices for diagnosis was determined with H & E as the gold standard. 75% of normal-appearing adjacent skin showed a biopsy result of actinic keratosis. OCT had 100% accuracy with the clinical biopsy and 80% accuracy with normal-appearing skin (subclinical) lesions. Clearance rates were determined using OCT and clinical examination. Patient results were divided based on their reaction score according to a standard reaction score scale.
CONCLUSION: Noninvasive imaging allows researchers to obtain a great deal of data on subclinical and clinical damage on the skin.
CORRESPONDING AUTHOR: Orit Markowitz, SUNY Downstate Medical Center, 450 Clarkson Ave, Brooklyn, NY 11203. E-mail: omarkowitzgmail.com.
CONFLICTS: Dr Markowitz has received grants from Amgen, LEO Pharma Inc, and Michelson Diagnostics; personal fees from LEO Pharma Inc and 3 Gen; and nonfinancial support from Caliber ID. Drs Feldman, Schwartz, Kalowitz, and Bienenfeld have nothing to disclose. Dr Siegel reports grants and personal fees from LEO Pharma, Inc, grants and nonfinancial support from Michelson Diagnostics, other from Caliber ID, outside the submitted work.

PA-12: Five-year interim results from the ESPRIT 10-year postmarketing surveillance registry of adalimumab for moderate-to-severe psoriasis

Thaçi D,1 Kerdel F,2 Bereswill M,3 Williams DA4
1Comprehensive Center for Inflammation Medicine, University Medical School Schleswig Holstein, Campus Lübeck, Germany.
2Florida Academic Dermatology Centers, Miami, Florida, USA.
3AbbVie Deutschland GmbH & Co KG, Ludwigshafen, Germany.
4AbbVie Inc, North Chicago, Ilinois, USA.

BACKGROUND: ESPRIT, a 10-year international observational registry, is prospectively evaluating long-term effectiveness and safety of adalimumab (ADA) in adults treated for moderate-to-severe chronic plaque psoriasis (NCT00799877).
OBJECTIVE: The current analysis determined interim safety and effectiveness over a 5-year period.
METHODS: ESPRIT enrolled patients (pts) who are continuing treatment with ADA from a current prescription or previous study participation, or initiating ADA within 4 weeks of entering the registry (New Prescription Population, New-Rx). The All-Treated Population (All-Rx) received at least 1 ADA dose in this registry. Pts are evaluated 3 and 6 months post enrollment, then every 6 months for up to 10 years. As-observed effectiveness parameters include Physician's Global Assessment (PGA) and quality of life (DLQI; US only). A standardized mortality ratio (SMR; ratio of observed to expected treatment-emergent deaths) of <1.0 indicates that the observed number of deaths was below expected in an age-, sex-, country-matched population. Incidence rates (IR) are reported for observational adverse events (AEs) as events per 100 pt years of observation (E/100PY).
RESULTS: This analysis collected data from 26 September 2008 through 30 November 2013 for 6059 pts who enrolled and were dosed during that time period (All-Rx), including 2580 (42.6%) New-Rx pts. Median registry exposure (range 14-1892 days) was 765 days for All-Rx and 677 days for New-Rx. 643 (10.6%) of All-Rx and 337 (13.1%) of New-Rx pts discontinued the registry; the most frequent reason was lost to follow-up (3.6% and 4.5%, respectively).
CONCLUSION: No new safety signals were observed with ADA treatment during this interim. IR serious infection and malignancies remained stable compared to the 4-year interim report.1 The observed number of deaths was below that expected. As-observed effectiveness remained stable through 60 months.
CORRESPONDING AUTHOR: David Williams, AbbVie Inc, 1 North Waukegan Road, North Chicago, IL 60064. E-mail: [email protected].
CONFLICTS: Dr Thaçi received honoraria from AbbVie, Amgen, Biogen-Idec, Celgene, Janssen, Leo, Novartis and Pfizer for participation on ad boards and as a speaker, and from AbbVie and Leo for consultancy; and received research grants from AbbVie, Leo and Pfizer. Dr Kerdel received honoraria from AbbVie, Amgen, Celgene, Janssen, Leo, Pfizer and Stiefel for participation as a speaker; and received grants from AbbVie, Amgen, AstraZeneca, Celgene, Janssen and Pfizer, for participation as an investigator. Drs Bereswill and Williams receive a salary as employees of AbbVie and may also receive AbbVie stock, stock options and/or stock grants.
1. Kerdel F, Thaçi D, Bereswill M, Williams DA. Fourth-year interim results from esprit, a 10-year postmarketing surveillance registry of adalimumab for moderate-to-severe psoriasis. J Eur Acad Dermatol Venerol. 2013;27(Suppl 4):1-77, Abs P174.

PA-13: Fixed combination aerosol foam calcipotriene 0.005% (CAL) plus betamethasone dipropionate 0.064% (BD) exhibits no impact on the HPA axis and calcium homeostasis in patients with extensive psoriasis vulgaris: a multicentre, single-arm, phase 2, 4-week MUSE study

Taraska V,1 Tuppal R,2 Olesen M,3 Bang Pedersen C,3 Papp K4
1The Derm Centre, Winnipeg, Canada.
2Oshawa Clinic, Oshawa, Canada.
3LEO Pharma A/S, Ballerup, Denmark.
4K Papp Clinical Research and Probity Medical Research, Waterloo Canada.

BACKGROUND: Ointment and gel formulations of fixed combination Cal plus BD have demonstrated favorable efficacy and safety profiles as first-line treatments. A new aerosol foam formulation has been developed.
OBJECTIVE: This study evaluated the potential systemic effects of Cal/BD foam on the hypothalamic–pituitary–adrenal (HPA) axis and calcium homeostasis in patients with extensive psoriasis vulgaris.
METHODS: In this multicenter, single-arm, Phase II, 4-week maximal-use systemic exposure (MUSE) trial, adult patients (≥18 years) with extensive psoriasis on the body and the scalp (15%-30% body surface area [BSA] including ≥30% scalp involvement) of moderate/severe disease severity according to the Physician's Global Assessment (PGA) applied Cal/BD foam once daily for 4 weeks. The primary endpoints were the number of patients with an abnormal adrenocorticotropic hormone (ACTH) challenge test (serum cortisol ≤18 mcg/dL after 30 minutes) at week 4, and change in albumin-corrected serum calcium (sCa), 24-hour urinary calcium excretion (24 hCa) and urinary calcium:creatinine ratio (Ca:Crea) from baseline to week 4. Adverse events (AEs) were reported throughout. Efficacy by PGA on body psoriasis was a secondary endpoint.
RESULTS: Thirty-seven patients received treatment and 35 completed the study. At baseline, 24% had severe disease on PGA; mean BSA involvement was 21%. Mean 62 g/week Cal/BD foam was used. All patients reaching week 4 exhibited normal responses to ACTH stimulation (100% [35/35] achieved serum cortisol >18 mcg/dL). Changes in all median and individual calcium homeostasis values from baseline to week 4 were minor and not clinically relevant; no patients had calcium homeostasis elevations at week 4. Median change from baseline to week 4 in sCa was –0.020 mmol/L, in 24hCa was –0.03 mmol/24h and in Ca:Crea was 0.05 mmol/g. Four of six patients with low sCa values at baseline shifted into the normal range (2.15 – 2.55 mmol/L) by week 4; one patient shifted from normal baseline to low levels. Seven patients shifted 24hCa values (three from low to normal, three from normal to low, one from high to normal; normal range 2.5 – 7.5 mmol/24 h). Elevated Ca:Crea values (0.225 – 8.2 mmol/g for women and 0.3 – 6.1 mmol/g for men) were not seen; the only shift was a patient with normal baseline values shifting to low week 4 values. Four patients (11%) reported six AEs of mostly mild or moderate intensity. Of these, one event was considered probably related to treatment (severe erythema). No serious AEs were reported. Cal/BD foam provided clear or almost clear disease status (treatment success) in 49% of patients according to PGA at week 4. Mild disease was achieved by 37% and the remainder had moderate disease.
LIMITATIONS: This trial enrolled patients with extensive disease so all patients received active treatment (placebo was unethical). Assessment bias is considered limited since most of the endpoints were laboratory data.
CONCLUSION: In patients with extensive psoriasis vulgaris treated once daily with Cal/BD foam for 4 weeks, we demonstrated no impact on the HPA axis and no clinically relevant effect on calcium homeostasis. Cal/BD foam also demonstrated a favorable safety profile.
CORRESPONDING AUTHOR: Victoria Taraska, The Derm Centre, 1385 Grant Avenue, Winnipeg, MB, R3M 1Z9, Canada. E-mail: [email protected].
CONFLICTS: Dr Taraska has been a speaker/investigator for LEO Pharma, Basilea, Amgen, Galderma, AbbVie, Allergan, Cipher, and Valeant. Dr Tuppal has been a speaker/investigator for Amgen, Pfizer, LEO Pharma, Galderma, Valeant, Novartis, and Schering (MSD). Drs Olsen and Bang Pedersen are employees of LEO Pharma. Dr Papp has been a consultant for Janssen, Johnson & Johnson, Kirin, Kyowa, LEO Pharma, Lypanosys, merck, Mitsubishi Pharma, Novartis, Pan Genetics, Pfizer, Roche, Merck-Serono, Takeda, UCB, and Vertex, a speakers' bureau member for Janssen, Merck, Novartis, and Pfizer, an investigator for Janssen, Kyowa, LEO Pharma, Merck, Novartis, Pfizer, Stiefel, and Takeda, a speaker for Janssen, Kyowa, Lypanosys, Merck, Mitsubishi Pharma, Novartis, Pfizer, Merck-Serono, Takeda, UCB, Vertex, and Wyeth, a steering committee member for Janssen, Kirin, Kyowa, Merck, Novartis, and Pfizer, and an advisory board member for Janssen, Merck, Novartis, Pfizer, and UCB.

PA-14: Impact of psoriasis severity and pain, itching and scaling on patient quality of life and work productivity

Korman NJ,1 Zhao Y,2 Cai B,2 Lobosco S,3 Pike J3
1University Hospitals Case Medical Center, Cleveland.
2Novartis Pharmaceuticals Corporation, East Hanover.
3Adelphi Real World, United Kingdom.

BACKGROUND: Psoriasis is a chronic immune mediated inflammatory systemic disease with major manifestations in the skin. Many psoriasis patients experience itching, painful skin, and scaling. It is important to understand how psoriasis disease severity and patient reported symptoms affect patients' health related quality of life (HRQoL) and work productivity.
OBJECTIVE: To explore the impact of psoriasis symptoms and severity on patient reported HRQoL and work productivity loss among patients in the United States.
METHODS: Data were extracted from the Adelphi 2011 and 2013 Psoriasis Disease Specific Programmes – two real-world surveys of dermatologists and their psoriasis patients in the US. Only patients who provided the self-completion form were included in this analysis. HRQoL was measured using the Dermatology Life Quality Index (DLQI) and EuroQOL 5-Dimension Health Questionnaire (EQ-5D). Work productivity loss was measured by the Work Productivity and Activity Impairment (WPAI) questionnaire. Three levels (none, mild, and moderate-to-severe) were constructed for psoriasis-related itching, painful skin, and scaling, respectively. The impact of overall psoriasis disease severity (mild, moderate, and severe) and level of itching, painful skin and scaling on DLQI, EQ-5D, and WPAI were examined, controlling for differences in demographics and co-morbidities.
RESULTS: A total of 694 patients were studied. The mean age was 44 years and 55% were male. Of all patients, 48%, 46%, and 6% had mild, moderate, and severe psoriasis, respectively. Controlling for differences in demographics and co-morbidities, increasing disease severity was associated with reduced HRQoL: EQ-5D scores decreased with severity levels (moderate vs mild: -0.04, severe vs mild: -0.18), while DLQI scores increased (moderate vs mild: 2.97, severe vs mild: 7.95) (all P < .05). Similarly, WPAI scores increased with severity levels, indicating increased work productivity loss (moderate vs mild: 11.77, severe vs mild: 18.73, both P < .05). Increased level of itching, painful skin and scaling was associated with a significant (P < .05) reduction in HRQoL (both EQ-5D and DLQI) and an increase in work productivity loss, controlling for cross-cohort differences in demographics and co-morbidities. Among psoriasis patients in the US, increasing degree of psoriasis disease severity and psoriasis-related itching, pain and scaling were associated with reduced HRQoL and work productivity.
LIMITATIONS: Only consulting patients were invited to participate. Therefore, the patient sample may not be representative of the wider psoriasis population.
CONCLUSION: Among psoriasis patients in the US, increasing degree of psoriasis disease severity and psoriasis-related itching, pain and scaling were associated with reduced HRQoL and work productivity.
CORRESPONDING AUTHOR: Yang Zhao, PhD, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936-1080. E-mail: [email protected]. com.
CONFLICTS: Drs Zhao and Cai are employed by Novartis Pharmaceuticals Corporation; Dr Korman is on the advisory board for Novartis Pharmaceuticals Corporation. Drs Lobosco and Pike have no conflicts to report.

PA-15: In vitro nail penetration and antifungal activity of tavaborole, a novel, boron-based pharmaceutical

Merchant T, Coronado D, Chanda S, Zane L, MD
Anacor Pharmaceuticals, Inc, Palo Alto, California, USA.
BACKGROUND: An effective topical antifungal medication must penetrate the nail plate at sufficient concentrations to eradicate the fungal infection. Tavaborole topical solution, 5% is a boron-based antifungal agent approved for the treatment of toenail onychomycosis due to Trichophyton rubrum or T. mentagrophytes.
OBJECTIVE: To assess the nail penetration and antifungal activity of tavaborole in four in vitro studies.
METHODS: In studies 1, 2, and 3, the in vitro nail penetration of tavaborole was assessed using ex vivo human nails. In study 1, nails were dosed once daily with a topical solution of tavaborole 10.5% or ciclopirox 8%; in study 2, nails were dosed once daily with a topical solution of tavaborole 5% or ciclopirox 8%. In studies 1 and 2, after 14 days of treatment, a liquid chromatography-tandem mass spectrometry method was used to determine the amount of drug in receptor samples. In study 3, nails were dosed with topical solutions of tavaborole 10%, ciclopirox 8%, amorolfine 5%, or placebo once daily for 5 days. Drug penetration was determined by measuring the zone of inhibition of T. rubrum. In study 4, the minimum inhibitory concentration (MIC; lowest concentration resulting in >90% reduction of fungal growth) of tavaborole was evaluated in vitro against 19 strains of fungi in the absence or presence of 5% keratin powder. The minimum fungicidal concentration (MFC; lowest concentration that eradicated >90% of fungi) of tavaborole against T. rubrum and T. mentagrophytes was also evaluated.
RESULTS: In study 1, mean (± standard deviation [SD]) tavaborole concentrations in the ventral/intermediate nail layer were significantly greater vs ciclopirox at day 15 (9.0 ± 4.1 vs 1.0 ± 1.5 µg/mg; P = .003). No significant difference was observed between concentrations of tavaborole and ciclopirox in the dorsal/intermediate nail layer. Tavaborole content in the receptor samples was significantly higher than ciclopirox (P < .03). In study 2, mean ± SD cumulative penetration of tavaborole 5% was significantly higher vs ciclopirox 8% at day 15 (524.7 ± 288.6 vs 13.0 ± 4.25 µg/cm2, respectively; P < .004). In study 3, tavaborole 10% solution exhibited zones of inhibition ranging from 11.5 mm to complete eradication of dermatophytes. No zones of inhibition for T. rubrum were observed with ciclopirox 8% or amorolfine 5%. In study 4, tavaborole demonstrated MIC values ranging from 0.25 – 2 µg/mL against all fungi tested; addition of 5% keratin powder to the media did not affect the MIC against T. rubrum. The MFC values for tavaborole against T. rubrum and T. mentagrophytes were 8 and 16 µg/mL, respectively.
LIMITATIONS: These studies are limited by their in vitro nature and use of human ex vivo fingernails.
CONCLUSION: Challenges in the successful treatment of onychomycosis with topical agents stem from the location of the infection deep within the nail unit. These findings provide in vitro evidence of the superior nail penetration of tavaborole 5% and 10% solutions through the nail plate compared with ciclopirox topical solution, 8%. Tavaborole demonstrated robust antifungal and fungicidal activity, with low MIC and MFC values in the presence or absence of keratin.
CORRESPONDING AUTHOR: Lee Zane, MD, Anacor Pharmaceuticals, Inc, 1020 East Meadow Circle, Palo Alto, CA 94303-4230. E-mail: [email protected].
CONFLICTS: All authors are employees and stockholders of Anacor Pharmaceuticals, Inc.

PA-16: In vitro study demonstrating nail penetration of tavaborole topical solution, 5% through multiple layers of nail polish

Vlahovic T,1 Coronado D,2 Chanda S,2 Merchant T,2 Zane L,2 Elewski BE3
1Temple University School of Podiatric Medicine, Philadelphia, Pennsylvania, USA.
2Anacor Pharmaceuticals, Palo Alto, California, USA.
3University of Alabama at Birmingham, Birmingham, Alabama, USA.

BACKGROUND: Topical antifungal therapies must effectively penetrate through the nail plate and into the nail bed to completely eradicate the fungal infection. Tavaborole topical solution, 5% [Anacor Pharmaceuticals] is a boron-based pharmaceutical agent approved by the US Food and Drug Administration (FDA) for the treatment of onychomycosis of the toenails. Tavaborole topical solution 5% has demonstrated a high amount of penetration through full-thickness human nail plates in vitro.
OBJECTIVE: The objective of this study was to evaluate the effect of nail polish on the nail penetration of tavaborole topical solution, 5%.
METHODS: Human cadaver fingernails from eight female donors were mounted on Vertical Diffusion Cells and were randomized to one of four treatment groups (n = 7 for each). Group 1 had one coat of home brand polish; group 2 had two coats of home brand polish; group 3 had one coat of salon brand polish; and group 4 had four coats of salon brand polish (one base coat, two coats of polish, and one final clear coat). The control group included one nail from each donor that was dosed unpainted. Tavaborole topical solution, 5% was applied once daily for 14 consecutive days at a dose of 25 µL/cm2. Penetration of tavaborole topical solution, 5% was measured daily by monitoring the tavaborole concentration in the receiving medium.
RESULTS: After 14 days, mean ± SD cumulative penetration of tavaborole was numerically higher in all groups that received nail polish (group 1: 1428 ± 841 µg/cm2; group 2: 1493 ± 1322 µg/cm2; group 3: 1227 ± 974 µg/cm2; group 4: 1179 ± 554 µg/cm2); mean penetration in the control group was 566 ± 318 µg/cm2.
LIMITATIONS: These studies were limited by their in vitro nature and use of human ex vivo fingernails.
CONCLUSION: Tavaborole topical solution, 5% effectively penetrated through four layers of nail polish.
CORRESPONDING AUTHOR: Lee Zane, MD, Anacor Pharmaceuticals, Inc, 1020 East Meadow Circle, Palo Alto, CA 94303-4230. E-mail: [email protected].
CONFLICTS: Ms Coronado, Dr Chanda, Dr Merchant, and Dr Zane are employees and stockholders of Anacor Pharmaceuticals, Inc. Dr Vlahovic is a remunerated speaker and advisory board participant for Anacor, Merz, and Valeant. Dr Elewski is a consultant for Anacor Pharmaceuticals, Inc.

PA-17: Long-term safety and efficacy of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate-to-severe psoriasis; efficacy and safety results from a phase 3, randomized controlled trial (ESTEEM 1)

Papp K,1 Reich K,2 Leonardi C,3 Kircik L,4 Chimenti S,5 Shah K,6 Hu C,6 Stevens RM,6 Day RM,6 Griffiths CEM7
1Probity Medical Research, Waterloo, Ontario, Canada.
2SCIderm Research Institute and Dermatologikum Hamburg, Hamburg, Germany.
3Saint Louis University School of Medicine, St. Louis, Missouri, USA.
4Physicians Skin Care, PLLC, Louisville, Kentucky, USA.
5University of Rome Tor Vergata, Rome, Italy.
6Celgene Corporation, Warren, New Jersey, USA.
7Dermatology Centre, University of Manchester, Manchester, United Kingdom.

BACKGROUND: Apremilast (APR), an oral phosphodiesterase 4 inhibitor, works intracellularly to regulate inflammatory mediators.
OBJECTIVE: To describe the long-term efficacy and safety of APR in patients with moderate-to-severe plaque psoriasis.
METHODS: In ESTEEM 1, patients with moderate-to-severe plaque psoriasis (PASI ≥ 12, BSA ≥ 10%, sPGA ≥ 3) were randomized 1:2 to placebo (PBO) or APR 30 mg BID (APR30). At Week 16, PBO patients were switched to APR30 through Week 32. At Week 32 patients treated with APR30 at baseline who achieved ≥75% reduction from baseline in PASI score (PASI-75) were rerandomized (1:1, blinded) to continue APR30 or receive PBO through Week 52. Upon loss of PASI-75, patients who were rerandomized to PBO resumed APR30.
RESULTS: 844 patients were randomized (mean psoriasis duration, 19.4 years; mean PASI score, 19.0; mean BSA, 24.7%). At Week 16, significantly more patients receiving APR30 achieved PASI-75 (33.1%) versus PBO (5.3%; P < .0001); primary endpoint. Mean percent change from baseline in PASI score was 52.1% for APR30 versus 16.7% for PBO (P < .0001). At Week 32, 154 patients randomized to APR30 at baseline were PASI-75 responders and were rerandomized to continue APR30 (n = 77) or switch to placebo (n = 77). In the randomized treatment withdrawal phase, 61.0% of 77 patients randomized to continue APR30 at Week 32 had PASI-75 at Week 52; 75.3% had ≥70% improvement in PASI score; mean percent change from baseline in PASI score at week 52 was -80.5%. Of patients switched to PBO who lost PASI-75 (median time: 5.1 weeks), 70.3% regained PASI-75 after restarting APR30. The duration of retreatment with APR30 through Week 52 ranged from 3.4 to 22.1 weeks. APR was generally well tolerated for up to 52 weeks. During the APR exposure period (defined as Weeks 0-52; including all patients who received APR, regardless of when initiated), 804 received ≥1 dose of APR30; adverse events (AEs) in ≥5% of patients were diarrhea (18.7%), URTI (17.8%), nausea (15.3%), nasopharyngitis (13.4%), tension headache (9.6%), and headache (6.5%). In APR-treated patients reporting diarrhea and nausea, the majority of the cases occurred within 2 weeks of the first dose, were predominantly mild in severity, and generally resolved within 1 month. The exposure-adjusted incident rate for AEs did not appear to increase over time, no new significant AEs emerged with continued exposure, and no clinically meaningful changes in laboratory measurements were reported. AEs were predominantly mild or moderate in severity. The occurrence of serious AEs was 4.2% and no specific serious AE was reported for >3 patients during the APR exposure period. Discontinuation rate due to AEs was low during the APR-exposure period (7.3%).
LIMITATIONS: Study limited to 52 weeks.
CONCLUSION: PR30 significantly reduced the severity of moderate-to-severe psoriasis over 16 weeks of treatment. The clinical response for APR30 was generally maintained in patients treated for 52 weeks. APR 30 demonstrated an acceptable safety profile and was generally well tolerated for up to 52 weeks. Most AEs were mild or moderate in severity and did not lead to discontinuation.
CORRESPONDING AUTHOR: Kim Papp, MD, Probity Medical Research, Waterloo, ON N2J Canada. E-mail: [email protected].
CONFLICTS: Dr Papp reports personal fees from Celgene Corporation during the conduct of the study, and personal fees from Abbott Laboratories, Amgen, Astellas, Biogen-Idec, BMS, Boehringer Ingelheim, Centocor, Forward Pharma, Genentech, Incyte, Isotechnika, Janssen Pharmaceuticals Inc, Johnson & Johnson, Kyowa Kirin, LEO Pharma, Eli Lilly, MedImmune, Merck Sharp & Dohme, Merck-Serono, Novartis, Pfizer Inc, Stiefel, Takeda Pharmaceuticals, UCB Inc, Wyeth, 3M, Akesis, Akros, Alza, Anacor, Baxter, Celtic, Cipher, Dow Pharma, Funxional Therapeutics, Galderma Laboratories, Kataka, Lypanosys, Medical Minds, Mitsubishi Pharma, and Vertex outside the submitted work. Dr Reich reports personal fees from Celgene Corporation during the conduct of the study, and personal fees from AbbVie Pharmaceuticals, Amgen, Biogen-Idec, Celgene Corporation, Centocor, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, LEO Pharma, Eli Lilly, Medac, MSD, Novartis, Pfizer Inc, Takeda, and Vertex outside the submitted work. Dr Leonardi reports personal fees from Celgene Corporation during the conduct of the study, and personal fees from Amgen, Celgene Corporation, Centocor, Galderma Laboratories, Genentech, GlaxoSmithKline, Eli Lilly, Novartis, Novo Nordisk, Pfizer Inc, Sirtris, Stiefel, Vascular Biogenics, and Wyeth outside the submitted work. Dr Kircik reports personal fees from Celgene Corporation during the conduct of the study, and personal fees from Abbott Laboratories, Acambis, Allergan, Amgen, Assos Pharma, Astellas Pharma US, Asubio, Berlex Laboratories (Bayer HealthCare Pharmaceuticals), Biogen-Idec, Biolife, Biopelle, Breckinridge Pharma, Colbar, Celgene Corporation, Centocor, CollaGenex, Combinatrix, Connetics, Coria, Dermik Laboratories, Dow Pharmaceutical Sciences, Dusa, Embil Pharmaceuticals, EOS, Ferndale Laboratories, Galderma Laboratories, Genentech, GlaxoSmithKline, Health Point, Intendis, Innovail, Johnson & Johnson, Laboratory Skin Care, LEO Pharma, 3M, Medical International Technologies, Merck, Medicis Pharmaceutical, Merz, Nano Bio, Novartis AG, Nucryst Pharmaceuticals, Obagi, Onset, OrthoNeutrogena, Promius, QLT, PharmaDerm, Pfizer Inc, Quatrix, Serono (Merck Serono International SA), SkinMedica, Stiefel Laboratories, TolerRx, Triax, Valeant Pharmaceuticals Intl, Warner-Chilcott, and ZAGE outside the submitted work. Dr Chimenti reports personal fees from Celgene Corporation during the conduct of the study, and personal fees from Abbott Laboratories, Celgene Corporation, Janssen Pharmaceuticals Inc, and Pfizer Inc outside the submitted work. Dr Shah is an employee of Celgene Corporation. C Hu is an employee of Celgene Corporation. Dr Stevens is an employee of Celgene Corporation. Dr Day is an employee of Celgene Corporation. Dr Griffiths reports personal fees from Celgene Corporation and from the National Institute for Health Research during the conduct of the study, and personal fees from AbbVie Pharmaceuticals, Actelion Pharmaceuticals Ltd, Amgen, Celgene Corporation, GlaxoSmithKline, Janssen Pharmaceuticals Inc, LEO Pharma, Eli Lilly, MSD, Novartis, Pfizer Inc, Trident, Sandoz and UCB Inc outside the submitted work.

PA-18: Major adverse cardiovascular events in the psoriasis longitudinal assessment and registry study: current status of observations

Gottlieb AB,1 Bissonnette R,2 Kerdel F,3 Naldi L,4 Papp K,5 Goyal K,6 Calabro S,6 Langhoff W,6 Fakharzadeh S,6 on behalf of the PSOLAR Steering Committee
1Tufts Medical Center, Boston, MA, USA.
2Innovaderm Research, Inc, Montreal, Quebec, Canada.
3Florida Academic Dermatology Centers, Miami, FL, USA.
4Centro Studi GISED, Ospendali Riuniti, Bergamo, Italy.
5K Papp Clinical Research and Probity Research, Waterloo, Ontario, Canada.
6Janssen Scientific Affairs, LLC., Horsham, PA, USA.

BACKGROUND: PSOLAR is a multicenter, longitudinal, observational study evaluating long-term safety and clinical outcomes for patients who are candidates for systemic therapy.
OBJECTIVE: To report the unadjusted cumulative rates of major adverse cardiovascular events (MACE) overall and by treatment groups in the Psoriasis Longitudinal Assessment and Registry (PSOLAR) study.
METHODS: MACE are defined as cardiovascular death, nonfatal stroke, and confirmed nonfatal myocardial infarction. Rates of MACE are assessed using 2 definitions of exposure based on: treatment at any time prior to and treatment within 91 days preceding the event. In cases of exposure to >1 therapy, the rule for attribution of MACE to a treatment group is ustekinumab first, infliximab/golimumab second, other biologics third (nearly all adalimumab or etanercept), or nonbiologic therapy fourth, which is consistent with the prespecified analytic plan.
RESULTS: PSOLAR is fully enrolled and as of the most recent data cut-off date (August 23, 2013) with 12095 patients and 31 818 cumulative patient-years of follow-up, reflecting a median duration of 2.5 years. Unadjusted MACE rates, based on exposure at any time, were: ustekinumab 0.34 events per 100 patient years (PY) [95% CI: 0.23, 0.48; 30/8870 PY]; infliximab/golimumab 0.38 per 100 PY [95% CI: 0.22, 0.62; 16/4205 PY]; other biologics 0.33 per 100 PY [95% CI: 0.24, 0.44; 43/13167 PY]; nonbiologic therapy 0.45 per 100 PY [95% CI: 0.29, 0.66; 25/5576 PY]; overall 0.36 per 100 PY [95% CI: 0.30, 0.43; 114/31818 PY]. Rates of MACE per 100 PY based on treatment received within 91 days of an event were: ustekinumab 0.29 events per 100 PY[95% CI: 0.17, 0.47; 16/5497 PY]; infliximab/golimumab 0.31 per 100 PY [95% CI: 0.14, 0.62; 8/2558 PY]; other biologics 0.28 per 100 PY [95% CI: 0.19, 0.40; 29/10341 PY]; nonbiologic therapy 0.45 per 100 PY [95% CI: 0.35, 0.58; 61/13421 PY]; overall 0.36 per 100 PY [95% CI: 0.30, 0.43; 114/31818 PY].
LIMITATIONS: Rates have not been adjusted for demographic and clinical differences among treatment groups and are subject to attribution rules.
CONCLUSION: With nearly 32000 PY of follow-up in the PSOLAR registry, the unadjusted MACE rates are generally comparable across biologic treatment groups. Future analyses may assess MACE outcomes with respect to differences in baseline and clinical characteristics and specific therapies.
CORRESPONDING AUTHOR: Kavitha Goyal, MD, Janssen Scientific Affairs, LLC, 850 Ridgeview Drive, Horsham, PA 19044. E-mail: [email protected].
CONFLICTS: Drs Gottlieb, Bissonnette, Kerdel, Naldi, and Papp have served as investigators for Janssen Scientific Affairs, LLC. Dr Goyal, M Calabro, Dr Langholff, and Dr Fakharzadeh are all employees of Janssen Scientific Affairs, LLC.

PA-19: Malignancies in the psoriasis longitudinal assessment and registry (PSOLAR) study: current status of observations.

Fiorentino D,1 Lebwohl M,2 Ho V,3 Langley R,4 Goyal K,5 Fakharzadeh S,5 Calabro S,5 Langholff W,5 on behalf of the PSOLAR Steering Committee
1Stanford University, Stanford, California, USA.
2Mount Sinai Medical Center, New York, New York, USA.
3University of British Columbia, Vancouver, British Columbia, Canada.
4Dalhousie University, Halifax, Nova Scotia, Canada.
5Janssen Scientific Affairs, LLC., Horsham, Pennsylvania, USA.

BACKGROUND: PSOLAR is a multicenter, longitudinal, observational study evaluating longterm safety and clinical outcomes for patients eligible to receive treatment for psoriasis with biologics and/or conventional systemic agents.
OBJECTIVE: To report the cumulative incidence of malignancies excluding nonmelanoma skin cancers (NMSC) in the PSOLAR study.
METHODS: The incidence of malignancies excluding NMSC (ie, basal/squamous cell carcinomas) in PSOLAR overall and by treatment groups is reported. Rates of malignancy are assessed using a definition of exposure based on whether patients had ever been exposed to a given therapy at any time prior to the event. In cases of exposure to >1 therapy, the rule for attribution of malignancy to a treatment group is ustekinumab first, infliximab/golimumab second, other biologics third (nearly all adalimumab or etanercept), or nonbiologic therapy fourth, which is consistent with the prespecified analytic plan.
RESULTS: PSOLAR is fully enrolled and as of the August 23, 2013 data cut has 31, 818 cumulative patient-years of follow up with 12,095 patients. Unadjusted cumulative rates of malignancy (excluding NMSC) overall and across treatment groups: overall 0.68 events per 100 patient years of observation (PYO; 95% CI: 0.59, 0.77; 215/31818), ustekinumab 0.51 per 100 PYO (95% CI: 0.37, 0.68; 45/8870 PYO), infliximab/golimumab (almost exclusively infliximab) 0.64 per 100 PYO [95% CI: 0.42, 0.93; 27/4205, other biologics (almost exclusively etanercept/ adalimumab) 0.74 per 100 PYO (95% CI: 0.60, 0.91; 98/13167), and nonbiologic therapy 0.81 per 100 PYO (95% CI: 0.59, 1.08; 45/5576). The cumulative rates per 100 PY for the overall registry population for the most frequent specific malignancies were: breast cancer 0.13 [40], prostate cancer 0.09 (30), lung cancer 0.08 (26), and melanoma 0.07 (22).
LIMITATIONS: Rates have not been adjusted for demographic and clinical differences among treatment groups and are subject to attribution rules.
CONCLUSION: In the current evaluation, reflecting a median duration of 2.5 years of follow-up, cumulative unadjusted rates of malignancies in PSOLAR are comparable across treatment groups. The most frequently reported malignancies in the registry are comparable with the most frequently reported malignancies in the general population. Additional evaluation of malignancies with accruing longitudinal exposure will be informative.
CORRESPONDING AUTHOR: Kavitha Goyal, MD, Janssen Scientific Affairs, LLC, 850 Ridgeview Drive, Horsham, PA 19044. E-mail: [email protected].
CONFLICTS: Drs Fiorentino, Lebwohl, Ho, and Langley served as investigators for Janssen Scientific Affairs, LLC. Dr Goyal, Dr Fakharzadeh, S Calabro, and Dr Langholff are employees of Janssen Scientific Affairs, LLC.

PA-20: Maximal use systemic exposure (MUSE) study evaluating AN2728, a novel boron-based small molecule, for the treatment of pediatric and adolescent subjects with mild-to-moderate atopic dermatitis.

Kircik L,1 Call R,2 Tschen E,3 Draelos ZD,4 Van Syoc M,5 Zane L,5 Hebert AA6
1DermResearch, PLLC, Louisville, Kentucky, USA.
2Clinical Research Partners, LLC, Henrico, Virginia, USA.
3Academic Dermatology Associates, Albuquerque, New Mexico, USA.
4Dermatology Consulting Services, High Point, North Carolina, USA.
5Anacor Pharmaceuticals, Inc, Palo Alto, California, USA.
6Dermatology Clinical Research Unit, University of TX Health Science Center, Houston, Texas, USA.

BACKGROUND: AN2728 is a novel boron-based compound that inhibits phosphodiesterase-4 activity and reduces the production of pro-inflammatory cytokines that may be associated with atopic dermatitis (AD).
OBJECTIVE: The objective of this open-label, maximal use study was to evaluate the systemic exposure, pharmacokinetics, and safety of AN2728 Ointment, 2% applied twice daily for 28 days for the treatment of AD in children and adolescents.
METHODS: The study enrolled 34 subjects with mild-to-moderate AD, defined as a score of 2 (mild) or 3 (moderate) on the 5-point Investigator's Static Global Assessment (ISGA) scale in three patient cohorts based on age and minimum percent of treatable body surface area (%BSA) affected: 2 -5 years old (≥35%), 6-11 years old (≥35%) and 12 - 17 years old (≥25%). During the first 8 days when pharmacokinetic assessments were performed, subjects were dosed in the clinic; dosing was performed at home thereafter. Disease severity was measured using ISGA (0, clear to 4, severe), signs/ symptoms score (0, none to 3, severe) and %BSA affected.
RESULTS: At Day 29, 65% of subjects achieved ISGA scores of clear or almost clear and 47% of subjects achieved scores of clear or almost clear with a >2-grade improvement from baseline. Marked reductions from baseline were observed across all the individual signs and symptoms of AD (pruritus, erythema, lichenification, excoriation and exudation) throughout the treatment period. Notably, mean pruritus scores improved by approximately 60% from baseline as early as 5 days into treatment. The mean %BSA affected decreased by an average of 78% across all subjects after 4 weeks of treatment. The most common treatment-related adverse events were application site reactions (occurring in 12 subjects) which generally were mild or moderate in severity and resolved spontaneously. One patient withdrew from the study due to application site pain. Pharmacokinetic results demonstrated low blood levels of AN2728 similar to those previously observed in adults after adjusting for %BSA treated.
LIMITATIONS: Potential limitations of this study include the open-label study design, the small sample size assessed, and the limited duration of treatment.
CONCLUSION: These results generated under maximal use conditions suggest that AN2728 Ointment, 2% may be safe and effective in subjects 2 years of age and older with mild-to-moderate AD.
CORRESPONDING AUTHOR: Lee Zane, MD, Anacor Pharmaceuticals, Inc, 1020 East Meadow Circle, Palo Alto, CA 94303-4230. E-mail: [email protected].
CONFLICTS: Dr Zane and Ms. Van Syoc are employees and stockholders of Anacor Pharmaceuticals, Inc Dr Kircik is a remunerated speaker for Abbott Laboratories, Allergan, Inc, Amgen, Inc, Assos Pharma, Astellas Pharma US, Inc, CollaGenex, Connetics Corporation, Dermik Laboratories, Embil Pharmaceuticals, Galderma Laboratories, LP, Genentech, Inc, Innocutis, Innovail, Johnson & Johnson, Leo, L'Oreal, 3M, Onset, OrthoNeutrogena, PharmaDerm, Serono (Merck Serono International SA), SkinMedica, Inc, Stiefel Laboratories, Inc, Triax, UCB, Valeant Pharmaceuticals Intl., and Warner-Chilcott; is a remunerated consultant for Allergan, Inc, Amgen, Inc, Anacor Pharmaceuticals, Colbar, CollaGenex, Connetics Corporation, Galderma Laboratories, LP, Genentech, Inc, Intendis, Johnson & Johnson, Laboratory Skin Care Inc, Leo, Medical International Technologies, Merck, Merz, Novartis AG, OrthoNeutrogena, Promius, PuraCap, SkinMedica, Inc, Stiefel Laboratories, Inc, UCB, Valeant Pharmaceuticals Intl., and ZAGE; is a remunerated advisory board member for Allergan, Inc, Anacor Pharmaceuticals, Biogen-Idec, Colbar, Celgene, Connetics Corporation, EOS, Ferndale Laboratories, LP, Galderma Laboratories, LP, Genentech, Inc, Intendis, Innocutis, Johnson & Johnson, Nano Bio, OrthoNeutrogena, Promius, SkinMedica, Inc, Stiefel Laboratories, Inc, Valeant Pharmaceuticals Intl., and Warner-Chilcott; is a remunerated investigator for Allergan, Inc, and QLT, Inc; has received research grant support as an investigator for Acambis, Amgen, Inc, Anacor Pharmaceuticals, Astellas Pharma US, Inc, Asubio, Berlex Laboratories (Bayer HealthCare Pharmaceuticals), Biolife, Biopelle, Breckinridge Pharma, Celgene, Centocor, Inc, CollaGenex, Combinatrix, Connetics Corporation, Coria, Dow Pharmaceutical Sciences, Inc, Dusa, Eli Lily, Ferndale Laboratories, LP, Galderma Laboratories, LP, Genentech, Inc, GlaxoSmithKline, PLC, Health Point, LTD, Intendis, Johnson & Johnson, Leo, L'Oreal, 3M, Maruho, Medical International Technologies, Merck, Medicis Pharmaceutical Corp, Nano Bio, Novartis AG, Noven Pharmaceuticals, Nucryst Pharmaceuticals Corp, Obagi, Onset, OrthoNeutrogena, Promius, Pharma-Derm, Pfizer, Quatrix, SkinMedica, Inc, Stiefel Laboratories, Inc, TolerRx, UCB, Valeant Pharmaceuticals Intl, Warner-Chilcott, and XenoPort; and is a stock shareholder in Johnson & Johnson. Dr Call is an investigator for Anacor Pharmaceuticals, Inc Dr Draelos has received funding from Dermatology Consulting Services to conduct research. Dr Hebert has received a grant from Anacor Pharmaceuticals, Inc. Dr Tschen is an investigator for Anacor Pharmaceuticals, Inc.

PA-21: Nearly pain-free self-administration of methotrexate (MTX) in patients using an auto-injector for subcutaneous use

Kivitz A,1 McLain D,2 Hill J,3 Freundlich B,4 Jaffe J5
1Altoona Center for Clinical Research, Duncansville, Pennsylvania, USA.
2McLain Medical Associates, Birmingham, Alabama, USA.
3Avail Clinical Research, DeLand, Florida, USA.
4University of Pennsylvania, Philadelphia, Pennsylvania, USA.
5Antares Pharma, Inc, Ewing, New Jersey, USA.

BACKGROUND: MTX is widely used as an effective, orally administered systemic therapy for severe psoriasis and rheumatoid arthritis (RA). Subcutaneous (SC) MTX improves bioavailability, which may result in better efficacy and tolerability. Self-administration of SC MTX via conventional vial and syringe is challenging for some patients. An auto-injector that delivers SC MTX is approved for use in adults with severe, active RA and adults with severe, resistant, disabling psoriasis.
OBJECTIVE: The purpose of this study was to determine the extent to which the MTX auto-injector addresses the concerns of patients currently receiving conventional SC administration.
METHODS: This was a phase 2, multicenter, open-label, single-dose, single-arm study involving 101 RA patients. The MTX dose (10, 15, 20, or 25 mg) administered was based on the patient's existing MTX regimen and disease status at time of enrollment. Administration-site pain was measured on a 100 mm visual analog scale (VAS), with 0 = no pain and 100 = worst pain imaginable. Injection-site erythema was measured on a scale of 0 to 4, with 0 = none and 4 = severe. Safety was assessed by recording treatment-emergent AEs (TEAEs) and evaluating administration sites before self-administration and at 0.25, 1, 6, and 24 hours after administration.
RESULTS: A total of 101 patients completed the study with 99 evaluable for pain (79.2% female; mean age, 60.9 years; disease duration, 13.3 years; 84.2% ACR Class II or III; 89.1% Functional Class II or III). All patients had been taking MTX for ≥3 months prior to study enrollment; 20% had previously used SC MTX. Mean administration-site pain (± SD) was 3.6 mm ± 9.1 mm on day 1 and 1.4 mm ± 3.2 mm on day 2. No erythema was reported by >88% of patients following injection of any dose of MTX auto-injector. TEAEs were reported by 3 patients (sick sinus syndrome, exostosis, and headache); none was considered related to the study drug. All patients, including those with moderate-to-severe functional limitations in dexterity, successfully used the auto-injector.
CONCLUSIONS: The MTX auto-injector was well tolerated. Improving the delivery of SC MTX with this first-in-class auto-injector may increase patient tolerance of self-administration and improve patient adherence to SC MTX treatment regimens.
CORRESPONDING AUTHOR: Alan Kivitz, MD, Altoona Center for Clinical Research, 175 Meadowbrook Lane, Duncansville, PA 16635. E-mail: [email protected].
CONFLICTS: Dr Kivitz reports grants from Antares Pharma, Inc, outside the submitted work. Dr McLain reports personal fees from Crescendo Bioscience, grants from Antares Pharma, Inc, grants from Astellas, grants from Astrazeneca, grants from Celgene, grants from Lilly, grants from MedImmune, grants from Novartis, grants and personal fees from Pfizer, grants from Teva, grants from UCB, outside the submitted work. Dr Hill has nothing to disclose. Dr Freundlich has received outside of the submitted work consulting fees from Antares Pharma, Inc, Bristol-Myers Squibb, and Celgene; and is a shareholder of Pfizer. Dr Jaffe is an employee of Antares Pharma, Inc.

PA-22: Non-serious and transient candidiasis in secukinumab-treated subjects: a pooled analysis of data from 10 clinical trials in moderate-to-severe plaque psoriasis

Reich K,1 Blauvelt A,2 Krueger J,3 Cooper S,4 Fox T,5
1Dermatologikum Hamburg and Georg-August-University Göttingen, Hamburg, Germany.
2Oregon Medical Research Center, Portland, Oregon, USA.
3The Rockefeller University, New York, New York, USA.
4Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA (former employee).
5Novartis Pharma AG, Basel, Switzerland.

BACKGROUND: Physiologically, interleukin (IL)-17A is involved in immune surveillance of mucocutaneous tissue, and genetic deficiencies in IL-17A function are associated with increased susceptibility to Candida infection.1 Consequently, anti–IL-17A therapies may confer increased risk of mucocutaneous candidiasis. Secukinumab, a fully human anti-IL-17A monoclonal antibody, demonstrated strong efficacy/tolerability in clinical studies of subjects with moderate-to-severe plaque psoriasis.
OBJECTIVE: Here we report the safety analysis of data pooled from secukinumab trials that assessed the mucocutaneous Candida infection risk.
METHODS: We pooled data from 10 randomized, double-blind, placebo-controlled, phase 2 and phase 3 studies. Subjects received subcutaneous secukinumab 300 mg (n = 1410; 1178 subject-years of exposure), secukinumab 150 mg (n = 1395; 1142 subject-years of exposure), etanercept 50 mg (n = 323; active comparator; 294 subject-years of exposure), or placebo (n = 793; 201 subject-years of exposure) for ≤ 52 weeks.
RESULTS: The overall incidence of candidiasis in the pooled dataset was low. Exposure-adjusted incidence (per 100 subject-years) was greater in the secukinumab 300 mg group (3.6), while incidence with secukinumab 150 mg (1.9) was similar to placebo (1.0) and etanercept (1.4). All Candida infections reported with secukinumab were mild or moderate in severity, localized to skin or mucosa and nonserious; 2 etanercept-treated subjects experienced severe cases. There were no chronic infections; all infections either self-resolved or responded to standard treatment, and none necessitated study treatment discontinuation.
LIMITATIONS: Data for etanercept regimen is available from only one phase 3. Placebo data were mostly from the first 12 weeks of treatment. Mode of administration varied between studies, and range of doses tested was broad (intravenous doses of 3 to 30 mg/kg and subcutaneous doses of 25 to 300 mg).
CONCLUSIONS: Candida infections with secukinumab in this pooled analysis were all mucocutaneous in origin, mild or moderate in severity, localized, and either self-resolving or responsive to standard treatment. Long-term data are needed to fully understand the impact of anti–IL-17A therapy on candidiasis risk. The data presented here suggest that therapeutic IL-17A inhibition with secukinumab does not confer any serious biologic consequences typically observed in individuals genetically deficient in this cytokine.
CORRESPONDING AUTHOR: Kristian Reich, Dermatologikum Hamburg, Stephanspalatz 5, Hamburg, 20354, Germany. E-mail: [email protected].
CONFLICTS: Dr Reich reports grants and personal fees from Novartis, during the conduct of the study; grants and personal fees from Abbvie, grants and personal fees from Amgen, grants and personal fees from Biogen IDEC, grants and personal fees from Celgene, grants and personal fees from Janssen-Cilag, grants and personal fees from Medac, grants and personal fees from Pfizer, grants and personal fees from Centocor, grants and personal fees from Covagen, grants and personal fees from GSK, grants and personal fees from Forward Pharma, grants and personal fees from Leo, grants and personal fees from Lilly, grants and personal fees from Levia, grants and personal fees from MSD, grants and personal fees from Vertex, grants and personal fees from Takeda, outside the submitted work; and Professor Kristian Reich has received honoraria as consultant and/or advisory board member and/or acted as paid speaker and/or participated in clinical trials sponsored by AbbVie, Amgen, Biogen-Idec, Celgene, Centocor, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, LEO Pharma, Lilly, Medac, MSD, Novartis, Ocean Pharma, Pfizer, Regeneron, Takeda, Vertex. Dr Blauvelt reports personal fees and other from Novartis, during the conduct of the study; personal fees and other from Amgen, personal fees and other from Eli Lilly & Co, personal fees and other from Janssen, personal fees and other from Merck, personal fees and other from Pfizer, personal fees from Anacor Pharmaceuticals, personal fees from Takeda Pharmaceuticals, personal fees from Baxter, personal fees from Momenta, personal fees from Celgene, personal fees from Regeneron, personal fees from Maruho, other from Cenotocor, outside the submitted work. Dr Krueger reports personal fees and other from Novartis, personal fees and other from Pfizer, other from Amgen, personal fees and other from Lilly, personal fees and other from Merck, personal fees and other from Kadmon, personal fees and other from Dermira, personal fees and other from Boehringer, other from Innovaderm, other from Kyowa, personal fees from BMS, personal fees from Serono, personal fees from BiogenIdec, personal fees and other from Jamssen, personal fees from Delenex, personal fees from AbbVie, personal fees from Sanofi, personal fees from Baxter, other from Paraxel, personal fees from Xenoport, personal fees from Kineta, during the conduct of the study. Dr Cooper reports personal fees from Novartis, during the conduct of the study. Dr Fox reports personal fees from Novartis, during the conduct of the study.
FUNDING/SUPPORT: The study was sponsored by Novartis Pharma AG, Basel, Switzerland.
1. Puel A, Cypowyj S, Maródi L, Abel L, Picard C, Casanova JL. Inborn errors of human IL-17 immunity underlie chronic mucocutaneous candidiasis. Curr Opin Allergy Clin Immunol. 2012;12(6):616-622.

PA-23: Patient perspectives in the management of psoriasis: US results from the population-based multinational assessment of psoriasis and psoriatic arthritis (MAPP) survey

Lebwohl MG,1 Armstrong AW,2 Van Voorhees AS,3 Kalb RE,4 Kavanaugh A5
1The Icahn School of Medicine at Mount Sinai, New York, New York, USA.
2Department of Dermatology, University of Colorado at Denver, Aurora, Colorado, USA.
3Department of Dermatology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
4Department of Dermatology, State University of New York at Buffalo School of Medicine and Biomedical Sciences Medical Group, Buffalo, New York, USA.
5University of California at San Diego, La Jolla, California, USA.

BACKGROUND: To gain further insight into real-world treatment trends and unmet needs from the patient and physician perspectives, the population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey of 3426 patients and 781 physicians in North America and Europe was conducted.
OBJECTIVE: The objective of this presentation is to report results from the subset of US patients participating in the MAPP survey.
METHODS: Telephone numbers for this household survey were randomly selected by list-assisted random digit dialing. Adults diagnosed with psoriasis and/or psoriatic arthritis (PsA) participated. Patients did not have to be currently under the care of a healthcare provider (HCP), a patient organization member, or receiving treatment.
RESULTS: From 52926 US households screened, 1005 adults completed the survey. The US household prevalence of psoriasis was 4.0%; the extrapolated population prevalence was 2.2%. A diagnosis of psoriasis alone was reported by 73.1% of patients; 26.9% indicated a diagnosis of PsA (± a separate diagnosis of psoriasis). Severe disease was reported by 29.5% of patients with psoriasis and 55.9% with PsA. The most important factors contributing to symptom severity in psoriasis patients were itching (36.1%) and location or size of skin lesions (21.8%). In PsA patients, the most important factors were pain or swelling of joints (48.1%) and itching (14.8%). Although most patients had seen an HCP in the past 12 months, ≈ 20% of patients who had not seen an HCP reported it was because they did not think their HCP could help. About 23% of psoriasis patients and 55% of PsA patients reported ever having a discussion with their current HCP about conventional oral or biologic therapies. Current or prior conventional oral therapy was reported by 14.8% of psoriasis and 52.2% of PsA patients; 30.3% (psoriasis) and 46.1% (PsA) of these patients were taking these medications at the time of the survey, whereas the majority had discontinued therapy. Only 8.6% of psoriasis patients reported ever having used biologic therapy versus 42.6% of PsA patients; ≈ 60% of these patients were receiving biologics at the time of the survey, whereas the rest had discontinued. At the time of the survey, 21.6% of patients reported no current treatment; 9.3% of psoriasis and 50.0% of PsA patients were receiving systemic therapy. Perceived treatment burden, safety/tolerability concerns, and lack of effectiveness were associated with treatment dissatisfaction and discontinuation.
LIMITATIONS: The MAPP survey was limited by factors such as accurate recall and interpretation of questions. Because the survey was blinded, patients could not be recontacted to clarify their answers. The survey design lacked a control group, such as healthy individuals or those with another chronic disease, which would have provided useful comparisons for disease burden and treatment satisfaction. Ethnicity and healthcare coverage was not accounted for, which may have impacted responses.
CONCLUSIONS: Psoriasis and PsA remain undertreated in the United States, marked by high treatment dissatisfaction and discontinuation. Several unmet needs are identified and warrant further attention.
CORRESPONDING AUTHOR: Mark Lebwohl, The Mount Sinai Medical Center, 5 E 98th St., 5th Floor, Box 1048, New York, NY 10029. E-mail: [email protected].
CONFLICTS: Dr Lebwohl reports personal fees from Celgene Corporation during the conduct of the study, and personal fees from Abbott Laboratories, Amgen, Anacor Pharmaceuticals, Inc, BioLineRx, Ltd., Coronado Biosciences, DermiPsor Ltd., Eli Lilly and Company, Galderma Laboratories, GlaxoSmithKline, Janssen Biotech Inc, LEO Pharma, Maruho Co. Ltd., Meda Pharmaceuticals, Novartis Pharmaceuticals Corporation, Pfizer Inc, Ranbaxy Inc, and Valeant Pharmaceuticals outside the submitted work. Dr Armstrong reports personal fees from Celgene Corporation during the conduct of the study, and personal fees from AbbVie Pharmaceuticals, Amgen, Eli Lilly, Janssen Pharmaceuticals Inc, Merck, and Pfizer Inc outside the submitted work. Dr Van Voorhees reports personal fees from Celgene Corporation during the conduct of the study, and personal fees from AbbVie Pharmaceuticals, Amgen, Celgene Corporation, Janssen Pharmaceuticals Inc, LEO Pharma, Novartis Pharmaceuticals Corporation, Pfizer Inc, and Warner Chilcott outside the submitted work. Dr Kalb reports personal fees from Celgene Corporation during the conduct of the study, and personal fees from AbbVie Pharmaceuticals, Amgen, Janssen Biotech Inc., Leo Pharma, Taro Pharmaceuticals, ApoPharma, and Eli Lilly outside the submitted work. Dr Cavanaugh reports personal fees from Celgene Corporation during the conduct of the study, and personal fees from AbbVie Pharmaceuticals, Amgen, Bristol-Myers Squibb, Celgene Corporation, Janssen Pharmaceuticals Inc, and UCB Inc outside the submitted work.

PA-24: Patient satisfaction with current psoriasis treatment

Korman NJ,1 Zhao Y,2 Roberts J,3 Pike J,3 Tran MH,2 Lu J2
1University Hospitals Case Medical Center, Cleveland.
2Novartis Pharmaceuticals Corporation, East Hanover.
3Adelphi Real World, United Kingdom.

BACKGROUND: Psoriasis patients often report dissatisfaction with treatment. However, it is less clear how the severity of key psoriasis symptoms (painful skin, itching and scaling) as well as overall disease severity influence this dissatisfaction.
OBJECTIVE: To explore treatment satisfaction among psoriasis patients.
METHODS: Data were extracted from the Adelphi 2011/2013 Psoriasis Disease Specific Programmes, two "Real World" surveys of US dermatologists and their patients. Dermatologists provided disease characteristics, while patients indicated their satisfaction with existing treatment. Severity (none, mild, moderate/severe) of psoriasis-related pain, itching and scaling, overall disease severity (mild, moderate, and severe) and therapy type were compared by patient satisfaction (satisfied vs dissatisfied). Multivariate regressions were performed to examine the relationship between patient satisfaction, key clinical symptoms and psoriasis overall disease severity, controlling for differences in patient demographics and comorbidities.
RESULTS: The sample comprised 633 psoriasis patients (56% male) with a mean age of 45. Overall, 18% of patients reported dissatisfaction with their psoriasis treatment. Dissatisfied patients were more likely to have moderate (65% vs 40%) or severe (21% vs 3%) psoriasis compared to patients who were satisfied (both P < .0001). Dissatisfied patients were also more likely to have more severe pain (30% moderate-to-severe pain vs 9%), itching (61% moderate-to-severe itching vs 25%), and scaling (68% moderate-to-severe scaling vs 33%) than satisfied patients (all P < .0001). Multivariate analyses confirmed these results.
LIMITATIONS: Only consulting patients were invited to participate. Therefore, the patient sample may not be representative of the wider psoriasis population.
CONCLUSION: Clinicians should be aware that some more severe psoriasis patients may be dissatisfied and in need of better treatment.
CORRESPONDING AUTHOR: Yang Zhao, PhD, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936-1080. E-mail: [email protected].
CONFLICTS: Drs Zhao, Tran, and Lu are employed by Novartis Pharmaceuticals Corporation; Dr Korman is on the advisory board for Novartis Pharmaceuticals Corporation. Drs Pike and Roberts have nothing to disclose.

PA-25: Persistence of biologic therapy in the Psoriasis Longitudinal Assessment and Registry (PSOLAR)

Menter A,1 Papp K,2 Krueger GG,3 Augustin M,4 Kerdel F,5 Gooderham M,6 Goyal K,7 Fakharzadeh S,7 Langholff W,7 Sermon J,8 Calabro S,7 Pariser D,9 on behalf of the PSOLAR Global Steering Committee
1Baylor University Medical Center, Dallas, Texas, USA.
2K Papp Clinical Research and Probity Medical Research, Waterloo, Ontario, Canada.
3University of Utah, Salt Lake City, Utah, USA.
4University Clinics of Hamburg, Hamburg, Germany.
5Florida Academic Dermatology Centers, Miami, Florida, USA.
6SKIN Centre for Dermatology and Probity Medical Research, Peterborough, Ontario, Canada.
7Janssen Scientific Affairs, LLC., Horsham, Pennsylvania,USA.
8Janssen-Cilag, Beerse, Belgium.
9Eastern Virginia Medical School and Virginia Clinical Research, Inc, Norfolk, Virginia, USA.

BACKGROUND: PSOLAR, a multicenter, longitudinal, observational study evaluating long-term safety and clinical outcomes for psoriasis (PsO) patients receiving or eligible to receive treatment with biologics and/or conventional systemic agents.
OBJECTIVE: We evaluated persistency (treatment longevity) of biologics for PsO.
METHODS: Duration of exposure was defined as time (in days) between first dose of biologic and the first of: 1) discontinuation 2) switch 3) registry withdrawal or 4) last database cutoff ( August 23, 2013). Separate analyses were performed for: 1st line (bio-naïve; ie, first biologic started on registry), 2nd line (second biologic started while on registry) and 3rd line usage (third biologic started while on registry) to reduce confounding associated with prior exposures. Baseline demographics and reasons for stop/switch were summarized. Persistence was assessed by Kaplan-Meier (KM) analysis for time to therapy stop/switch separately for ustekinumab (UST), infliximab (IFX), adalimumab (ADA), and etanercept (ETN). Cox proportional hazard regression was used to compare time to stop/switch of UST with time to stop/switch of other biologics for each cohort.
RESULTS: The highest initiations were attributed to UST (1833) and ADA (1303) with lower for ETN (537) and IFX (327). Among UST starts, the proportions of 1st, 2nd and 3rd line usage were 20%, 31%, and 30%; ADA starts 31%, 48%, and 15%; ETN starts 54%, 29% and 13%; IFX starts 19%, 28% and 32%, respectively. Baseline demographics were generally comparable across biologics and cohorts, with some variability: prevalence of severe PsO was greater for UST and IFX vs ADA and ETN (higher BSA and higher proportions of patients with PGA score of 4 and 5). Fewer patients discontinued UST than IFX, ETN, and ADA, regardless of line of therapy. For first line starts, a better persistence was observed for UST vs the other biologics based on statistically significant differences in time to stop/switch for each biologic vs UST (IFX vs UST: HR3.04; CI:1.66-5.57; P = .0003; ADA vs UST: HR4.99; CI:3.39-7.35; P < .0001; ETN vs UST: HR5.59; CI:3.77-8.29; P < .0001). Similar results were observed for analysis of 2nd and 3rd line starts. Median duration of therapy was also generally longer for UST vs the 3 anti-TNF therapies. Reasons for stop/switch were similar across biologics and cohorts (most frequent reason-lack of efficacy). Data were not adjusted for variability such as socioeconomic factors (eg, access to medication), setting of administration (self vs HCP office), and region.
CONCLUSION: Persistence of ustekinumab therapy in PSOLAR was significantly better than anti-TNF therapies in biologic-naïve and experienced PsO patients, with lower rates of stopping/switching and higher median days on therapy.
CORRESPONDING AUTHOR: Kavitha Goyal, MD, Janssen Scientific Affairs, LLC, 850 Ridgeview Drive, Horsham, PA 19044. E-mail: [email protected].
CONFLICTS: Drs Menter, Papp, Krueger, Augustin, Kerdel, Gooderham, and Pariser have served as investigators for Janssen Scientific Affairs, LLC. Drs Goyal, Fakharzadeh, Langholff, and Sermon, and S. Calabro are all employees of Janssen Scientific Affairs, LLC

PA-26: Real-life treatment profile of calcipotriene/betamethasone topical suspension in patients with psoriasis vulgaris

Bagel J,1 Levi E,2 Goncalves J2
1Psoriasis Treatment Center of Central New Jersey, East Windsor, New Jersey, USA.
2LEO Pharma Inc; Parsippany, New Jersey, USA.

BACKGROUND: Randomized clinical trials play an important role in demonstrating the efficacy and safety of a therapeutic regimen although they often present unrealistically high estimates of patient-reported outcomes (PROs). Noninterventional studies using real-world patient populations and capturing PROs can provide realistic insights into patients' treatment experiences. Topical therapy with calcipotriene plus betamethasone dipropionate (CBD) fixed combination suspension has been shown to be effective and well tolerated in patients with psoriasis vulgaris.
OBJECTIVE: The purpose of this study was to document experiences with CBD topical suspension in a US clinical dermatology setting using PROs.
METHODS: This was a prospective, noninterventional, one-arm, multicenter study. Patients were ≥18 years of age with a clinical diagnosis of psoriasis vulgaris involving the scalp and/or body. Patients used CBD topical suspension once daily for up to 8 weeks, with a maximum of 100 g of medication per week. Data were collected at baseline and week 8, and one time at home (week 2). Patient-reported assessments were collected using the Dermatology Life Quality Index questionnaire (DLQI); patient's global assessment (PtGA) of disease severity, using a 5-point scale (clear, very mild, mild, moderate, or severe); a 0-100 graduated visual analogue scale (Itch VAS) of patient-reported level of itching; and the Treatment Satisfaction Questionnaire of Medication-9 (TSQM-9). Adverse events (AEs) and treatment adherence were assessed at the end of the study.
RESULTS: A total of 147 patients, mean age 49.1 years, were included in the intention-to-treat analyses. The mean absolute change from baseline in DLQI score (± SD) was -4.2 ± 5.28 at week 2 and -5.5 ± 5.93 at week 8, both P< .0001. Mean percent change in Itch VAS score was significantly reduced from baseline to week 2 (-19% ± 25.94%, P< .0001) and week 8 (-28.6% ± 29.14%, P< .0001). The percentage of patients with a PtGA score of very mild or mild was 60.2% at week 8 and 34.1% at week 2. Mean TSQM-9 scores for effectiveness, convenience, and satisfaction domains ranged from 65.13 to 74.39 after treatment initiation. The percentage of patients with a ≥5-point change in DLQI total score was 38.2% and 47.7% at weeks 2 and 8, respectively. Two patients reported treatment-emergent AEs that were deemed not related to study drug.
CONCLUSION: The results of this noninterventional study show that treatment with CBD topical suspension is efficacious and well tolerated and improves QoL in patients with localized psoriasis vulgaris.
CORRESPONDING AUTHOR: Jerry Bagel, Psoriasis Treatment Center of Central New Jersey, 59 One Mile Road, East Windsor, NJ 08520. E-mail: [email protected].
CONFLICTS: Dr Bagel has received outside of the submitted work grants and personal fees from LEO, Abbvie, Janssen, Novartis, Eli Lilly and Celgene; personal fees from Amgen; and grant support from Boehringer. Dr Levi was an employee of LEO Pharma Inc at the time of the study. She is currently an employee at Celgene Corporation. Dr Goncalves is an employee of LEO Pharma Inc.

PA-27: Results after at least 52 weeks of open-label treatment with ixekizumab in a phase 2 study in chronic plaque psoriasis

Gordon, K,1 Leonardi C,2 Lebwohl M,3 Cameron G,4 Erickson J,4 Braun D,4 Banerjee S,4 Heffernan M4
1Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
2St. Louis University School of Medicine, St, Louis, Missouri, USA.
3The Mount Sinai School of Medicine, New York, New York, USA.
4Eli Lilly and Company, Indianapolis, Indiana, USA.

BACKGROUND: Ixekizumab, an anti-IL-17A monoclonal antibody, has been shown to be effective in patients with moderate-to-severe chronic plaque psoriasis following 20 weeks of randomized, placebo-controlled therapy in a phase 2 study.1
OBJECTIVE: The efficacy and safety of ixekizumab after at least 52 weeks of additional treatment in an open-label extension (OLE) were evaluated.
METHODS: In this phase 2 study, patients received ixekizumab (10, 25, 75, or 150 mg) or placebo subcutaneously at 0, 2, 4, 8, 12, and 16 weeks during a randomized treatment period (RTP).1 At Week 20, patients entered a treatment-free period (Weeks 20 to 32) and were eligible to enter an OLE at Week 32 or at the time of treatment response falling below a PASI 75. Patients who entered the OLE were treated with 120 mg ixekizumab subcutaneously every 4 weeks. Efficacy was evaluated after 52 weeks in the OLE, and safety was evaluated over at least 52 weeks of treatment in the OLE.
RESULTS: Of the 129 patients who completed the RTP, 120 entered the OLE, and 86% (103/120) completed at least 52 weeks of OLE treatment. Responses of PASI 75, PASI 90, and PASI 100 were observed in 88% (101/115), 65% (75/115), and 42% (48/115) of patients after 12 weeks in the OLE and in 90% (92/102), 79% (81/102), and 57% (58/102) of patients after 52 weeks in the OLE. The mean percent improvement in PASI from the baseline of the RTP was 87% after 12 weeks and 91% after 52 weeks in the OLE. Among patients initially assigned to placebo (n = 22), a response of PASI 75, PASI 90, or PASI 100 was observed in 95% (19/20), 70% (14/20), and 50% (10/20) of patients after 12 weeks in the OLE and 95% (18/19), 95% (18/19), and 63% (12/19) of patients after 52 weeks in the OLE. Overall, 67% of patients had a treatment-emergent adverse event during the OLE, the most common being nasopharyngitis (10%), upper respiratory tract infection (8%), sinusitis (4%), and diarrhea (4%). Serious adverse events were reported for 8% of patients during the OLE. During the OLE, there were no deaths and no cases of tuberculosis or invasive fungal infections.
LIMITATIONS: Only descriptive analyses were feasible due to the open-label design, lack of continuous therapy, and limited number of subjects in this phase 2 OLE. Evaluation of more subjects in a longer-term study may extend these findings.
CONCLUSION: Clinical responses to ixekizumab observed after Week 12 in the OLE were maintained or improved after 52 weeks in the OLE. In addition, patients who received placebo in the RTP responded to ixekizumab treatment in the OLE at rates similar to those seen in patients treated with ixekizumab in the RTP.1 Safety signals observed over at least 52 weeks of observation were consistent with previously reported results in the RTP in this patient population.
CORRESPONDING AUTHOR: Kenneth Gordon, Dept of Dermatology, Northwestern University, NMH/Galter Room 19-150, 675 N. Saint Clair, Chicago, IL 60611. E-mail: [email protected].
CONFLICTS: Dr Gordon has received research support from and/or consulted for Abbvie, Amgen, Eli Lilly, Celgene, Janssen, Novartis, and Pfizer. Dr Lebwohl has been a consultant and/or investigator for AbbVie, Amgen, Celgene, Eli Lilly, GSK-Stiefel, Janssen, Leo, Novartis, and Pfizer. Dr Leonardi has been a consultant and/or investigator for Abbvie, Amgen, Anacor, Celgene, Coherus, Eli Lilly, Galderma, Janssen, Leo, Maruho, Merck, Pfizer, Novartis, Novo Nordisk, Sandoz, Stiefel, Tolmar, UCB, Warner Chilcott, and Wyeth. Drs Cameron, Erickson, Braun, Banerjee, and Heffernan are current or past employees and minor stock shareholders of Eli Lilly and Company. Dr Banerjee is currently an employee of Bristol Myers Squibb.
FUNDING/SUPPORT: This study was sponsored by Eli Lilly and Company, Indianapolis, USA
1. Leonardi C, Matheson R, Zachariae C, et al. Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. N Engl J Med. 2012;366(13):1190-1199.

PA-28: Secukiinumab efficacy by subject age in moderate-to-severe plaque psoriasis: pooled subgroup analyses of four phase 3 clinical studies

Warren RB,1 Gisondi P,2 Morita A,3 Guettner A,4 Cooper S5
1University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.
2University of Verona, Verona, Italy.
3Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
4Novartis Pharma AG, Basel, Switzerland.
5Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA (former employee).

BACKGROUND: Secukinumab, a fully human anti–interleukin-17A monoclonal antibody, has been evaluated in large phase 3 studies for efficacy, safety, and tolerability in subjects with moderate-to-severe plaque psoriasis. Patient characteristics such as age may impact the efficacy and safety of biologics used to treat psoriasis.
OBJECTIVE: Here, we assessed the relationship between subject age, and efficacy and safety of secukinumab in set of pooled data from phase 3 trials.
METHODS: Four randomized, double-blind, placebo-controlled, multicenter, 52-week, phase 3 studies were included in this pooled age-subgroup analysis. Subjects were treated with subcutaneous secukinumab 300 mg or 150 mg, etanercept 50 mg or placebo. Data were collated by patient age range: <65 years (n = 2232), ≥65 years (n = 167), and >75 years (n = 29). Efficacy was measured as a ≥75% and ≥90% improvement from baseline in Psoriasis Area and Severity Index score (PASI 75, PASI 90) and modified 5-point investigator's global assessment (IGA mod 2011) 0/1 response at Week 12 and maintenance of response through Week 52.
RESULTS: Secukinumab treatment resulted in higher clinical response rates at Week 12 vs placebo or etanercept across the age subgroups. In <65 years subgroup, PASI 75 responses at Week 12 were 80.3% (300 mg), 68.8% (150 mg), 43.6% (etanercept), and 4.3% (placebo); PASI 90 responses were 57.0% (300 mg), 41.2% (150 mg), 20.3% (etanercept), and 1.2% (placebo); and IGA mod 2011 0/1 responses were 65.4% (300 mg), 51.1% (150 mg), 27.2% (etanercept), and 2.3% (placebo). In ≥65 years subgroup, PASI 75 responses at Week 12 were 68.1% (300 mg), 74.1% (150 mg), 50.0% (etanercept), and 2.3% (placebo); PASI 90 responses were 51.1% (300 mg), 39.7% (150 mg), 27.8% (etanercept), and 0% (placebo); and IGA mod 2011 0/1 responses were 59.6% (300 mg), 55.2% (150 mg), 27.8% (etanercept), and 0% (placebo). These high clinical responses with secukinumab were sustained in the majority of subjects to Week 52 across age subgroups. Subjects ≥65 years (vs those <65 years) appeared to experience more SAEs; however, the subject number was small in this subgroup.
LIMITATIONS: Data for ≥75 years of age subgroup are not shown due to the limited number of subjects. Data on the etanercept is available from only one phase 3 study.
CONCLUSION: Secukinumab provided higher and sustained clinical efficacy compared to placebo and etanercept in subjects <65 and ≥65 years. No age-related trends in total AEs were identified with secukinumab.
CORRESPONDING AUTHOR: Richard Warren, University of Manchester, Salford Royal Foundation Hospital, Salford, Manchester M6 8HD, UK. E-mail: [email protected].
CONFLICTS: Dr Warren reports grants and personal fees from Novartis, during the conduct of the study; grants and personal fees from Pfizer, grants and personal fees from Leo, grants and personal fees from Janssen, grants and personal fees from Abbvie, grants and personal fees from MSD, outside the submitted work. Dr Gisondi reports personal fees and other from Eli Lilly, personal fees and other from Abbvie, personal fees and other from Pfizer, personal fees and other from MSD, personal fees and other from Jansenn, from null, outside the submitted work. Dr Morita reports grants and personal fees from Novartis, during the conduct of the study; grants and personal fees from Abbvie, grants and personal fees from Mitsubishi-Tnabe, grants and personal fees from Janssen, grants and personal fees from Eli Lilly, grants and personal fees from Kyowa-Kirin, grants and personal fees from Leo, grants and personal fees from Maruho, grants and personal fees from MSD, outside the submitted work. Dr Guettner reports personal fees from Novartis, during the conduct of the study. Dr Cooper reports personal fees from Novartis, during the conduct of the study.
FUNDING/SUPPORT: The study was sponsored by Novartis Pharma AG, Basel, Switzerland.

PA-29: Secukinumab is efficacious in subjects with moderate-to-severe plaque psoriasis and concomitant psoriatic arthritis: a subanalysis of the ERASURE study

Blauvelt A,1 Gottlieb AB,2 Sigurgeirsson B,3 Martin R,4 Papavassilis C5
1Oregon Medical Research Center, Portland, Oregon, USA.
2Tufts Medical Center, Boston, Massachusetts, USA.
3University of Iceland, Reykjavik, Iceland.
4Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
5Novartis Pharma AG, Basel, Switzerland.

BACKGROUND: Secukinumab, a fully human anti–interleukin-17A monoclonal antibody, demonstrated superior efficacy compared with placebo at Week 12 and long-term efficacy with an acceptable safety profile at Week 52 in subjects with moderate-to-severe plaque psoriasis. Psoriatic arthritis (PsA) is a common comorbidity in persons with psoriasis and may confer a substantial disability burden.
OBJECTIVE: This subanalysis was conducted in subjects with psoriasis and comorbid PsA as stated on Psoriasis Arthritis History eCRF at screening.
METHODS: ERASURE (NCT01365455) was a 52-week, randomized, double-blind, placebo-controlled, multicenter, phase 3 study. Subjects aged ≥18 years were randomized (1:1:1) to subcutaneous secukinumab 300 mg, 150 mg, or placebo once weekly for 4 weeks, then starting at Week 4, every 4 weeks through Week 48. In this subanalysis, the effect of secukinumab in subjects with a history of PsA was evaluated with the Psoriasis Area and Severity Index (PASI) and the Health Assessment Questionnaire–Disability Index (HAQ-DI).
RESULTS: In the overall study population at Week 12, PASI 75 responses were 82% (secukinumab 300 mg), 72% (150 mg), and 5% (placebo) (P < .0001 for each secukinumab dose vs placebo). In the subpopulation with concomitant PsA (n = 171), baseline PASI and HAQ-DI scores were balanced across treatments. PASI 75 responses at Week 12 were 68% (300 mg), 70% (150 mg), and 4% (placebo); PASI 90 responses were 53% (300 mg), 44% (150 mg), and 0% (placebo). PASI 75 and PASI 90 scores were maintained up to 1 year (PASI 75: 68% [300 mg], 61% [150 mg]; PASI 90: 56% [300 mg], 37% [150 mg]). Physical function as measured by HAQ-DI change from baseline was significantly greater at Weeks 4 and 12 with 300 mg versus placebo (P < .05). HAQ–DI responses were more pronounced in subjects with more disability. In subjects with baseline HAQ-DI ≥0.5, reduction in HAQ-DI score was statistically significantly greater for 150 mg at Week 12 and for 300 mg at Weeks 4 and 12 versus placebo and responses continued up to Week 52. Secukinumab was well tolerated with no unexpected safety findings.
LIMITATIONS: Since this was a subgroup analysis, the sample size was small. Postweek 12, data could not be compared between secukinumab and placebo due to limited number of subjects continuing on placebo.
CONCLUSION: In subjects with psoriasis and concomitant PsA, secukinumab was associated with superior improvement in skin symptoms and physical functioning versus placebo.
CORRESPONDING AUTHOR: Andrew Blauvelt, Oregon Medical Research Center, 9495 SW Locust Street, Suite G, Portland, OR 97223. E-mail: [email protected].
CONFLICTS: Dr Blauvelt reports personal fees and other from Novartis, during the conduct of the study; personal fees and other from Amgen, personal fees and other from Eli Lilly & Co, personal fees and other from Janssen, personal fees and other from Merck, personal fees and other from Pfizer, personal fees from Anacor Pharmaceuticals, personal fees from Takeda Pharmaceuticals, personal fees from Baxter, personal fees from Momenta, personal fees from Celgene, personal fees from Regeneron, personal fees from Maruho, other from Cenotocor, outside the submitted work. Dr Gottlieb reports grants, personal fees and other from Novartis, during the conduct of the study; grants, personal fees and other from Amegen, personal fees and other from Astellas, grants, personal fees and other from Centocor (Janssen), Inc, grants, personal fees and other from Celgene Corp, personal fees and other from BMS, personal fees and other from Beiersdorf, Inc, grants, personal fees and other from Abbott Labs. (Abbvie), personal fees and other from TEVA, personal fees and other from Actelion, personal fees and other from UCB, personal fees and other from Novo Nordisk, personal fees and other from Dermipsor Ltd, personal fees and other from Incyte, grants, personal fees and other from Pfizer, personal fees and other from Canfite, grants, personal fees and other from Lilly,, grants, personal fees and other from Coronado, personal fees and other from Vertex, personal fees and other from Karyopharm, personal fees and other from CSL Behring Biotherapies for Life, personal fees and other from GSK, personal fees and other from Akros Pharma Inc, grants, personal fees and other from Immune Control, grants, personal fees and other from Merck, grants, personal fees and other from Lerner Medical Devices Inc, grants, personal fees and other from Xenoport , grants from Levia, personal fees and other from Catabasis, personal fees and other from Sanofi Aventis, personal fees and other from DUSA, outside the submitted work. Dr Sigurgeirsson reports personal fees and other from Novartis, during the conduct of the study. Dr Martin reports other from Novartis (full time employee), during the conduct of the study. Dr Papavassilis reports other from Novartis Pharma AG, Basel, Switzerland, other from Novartis Pharma AG, Basel, Switzerland, during the conduct of the study; In addition, Dr Papavassilis has a patent Novartis Pharma AG pending and Full time Novartis employee and own Novartis stock.
FUNDING/SUPPORT: The study was sponsored by Novartis Pharma AG, Basel, Switzerland.

PA-30: Secukinumab efficacy in subjects with moderate-to-severe plaque psoriasis and concomitant psoriatic arthritis over 52 weeks: a subanalysis of the FIXTURE study

Philipp S,1 Fretzin S,2 Papavassilis C3
1Charité Universitätsmedizin Berlin, Berlin, Germany.
2Dawes Fretzin Clinical Research Group LLC, Indianapolis, Indiana, USA.
3Novartis Pharma AG, Basel, Switzerland.

BACKGROUND: Secukinumab, a fully human anti–interleukin-17A monoclonal antibody, demonstrated superior efficacy in subjects with moderate-to-severe plaque psoriasis at Week 12 (vs placebo and etanercept) and long-term efficacy with acceptable safety profile at Week 52 (vs etanercept). Psoriatic arthritis (PsA) is a common comorbidity in psoriasis patients and may confer a substantial disability burden.
OBJECTIVE: This subanalysis was conducted in subjects with psoriasis and comorbid PsA confirmed by CASPAR criteria or Psoriasis Arthritis History eCRF at screening.
METHODS: FIXTURE (NCT01358578) was a randomized, double-blind, active comparator and placebo-controlled, multicenter phase 3 study. Subjects aged ≥18 years were randomized (1:1:1:1) to subcutaneous secukinumab 300 or 150 mg (at baseline and Weeks 1, 2, 3, then q4wk starting at Week 4; n = 327 for each dose), etanercept 50 mg (2x/wk for 12 weeks, then 1x/wk; n = 326), or placebo (n = 326). In this subanalysis, the effect of secukinumab in subjects with a history of PsA was evaluated with the Psoriasis Area and Severity Index (PASI) and the Health Assessment Questionnaire–Disability Index (HAQ-DI) at baseline and Weeks 4, 12, 24, 36, and 52.
RESULTS: In the overall study population at Week 12, PASI 75 responses were 77% (secukinumab 300 mg), 67% (150 mg), 44% (etanercept), and 5% (placebo; (P < .0001 for each secukinumab dose vs placebo and etanercept). In the subpopulation with concomitant PsA (n = 192), baseline PASI and HAQ-DI scores were balanced across treatments. In these patients, PASI 75 responses at Week 12 were 72% (300 mg), 59% (150 mg), 39% (etanercept), and 2% (placebo); PASI 90 responses were 44% (300 mg), 39% (150 mg), 18% (etanercept), and 2% (placebo). PASI 75 responses at Week 52 were 66% (300 mg), 59% (150 mg) and 57% (etanercept); PASI 90 responses were 58% (300 mg), 31% (150 mg) and 27% (etanercept). Physical function as measured by HAQ-DI change from baseline was significantly improved at Weeks 4 and 12 with secukinumab 300 mg versus placebo (P < .05). Improvements in physical functioning were more pronounced in subjects with greater disability at Baseline (HAQ-DI score ≥ 0.5). In subjects with baseline HAQ-DI ≥ 0.5, reduction in HAQ-DI score was statistically significantly greater for 300 mg and 150 mg at Weeks 4 and 12 versus placebo and responses continued up to Week 52. Secukinumab was well tolerated with no unexpected safety findings.
LIMITATIONS: Since this was a subgroup analysis, the sample size was small. Postweek 12 data could not be compared between secukinumab and placebo due to limited number of subjects continuing on placebo.
CONCLUSION: Secukinumab is an effective treatment for rapidly reducing psoriasis and improving physical function in subjects with concomitant psoriatic arthritis.
CORRESPONDING AUTHOR: Sandra Philipp, Klinik fur Dermatologie, Venerologie und Allergologie, Charité Universitätsmedizin Berlin, Chariteplaz 1, Berlin, D-10117, Germany. E-mail: [email protected].
CONFLICTS: D. Philipp reports grants and personal fees from Novartis, during the conduct of the study; grants and personal fees from Abbott, grants and personal fees from Amgen, grants and personal fees from Allmiral, grants and personal fees from Biogen IDEC, grants and personal fees from Biotie Therapies, grants and personal fees from Bayer, grants and personal fees from Celgene, personal fees from Galderma, grants from Intendis, grants and personal fees from Janssen-Cilag, grants and personal fees from Merck, grants and personal fees from Pfizer, outside the submitted work. Dr Fretzin reports grants and personal fees from Abbvie, grants and personal fees from Janssen Biotech, grants and personal fees from Amgen, grants and personal fees from Celgene, grants and personal fees from Pfizer , outside the submitted work. Dr Papavassilis reports other from Novartis Pharma AG, Basel, Switzerland, other from Novartis Pharma AG, Basel, Switzerland, during the conduct of the study; In addition, Dr Papavassilis has a patent Novartis Pharma AG pending and Full time Novartis employee and own Novartis stock.
FUNDING/SUPPORT: The study was sponsored by Novartis Pharma AG, Basel, Switzerland.

PA-31: Secukinumab efficacy stratified by body weight in subjects with moderate-to-severe plaque psoriasis: a subanalysis from the ERASURE study.

Rich P,1 Kingo K,2 Marmur E,3 Papavassilis C4
1Oregon Dermatology and Research Center, Portland, Oregon, USA.
2University of Tartu, Ravila, Tartu, Estonia.
3Mount Sinai Hospital, Marmur Medical, New York, New York, USA.
4Novartis Pharma AG, Basel, Switzerland.

BACKGROUND: Secukinumab (AIN457), a fully human anti–interleukin-17A monoclonal antibody, was evaluated to assess the efficacy of 2 doses (150 and 300 mg subcutaneous) at Week 12 and to assess safety, tolerability, and long-term efficacy (52 weeks) compared with placebo in subjects with moderate-to-severe plaque psoriasis. Obesity is present in approximately one-third of persons with psoriasis and may correlate with reduced efficacy for some biologic therapies.
OBJECTIVE: Here we evaluated the effect of body weight on response to treatment with secukinumab.
METHODS: ERASURE (NCT01365455) was a randomized, double-blind, placebo-controlled, multicenter, phase 3 study. Subjects aged ≥18 years were randomized 1:1:1 to subcutaneous secukinumab 300 mg, 150 mg, or placebo, given at baseline and Weeks 1, 2, and 3, followed by dosing every four weeks, starting at Week 4, until Week 48. This analysis evaluated the effects of baseline body weight (<90 kg or ≥90 kg) on Psoriasis Area and Severity index (PASI) and modified 5-point investigator's global assessment (IGA mod 2011) 0/1 responses.
RESULTS: The baseline body weight was <90 kg in 425 subjects and ≥90 kg in 312 subjects. The proportion of subjects achieving PASI 75, PAS 90, and IGA mod 2011 0/1 responses at Week 12 was significantly greater with either secukinumab dose vs placebo in both body weight subgroups. In <90 kg subgroup, PASI 75 responses at Week 12 were 88.7% (300 mg), 74.3% (150 mg), and 4.2% (placebo); PASI 90 responses were 69.7% (300 mg), 45.0% (150 mg), and 1.4% (placebo); and IGA mod 2011 0/1 responses were 72.5% (300 mg), 53.2% (150 mg), and 2.1% (placebo) (P < .0001 for each secukinumab dose vs placebo). In ≥90 kg subgroup, PASI 75 responses were 71.8% (300 mg), 68.0% (150 mg), and 4.8% (placebo); PASI 90 responses were 44.7% (300 mg), 31.1% (150 mg), and 1.0% (placebo); and IGA mod 2011 0/1 responses were 55.3% (300 mg), 48.5% (150 mg), and 2.9% (placebo) (P < .0001 for each secukinumab dose vs placebo). Efficacy was maintained to Week 52. Secukinumab 300 mg showed consistently higher response rates than the 150-mg dose, irrespective of body weight. Secukinumab was well tolerated with no unexpected safety findings.
LIMITATIONS: Postweek 12, data could not be compared between secukinumab and placebo due to limited number of subjects continuing on placebo. This study was not designed to statistically compare efficacy parameters between secukinumab doses.
CONCLUSION: Secukinumab provided high and sustained improvement in subjects with moderate-to-severe plaque psoriasis, regardless of baseline body weight stratum.
CORRESPONDING AUTHOR: Phoebe Rich, MD, Oregon Dermatology and Research Center, 2565 NW Lovejoy Street, Portland, OR 97210. E-mail: [email protected].
CONFLICTS: Dr Rich reports grants and personal fees from Novartis, during the conduct of the study; grants and personal fees from Amgen, grants and personal fees from Anacor, grants and personal fees from Celgene, grants and personal fees from Cutanea, grants and personal fees from Eli Lilly, grants and personal fees from Galderma, grants and personal fees from Janssen-Ortho, grants and personal fees from Merck, grants and personal fees from Otsuka, grants and personal fees from Pfizer, grants and personal fees from Tolmar, grants and personal fees from Topica, grants and personal fees from Valeant, grants and personal fees from Viomet, grants and personal fees from XOMA, outside the submitted work. Dr Kingo has nothing to disclose. Dr Marmur has nothing to disclose. Dr Papavassilis reports other from Novartis Pharma AG, Basel, Switzerland, other from Novartis Pharma AG, Basel, Switzerland, during the conduct of the study; In addition, Dr Papavassilis has a patent Novartis Pharma AG pending and Full time Novartis employee and own Novartis stock.
FUNDING/SUPPORT: The study was sponsored by Novartis Pharma AG, Basel, Switzerland.

PA-32: Secukinumab impact on itching, pain, and scaling versus placebo and etanercept in psoriasis (FIXTURE study)

Strober B,1,2 Zhao Y,3 Tran M,3 Gottlieb A4
1University of Connecticut Health Center, Farmington, Connecticut, USA.
2Probity Medical Research, Waterloo, Ontario.
3Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
4Tufts Medical Center, Boston, Massachusetts, USA.

BACKGROUND: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, was evaluated in a phase 3 clinical study at weeks 12 (vs placebo and etanercept) and 52 (vs etanercept) for efficacy and safety in subjects with moderate-to-severe plaque psoriasis. Psoriasis patients frequently report pain, itching, and scaling.
OBJECTIVE: Treatment effect was measured via the Psoriasis Symptom Diary (PSD) through week 12, which measures psoriasis-related characteristics subjects have reported as important and relevant.
METHODS: FIXTURE was a randomized, double-blind, active-comparator– and placebo-controlled, multicenter phase 3 study conducted from June 2011 to June 2013. It consisted of 3 periods: screening (1-4 weeks), induction (12 weeks), and maintenance (40 weeks). Subjects were randomized 1:1:1:1 (stratified by body weight and geographic region) to 1 of 4 treatment groups: secukinumab 150 mg, secukinumab 300 mg, placebo, or etanercept 50 mg, all administered s.c. (secukinumab and placebo: weekly for 4 weeks, then once every 4 weeks; etanercept: twice weekly). Coprimary and other secondary endpoints have been reported. The 16-item PSD was completed during the first 12 weeks of treatment. The diary was completed daily using a 0-to-10 numerical rating scale via an e-diary between 4:00 pm to 11:45 pm. Focusing on psoriasis-related pain, itching, and scaling, weekly averages were derived for each item. The change from baseline to Week 12 for the weekly average (primary analysis), was calculated. Analyses of covariance with treatment, geographical region, body weight, and baseline value as covariate were performed. Differences between treatment groups were determined using least-square means and t-tests using the pooled error term from the linear model.
RESULTS: PSD data are available for 530 subjects (post baseline); 459 subjects completed at 12 weeks post baseline. Subjects treated with secukinumab 150 mg and 300 mg reported significantly greater improvements in itching (LS mean change [SE]) (4.92 [0.25], 4.93 [0.25]), pain (4.10 [0.28], 4.48 [0.28]), and scaling (4.89 [0.24], 4.93 [0.26]) than those treated with etanercept (3.80 [0.26], 3.48 [0.25], 3.74 [0.26], respectively; all P < .05) or placebo (0.54 [0.20], 0.33 [0.22], 0.42 [0.22], respectively; all P < .0001).
LIMITATIONS: A limitation of this study was that the PSD was voluntary and completed by approximately 40% of subjects. Evaluations of the clinical and demographic characteristics of the sample provide evidence that subjects who completed the PSD are similar to the overall trial population. CONCLUSION: Secukinumab 150 mg and 300 mg significantly improves patient-reported itching, pain, and scaling compared to etanercept and placebo.
CORRESPONDING AUTHOR: Yang Zhao, PhD, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936-1080. E-mail: yang-3. [email protected].
CONFLICTS: Dr Strober has served as part of the Speakers' Bureau for AbbVie; as a consultant for AbbVie, Amgen, Celgene, Dermira, Janssen, Leo, Lilly, Maruho, Medac, Merck, Novartis, Pfizer, Stiefel/GlaxoSmithKline, UCB; as an investigator for AbbVie, Amgen, Novartis, Lilly, Janssen, and Merck; as a Scientific Director for CORRONA Psoriasis Registry; and receives grant support through the University of Connecticut from AbbVie and Janssen. Dr Zhao is a full-time employee of Novartis. Dr Tran is a former Novartis employee and is currently employed at Sanofi. Dr Gottlieb has consulted or served on advisory boards through Tufts Medical Center for Amgen Inc; Astellas, Akros, Centocor (Janssen), Inc; Celgene Corp, Bristol Myers Squibb Co, Beiersdorf, Inc, Abbott Labs. (Abbvie), TEVA, Actelion, UCB, Novo Nordisk, Novartis, Dermipsor Ltd, Incyte, Pfizer, Canfite, Lilly, Coronado, Vertex, Karyopharm, CSL Behring Biotherapies for Life, Glaxo Smith Kline, Xenoport, Catabasis, Sanofi Aventis, DUSA. Dr Gottlieb has participated in research/educational grants through Tufts Medical Center for Centocor (Janssen), Amgen, Abbott (Abbvie), Novartis, Celgene, Pfizer, Lilly, Coronado, Levia, and Merck.

PA-33: Secukinumab impact on patient-reported psoriasis symptoms: the psoriasis symptom diary (ERASURE study)

Lebwohl M,1 Karpov A,2 Zhao Y,3 Elewski B4
1Mt. Sinai Medical Center, New York, New York, USA.
2Novartis Pharma AG, Basel, Switzerland.
3Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
4University of Alabama, Birmingham, Alabama, USA.

BACKGROUND: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, was evaluated in a phase 3 clinical study at week 12 (vs placebo) for efficacy and safety in subjects with moderate-to-severe plaque psoriasis.
OBJECTIVE: Treatment effect was measured via the Psoriasis Symptom Diary (PSD), which measures psoriasis-related characteristics that subjects have reported as important and relevant to their disease and treatment.
METHODS: ERASURE was a randomized, double-blind, placebo-controlled, multicenter phase 3 study conducted from January 2011 to February 2013. Subjects aged ≥18 years were randomized 1:1:1 to one of three subcutaneous treatment groups: secukinumab 150 mg, secukinumab 300 mg, or placebo (weekly for 4 weeks, then once every 4 weeks). Coprimary and other secondary endpoints have been previously reported. The 16-item PSD was completed during the first 12 weeks of treatment (induction). Each item was completed daily, using a 0-to-10 numerical rating scale via an e-diary that allowed completion only from 4:00 pm to 11:45 pm. Focusing on psoriasis-related pain, itching, and scaling, weekly averages were derived for each item. The change from baseline to week 12 for the weekly average (primary analysis) was calculated. Analyses of covariance with treatment, geographical region, body weight, and baseline value as covariate were performed. Differences between treatment groups were determined using least-square means and t-tests using the pooled error term from the linear model. RESULTS: PSD data were available for 249 subjects. Subjects treated with secukinumab 150 mg or 300 mg had significantly greater improvements in itching (4.86 [0.30], 5.45 [0.28]) than those treated with placebo (0.22 [0.26]), as well as significantly greater improvements in pain (3.92 [0.34], 4.59 [0.32]) versus (–0.06 [0.25]) and significantly more improvement in scaling (4.74 [0.31], 5.49 [0.29]) versus (0.11 [0.25]) (all P< 0.0001).
LIMITATIONS: A limitation of this study was that the PSD was voluntary and completed by approximately 40% of subjects. Evaluations of the clinical and demographic characteristics of the sample provide evidence that subjects who completed the PSD are similar to the overall trial population.
CONCLUSION: Secukinumab 150 mg or 300 mg significantly improves patient-reported itching, pain, and scaling compared with placebo.
CORRESPONDING AUTHOR: Yang Zhao, PhD, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936-1080. E-mail: [email protected].
CONFLICTS: Dr Lebwohl has served as a consultant/investigator; received grants, honoraria and/or fees from AbbVie, Amgen, Celgene, Eli Lilly, GSK-Stiefel, Janssen, Novartis, Pfizer, UCB Pharma/Dermira; Lilly, Merck, LEO Pharmaceuticals, Abbott, Anacor Pharmaceuticals Inc, BioLineRX Ltd, Coronado Biosciences, Galderma, Maruho Co Ltd, Meda Pharmaceuticals, Valeant, Ranbaxy, and Dermipsor. Dr Karpov is a full-time employee of Novartis Pharma AG, Switzerland. Dr Zhao is a full-time employee of Novartis Pharmaceuticals Corporation. Dr Elewski has received grants and/or fees from Novartis Pharma AG, Janssen Pharma, Lilly, Pfizer, Merck, Abbvie and Amgen.

PA-34: Secukinumab is associated with faster onset of efficacy than etanercept in moderate-to-severe plaque psoriasis: an analysis from the FIXTURE phase 3 study

Lebwohl M,1 Langley R,2 Reich K,3,4 Löffler J,5 Papavassilis C,5 Fox T5
1Mount Sinai Hospital, New York, New York, USA.
2Dalhousie University, Halifax, Nova Scotia, Canada.
3Dermatologikum Hamburg, Hamburg, Germany.
4Georg-August-Universität, Göttingen, Germany.
5Novartis Pharma AG, Basel, Switzerland.

BACKGROUND: Secukinumab (AIN457), a fully human anti–interleukin-17A monoclonal antibody, was evaluated for efficacy and safety vs placebo and etanercept in a phase 3 study of subjects with moderate-to-severe plaque psoriasis. Speed of symptom relief is an important outcome of psoriasis therapy from the patient perspective. In one survey, patients ranked time to 50% improvement (ie, moderate improvement) in psoriasis symptoms as one of the most important outcomes of therapy.1
OBJECTIVE: To evaluate the time to 50% improvement, we analyzed the speed of onset of secukinumab vs etanercept.
METHODS: FIXTURE (NCT01358578) was a randomized, double-blind, double-dummy active-and placebo-controlled, multicenter, 52-week, phase 3 study. Subjects aged ≥18 years were randomized 1:1:1:1 to subcutaneous secukinumab 300 or 150 mg (at baseline and Weeks 1, 2, 3, then q4wk starting at Week 4; n = 327 for each dose), etanercept 50 mg (2x/wk for 12 weeks, then 1x/wk; n = 326), or placebo (n = 326). Co-primary objectives were superiority of secukinumab vs placebo in Psoriasis Area and Severity Index (PASI) 75 and modified 5-point investigator's global assessment (IGA mod 2011) 0/1 responses at Week 12; these results were previously reported.2
RESULTS: Median time to 50% reduction in mean PASI score (95% CI), indicative of moderate symptom improvement, occurred significantly faster with each secukinumab dose vs etanercept: at 3 weeks (2.8 – 3.2) with 300 mg and 4 weeks (3.7 – 4.2) with 150 mg vs 7 weeks (6.3 – 7.7) with etanercept (P < .0001 for each secukinumab dose vs etanercept; P < 0.0001 for 300 mg vs 150 mg). Differentiation of response was evident by Week 2, with 34% reduction in mean PASI score for 300 mg and 26% for 150 mg vs 20% reduction with etanercept. Symptoms continued to improve with secukinumab after rapid efficacy onset; and response rates sustained up to Week 52. Overall, the rate of AEs was similar across all treatments.2
CONCLUSION: Onset of efficacy in alleviating psoriasis symptoms was significantly faster with each dose of secukinumab compared with etanercept in this pivotal phase 3 study. The 300-mg dose of secukinumab showed the fastest onset of improvement in symptoms.
CORRESPONDING AUTHOR: Mark Lebwohl, The Mount Sinai Medical Center, 5 E 98th St., 5th Floor, Box 1048, New York, NY 10029. E-mail: [email protected].
CONFLICTS: Dr Lebwohl reports grants and personal fees from Novartis, during the conduct of the study; personal fees from Abbott, grants and personal fees from Amgen, personal fees from Anacor Pharmaceuticals, Inc, personal fees from BioLineRX, Ltd, grants and personal fees from Celgene Corporation, personal fees from Columbia laboratories, Inc, personal fees from Coronado Biosciences, other from Dermipsor, personal fees from Eli Lilly & Co, personal fees from Galderma, personal fees from GlaxoSmithKline-Stiefel, grants and personal fees from Janssen Ortho Biotech, grants and personal fees from LEO Pharmaceuticals, personal fees from Maruho Co, Ltd, personal fees from Meda Pharmaceuticals, personal fees from Pfizer, grants and personal fees from Ranbaxy, personal fees from Thesan Pharmaceuticals, personal fees from Valeant, other from AbGenomics, other from Clinuvel, outside the submitted work. Dr Langley reports personal fees and other from Novartis, during the conduct of the study; personal fees and other from AbbVie, personal fees and other from Amgen, personal fees from Celgene, personal fees and other from Leo, personal fees and other from Merck Serono, personal fees and other from Pfizer, other from Lily, outside the submitted work. Dr Reich reports grants and personal fees from Novartis, during the conduct of the study; grants and personal fees from Abbvie, grants and personal fees from Amgen, grants and personal fees from Biogen IDEC, grants and personal fees from Celgene, grants and personal fees from Janssen-Cilag, grants and personal fees from Medac, grants and personal fees from Pfizer, grants and personal fees from Centocor, grants and personal fees from Covagen, grants and personal fees from GSK, grants and personal fees from Forward Pharma, grants and personal fees from Leo, grants and personal fees from Lilly, grants and personal fees from Levia, grants and personal fees from MSD, grants and personal fees from Vertex, grants and personal fees from Takeda, outside the submitted work; and Professor Kristian Reich has received honoraria as consultant and/or advisory board member and/or acted as paid speaker and/or participated in clinical trials sponsored by AbbVie, Amgen, Biogen-Idec, Celgene, Centocor, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, LEO Pharma, Lilly, Medac, MSD, Novartis, Ocean Pharma, Pfizer, Regeneron, Takeda, Vertex. Dr Löffler reports personal fees from Novartis, during the conduct of the study. Dr Papavassilis reports other from Novartis Pharma AG, Basel, Switzerland, other from Novartis Pharma AG, Basel, Switzerland, during the conduct of the study; In addition, Dr Papavassilis has a patent Novartis Pharma AG pending and Full time Novartis employee and own Novartis stock. Dr Fox reports personal fees from Novartis (employee), during the conduct of the study.
FUNDING/ SUPPORT: The study was sponsored by Novartis Pharma AG, Basel, Switzerland.
1. Seston EM, Ashcroft DM, Griffiths CE. Balancing the benefits and risks of drug treatment : a stated-preference, discrete choice experiment with patients with psoriasis. Arch Dermatol. 2007;143(9):1175-1179.
2. Langley R, Elewski BE, Lebwohl M, et al; ERASURE Study Group ; FIXTURE Study Group. N Engl J Med. 2014;371(4):326-338.

PA-35: Secukinumab sustainability of response in subjects with moderate-to-severe plaque psoriasis over 52 weeks: a subanalysis from the fixture study

Reich K,1 Puig L,2 Draelos Z,3 Papavassilis C4
1Dermatologikum Hamburg and Georg-August-Universität, Göttingen, Germany.
2Hospital de Sant Pau, Barcelona, Spain.
3Dermatology Consulting Services, High Point, North Carolina, USA.
4Novartis Pharma AG, Basel, Switzerland.

BACKGROUND: Results from the FIXTURE phase 3 clinical study have demonstrated the superior efficacy and safety of secukinumab (a fully human anti–interleukin-17A monoclonal antibody) in subjects with moderate-to-severe plaque psoriasis at Week 12 (vs placebo and etanercept), and at Week 52 (vs etanercept).
OBJECTIVE: In this subanalysis, we evaluated the sustainability of response to secukinumab to Week 52.
METHODS: This was a multicenter, double-blind, double-dummy, active- and placebo-controlled study (NCT01358578). Subjects aged ≥18 years were randomized (1:1:1:1) to subcutaneous secukinumab 300 or 150 mg (at baseline and Weeks 1, 2, 3, then q4wk starting at Week 4; n = 327 for each dose), etanercept 50 mg (2x/wk for 12 weeks, then 1x/wk; n = 326), or placebo (n = 326). For this subanalysis of data to Week 52, summary statistics by treatment group were tabulated for percentage of subjects who sustained a ≥75 %, ≥90% and 100% improvement from baseline in Psoriasis Area and Severity Index score (PASI 75, PASI 90 and PASI 100) or a score of 0/1 on a modified 5-point investigator's global assessment (IGA mod 2011 0/1). A sensitivity analysis was performed with multiple imputations.
RESULTS: The primary endpoint of superior PASI 75 and IGA mod 2011 0/1 responses at Week 12 with secukinumab 300 mg and 150 mg vs placebo was met; similarly responses were superior vs etanercept (P < .001 for each dose vs comparators). Clinical response rates further improved to Week 16, with percentage of PASI 75, PASI 90, PASI 100 and IGA mod 2011 0/1 responders being, respectively, 90.1%, 74.6%, 38.1% and 78.5% in the secukinumab 300 mg group; 79.4%, 56.0%, 26.7% and 64.3% in the secukinumab 150 mg group; and 63.0%, 34.0%, 8.9% and 42.6% in the etanercept group. At Week 52, PASI 75, PASI 90, PASI 100 and IGA mod 2011 0/1 responses were sustained, respectively, in 87.3%, 70.6%, 39.4% and 75.4% of subjects in the secukinumab 300 mg group; 72.8%, 49.3%, 22.3% and 57.0% in the secukinumab 150 mg group; and 66.2%, 39.0%, 12.7% and 45.5% in the etanercept group. For all PASI 75 and IGA mod 2011 0/1 responses, numerically higher response rates were seen with the secukinumab 300 mg as compared with the 150 mg dose through Week 52. Secukinumab was well tolerated with no unexpected safety findings.
LIMITATIONS: Postweek 12 data could not be compared between secukinumab and placebo due to limited number of subjects continuing on placebo.
CONCLUSION: These results showed a sustained high response to secukinumab in subjects with moderate-to-severe plaque psoriasis over 52 weeks vs etanercept.
CORRESPONDING AUTHOR: Kristian Reich, Dermatologikum Hamburg, Stephanspalatz 5, Hamburg, 20354, Germany. E-mail: [email protected]
CONFLICTS: Dr Reich reports grants and personal fees from Novartis, during the conduct of the study; grants and personal fees from Abbvie, grants and personal fees from Amgen, grants and personal fees from Biogen IDEC, grants and personal fees from Celgene, grants and personal fees from Janssen-Cilag, grants and personal fees from Medac, grants and personal fees from Pfizer, grants and personal fees from Centocor, grants and personal fees from Covagen, grants and personal fees from GSK, grants and personal fees from Forward Pharma, grants and personal fees from Leo, grants and personal fees from Lilly, grants and personal fees from Levia, grants and personal fees from MSD, grants and personal fees from Vertex, grants and personal fees from Takeda, outside the submitted work; and Professor Kristian Reich has received honoraria as consultant and/or advisory board member and/or acted as paid speaker and/or participated in clinical trials sponsored by AbbVie, Amgen, Biogen-Idec, Celgene, Centocor, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, LEO Pharma, Lilly, Medac, MSD, Novartis, Ocean Pharma, Pfizer, Regeneron, Takeda, Vertex. Dr Puig reports grants and personal fees from Novartis, during the conduct of the study; grants and personal fees from Abbvie, grants and personal fees from Amgen, personal fees from Boehringer, personal fees from Celgene, grants and personal fees from Janssen, grants and personal fees from Leo-Pharma, grants and personal fees from Lilly, grants and personal fees from MSD, grants and personal fees from VBL, personal fees from Merck-Serono, outside the submitted work. Dr Draelos reports grants from Novartis, during the conduct of the study. Dr Papavassilis reports other from Novartis Pharma AG, Basel, Switzerland, other from Novartis Pharma AG, Basel, Switzerland, during the conduct of the study. In addition, Dr Papavassilis has a patent Novartis Pharma AG pending and Full time Novartis employee and own Novartis stock.
FUNDING/ SUPPORT: The study was sponsored by Novartis Pharma AG, Basel, Switzerland.

PA-36: Secukinumab vs placebo or etanercept on time to response on itching, pain, and scaling (FIXTURE study)

Elewski B,1 McLeod L,2 Zhao Y,3 Mallya U,3 Lebwohl M4
1University of Alabama, Birmingham, Alabama, USA.
2Health Solutions, Research Triangle Park, North Carolina, USA.
3Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
4Mt. Sinai Medical Center, New York, New York, USA.

BACKGROUND: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, was evaluated in a phase 3 clinical study at weeks 12 (vs placebo and etanercept) and 52 (vs etanercept) for efficacy and safety in subjects with moderate-to-severe plaque psoriasis. Psoriasis patients frequently report pain, itching, and scaling.
OBJECTIVE: Time to symptom response was evaluated using the Psoriasis Symptom Diary (PSD) through week 12, which measures psoriasis-related characteristics subjects have reported as important and relevant to their disease and treatment.
METHODS: Time to symptom response was evaluated using the Psoriasis Symptom Diary (PSD) through week 12, which measures psoriasis-related characteristics subjects have reported as important and relevant to their disease and treatment.
RESULTS: PSD data are available for 530 subjects with baseline and at least 1 week postbaseline. Results indicated that both secukinumab treatment groups have significantly different K-M curves indicating significantly shorter time to itching, pain and scaling response with secukinumab. The Cox model results support the K-M results. Starting at week 2, secukinumab treatment achieves a higher percentage of patients with itching, pain and scaling response than placebo or etanercept.
LIMITATIONS: A limitation of this study was that the PSD was voluntary and completed by approximately 40% of subjects. Evaluations of the clinical and demographic characteristics of the sample provide evidence that subjects who completed the PSD are similar to the overall trial population.
CONCLUSION: Results indicated that both secukinumab treatment groups have significantly different K-M curves in comparison to placebo and etanercept indicating significantly shorter time to itching, pain and scaling response with secukinumab starting at week 2.
CORRESPONDING AUTHOR: Yang Zhao, PhD, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936-1080. E-mail: [email protected].
CONFLICTS: Dr Elewski has received grants and/or fees from Novartis Pharma AG, Janssen Pharma, Lilly, Pfizer, Merck, Abbvie and Amgen. Dr McLeod is a full-time employee of RTI Health Solutions. Dr Zhao is a full-time employee of Novartis. Dr Mallya is a former full-time employee of Novartis, currently employed at Sanofi. Dr Lebwohl has served as a consultant/investigator; received grants, honoraria and/or fees from AbbVie, Amgen, Celgene, Eli Lilly, GSK-Stiefel, Janssen, Novartis, Pfizer, UCB Pharma/Dermira; Lilly, Merck, LEO Pharmaceuticals, Abbott, Anacor Pharmaceuticals Inc, BioLineRX Ltd, Coronado Biosciences, Galderma, Maruho Co Ltd, Meda Pharmaceuticals, Valeant, Ranbaxy, and Dermipsor.

PA-37: Secukinumab's time to psoriasis response on patient-reported psoriasis symptoms (ERASURE study)

Gottlieb AB,1 Zhao Y,2 Odom D,3 Tran MH,2 Strober B,4,5
1Tufts Medical Center, Boston, Massachusetts, USA.
2Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
3Health Solutions, Research Triangle Park, North Carolina, USA.
4University of Connecticut Health Center, Farmington, Connecticut, USA.
5Probity Medical Research, Waterloo, Ontario.

BACKGROUND: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, was evaluated in a phase 3 clinical study at week 12 (vs placebo) for efficacy and safety in subjects with moderate-to-severe plaque psoriasis.
OBJECTIVE: Time to symptom response was evaluated using the Psoriasis Symptom Diary (PSD), which measures psoriasis-related characteristics that subjects have reported as important and relevant to their disease and treatment.
METHODS: ERASURE was a randomized, double-blind, placebo-controlled, multi-center phase 3 study conducted from January 2011 to February 2013. It consisted of four periods: screening (1-4 weeks), induction (12 weeks), maintenance (40 weeks), and follow-up (8 weeks). Subjects aged ≥18 years were randomized 1:1:1 to one of three subcutaneous treatment groups: secukinumab 150 mg, secukinumab 300 mg, or placebo (weekly for 4 weeks, then once every 4 weeks). Coprimary and other secondary endpoints have been reported. The 16-item PSD was completed during the first 12 weeks of treatment. Each item was completed daily using a 0-to-10 numerical rating scale via an e-diary that allowed completion only from 4:00 pm to 11:45 pm. Focusing on psoriasis-related pain, itching, and scaling, weekly averages were derived for each item, with higher scores indicating greater severity. Time to response was defined as the period from the randomization date to the response date when a prespecified point improvement from baseline had occurred (2.2 points for itching, 2.2 points for pain, and 2.3 points for scaling). Median time to response and percentage of subjects identified as responders for itching, pain, and scaling were estimated using Kaplan-Meier methods by treatment group. Hazard ratios were also computed using a Cox proportional hazards regression model.
RESULTS: PSD data are available for 284 subjects with baseline and at least 1 week postbaseline. Results indicated that both secukinumab treatment groups have significantly different K-M curves indicating significantly shorter time to itching, pain, and scaling response with secukinumab. The Cox model results support the K-M results. Starting at week 3, secukinumab treatment achieves a higher percentage of patients with itching, pain, and scaling response than placebo.
LIMITATIONS: A limitation of this study was that the PSD was voluntary and completed by approximately 40% of subjects. Evaluations of the clinical and demographic characteristics of the sample provide evidence that subjects who completed the PSD are similar to the overall trial population.
CONCLUSION: Patients receiving secukinumab reported significantly shorter time to meaningful improvement of symptoms of itching, pain, and scaling than patients receiving placebo, and improvements were seen as early as Week 3.
CORRESPONDING AUTHOR: Yang Zhao, PhD, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936-1080. E-mail: yang-3. [email protected].
CONFLICTS: Dr Gottlieb has consulted or served on advisory boards through Tufts Medical Center for Amgen Inc; Astellas, Akros, Centocor (Janssen), Inc; Celgene Corp, Bristol Myers Squibb Co, Beiersdorf, Inc, Abbott Labs. (AbbVie), TEVA, Actelion, UCB, Novo Nordisk, Novartis, Dermipsor Ltd, Incyte, Pfizer, Canfite, Lilly, Coronado, Vertex, Karyopharm, CSL Behring Biotherapies for Life, Glaxo Smith Kline, Xenoport, Catabasis, Sanofi Aventis, DUSA. Dr Gottlieb has participated in research/educational grants through Tufts Medical Center for Centocor (Janssen), Amgen, Abbott (AbbVie), Novartis, Celgene, Pfizer, Lilly, Coronado, Levia, and Merck. Dr Zhao is a full-time employee of Novartis. Ms Odom is a full-time employee of RTI Health Solutions. Dr Tran is a former Novartis employee and is currently employed at Sanofi. Dr Strober has served as a speaker, consultant, or investigator for AbbVie, Amgen, Celgene, Dermira, Janssen, Leo, Lilly, Maruho, Medac, Merck, Novartis, Pfizer, Stiefel/GlaxoSmithKline, and UCB; as a Scientific Director for CORRONA Psoriasis Registry; and receives grant support through the University of Connecticut from AbbVie and Janssen.

PA-38: Serious infection events in the psoriasis longitudinal assessment and registry study: current status of observations.

Kalb R,1 Fiorentino D,2 Lebwohl M,3 Leonardi C,4 Toole J,5 Goyal K,6 Calabro S,6 Langholff W,6 Fakharzadeh S,6 on behalf of the PSOLAR Steering Committee
1SUNY at Buffalo, School of Medicine and Biological Sciences, Buffalo, New York, USA.
2Stanford University, Stanford, California, USA.
3Mount Sinai Medical Center, New York, New York, USA.
4Central Dermatology, St. Louis, Missouri, USA.
5University of Manitoba, Dermadvances Research, Winnipeg, Manitoba, Canada.
6Janssen Scientific Affairs, LLC., Horsham, Pennsylvania, USA.

BACKGROUND: PSOLAR is a multicenter, longitudinal, observational study evaluating long-term safety and clinical outcomes for patients eligible to receive treatment for psoriasis with systemic agents.
OBJECTIVE: To report the cumulative rates of serious infections in the Psoriasis Longitudinal Assessment and Registry (PSOLAR) study.
METHODS: PSOLAR is a multicenter, longitudinal, observational study evaluating long-term safety and clinical outcomes for patients eligible to receive treatment for psoriasis with systemic agents. Serious infections are defined as serious events (e.g. requiring hospitalization) classified into the MedDRA system organ class of Infections and infestations. The rates of serious infections in PSOLAR overall and by treatment groups are reported through the most recent data cut-off date (August 23, 2013) using exposure within 91 days preceding the event. In cases of exposure to >1 therapy, the rule for attribution of serious infections to a treatment group is ustekinumab first, infliximab/golimumab second, other biologics third (nearly all adalimumab or etanercept), or nonbiologic therapy fourth, which is consistent with the prespecified analytic plan.
RESULTS: PSOLAR is fully enrolled with 12,095 patients reflecting 31,818 cumulative patient-years of follow up. The median duration of follow-up is 2.5 years. Unadjusted rates of serious infection, based on exposure within 91 days preceding the event were: ustekinumab 0.95 events per 100 patient years of observation (PY; 95% CI: 0.71, 1.24; 52/5497 PY), infliximab 2.77 per 100PY (95% CI: 2.15, 3.51; 68/2457 PY), etanercept 1.67 events per 100 PY (95% CI: 1.32, 2.09; 78/4666 PY), adalimumab 1.88 per PY (95% CI: 1.54, 2.27; 106/5645 PY), nonbiologics 1.26 per 100 PY (95% CI: 1.08, 1.46; 169/13421 PY), and overall 1.50 (95% CI: 1.37, 1.64; 478/31817).
LIMITATIONS: Rates have not been adjusted for demographic and clinical differences among treatment groups and are subject to attribution rules.
CONCLUSION: With nearly 32,000 patient-years of follow-up, the overall rate of unadjusted cumulative rate of serious infections in the PSOLAR registry population is 1.50 per 100 PY. The rates of serious infection for ustekinumab and the no biologic treatment groups are lower than rates for infliximab, adalimumab and etanercept. Future analyses may characterize infections further and adjust for differences among treatment groups.
CORRESPONDING AUTHOR: Kavitha Goyal, MD, Janssen Scientific Affairs, LLC, 850 Ridgeview Drive, Horsham, PA 19044. E-mail: [email protected]. com.
CONFLICTS: Drs Kalb, Fiorentino, Lebwohl, Leonardi, and Toole served as investigators for Janssen Scientific Affairs, LLC. Dr Goyal, S Calabro, Dr Langholff, and Dr Fakharzadeh are employees of Janssen Scientific Affairs, LLC.

PA-39: Tavaborole: the first benzoxaborole compound investigated for the treatment of onychomycosis represents a new class of antifungal agents with a unique mechanism of action

Del Rosso JQ,1 Kircik L,2 Plattner JJ,3 Rosen T,4 Zane L,3 Rock F3
1Las Vegas Skin & Cancer Clinics, Las Vegas, Nevada, USA.
2DermResearch, PLLC, Louisville, Kentucky, USA.
3Anacor Pharmaceuticals, Inc, Palo Alto, California, USA.
4Michael E. DeBakery VA Medical Center, Houston, Texas, USA.

BACKGROUND: Tavaborole is a low molecular weight (152 kDa) hydrophilic compound with broad-spectrum antifungal activity against a variety of dermatophytes, yeasts and molds. Its mechanism of action (MOA) differs from currently available topical and systemic antifungal agents.
OBJECTIVE: To describe the unique MOA of tavaborole, a small boron-based molecule with broad spectrum antifungal activity and a high level of nail penetration.
METHODS: Tavaborole is a boron-based compound of the benzoxaborole structural class developed to achieve low molecular weight, high water solubility, and potent antifungal activity needed to treat onychomycosis. It effectively penetrates the nail plate after topical application. Since Trichophyton rubrum is refractory to most genetic techniques, the more genetically tractable fungi Saccharomyces cerevisiae was used to determine the MOA of tavaborole in vivo. Characterization of isolated tavaborole-resistant mutant yeast mapped mutations to CDC60, a gene that codes for the cytoplasmic enzyme leucyl-tRNA synthetase (LeuRS). This and biochemical characterizations permitted the identification of the inhibitory MOA of tavaborole in susceptible fungi.
RESULTS: The aminoacyl-tRNA synthetase (AARS) family of enzymes play a pivotal role in protein synthesis, and LeuRS is an AARS. These enzymes function to maintain and translate genetic code within DNA. LeuRS possesses a proofreading or editing mechanism that corrects enzymatic mistakes. Proofreading occurs on a separate editing active site. Tavaborole targets fungal cytoplasmic LeuRS by binding to the editing site together with tRNA. There, tRNA is trapped, preventing further cellular protein synthesis and resulting in fungal growth inhibition. Tavaborole has high fungal specificity with low affinity for mammalian AARS. This MOA is novel among currently available antifungal agents and tavaborole is the first compound in the benzoxaborole approved by the FDA for the treatment of toenail onychomycosis caused by dermatophytes.
LIMITATIONS: This study is limited by its in vivo, exploratory nature.
CONCLUSION: Tavaborole is a highly specific protein synthesis inhibitor targeting fungal cytoplasmic LeuRS, an AARS. The MOA of tavaborole is distinct from imidazole, triazole, allylamine, and benzylamine antifungal compounds, which block ergosterol synthesis. It also differs from other AARS inhibitors by binding to the editing domain. Tavaborole represents a new antifungal agent class with a unique MOA.
CORRESPONDING AUTHOR: Lee Zane, MD, Anacor Pharmaceuticals, Inc, 1020 East Meadow Circle, Palo Alto, CA 94303-4230. E-mail: [email protected].
CONFLICTS: Drs Zane, Rock, and Plattner are employees and stockholders of Anacor Pharmaceuticals, Inc. Dr Del Rosso is a consultant and speaker for the following companies that have existing products, commercial interest, and/or research interest in fungal infections including onychomycosis: Anacor Pharmaceuticals, Inc, Aqua Pharmaceuticals, Merz Pharmaceuticals, and Valeant Pharmaceuticals. Dr Kircik is a remunerated speaker for Abbott Laboratories, Allergan, Inc, Amgen, Inc, Assos Pharma, Astellas Pharma US, Inc, CollaGenex, Connetics Corporation, Dermik Laboratories, Embil Pharmaceuticals, Galderma Laboratories, LP, Genentech, Inc, Innocutis, Innovail, Johnson & Johnson, Leo, L'Oreal, 3M, Onset, OrthoNeutrogena, PharmaDerm, Serono (Merck Serono International SA), SkinMedica, Inc, Stiefel Laboratories, Inc, Triax, UCB, Valeant Pharmaceuticals Intl., and Warner-Chil=cott; is a remunerated consultant for Allergan, Inc, Amgen, Inc, Anacor Pharmaceuticals, Colbar, CollaGenex, Connetics Corporation, Galderma Laboratories, LP, Genentech, Inc, Intendis, Johnson & Johnson, Laboratory Skin Care Inc, Leo, Medical International Technologies, Merck, Merz, Novartis AG, OrthoNeutrogena, Promius, PuraCap, SkinMedica, Inc, Stiefel Laboratories, Inc, UCB, Valeant Pharmaceuticals Intl., and ZAGE; is a remunerated advisory board member for Allergan, Inc, Anacor Pharmaceuticals, Biogen-Idec, Colbar, Celgene, Connetics Corporation, EOS, Ferndale Laboratories, LP, Galderma Laboratories, LP, Genentech, Inc, Intendis, Innocutis, Johnson & Johnson, Nano Bio, OrthoNeutrogena, Promius, SkinMedica, Inc, Stiefel Laboratories, Inc, Valeant Pharmaceuticals Intl., and Warner-Chilcott; is a remunerated investigator for Allergan, Inc, and QLT, Inc; has received research grant support as an investigator for Acambis, Amgen, Inc, Anacor Pharmaceuticals, Astellas Pharma US, Inc, Asubio, Berlex Laboratories (Bayer HealthCare Pharmaceuticals), Biolife, Biopelle, Breckinridge Pharma, Celgene, Centocor, Inc, CollaGenex, Combinatrix, Connetics Corporation, Coria, Dow Pharmaceutical Sciences, Inc, Dusa, Eli Lily, Ferndale Laboratories, LP, Galderma Laboratories, LP, Genentech, Inc, GlaxoSmithKline, PLC, Health Point, LTD, Intendis, Johnson & Johnson, Leo, L'Oreal, 3M, Maruho, Medical International Technologies, Merck, Medicis Pharmaceutical Corp, Nano Bio, Novartis AG, Noven Pharmaceuticals, Nucryst Pharmaceuticals Corp, Obagi, Onset, OrthoNeutrogena, Promius, PharmaDerm, Pfizer, Quatrix, SkinMedica, Inc, Stiefel Laboratories, Inc, TolerRx, UCB, Valeant Pharmaceuticals Intl, Warner-Chilcott, and XenoPort; and is a stock shareholder in Johnson & Johnson. Dr Rosen is a consultant for Anacor Pharmaceuticals, Inc.

PA-40: Tofacitinib vs etanercept or placebo in moderate-to-severe chronic plaque psoriasis

Bachelez H,1 Van De Kerkhof PCM,2 Strohal R,3 Kubanov A,4 Valenzuela F,5 Lee JH,6 Yakusevich V,7 Chimenti S,8 Papacharalambous J,9 Proulx J,9 Gupta P,9 Tan H,9 Tawadrous M,9 Valdez H,10, Wolk R9
1Department of Dermatology, Sorbonne Paris Cité Université Paris Diderot, APHP Hôpital Saint-Louis, Paris, France.
2Department of Dermatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
3Department of Dermatology and Venereology, Federal Academic Teaching Hospital of Feldkirch, Feldkirch, Austria.
4Department of Dermatology and Venereology, State Research Centre of Dermatology and Venereology, Ministry of Health, Moscow, Russia.
5Department of Dermatology, University of Chile Clinical Hospital, Santiago, Chile.
6Department of Dermatology, Sungkyunkwan University School of Medicine, Samsung Medical Centre, Seoul, South Korea.
7Department of Dermatology, Soloviev's Clinical Hospital For Urgent Medical Care, Yaroslav, Russia.
8Department of Dermatology, University of Rome, Rome, Italy.
9Pfizer Inc, Groton, Connecticut, USA.
10Pfizer Inc, New York, New York, USA.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor being investigated for the treatment of psoriasis.
OBJECTIVE: To compare tofacitinib efficacy and safety with high-dose etanercept in patients with moderate-to-severe chronic plaque psoriasis.
METHODS: In this Phase 3, multicenter, double-dummy, 12 week, noninferiority trial (ClinicalTrials.gov NCT01241591), 1101 adult patients with chronic plaque psoriasis were randomized (3:3:3:1) and treated with tofacitinib 5 mg twice daily (BID) (n = 329), tofacitinib 10 mg BID (n = 330), etanercept 50 mg subcutaneously twice weekly (BIW) (n = 335), or placebo (n = 107). Primary efficacy endpoints were the proportion of patients at Week 12 with ≥75% reduction from baseline in Psoriasis Area and Severity Index (PASI) score (PASI75 response); achieving a Physician's Global Assessment (PGA) score of 'clear' or 'almost clear' (PGA response). Secondary efficacy endpoints included time to PASI75 response; the proportion of patients achieving clinically meaningful improvement in Dermatology Life Quality Index (DLQI) score (≥5 point reduction from baseline) at Week 12; the proportion of patients at Week 12 with PASI75 or PASI50-75 with DLQI score ≤5. Safety was also assessed.
RESULTS: At Week 12, PASI75 response was achieved by 39.5%, 63.6%, 58.8%, and 5.6% of patients receiving tofacitinib 5 mg BID, tofacitinib 10 mg BID, etanercept, and placebo, respectively. A PGA response at Week 12 was achieved by 47.1%, 68.2%, 66.3%, and 15.0% of patients in the tofacitinib 5 mg BID, tofacitinib 10 mg BID, etanercept, and placebo groups, respectively. Tofacitinib 10 mg BID was noninferior to etanercept 50 mg BIW and superior to placebo based on PASI75 and PGA responses; the tofacitinib 5 mg BID dose did not meet noninferiority criteria vs high-dose etanercept. Median time (weeks) to PASI75 response was shorter with tofacitinib 10 mg BID (8.6) than etanercept (12.1) and tofacitinib 5 mg BID (12.6). A clinically meaningful reduction in DLQI score was achieved by 66.3%, 78.2%, 74.7%, and 31.8% of patients receiving tofacitinib 5 mg BID, tofacitinib 10 mg BID, etanercept, and placebo, respectively. PASI75 or PASI50–75 with DLQI score ≤5 was achieved by 55.3%, 73.8%, 73.7%, and 12.2% of patients receiving tofacitinib 5 mg BID, tofacitinib 10 mg BID, etanercept, and placebo, respectively. Serious adverse events (AEs) and discontinuations due to AEs occurred in a low and similar proportion of patients in all treatment groups. The most common AEs were infections (mostly nasopharyngitis and upper respiratory tract infections). Injection site reactions were more common among etanercept-treated patients, whereas increases in cholesterol and creatine phosphokinase were more common in tofacitinib-treated patients.
LIMITATIONS: This study assessed tofacitinib treatment for psoriasis up to Week 12 based on etanercept design. The long-term efficacy and safety of tofacitinib for chronic psoriasis was not studied.
CONCLUSION: Both doses of tofacitinib were efficacious in patients with moderate-to-severe chronic plaque psoriasis. Tofacitinib 10 mg BID or etanercept 50 mg BIW resulted in a range of ~60-70% of patients achieving PASI75 and PGA responses, almost 80% achieving clinically meaningful improvements in DLQI, and >70% achieving 'PASI75 or PASI50-75 with DLQI score ≤5' response. Tofacitinib 10 mg BID was noninferior to etanercept for PASI75 and PGA responses at Week 12, and had a shorter time to PASI75 response than etanercept. No unexpected safety signals were observed compared to those in prior tofacitinib Phase 3 studies.
CORRESPONDING AUTHOR: Jocelyn Papacharalambous, Pfizer Inc, 445 Eastern Point Rd., Groton, CT 06340. E-mail: [email protected].
CONFLICTS: Dr Bachelez reports personal fees from Pfizer Inc during the conduct of the study; personal fees from Abbvie, Amgen, Boehringer, Celgene, Janssen, Leo Pharma, Lilly, Novartis, MSD, and Sandoz outside the submitted work. Dr van de Kerkhof reports grants and personal fees from Pfizer Inc during the conduct of the study; personal fees from Celgene, Centocor, Almirall, Abbotyt, Galderma, Novartis, Sandoz, and Mitsubishi, grants and personal fees from Amgen, Ely Lilly, Janssen Cilag and Leo Pharma, grants from Basilea, Abbvie and Phillips Lighting outside the submitted work. Dr Strohal reports personal fees from Pfizer Inc during the conduct of the study; personal fees from Meda Pharmaceuticals, Menarini Pharmaceuticals, Novartis, Chemomedica and Panten Biotechnologies, grants and personal fees from Schulke and Mayr, Lohmann & Rauscher, Stockhausen, Smith & Nephew, Urgo, grants from 3M-Woundcare and Enjo Commercials outside the submitted work. Dr Valenzuela reports grants and personal fees from Pfizer Inc during the conduct of the study; grants and personal fees from AbbVie, Janssen, Eli Lilly, Merck and Novartis outside the submitted work. Drs Kubanov, Lee, and V Yakusevich have nothing to disclose. Dr Chimenti reports personal fees from Pfizer during the conduct of the study; grants and personal fees from Abbvie, grants and personal fees from Novartis, grants and personal fees from Merck, grants and personal fees from Janssen-Cilag outside the submitted work. Drs Papacharalambous, Proulx, Gupta, Tan, Tawadrous, Valdez, and Wolk are employees and shareholders of Pfizer Inc.

PA-41: Withdrawal and retreatment of tofacitinib in moderate-to-severe chronic plaque psoriasis

Bissonnette R,1 Iversen L,2 Sofen H,3 Griffiths CEM,4 Foley P,5 Romiti R,6 Bachinsky M,7 Rottinghaus ST,7 Tan H,7 Proulx J,7 Valdez H,8 Mallbris L,9 Gupta P,7 Wolk R7
1Innovaderm Research, Department of Clinical Research, Montreal, Quebec, Canada.
2Aarhus University Hospital, Department of Dermatology, Aarhus, Denmark.
3UCLA School of Medicine, Department of Medicine/ Dermatology, Los Angeles, CA, USA.
4The Dermatology Centre, University of Manchester, Manchester Academic Health Science Centre, Department of Dermatology, Manchester, United Kingdom.
5The University of Melbourne, Skin and Cancer Foundation Inc, Department of Dermatology, Carlton, Australia.
6Hospital Das Clínicas Da Faculdade De Medicina Da Universidade De São Paulo, Department of Dermatology, São Paulo, Brazil.
7Pfizer Inc, Groton, CT, USA.
8Pfizer Inc, New York, NY, USA.
9Pfizer Inc, Collegeville, PA, USA.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor being investigated for the treatment of psoriasis.
OBJECTIVE: To assess the efficacy and safety of tofacitinib withdrawal and retreatment in patients with moderate-to-severe chronic plaque psoriasis.
METHODS: In this double-blind, Phase 3 trial (NCT01186744), patients received treatment with tofacitinib 5 mg twice daily (BID) (n = 331) or tofacitinib 10 mg BID (n = 335) for 24 weeks. At Week 24 patients achieving both ≥75% reduction in Psoriasis Area and Severity Index (PASI) score from baseline (PASI75 response) and a Physician's Global Assessment of 'clear' or 'almost clear' (PGA response) were rerandomized 3:1 to receive placebo (treatment withdrawal) or the initial tofacitinib dose. At relapse (>50% loss of Week 24 PASI response) or Week 40, patients were retreated with the initial tofacitinib dose. The primary efficacy endpoints included: the proportion of patients maintaining PASI75 or PGA responses during treatment withdrawal; the proportion of relapsers (defined above) regaining a PASI75 response upon retreatment and, among patients who lost a PGA response, the proportion who regained a PGA response. Secondary efficacy endpoints included: the proportion of patients achieving a PASI75 or PGA response at Week 24; the median time for PASI75 and PGA responses; and the proportion of patients achieving a clinically meaningful improvement (≥5 point reduction from baseline) in Dermatology Life Quality Index (DLQI) at Week 24 and after retreatment.
RESULTS: During initial treatment with tofacitinib 5 and 10 mg BID, respectively, 39.0% and 59.4% of patients achieved PASI75 responses, and 37.2% and 55.2% achieved PGA responses; median time to PASI75 or PGA responses was 24 weeks with tofacitinib 5 mg BID, and 9 weeks (PASI75) and 8 weeks (PGA) with tofacitinib 10 mg BID. By Week 4 of initial treatment 60.0% and 75.4% of patients achieved a reduction in DLQI score of ≥5 points from baseline, which was sustained throughout the 24 weeks. In patients rerandomized after initial treatment, PASI75 and PGA response were maintained up to Week 40 with continuous tofacitinib 5 or 10 mg BID treatment (PASI75, 56.2% and 62.3%; PGA, 49.9% and 63.9%, respectively), but declined in patients withdrawn from tofacitinib (PASI75, 23.3% and 26.1%; PGA, 22.9% and 18.0%, respectively). After 16 weeks of retreatment with tofacitinib 5 mg and 10 mg BID, respectively, 31.6% and 50.9% of relapsers achieved PASI75 responses, 41.4% and 49.0% regained PGA responses, and 47.5% and 64.5% of patients with a DLQI score of ≥5 at the start of retreatment achieved a ≥5 point reduction in DLQI score from baseline. No patient experienced psoriasis rebound upon treatment withdrawal. The patterns of adverse events or laboratory abnormalities were similar to those previously observed with tofacitinib; laboratory abnormalities were generally reversible upon withdrawal.
LIMITATIONS: The retreatment period (16 weeks) was shorter than the initial treatment period (24 weeks), precluding the assessment of responses to retreatment over longer periods. Only PASI75 and PGA responders were evaluated in the treatment withdrawal and retreatment stages. A large degree of relapse was allowed before patients were retreated.
CONCLUSION: Tofacitinib 5 mg and 10 mg BID improved plaque psoriasis during 24 weeks of initial treatment. Patients remaining on therapy maintained better efficacy than those with treatment withdrawal. Among patients who relapsed, up to half recaptured their response with tofacitinib after 16 weeks of re-treatment.
CORRESPONDING AUTHOR: Robert Bissonnette, Innovaderm Research, 1851 Sherbrooke East, Suite 502, Montreal H2K 4L5 Canada. E-mail: [email protected].
CONFLICTS: Dr Bissonnette reports grants and personal fees from Pfizer Inc during the conduct of the study; grants and personal fees from AbbVie, Amgen, Apopharma, Astellas, Celgene, Eli-Lilly, Incyte, Janssen, Leo Pharma, Merck, Novartis and Tribute outside the submitted work. Dr L Iversen reports grants and personal fees from Pfizer Inc during the conduct of the study; grants and personal fees from AbbVie, Amgen, Celgene, Eli-Lilly, Janssen, Leo Pharma, Novartis, Almirall, Centocor, MSD and UCB outside the submitted work. Dr Sofen reports grants and personal fees from Pfizer, during the conduct of the study; grants and personal fees from Celgene, grants and personal fees from Janssen, grants and personal fees from Amgen, grants and personal fees from Novartis, grants and personal fees from Eli-Lilly, grants and personal fees from Merck outside of the submitted work. Dr C Griffiths reports grants and personal fees from Pfizer Inc during the conduct of the study; grants and personal fees from AbbVie, Actelion, Biotest, Celgene, Eli-Lilly, Incyte, Janssen, LEO Pharma, MSD, Novartis, Sandoz, Stiefel UK, Trident, Zymogenetics and UCB outside the submitted work. Dr Foley reports personal fees from Wyeth/Pfizer Inc during the conduct of the study; grants and personal fees from Galderma, LEO/Peplin, Ascent, Clinuvel, Aspen, Janssen, CSL, Novartis, 3M/iNova/ Valeant, GSK/Stiefel, Abbott/AbbVie, Biogenldec, Merck Serono, Schering-Plough/MSD, Amgen, Celgene, Roche, Actelion, Sanofi Aventis, MedyTox, Shape and BMS and Eli-Lilly, personal fees from Australian Ultraviolet Services, Mayne Pharma and Roche outside the submitted work. Dr Romiti reports grants and personal fees from Pfizer Inc during the conduct of the study; grants and personal fees from AbbVie, Eli-Lilly, Galderma, Janssen, LEO-Pharma and Novartis outside the submitted work. M Bachinsky, Drs Rottinghaus, Tan, Proulx, Valdez, Mallbris, Gupta, and Wolk are employees and shareholders of Pfizer Inc during the conduct of the study.
Vol. 33, December 2014, Seminars in Cutaneous Medicine and Surgery (Supplement 5) S87