Update on TNF Inhibitors in Dermatology
Jeffrey M. Sobell, MD*
Assistant Professor of Dermatology
Tufts University School of Medicine
Director, Psoriasis Treatment Center
Chestnut Hill, Massachusetts
Emerging data describe new potential indications for tumor necrosis factor (TNF) inhibitors in dermatology, including pediatric psoriasis and hidradenitis suppurativa. New biosimilar TNF agents are in late stages of development and may be available in the United States in the near future. Biosimilar agents are similar but not identical to available TNF inhibitors, and approval requires extensive analytic, toxicity, pharmacokinetic, pharmacodynamic, and clinical testing. Semin Cutan Med Surg 35(supp6):S104-S106 © 2016 published by Frontline Medical Communications
Biosimilars; hidradenitis suppurativa; pediatric psoriasis; psoriasis; TNF inhibitors
Tumor necrosis factor (TNF) inhibitors have been approved for the treatment of adult patients with psoriasis for a dozen years, starting with etanercept and followed by infliximab and adalimumab. Current evidence also suggests that TNF inhibitors can be safe and effective for pediatric patients, and new biosimilars are also in late stages of development. Finally, the TNF inhibitor adalimumab was recently approved for a new dermatologic indication, hidradenitis suppurativa.
Psoriasis is relatively common in the pediatric population. For example, approximately 40% of adults with psoriasis report onset during childhood.1 The use of etanercept for pediatric psoriasis was initially evaluated in a phase III trial (n=211) that included a 12-week double-blind treatment period, followed by 24 weeks of open-label treatment and a 12-week double-blind withdrawal period. 2
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Participants should read the CE information below, review the activity in its entirety, and complete the online post-test and evaluation. Upon completing this activity as designed and achieving a passing score on the post-test, you will be directed to a Web page that will allow you to receive your certificate of credit via e-mail or you may print it out at that time.
Research continues to expand our understanding of the pathophysiology and management of skin diseases and age-related skin damage. Based on this evidence, new pharmacologic agents and medical devices continue to be developed, researched, and approved for use in the United States. New evidence and therapies have been developed for acne vulgaris, rosacea, psoriasis, onychomycosis/tinea, and facial rejuvenation. Clinicians need to understand the safety and efficacy of these new therapies in specific patient types.
Acne vulgaris affects 40 to 50 million people in the United States, with a prevalence as high as 85% in teenagers. A wide range of effective treatment strategies are now available to manage acne vulgaris, and new agents continue to be developed, offering an enhanced range of options. Psoriasis is an inflammatory skin disease for which a variety of agents, including several tumor necrosis factor (TNF) inhibitors, are approved for treatment. Recently, the use of TNF inhibitors for pediatric psoriasis has been investigated, and new biosimilar agents are in late stages of development for psoriasis. Clinicians may be reluctant to use TNF inhibitors in children with psoriasis and do not yet have clinical experience with biosimilar agents.
Rosacea is a common chronic skin condition affecting the face, affecting approximately 14 million Americans. No cure exists for rosacea, but health care professionals have several options to treat the symptoms, including new agents to treat facial erythema and inflammation. The use of these agents requires an understanding of their safety and use in combination therapy. Onychomycosis and tinea pedis are common fungal infections affecting the nails and feet, respectively. Newly approved topical agents for onychomycosis and tinea have demonstrated high cure rates in clinical studies.
Among the most common cosmetic procedures performed in the United States are the use of botulinum toxin A, soft tissue fillers, and laser treatments. In the last decade, a multitude of new products and devices have been developed for these indications, including new soft tissue fillers and novel laser technologies. The increased availability of options also increases the challenge of selecting the most appropriate agent or combination of agents for each patien
By reading and studying this supplement, participants should be better able to:
- Integrate into daily practice evidence-based recommendations on new and emerging therapies for common and uncommon dermatologic diseases
- Implement updated strategies for managing acne, rosacea, and psoriasis
- Discuss the use of biologic agents in the treatment of adult and pediatric psoriasis
- Review the status of biosimilars for use in dermatology
- Incorporate the recent advances in the treatment of acne vulgaris
- Discuss the safety, efficacy, and dosing of antibiotics for acne vulgaris
- Analyze emerging treatments for tinea and onychomycosis
- Identify the considerations in the selection of appropriate filler agents for treating different areas of the face
- Compare and contrast the efficacy and safety of agents, devices, and techniques currently available in aesthetic and procedural dermatology
- Determine the appropriate nonsurgical techniques for facial rejuvenation
- Describe the appropriate use of neuromodulators in the treatment of the aging face.
Individuals in a position to control the content of this educational activity are required to disclose: 1) the existence of any relevant financial relationship with any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients with the exemption of non-profit or government organizations and nonhealth care related companies, within the past 12 months; and 2) the identification of a commercial product/device that is unlabeled for use or an investigational use of a product/device not yet approved.
Joseph F. Fowler, Jr, MD
Consultant: Bayer Healthcare, Galderma Laboratories, L.P., GlaxoSmithKline, Johnson & Johnson, Medimetriks Pharmaceuticals, Inc., Ranbaxy Laboratories Ltd., SmartPractice Dermatology/Allergy, Valeant Pharmaceuticals North America LLC; Speakers Bureau: Galderma, SmartPractice, Valeant; Grant/Research Support: AbbVie Inc., Allergan, Inc., Amgen Inc., Anacor Pharmaceuticals, Inc., Bayer, Celgene Corporation, Centocor, Inc., Chugai Pharma USA, Inc., Dow Chemical Company, Eli Lilly and Company, Galderma, Genentech, Inc., Innovaderm Research Inc., Janssen Biotech, Inc., Johnson & Johnson, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Onset Dermatologics, LLC, Pfizer Inc., Precision Dermatology, Regeneron Pharmaceuticals, Inc., SmartPractice, Taisho Pharmaceutical Co., Ltd., Taro Pharmaceutical Industries Ltd., Valeant
Theodore Rosen, MD
Scientific Advisory Board: Anacor Pharmaceuticals, Inc., Merz Pharma North America Inc., Valeant
Jeffrey M. Sobell, MD
Grant/Research Support: Amgen, Celgene, Eli Lilly, Janssen, Merck, Novartis; Consultant: AbbVie, Amgen, Celgene, Eli Lilly, Janssen; Speakers Bureau: AbbVie, Amgen, Celgene, Janssen, Novartis
Nowell Solish, MD, FRCP(C)
Consultant/Grant/Research Support: Allergan, Galderma, Indeed Labs, Inc., Merz, Revance Therapeutics, Inc., Valeant
Linda F. Stein Gold, MD
Consultantand Scientific Advisory Board: Anacor, Bayer, Eli Lilly, Foamix Pharmaceuticals Inc., Galderma, LEO Pharma Inc., Medimetrix Pharmaceuticals, Inc., Novartis, Pfizer, Taro
Christopher B. Zachary, MBBS, FRCP
Consultant: Kythera Biopharmaceuticals, Inc., Sciton, Inc., Solta Medical; Scientific Advisory Board: Sciton and ZELTIQ Aesthetics, Inc.
In order to help ensure content objectivity, independence, and fair balance, and to ensure that the content is aligned with the interest of the public, CCOE has resolved all potential and real conflicts of interest through content review by a non-conflicted, qualified reviewer. This activity was peer-reviewed tor relevance, accuracy of content, and balance of presentation by: Jean Sines, RN, BSN, Staff Nurse, Department of Dermatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ. Ms. Sines has no relevant financial relationships to disclose.
Field Testers: This activity was pilot-tested for time required by: Physicians: Brian Lee, MD, Sima Patel, DO, and Vijay Vanchinathan, MD. Nurses: Geraldine Bocchieri, RN, BSN, Kathleen Brown, LPN, and Stacy Johnson, RN. The field testers have no relevant financial relationships to disclose.
Rutgers, The State University of New Jersey: Tristan Nelsen, MNM, CMP, and Elizabeth Ward, MSJ, have no relevant financial relationships to disclose.
Global Academy for Medical Education Staff: Shirley V. Jones, MBA; Sylvia H. Reitman, MBA, DipEd; and Josh Kilbridge have no relevant financial relationships to disclose.
Off-Label/Investigational Use Disclosure
This activity discusses the off-label use of the following approved agents: adalimumab, cyclosporine ophthalmic emulsion, doxycycline, etanercept, fluconazole, isotretinoin, itraconazole, ketoconazole, methotrexate, minocycline (oral and foam), secukinumab, ustekinumab, and tumor necrosis factor inhibitors as a class.
Contact Information for Technical Questions
Please technical questions or concerns to Global Academy for Medical Education at 973-290-8225 or email [email protected].
This continuing medical education (CME/CE) supplement was developed from faculty presentations at the Skin Disease Education Foundation’s 40th Annual Hawaii Dermatology Seminar™, February 14-19, 2016. The Guest Editors/Faculty acknowledge the editorial assistance of Global Academy for Medical Education, LLC, and Josh Kilbridge, medical writer, in the development of this supplement. The manuscript was reviewed and approved by the Guest Editors as well as the Editors of Seminars in Cutaneous Medicine and Surgery for publication as a supplement to the journal. This activity was developed under the direction of the Faculty/Guest Editors, Global Academy for Medical Education, and Rutgers. The ideas and opinions expressed in this supplement are those of the Guest Editors and do not necessarily reflect the views of the supporters, Global Academy for Medical Education, Rutgers, or the Publisher.
Copyright © 2016 by Global Academy for Medical Education, LLC and Rutgers, The State University of New Jersey. All rights reserved. No part of this publication may be reproduced or transmitted in any form, by any means, without prior written permission of Global Academy for Medical Education and Rutgers. Global Academy for Medical Education and Rutgers will not assume responsibility for damages, loss, or claims of any kind arising from or related to the information contained in this publication, including any claims related to the products, drugs, or services mentioned herein.
1. Feldman SR, Huang WW, Huynh TT. Current drug therapies for rosacea: A chronic vascular and inflammatory skin disease. J Manag Care Spec Pharm. 2014;20:623-629.
2. Del Rosso JQ. Advances in understanding and managing rosacea: Part 1: Connecting the dots between pathophysiological mechanisms and common clinical features of rosacea with emphasis on vascular changes and facial erythema. J Clin Aesthet Dermatol. 2012;5:16-25.
3. Piwnica D, Rosignoli C, de Ménonville ST, et al. Vasoconstriction and anti-inflammatory properties of the selective α-adrenergic receptor agonist brimonidine. J Dermatol Sci. 2014;75:49-54.
4. Fowler J, Jarratt M, Moore A, et al. Once-daily topical brimonidine tartrate gel 0.5% is a novel treatment for moderate to severe facial erythema of rosacea: Results of two multicentre, randomized and vehicle-controlled studies. Br J Dermatol. 2012;166:633-641.
5. Jackson JM, Fowler J, Moore A, et al. Improvement in facial erythema within 30 minutes of initial application of brimonidine tartrate in patients with rosacea. J Drugs Dermatol. 2014;13:699-704.
6. Ilkovitch D, Pomerantz RG. Brimonidine effective but may lead to significant rebound erythema. J Am Acad Dermatol. May 2014;70:e109-e110.
7. Migden MR, Guminski A, Gutzmer R, et al. Treatment with two different doses of sonidegib in patients with locally advanced or metastatic basal cell carcinoma (BOLT): A multicentre, randomised, double-blind phase 2 trial. Lancet Oncol. 2015;16:716-728.
8. Moore A, Kempers S, Murakawa G, et al. Long-term safety and efficacy of oncedaily topical brimonidine tartrate gel 0.5% for the treatment of moderate to severe facial erythema of rosacea: Results of a 1-year open-label study. J Drugs Dermatol. 2014;13:56-61.
9. Routt ET, Levitt JO. Rebound erythema and burning sensation from a new topical brimonidine tartrate gel 0.33%. J Am Acad Dermatol. 2014;70:e37-e38.
10. Swanson LA, Warshaw EM. Allergic contact dermatitis to topical brimonidine tartrate gel 0.33% for treatment of rosacea. J Am Acad Dermatol. 2014;71:832-833.
11. Dourmishev AL, Dourmishev LA, Schwartz RA. Ivermectin: Pharmacology and application in dermatology. Int J Dermatol. 2005;44:981-988.
12. Labro MT. Anti-inflammatory activity of macrolides: A new therapeutic potential? J Antimicrob Chemother. 1998;41(suppl B):37-46.
13. Stankiewicz M, Cabaj W, Jonas WE, Moore LG, Millar K, Ng Chie W. Influence of ivermectin on cellular and humoral immune responses of lambs. Vet Immunol Immunopathol. 1995;44:347-358.
14. Ci X, Li H, Yu Q, et al. Avermectin exerts anti-inflammatory effect by downregulating the nuclear transcription factor kappa-B and mitogen-activated protein kinase activation pathway. Fundam Clin Pharmacol. 2009;23:449-455.
15. Stein L, Kircik L, Fowler J, et al. Efficacy and safety of ivermectin 1% cream in treatment of papulopustular rosacea: Results of two randomized, double-blind, vehicle-controlled pivotal studies. J Drugs Dermatol. 2014;13:316-323.
16. Stein Gold L, Kircik L, Fowler J, et al. Long-term safety of ivermectin 1% cream vs azelaic acid 15% gel in treating inflammatory lesions of rosacea: Results of two 40-week controlled, investigator-blinded trials. J Drugs Dermatol. 2014;13:1380-1386.
17. Taieb A, Ortonne JP, Ruzicka T, et al. Superiority of ivermectin 1% cream over metronidazole 0.75% cream in treating inflammatory lesions of rosacea: A randomized, investigator-blinded trial. Br J Dermatol. 2015;172:1103-1110.
18. Draelos ZD, Elewski BE, Harper JC, et al. A phase 3 randomized, double-blind, vehicle-controlled trial of azelaic acid foam 15% in the treatment of papulopustular rosacea. Cutis. 2015;96:54-61.
19. Bevins CL, Liu FT. Rosacea: Skin innate immunity gone awry? Nat Med. 2007; 13:904-906.
20. Yamasaki K, Di Nardo A, Bardan A, et al. Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nat Med. 2007;13:975-980.
21. Kanada KN, Nakatsuji T, Huang EY, Gallo RL. Inhibition of cathelicidin processing enzymes as therapy for rosacea. Presented at: 71st Annual Meeting of the Society for Investigative Dermatology; May 4-7, 2011; Phoenix, AZ.
22. Ryan ME, Usman A, Ramamurthy NS, Golub LM, Greenwald RA. Excessive matrix metalloproteinase activity in diabetes: Inhibition by tetracycline analogues with zinc reactivity. Curr Med Chem. 2001;8:305-316.
23. Del Rosso JQ, Schlessinger J, Werschler P. Comparison of anti-inflammatory dose doxycycline versus doxycycline 100 mg in the treatment of rosacea. J Drugs Dermatol. 2008;7:573-576.
Publication of this CME/CE article was jointly provided by Rutgers, The State University of New Jersey, and Global Academy for Medical Education, LLC, with Skin Disease Education Foundation (SDEF) and is supported by educational grants from AbbVie Inc., Bayer Healthcare, Merz Pharma North America Inc., and Valeant Pharmaceuticals North America LLC.
Dr Fowler and Dr Zachary have received an honorarium for their participation in this activity. They acknowledge the editorial assistance of Josh Kilbridge, medical writer, and Global Academy for Medical Education in the development of this continuing medical education journal article.
Joseph F. Fowler, Jr, MD, Consultant: Bayer, Galderma Laboratories, L.P., GlaxoSmithKline, Johnson & Johnson, Medimetriks Pharmaceuticals, Inc., Ranbaxy Laboratories Ltd., SmartPractice Dermatology/Allergy, Valeant; Speakers Bureau: Galderma, SmartPractice, Valeant; Grant/ Research Support: AbbVie, Allergan, Inc., Amgen Inc., Anacor Pharmaceuticals, Inc., Bayer, Celgene Corporation, Centocor, Inc., Chugai Pharma USA, Inc., Dow Chemical Company, Eli Lilly and Company, Galderma, Genentech, Inc., Innovaderm Research Inc., Janssen Biotech, Inc., Johnson & Johnson, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Onset Dermatologics, LLC, Pfizer Inc., Precision Dermatology, Regeneron Pharmaceuticals, Inc., SmartPractice, Taisho Pharmaceutical Co., Ltd., Taro Pharmaceutical Industries Ltd., Valeant.
Christopher B. Zachary, MBBS, FRCP, Consultant: Kythera Biopharmaceuticals, Inc., Sciton, Inc., Solta Medical; Scientific Advisory Board: Sciton and ZELTIQ Aesthetics, Inc
Address reprint requests to: Christopher B. Zachary, MBBS, FRCP, Dermatology, UC Irvine Health, 118 Med Surge I, Irvine, CA 92697, [email protected]
1085-5629/13/$-see front matter © 2016 Frontline Medical Communications doi:10.12788/j.sder.2016.032