LAS VEGAS – A number of drugs are showing promise for the treatment of psoriatic arthritis, but broader improvements are needed with respect to treatment strategies, according to Dr. Iain McInnes.
Earlier diagnosis, appropriate therapies, and treating to target are among the topics he covered in a presentation on maximizing patient outcomes at the annual Perspectives in Rheumatic Diseases.
A recent study demonstrated that even a 6-month delay in the diagnosis of psoriatic arthritis is associated with worse long-term outcomes on several measures. In that study of 283 patients (Ann. Rheum. Dis. 2014 Feb. 13 [doi: 10.1136/annrheumdis-2013-204858]), the median lag time from disease onset to first rheumatological assessment was 1 year, with only 30% of patients being seen by a rheumatologist within 6 months.
Multiple stepwise regression analysis showed that late consulters had a greater risk of developing peripheral joint erosions (odds ratio, 4.25) and had worse Health Assessment Questionnaire scores (odds ratio, 2.2).
One finding that could help with earlier diagnosis is detection of early entheseal involvement, said Dr. McInnes, professor of medicine and director of the Institute of Infection, Immunity and Immunology at the University of Glasgow (Scotland).
Subclinical entheseal involvement appears to predict psoriatic arthritis in patients presenting with psoriasis, he said at the conference.
In one study, the mean Glasgow Ultrasound Enthesitis Scoring System (GUESS) score was 7.9 in patients with psoriasis, compared with 2.9 in controls, and in another study, thickness of the quadriceps tendon was a significant predictor of the development of psoriatic arthritis in those with psoriasis.
A key challenge in maximizing outcomes in psoriatic arthritis is that rheumatoid arthritis and psoriatic arthritis are typically treated as homogeneous for the purposes of drug development, but the two diseases have distinct clinical phenotypes and time course, tissue distribution, tissue cell/molecular features, genetic susceptibility, and probably impact of immune senescence.
In fact, while disease-modifying antirheumatic drugs are included in European League Against Rheumatsm (EULAR) treatment guidelines for psoriatic arthritis, the Methotrexate in Psoriatic Arthritis (MIPA) trial, a 6-month, double-blind, randomized, placebo-controlled trial of methotrexate, showed no benefit for key psoriatic arthritis endpoints at 3 and 6 months (Rheumatology 2012;51:1368-77).
Data on methotrexate combination therapy is limited, but existing clinical trials and registry data show no clear evidence of benefit. Methotrexate also has long-term toxicity issues.
In studies of patients who received anti–tumor necrosis factor therapy, 59%-69% of patients achieved 20% improvement (ACR 20 response), 37%-50% achieved 50% improvement (ACR 50 response), and up to 52% of patients achieved minimal disease activity at various time points. Also, radiographic progression was improved with anti-TNF therapy vs. placebo. However, TNF inhibitors lose efficacy over time in some patients, and are associated with an increased risk of infection.
Other disappointments or unmet needs in psoriatic arthritis are dichotomous skin and joint responses to biologics, lack of established predictors of response to biologics, lack of a cure, and difficulties in achieving sustained remission, Dr. McInnes said.
Future therapeutic options, including several drugs in development, include drugs that target cytokines and their receptors, such as ustekinumab, which targets IL-12/23; secukinumab and ixekizumab, which target IL-17; and brodalumab, which targets IL-17 receptor A. Other potential targets include IL-6 and the IL-6 receptor and IL-23 and the IL-23 receptor.
Studies of ustekinumab, for example, demonstrate beneficial effects on enthesitis, dactylitis, and modified van der Heijde-Sharp score.
Drugs that target intracellular signaling pathways are also being studied in psoriatic arthritis, including JAK family agents such as tofacitinib and phosphodiesterase inhibitors like apremilast.
As for strategies to improve outcomes, the Tight Control in Psoriatic Arthritis (TICOPA) study provided a rationale for treating to target. Current recommendations call for a target of remission or low disease activity.
The availability of highly effective biologics makes minimal level of disease activity a realistic treatment target, Dr. McInnes said.
The conference was held by Global Academy for Medical Education. Global Academy for Medical Education and this news organization are owned by Frontline Medical Communications.
Dr. McInnes reported receiving research/grant support from Pfizer, Bristol-Myers Squibb, AstraZeneca, and Novo Nordisk, and serving as a consultant to Novartis, Bristol-Myers Squibb, Pfizer, and Galapagos. He is a member of scientific advisory boards for AstraZeneca, Crescendo Bioscience, and Janssen Biotech.