GRADE Evaluation of Systemic Therapies for Psoriatic Arthritis

A systematic review, meta-analysis, and Grading of Recommendations Assessment, Development and Evaluation (GRADE) consideration of approved systemic treatments for psoriatic arthritis (PsA) were conducted, with the results demonstrating that the majority of biologic agents are effective for most outcomes, although the certainty varied. Findings from the analysis were published in the Journal of the European Academy of Dermatology and Venereology.

Highlighting that direct comparisons between treatment arms from different trials should be avoided, the investigators performed a systematic search in 3 databases that had last been updated in September 2017. Data were obtained regarding ≥20% improvement/≥50% improvement in American College of Rheumatology in American College of Rheumatology Response Criteria (ACR 20/50), Health Assessment Questionnaire – Disability Index (HAQ-DI), Short Form Health Survey 36 (SF-36), and the rate of patients who experienced ≥1 adverse event after 16 to 24 weeks of treatment. The quality of evidence was assessed with the use of GRADE.

The coprimary outcomes were ACR 20 and the rate of patients who experienced ≥1 adverse event. Secondary outcomes included ACR 50, HAQ-DI, and the rate of patients who experienced ≥1 serious adverse event. Population/intervention/comparator/outcome and eligibility criteria were prespecified.

A total of 20 trials were included in the analysis. The selected trials evaluated adalimumab (ADA), apremilast (APR), certolizumab pegol (CZP), etanercept (ETN), golimumab (GOL), infliximab (INF), ixekizumab (IXE), leflunomide (LEF), methotrexate (MTX), secukinumab (SEC), sulfasalazine (SSZ), and ustekinumab (UST). Overall, 3 of the trials compared 2 active substances, with ACR 20 results as follows: (1) INF + MTX vs MTX alone: risk ratio [RR], 1.40; 95% CI, 1.07-1.84; very-low-quality evidence; (2) IXE every 2 weeks vs ADA every 2 weeks: RR, 1.08; 95% CI, 0.86-1.36; very-low-quality evidence; and (3) LEF vs MTX: RR, 1.01; 95% CI, 0.84-1.21; low-quality evidence.

Moreover, 18 drug vs placebo comparisons were included in the study. With respect to ACR 20/50, HAQ-DI, and SF-36, the active treatment was shown to be efficacious, with the quality of evidence mostly moderate to low (15 of 18 comparisons). In addition, the quality of evidence for serious adverse events was mostly low, with differences between the therapies being rare. In 3 placebo-controlled, comparator studies, LEF, MTX, and SSZ did not demonstrate statistically significant superiority in ACR 20/50.

Other than the established treatment of anti-tumor necrosis factor antibodies (ADA, CZP, ETN, GOL, INF) and UST for patients with PsA, the newer interleukin-17 antibodies (IXE, SEC) and APR have also shown efficacy for the treatment of PsA. According to the results of just 1 comparative trial and 1 medication each, the new drug class of anti- interleukin-17 antibodies appears to be equally effective as the group of anti-tumor necrosis factor antibodies for patients with PsA. The effectiveness of APR, however, is currently unclear.

The investigators concluded that current treatment algorithms can be based on very few head-to-head trials, with the continued need to always take into account real-world data and expert experience.

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Reference

Dressler C, Eisert L, Pham Thi PA, Nast A. Efficacy and safety of systemic treatments in psoriatic arthritis. a systematic review, meta-analysis and GRADE evaluation [published online February 8, 2019]. J Eur Acad Dermatol Venereol. doi: 10.1111/jdv.15482