Most Systemic Therapies Safe and Effective for the Treatment of Psoriatic Arthritis

A systematic literature review revealed that the majority of systemic therapies used to treat psoriatic arthritis (PsA) — including biologic and targeted synthetic disease-modifying antirheumatic drugs such as tumor necrosis factor inhibitors and interleukin blockers — were safe and effective, according to a report published in the Journal of the European Academy of Dermatology and Venereology.

Although many people with plaque psoriasis also have PsA, there are no existing concise overviews characterizing the safety and efficacy of the various available systemic treatment options for combatting joint and entheseal disease manifestations.

Investigators searched 3 databases between March and September 2017 for randomized controlled trials involving PsA systemic therapies: Ovid MEDLINE, Ovid Embase, and the Cochrane Central Register of Controlled Trials. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines were used to evaluate the quality of evidence from each trial. Primary outcomes at 16 to 24 weeks were a ≥20% improvement in the American College of Rheumatology criteria (ACR20) and the adverse event (AE) rate for individuals with at least 1 AE. Secondary outcomes included a ≥50% ACR improvement (ACR50), results of the Short Form Health Survey 36 (SF-36) and Health Assessment Questionnaire – Disability Index, and the rate of serious AEs. Risk ratios (RR) were calculated.

A total of 21 trials were included for analysis, comprising 3 head-to-head comparisons of active substances and 18 studies that compared active treatment with placebos. In the former category, ACR20 results yielded RRs of 1.40 (95% CI, 1.07-1.84) for infliximab plus methotrexate vs methotrexate alone (GRADE=very low quality), 1.08 (95% CI, 0.86-1.36) for ixekizumab biweekly vs adalimumab biweekly (GRADE=very low quality), and 1.01 (95% CI, 0.84-1.21) for leflunomide vs methotrexate (GRADE=low quality).

For the drug vs placebo comparisons, results on ACR20/50, SF-36, and Health Assessment Questionnaire – Disability Index demonstrated good efficacy of the active treatment (GRADE = low to moderate on 15/18 trials) in most cases. Exceptions to this finding were 3 trials that involved placebo comparisons with leflunomide, methotrexate, and sulfasalazine, where no clear ACR20/50 superiority was detected. The ACR20 RRs ranged from 1.29 for sulfasalazine to 4.92 for golimumab, with most (10/18) trials receiving a GRADE rating of moderate quality.

There were no significant differences found in the rate of AEs (RR range, 0.96 to 1.41) or serious AEs between the majority of treatment and placebo groups (GRADE=mostly low quality), with the exception of trials involving apremilast and ixekizumab vs placebo, where AE rates were lower in the placebo groups.

Study limitations included not searching grey literature repositories or conference abstracts, nonassessment of publication bias, and lack of resources to contact original authors regarding their data.

“The majority of biologics were effective for most outcomes, but the certainty varied,” summarized the authors, while cautioning, “…direct comparison between treatment arms from different trials should be avoided.” They recommended that future research involve network meta-analyses and more head-to-head comparisons.

Disclosures: This review resulted from a larger project supported by Novartis. Please see original article for conflicts of interest statement.

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