Efficacy of Methotrexate in the Treatment of Psoriatic Arthritis: A Critical Literature Review

Sammanfattning: Background: Psoriatic arthritis (PsA) is an inflammatory joint disease occurring in up to 30% of psoriasis patients. Relatively few clinical trials assess PsA treatment and data presentation in these are far from uniform making comparisons difficult. Objectives: To perform a literature review on methotrexate (MTX) efficacy in PsA. Research questions were: What evidence support MTX monotherapy in PsA? Does combination with MTX improve anti-TNF (anti-tumor necrosis factor) treatment outcomes in PsA? Methods: MEDLINE and Embase were searched until May 2019. This was supplemented by manually searching bibliographies of international treatment guidelines. For the review of efficacy of MTX monotherapy, trials comparing MTX monotherapy versus placebo, other conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), non-steroidal anti-inflammatory drugs (NSAIDs) or glucocorticoids were considered. For the comparison of TNFi monotherapy versus combination with MTX, randomized controlled trials (RCTs) comparing TNFi monotherapy (adalimumab/etanercept/certolizumab pegol/golimumab/infliximab) or in combination with MTX versus placebo were considered, as were RCTs comparing the combination of TNFi plus MTX to TNFi monotherapy. Results: In four trials comparing MTX monotherapy to placebo or no additional intervention, superiority of MTX was demonstrated for only a few outcomes. Some indirect support for MTX efficacy also exists from three out of four studies comparing MTX to other active treatments. Findings were limited by the generally small numbers of patients included, relatively high placebo responses and by the low MTX dosages used. The review of secondary analyzes from 11 trials comparing TNFi monotherapy versus combination with MTX showed numerically little or no additional effect of combination therapy on treatment response regardless of TNFi. In contrast, several studies suggest combination therapy to increase adherence to TNFi-s. Conclusions: Evidence from placebo-controlled trials for the efficacy of MTX monotherapy in PsA is sparse and generally of low quality, although some positive results do exist. Efficacy of TNFi-s does not seem to improve by combination with MTX, whereas TNFi adherence may be enhanced by such combination.