Methotrexate is not disease modifying in psoriatic arthritis: The MIPA trial

Background: Methotrexate (MTX) is widely used as a disease modifying drug (DMARD) in psoriatic arthritis (PsA) without definitive supporting clinical trial evidence. We tested its effectiveness in the first large multicentre randomised controlled trial (RCT) of MTX in active PsA (MIPA). Methods: A 6-month double-blind RCT compared oral MTX (15mg/week) with placebo in patients with active PsA. The primary outcome measure was the PsA Response Criteria (PsARC); other composite measures included ACR20 and DAS28. We analysed changes in individual measures including “disease modifying” (joint counts, HAQ, ESR and CRP) and “symptom modifying” (global assessments and pain) measures, skin and nail scores. Results: 462 patients were screened and 221 recruited. 71/109 (65%) of those who received MTX and 77/112 (69%) of those who received placebo completed 6 months therapy. 19 patients (11 MTX, 8 placebo) withdrew for toxicity and 22 (8 MTX, 14 placebo) for inefficacy. No significant treatment effects were seen on PsARC, ACR20 and DAS28 at 3 or 6 months using intention to treat logistic regression analysis (including multiple imputations for missing data and adjustment for age and sex). (Figure presented) There were also no significant treatment effects on tender and swollen joint counts, ESR, CRP, HAQ, pain and nail scores using ordinal linear regression analyses (adjusted for age, sex, baseline scores and disease duration). Patient and physician global scores and skin scores did improve with MTX compared to placebo but at 6 months only (p=0.03, p=0.02 and p=0.02). Separate analysis of polyarticular and oligoarticular PsA subsets also showed no treatment effect for PsARC, ACR20 and DAS28 at 3 or 6 months. Conclusions: Contrary to general opinion, MTX does not act as a DMARD in PsA but has only borderline “symptom modifying” properties. Its value in active PsA is questionable when there are other agents, such as leflunomide and TNF-inhibitors, which are true DMARDs. This has important implications for current national and international guidance for the treatment of PsA.