Treating Early Undifferentiated Arthritis: A Systematic Review and Meta-Analysis of Direct and Indirect Trial Evidence

Objective: We undertook a systematic review and meta-analysis of direct and indirect trial evidence to evaluate the efficacy of treatments for patients with undifferentiated arthritis (UA). Methods: We searched 4 electronic databases from inception to January 2016, clinicaltrials.gov, and bibliographies of relevant articles. Two reviewers independently screened and evaluated the studies. The primary outcome was development of rheumatoid arthritis (RA). Results: Nine studies were included. Interventions included methotrexate, abatacept, infliximab, intraarticular or intramuscular glucocorticoids, and radiation synovectomy. Treating patients resulted in lower rates of RA at 12 months compared to placebo or no treatment (odds ratio [OR] 0.49 [95% confidence interval (95% CI) 0.26, 0.90]). From direct meta-analysis, patients treated with methotrexate were less likely to develop RA at 12 months compared to patients treated without methotrexate (OR 0.13 [95% CI 0.03, 0.48]). This difference was no longer significant at 30 or 60 months. From indirect comparisons, most interventions showed decreased risk of developing RA compared to placebo at 12 months, reaching statistical significance for methotrexate (OR 0.16 [95% CI 0.08, 0.33]) and intramuscular methylprednisolone (OR 0.72 [95% CI 0.53, 0.99]). Most individual interventions included a limited number of studies. Conclusion: Treating patients with UA resulted in a statistically significant delay in the development of RA, with the largest effect observed for methotrexate. These findings suggest that there is a window of opportunity to treat patients with UA early, to delay subsequent progression to RA.