Comparative Effectiveness and Safety of the JAK Inhibitors and Biologic Disease-Modifying Antirheumatic Drugs in...

We evaluated the efficacy and safety profiles of JAK inhibitors (JAKi) and biologic disease-modifying antirheumatic drugs (bDMARDs) when used with or without methotrexate (MTX) for the treatment of nonsystemic forms of juvenile idiopathic arthritis (nsJIA).

Randomized clinical trials (RCTs) investigating efficacy and safety outcomes of JAKi or bDMARDs for the nsJIA population up to 2023 were searched in ClinicalTrial.gov, PubMed, EMBASE, and Cochrane databases. Bayesian arm-based network meta-analysis compared efficacy as measured by Juvenile Idiopathic Arthritis-American College of Rheumatology 70 (JIA-ACR70) improvement and safety based on rates of serious adverse events (SAEs) among all therapies.

Eligible studies included 45 citations from 16 RCTs (7 parallel and 9 withdrawal trials) with a total of 1,821 participants that investigated nine bDMARDs, three with and six without MTX co-treatment, and two JAKis (tofacitinib and baricitnib). The reported SAE incidence rates ranged from 0 to 0.3 per person-year of follow-up; none of the pairwise comparisons were statistically significant. The JIA-ACR70 improvement by 16 weeks of treatment ranged from 11.3% to 89.5%. Compared with controls, significant JIA-ACR70 improvements were observed for etanercept, golimumab, and all three combination therapies (adalimumab+MTX, etanercept+MTX, and infliximab+MTX), with odds ratios ranging from 2.97 to 3.99. No significant pairwise comparisons between bDMARDs and JAKi versus bDMARDs were noted.

Overall, no significant evidence was found for efficacy and safety profiles in pairwise comparisons of JAKis and bDMARDs. Future studies will expand the meta-analysis by including non-RCT studies and individual participant data.