Comparative Efficacy and Safety of JAK Inhibitors in the Management of Rheumatoid Arthritis: A Network Meta-Analysis

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Background/objective: Janus Kinase inhibitors (JAKinibs) are effective and well-tolerated targeted therapies for rheumatoid arthritis (RA). The comparative efficacy and safety of different JAKinibs remains unclear. This network meta-analysis (NMA) aimed to assess the relative efficacy and safety of different available JAKinibs. Methods: Searches were conducted on PubMed, CENTRAL, and ClinicalTrials.gov for randomized, double-blind, placebo-controlled trials comparing JAKinibs in RA patients. A frequentist NMA using the Netmeta package in R (R.4.3.0) was performed to evaluate both efficacy and safety outcomes. Continuous outcomes were presented as mean differences (MDs) and binary outcomes as relative risks (RR) with 95% confidence intervals (CI). The Cochrane risk of bias tool was used to assess the risk of bias in the included trials. Results: The analysis encompassed 39 trials with a total of 16,894 participants. Six JAKinibs (tofacitinib, baricitinib, upadacitinib, decernotinib, peficitinib, and filgotinib) were compared. Decernotinib at a dose of 300 mg showed a higher ACR50 response than other JAKinibs (RR = 7.55, 95% CI: 3.48 to 16.39, p < 0.01, surface under the cumulative ranking curve (SUCRA): 0.92). Tofacitinib at a dose of 1 mg twice daily had a significantly lower incidence of adverse drug reactions (ADRs) compared to other JAKinibs (RR = 0.80, 95% CI: 0.65 to 0.99, p = 0.04, SUCRA: 0.89), filgotinib 100 mg had a significantly lower infection risk (RR = 0.40, 95% CI: 0.21 to 0.79, p < 0.01, SUCRA: 0.90), whereas baricitinib 4 mg had the significantly highest herpes zoster risk (RR = 4.79, 95% CI: 1.03 to 22.21, p = 0.05, SUCRA: 0.11) compared to other JAKinibs. Conclusions: This NMA’s results indicate that commercially available JAKinibs show superior ACR responses and have comparable tolerability to placebo.

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