Relative effectiveness and safety of interleukin-6 and Janus kinase inhibitors versus adalimumab in patients with rheumatoid arthritis: a network meta-analysis

Objective The relative efficacy and tolerability of interleukin-6 (IL-6) and Janus kinase (JAK) inhibitor therapies were compared with those of adalimumab in patients with rheumatoid arthritis (RA) and inadequate responses to methotrexate (MTX). Methods We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and safety of IL-6 inhibitors, JAK inhibitors, and adalimumab in patients with RA and inadequate responses to MTX. Results Seven RCTs, which included 4428 patients (1066 for IL-6 inhibitors and 3362 for JAK inhibitors), met the inclusion criteria. IL-6 inhibitors were placed at the top left of the league table diagonal (Odds ratio, OR 1.43; 95% CrI 1.12-1.82) as these were correlated with the most beneficial ACR20 response rate. Conversely, the placebo was placed at the bottom right of the league table diagonal as it was correlated with the least desirable effects. IL-6 and JAK inhibitors produced a substantial ACR20 response relative to adalimumab. The surface under the cumulative ranking curve (SUCRA) revealed that treatment with IL-6 inhibitors had the greatest ability to reach the ACR20 response rate (SUCRA = 0.826), followed by treatment with JAK inhibitors (SUCRA = 0.672) and adalimumab (SUCRA = 0.001). The ACR50 and ACR70 rates displayed patterns similar to the ACR20 response rate. With regard to serious adverse events (SAEs), the SUCRA rating likelihood showed that adalimumab was likely to be the best intervention, followed by JAK and IL-6 inhibitors. Conclusion Both IL-6 and JAK inhibitors are more effective than adalimumab and have similar effects in patients with RA and an inadequate response to MTX. Adalimumab is likely to be safer than JAK and IL-6 inhibitors.