Relative efficacy and safety of tofacitinib, baricitinib, upadacitinib, and filgotinib in comparison to adalimumab in patients with active rheumatoid arthritis

Objective The relative efficacy and tolerability of tofacitinib, baricitinib, upadacitinib, and filgotinib compared to adalimumab were assessed in rheumatoid arthritis (RA) patients with 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 tofacitinib, baricitinib, upadacitinib, filgotinib, and adalimumab in RA patients with inadequate responses to MTX. Results Four RCTs comprising 5451 patients met the inclusion criteria. Baricitinib 4x202f;mg + MTX and upadacitinib 15x202f;mg + MTX showed a significantly higher American College of Rheumatology 20% (ACR20) response rate than adalimumab 40x202f;mg + MTX. Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that baricitinib 4x202f;mg + MTX had the highest probability of being the best treatment for achieving the ACR20 response rate, followed by upadacitinib 15x202f;mg + MTX, tofacitinib 5x202f;mg + MTX, filgotinib 200x202f;mg + MTX, filgotinib 100x202f;mg + MTX, adalimumab 40x202f;mg + MTX, and placebo + MTX. Upadacitinib 15x202f;mg + MTX and baricitinib 4x202f;mg + MTX showed significantly higher ACR50 and ACR70 response rates than adalimumab 40x202f;mg + MTX. For herpes zoster infection, the ranking probability based on SUCRA indicated that placebo + MTX was likely to be the safest treatment, followed by filgotinib 200x202f;mg + MTX, filgotinib 100x202f;mg + MTX, adalimumab 40x202f;mg + MTX, tofacitinib 5x202f;mg + MTX, upadacitinib 15x202f;mg + MTX, and baricitinib 4x202f;mg + MTX. No statistically significant differences were found between the intervention groups in terms of safety. Conclusion In RA patients with an inadequate response to MTX, baricitinib 4x202f;mg + MTX and upadacitinib 15x202f;mg + MTX showed the highest ACR response rates, suggesting a difference in efficacy among the different JAK inhibitors.