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

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).

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.

Four RCTs comprising 5451 patients met the inclusion criteria. Baricitinib 4 mg + MTX and upadacitinib 15 mg + MTX showed a significantly higher American College of Rheumatology 20% (ACR20) response rate than adalimumab 40 mg + MTX. Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that baricitinib 4 mg + MTX had the highest probability of being the best treatment for achieving the ACR20 response rate, followed by upadacitinib 15 mg + MTX, tofacitinib 5 mg + MTX, filgotinib 200 mg + MTX, filgotinib 100 mg + MTX, adalimumab 40 mg + MTX, and placebo + MTX. Upadacitinib 15 mg + MTX and baricitinib 4 mg + MTX showed significantly higher ACR50 and ACR70 response rates than adalimumab 40 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 200 mg + MTX, filgotinib 100 mg + MTX, adalimumab 40 mg + MTX, tofacitinib 5 mg + MTX, upadacitinib 15 mg + MTX, and baricitinib 4 mg + MTX. No statistically significant differences were found between the intervention groups in terms of safety.

In RA patients with an inadequate response to MTX, baricitinib 4 mg + MTX and upadacitinib 15 mg + MTX showed the highest ACR response rates, suggesting a difference in efficacy among the different JAK inhibitors.