Comparison of the efficacy and safety of tofacitinib and upadacitinib in patients with active rheumatoid arthritis: A Bayesian network meta-analysis of randomized controlled trials

Objectives The relative efficacy and safety of tofacitinib and upadacitinib were assessed in patients with rheumatoid arthritis (RA) with an inadequate response to conventional synthetic (cs) or biologic (b) disease-modifying anti-rheumatic drugs (DMARDs). Method 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 and upadacitinib in combination with methotrexate (MTX) in RA patients with an inadequate cs- or b-DMARD response. Results Nine RCTs including 5794 patients met the inclusion criteria. There were 15 pairwise comparisons including 10 direct comparisons of 6 interventions. Upadacitinib 15 mg + MTX and upadacitinib 30 mg + MTX were among the most effective treatments for active RA with an inadequate cs- or b-DMARD response, followed by tofacitinib 10 mg + MTX, tofacitinib 5 mg + MTX, and adalimumab + MTX. Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that upadacitinib 15 mg + MTX and upadacitinib 30 mg + MTX had the highest probability of being the best treatment in terms of the American College of Rheumatology 20 response rate (SUCRA = 0.820, 0.762), followed by tofacitinib 10 mg + MTX (SUCRA = 0.623), tofacitinib 5 mg + MTX (SUCRA = 0.424), adalimumab + MTX (SUCRA = 0.371), and placebo + MTX (SUCRA = 0.001). No significant differences were observed in the incidence of serious adverse events after treatment with tofacitinib + MTX, upadacitinib + MTX, adalimumab + MTX, or placebo + MTX. Conclusions In RA patients with an inadequate response to cs- or b-DMARDs, upadacitinib 15 mg + MTX and upadacitinib 30 mg + MTX were the most efficacious interventions and were not associated with significant risks of serious adverse events.