Comparative efficacy and safety of 15 and 30 mg upadacitinib administered to patients with active rheumatoid arthritis: a Bayesian network meta-analysis of randomized controlled trials

Objectives: We assessed the relative efficacy and safety of once-daily administration of 15 and 30 mg upadacitinib (a JAK1-selective inhibitor) in patients with active rheumatoid arthritis (RA). Methods: We conducted a Bayesian network meta-analysis to combine the direct and indirect evidence from randomized controlled trials (RCTs) that examined the efficacy and safety of upadacitinib in patients with active RA. Results: Five RCTs involving 4381 patients met the inclusion criteria. There were 15 pairwise comparisons, including eight direct comparisons and six interventions. The ACR20 response rate was significantly higher in the upadacitinib 15 and 30 mg + MTX (methotrexate) groups than in the MTX group (OR: 4.98, 95% CrI: 2.66–10.10; OR: 4.73, 95% CrI: 2.25–10.98). Adalimumab 40 mg + MTX, upadacitinib 30 mg, and upadacitinib 15 mg groups showed a significantly higher ACR20 response rate than did the MTX group. Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that upadacitinib 15 mg + MTX was likely to achieve the best ACR20 response rate (SUCRA = 0.838), followed by upadacitinib 30 mg + MTX, adalimumab 40 mg + MTX, upadacitinib 30 mg, upadacitinib 15 mg, and MTX (SUCRA = 0.784, 0.495, 0.471, 0.404, and 0.008, respectively). The safety based on the number of serious adverse events (SAEs) did not differ significantly among the six interventions. Conclusions: Upadacitinib 15 and 30 mg administration once daily in combination with MTX was the most efficacious intervention for active RA, with no significant risk for SAEs.