This study assessed the comparative effectiveness of the JAK1/2 inhibitors, tofacitinib and baricitinib, in patients with rheumatoid arthritis (RA) using a network meta-analysis and Cochrane systematic review of randomized controlled trials from 7 electronic databases and 2 trial registries. Included trials compared tofacitinib or baricitinib alone or in combination with methotrexate (MTX) versus placebo, MTX, or other traditional or biologic disease-modifying antirheumatic drugs. The primary outcome assessed in the network meta-analysis was American College of Rheumatology (ACR) 50% improvement criteria (ACR50); secondary outcomes included remission according to the Disease Activity Score (DAS28), functional ability measured by the Health Assessment Questionnaire, and serious adverse events (SAEs).
Of the 21 trials that met the inclusion criteria (n = 9839), 14 evaluated tofacitinib and 7 evaluated baricitinib; 2 of the tofacitinib trials were at high risk for reporting bias; selection and performance bias could not be evaluated in all 7 trials. The patient demographics were mostly female (74%-96%), median age of 48 to 56 years, and disease duration of 2.7 to 13 years. Compared with placebo, all drug combinations were effective in achieving ACR50 at 12 weeks, including (from most to least effective) baricitinib 8 mg + MTX, tofacitinib 10 mg + MTX, tofacitinib 5 mg + MTX, baricitinib 2 mg + MTX, baricitinib 4 mg + MTX, baricitinib 4-mg monotherapy, adalimumab + MTX, tofacitinib 10-mg monotherapy, tofacitinib 10-mg monotherapy, MTX, and adalimumab monotherapy. Of these, the most effective combinations were tofacitinib 10 mg + MTX (ACR50, 11.3; 5.9-21.4) and baricitinib 8 mg + MTX (ACR50, 13.5; 5.8-31.3); these 2 combinations were also the most effective compared with MTX (4.6 [3.5, 6.2] and 5.6 [3.1, 10.1], respectively). In terms of the secondary outcome of DAS28, the most effective drugs compared with MTX were (from most to least effective) tofacitinib 10 mg + MTX, adalimumab + MTX, tofacitinib 5 mg + MTX, baricitinib 4 mg + MTX, baricitinib 8 mg + MTX, baricitinib 4 mg + MTX, tofacitinib 10-mg monotherapy, baricitinib 4 mg, tofacitinib 5-mg monotherapy, and placebo. In terms of safety outcomes, SAEs were less likely to occur in the placebo, tofacitinib 5 mg + MTX, tofacitinib 10 mg + MTX, MTX, baricitinib 8 mg + MTX, adalimumab, tofacitinib 10-mg monotherapy, tofacitinib 5 mg, baricitinib 4 mg + MTX, baricitinib 4 mg, and adalimumab + MTX groups; the class differences for SAEs between tofacitinib and baricitinib were small, and not considered clinically meaningful.
These results showed that tofacitinib 10 mg and baricitinib 8 mg combined with MTX were among the most efficacious options assessed in this study for patients with RA, with similar safety outcomes.
Zamora N, et al. ACR 2017. Abstract 531.