Background/Purpose: To explore the comparative effectiveness of tofacitinib or baricitinib in patients with rheumatoid arthritis (RA) following a systematic review of randomized trials, by performing a network meta-analysis inferring from both direct and indirect evidence.

Methods: We used the data of the Cochrane systematic reviews on tofacitinib and baricitinib for treating rheumatoid arthritis. For both reviews, the searches were performed in seven electronic databases and two trial registries. Retrieved records were screened independently by 2 investigators to include controlled trials comparing tofacitinib or baricitinib alone or in combination with methotrexate versus placebo, methotrexate or other traditional or biologic DMARDs. Published and unpublished trials were considered. Quality appraisal and data extraction from the included studies was done independently by 2 investigators. For the network meta-analysis the primary outcome was American College of Rheumatology (ACR) 50% improvement criteria (ACR50) and secondary outcomes included remission according to the Disease Activity Score (DAS28), functional ability measured by the Health Assessment Questionnaire (HAQ), and serious adverse events as defined by the individual trials.

Results: Out of 2,673 unique citations, 21 trials met the inclusion criteria (9,839 patients). Most patients were female (74 to 96%) with a mean age and disease duration ranging from 48-56 years and 2.7-13 years, respectively. For the tofacitinib trials, 2 out 14 trials were at high risk of reporting bias. For the baricitinib trials, selection bias could not be evaluated in 6 out 7 trials and for selection and performance bias in 7 out of 7. The network plot for the ACR50 included 12 nodes (i.e., daily doses: tofacitinib monotherapy 5 and 10 mgs, combined with methotrexate 5 and 10 mg, baricitinib monotherapy 4 mg, baricitinib combined with methotrexate 2, 4, and 8 mgs, adalimumab monotherapy, adalimumab combined with methotrexate, methotrexate and placebo). The relative effect achieving an ACR 50 at 12 weeks against placebo in descending order were: Bari8+MTX (13.5; 5.8-31.3), Tofa10+MTX (11.3; 5.9- 21.4), Tofa5+MTX (10.5; 5.4-20.2), Bari2+MTX (9.6; 4.5-19.4), Bari4+MTX (9.5; 5.0-17.9), Bari4 (6.79; 3.2-14.3), ADA+MTX (6.8; 3.5-13.3), Tofa10 (6.2; 3.8-9.9), Tofa5 (5.1; 3.3-8.1), MTX (2.4; 1.4-4.4), and ADA (1.9; 0.8-4.7). When comparing indirectly, the only differences were observed in favor of baricitinib+MTX compared with tofacitinib alone. For DAS 28 there were 11 nodes and the order was (from most to least effective): Tofa10+MTX, ADA+MTX, Bari8+MTX, Bari4+MTX, Tofa5+MTX, Bari2+MTX, Tofa10, Bari4, Tofa5, and MTX. Serious adverse events were less likely to occur in the PBO, ADA, Tofa5+MTX, Tofa10+MTX, MTX, Bari8+MTX, Tofa10, Tofa5, Bari4+MTX, Bari4, and Ada+MTX.

Conclusion: All drug combinations were effective compared with placebo in reducing at least 50% of symptoms or achieving remission at 12 weeks. Tofacitinib 10 mg and baricitinib 8 mg combined with methotrexate were among the most efficacious options. Serious adverse events were less likely with the tofacitinib groups, although the within-class differences were small and may not be clinically meaningful.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/comparative-effectiveness-of-tofacitinib-versus-baricitinib-in-rheumatoid-arthritis-using-a-systematic-review-and-network-meta-analysis-of-randomized-trials/