FRI0158 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
Authors: Young Ho Lee, Gwan Gyu Song
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> A class of targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARDs) has emerged as an alternative treatment option for rheumatoid arthritis (RA). Tofacitinib is an orally administered JAK (Janus kinase) inhibitor with functional cellular specificity for JAK-1 and JAK-3 over JAK-2 and upadacitinib, a new JAK inhibitor, has been engineered to confer greater selectivity for JAK1 than for JAK2, JAK3, and Tyk2. <h3>Objectives:</h3> The aim of this study is to assess the relative efficacy and safety of tofacitinib and upadacitinib at different doses were assessed in patients with RA with an inadequate response to conventional synthetic (cs) or biologic (b) DMARDs. <h3>Methods:</h3> 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. <h3>Results:</h3> Nine RCTs including 5,794 patients met the inclusion criteria. There were 15 pairwise comparisons including 10 direct comparisons of six 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 40 mg+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 ACR20 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. <h3>Conclusion:</h3> 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. <h3>References:</h3> [1] Kremer J, Li ZG, Hall S, et al. (2013) Tofacitinib in combination with nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis: a randomized trial. Ann Intern Med 159:253-261 [2] Catalá-López F, Tobías A, Cameron C, Moher D, Hutton B (2014) Network meta-analysis for comparing treatment effects of multiple interventions: an introduction. Rheumatology international 34:1489-1496 [3] Genovese MC, Fleischmann R, Combe B, Hall S, Rubbert-Roth A, Zhang Y, Zhou Y, Mohamed M-EF, Meerwein S, Pangan AL (2018) Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease-modifying anti-rheumatic drugs (SELECT-BEYOND): a double-blind, randomised controlled phase 3 trial. The Lancet <h3>Disclosure of Interests:</h3> None declared