FRI0089 COMPARATIVE EFFICACY (ACR 20) OF TOCILIZUMAB TO OTHER TARGETED IMMUNE MODULATORS (TIM) FOR RHEUMATOID ARTHRITIS: A NETWORK META-ANALYSIS (NMA)
Authors: J. Dang, J. Uyei, Y. Jiang, R. Singh, P. Bilir, A. Karabis, J. Munakata, M. Michalska, J. H. Best
Journal: Annals of the Rheumatic Diseases (2020)

Background: Clinical trial and real-world evidence have both firmly established efficacy and safety of intravenous (IV) and subcutaneous (SC) tocilizumab, both as monotherapy or in combination with a conventional disease modifying antirheumatic drug (cDMARD). However, tocilizumab’s relative efficacy to the new Janus kinase (JAK) inhibitor class of therapies is less certain, given the lack of head-to-head trials. Objectives: To evaluate the relative efficacy of: 1) combination tocilizumab plus cDMARD to other TIMs plus a cDMARD in TIM-naïve or mixed (&lt;20% TIM-experienced) adults with moderate to severe RA; 2) tocilizumab monotherapy to other TIM monotherapies in TIM-naïve or mixed adults with moderate to severe RA. Efficacy was defined as achievement of an ACR20 response or better at 24 weeks. Methods: Randomized controlled trials (RCTs) were selected from a recent systematic literature review conducted by the Institute for Clinical and Economic Review (ICER), as well as from a trial for upadacitinib (SELECT-COMPARE, NCT02629159 ), which was not included in the ICER 2017 report. Treatments included JAK inhibitors (upadacitinib, baricitinib, and tofacitinib), tumor necrosis factor alpha inhibitors (TNFi; adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab), and other non-TNFis (rituximab, sarilumab, tocilizumab, and abatacept). A Bayesian NMA was performed in OpenBUGS and R to evaluate comparative efficacy using a random effects model for combination therapy and fixed effects model for monotherapy. Model selection was based on deviance information criterion. Forest plots of relative risks (RR) are presented. Results: In combination therapy analysis, a total of 35 studies were included with a pooled study population of 17,508 patients. Study populations were predominantly female (mean 79%, range 39-95%), and had a baseline mean age of 52 years (range 47-58), mean disease duration of 8 years (range 2-12), and mean DAS28 score of 6 (range 5-7). When compared to cDMARD, all TIMs were 1.69 to 2.22 times more likely to achieve an ACR20 response or better at 24 Weeks (statistically significant) (Figure 1). In pair-wise comparison, tocilizumab IV and SC did not differ from all other TIMs, including JAK inhibitors (no statistically significant difference). In monotherapy analysis, a total of 5 studies were included with a pooled study population of 1,189 patients. Study populations were predominantly female (mean 82%, range 75-90%), had a baseline mean age of 53 years (range 51-54), mean disease duration of 6 years (range 2-9), and mean DAS28 score of 6 (range 5-7). When compared to cDMARD, all TIMs were 1.65 to 1.84 times more likely to achieve ACR20 response or better (statistically significant) (Figure 2). In pair-wise comparison, tocilizumab IV was associated with a greater likelihood of achieving an ACR20 response or better compared to adalimumab (RR=1.10, 95% credible interval (Crl) = 1.03,1.29). Conclusion: Results of this NMA demonstrate similar efficacy (ACR20 at week 24) between tocilizumab (IV and SC) and other TIMs, including new JAK inhibitors, when used in combination with a cDMARD among TIM-naïve/mixed patient populations. Tocilizumab IV monotherapy had more favorable efficacy than adalimumab monotherapy. Patients unable to tolerate cDMARDs may experience additional value from tocilizumab compared to adalimumab. Acknowledgments: This study was sponsored and funded by Genentech, Inc. Disclosure of Interests: Joseph Dang Shareholder of: Genentech, Inc., Employee of: Genentech, Inc., Jennifer Uyei: None declared, Yilin Jiang: None declared, Rajpal Singh: None declared, Pinar Bilir: None declared, Andreas Karabis: None declared, Julie Munakata: None declared, Margaret Michalska Shareholder of: Genentech, Inc., Employee of: Genentech, Inc., Jennie H. Best Shareholder of: Genentech, Inc., Employee of: Genentech, Inc.