Indirect Comparison of Tocilizumab and Other Biologic Agents in Patients with Rheumatoid Arthritis and Inadequate Response to Disease-Modifying Antirheumatic Drugs
published online 12 March 2010.
Objectives
To compare the patterns of American College of Rheumatology (ACR) response between tocilizumab and other biologic agents in patients with rheumatoid arthritis who have inadequate response to disease-modifying antirheumatic drugs (DMARD-IR).
Methods
Systematic literature review identified similarly designed double-blind, randomized, placebo-controlled trials over an 18-year period that investigated the effectiveness of abatacept (2), rituximab (2), and TNF-α inhibitors etanercept, infliximab, and adalimumab (11) in DMARD-IR patients; data from 3 placebo-controlled, phase 3 trials for tocilizumab, a newly developed IL-6 inhibitor, were included. The endpoint of interest was ACR20/50/70 response criteria at 24 to 30 weeks. Results were analyzed simultaneously using Bayesian mixed-treatment comparison techniques. Nonoverlapping ACR response rates (<ACR20, ACR20-50, ACR50-70, >ACR70) for each agent were compared among treatments to identify differences in ACR response pattern. Separate analyses of overlapping ACR20/50/70 responses were conducted to identify the source of any differences. Results were expressed as relative risk of ACR20/50/70 response and associated 95% credible interval (CrI).
Results
Patterns across nonoverlapping ACR response levels varied significantly across treatments. In subsequent analyses, the effectiveness of tocilizumab appeared to be comparable to that of other biologic agents for ACR20 and ACR50 responses but greater for ACR70. Specifically, tocilizumab had greater ACR70 responses than both TNF-α inhibitors (relative risk = 1.8; CrI = 1.2, 2.6) and abatacept (relative risk = 2.0; CrI = 1.3, 3.1).
Conclusions
Among DMARD-IR patients, tocilizumab shows a pattern of response that differs from that of other biologic agents. Post-hoc analyses suggest that the difference lies in a higher likelihood of ACR70 response with tocilizumab.
⁎Project Manager, Mapi Values, Houten, The Netherlands
†Professor of Medicine and Epidemiology and Preventive Medicine, Departments of Medicine and Epidemiology and Preventive Medicine, University of Maryland School of Medicine, Baltimore, MD
‡Professor of Clinical Epidemiology, Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands
Address correspondence and reprint requests to: Jeroen P. Jansen, PhD, Mapi Values, 133 Portland Street, Boston, MA 02114 USA
This study was funded by Hoffmann La-Roche.
Neil Wintfeld and Adrian Kielhorn are employees of Hoffmann La-Roche. Gert J. D. Bergman and Jeroen P. Jansen are employees of Mapi Values. Mapi Values received fees to perform the analysis. Marc Hochberg is a consultant to or a member of an advisory board for Abbott, Amgen, Bristol-Myers Squibb, Hoffman La-Roche, and UCB, Inc. Maarten Boers is a consultant for GlaxoSmithKline, Sanofi, Genentech, Hoffmann La-Roche, MedImmune, Novartis, Schering-Plough, AstraZeneca, Nitec, NicOx, Savient, Combinatorx, Merck Serono, Augurex, and Mapi Values.
ABSTRACT