Indirect comparison of tocilizumab and other biologic agents in patients with rheumatoid arthritis and inadequate response to disease-modifying antirheumatic drugs.
OBJECTIVE
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-alpha 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-alpha 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.
Bergman
Gert J D
GJ
Mapi Values, Houten, The Netherlands.
Hochberg
Marc C
MC
Boers
Maarten
M
Wintfeld
Neil
N
Kielhorn
Adrian
A
Jansen
Jeroen P
JP
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D004311:Double-Blind Method; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D017211:Treatment Failure; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; C502936:tocilizumab