The addition of tocilizumab to DMARD therapy for rheumatoid arthritis: a meta-analysis of randomized controlled trials.
OBJECTIVE
Tocilizumab is a humanized monoclonal antibody that binds to the interleukin-6 receptor. The purpose of this study was to evaluate the effect of adding tocilizumab to disease-modifying antirheumatic drug (DMARD) therapy for the treatment of rheumatoid arthritis (RA).


METHODS
We performed a meta-analysis of relevant randomized controlled trials (RCTs) identified in PubMed, Cochrane library, and Embase. The primary efficacy outcome was the proportion of patients with a 20% improvement in RA signs and symptoms according to American College of Rheumatology (ACR) criteria (ACR20 response). The primary safety outcomes were the proportion of patients reporting at least one adverse event and the proportion of patients reporting at least one serious adverse event.


RESULTS
Four RCTs, involving 2701 patients, were included in our meta-analysis. The addition of tocilizumab to therapeutic regimens with DMARDs was associated both clinically and statistically with an increased number of patients achieving the ACR20 response [8 mg/kg, risk ratio (RR) 2.53, 95% confidence interval (CI) 1.89-3.39; 4 mg/kg, RR 1.96, 95% CI 1.40-2.73], as well as the ACR50 and ACR70 response, and showing remission according to the Disease Activity Score based on 28 joints. However, the benefits were gained at the expense of the tendency of the patient to experience more adverse events (8 mg/kg, RR 1.12, 95% CI 1.03-1.20; 4 mg/kg, RR 1.08, 95% CI 1.00-1.17). The new finding was that the clinical benefit from the increased tocilizumab dose (from 4 to 8 mg/kg) was not correlated with a higher incidence of adverse events.


CONCLUSIONS
The superior efficacy of combined tocilizumab + DMARD therapy is associated with the tendency for the patient to have more adverse events. Consequently, the benefits and disadvantages of such combined treatments should be carefully balanced against each other in RA therapy. We suggest that 8 mg/kg every 4 weeks should be the recommended dose of tocilizumab.
An
Mao Mao
MM
Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China.
Zou
Zui
Z
Shen
Hui
H
Zhang
Jun Dong
JD
Cao
Yong Bing
YB
Jiang
Yuan Ying
YY
D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D019947:Receptors, Interleukin-6; C502936:tocilizumab