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The addition of tocilizumab to DMARD therapy for rheumatoid arthritis: a meta-analysis of randomized controlled trials

  • Pharmacodynamics
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Abstract

Purpose

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.

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Conflict of interest

The authors state that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmacology, School of Pharmacy, Second Military Medical University, 325 Guo He Road, Shanghai, 200433, People’s Republic of China

    Mao Mao An, Jun Dong Zhang, Yong Bing Cao & Yuan Ying Jiang

  2. Department of Clinical Pharmacology, Chinese People’s Liberation Army General Hospital, 28 Fuxing Road, Beijing, 100853, People’s Republic of China

    Mao Mao An

  3. Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai, 200433, People’s Republic of China

    Zui Zou

  4. Chinese Academy of Medical Sciences and Peking Union Medical College, FuWai Hospital and Cardiovascular Institute, 167 Beilishi Road, Beijing, 100037, People’s Republic of China

    Hui Shen

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  1. Mao Mao An
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Correspondence to Yuan Ying Jiang.

Additional information

Mao Mao An and Zui Zou contributed equally to this article and can be considered to be co-first authors

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An, M.M., Zou, Z., Shen, H. et al. The addition of tocilizumab to DMARD therapy for rheumatoid arthritis: a meta-analysis of randomized controlled trials. Eur J Clin Pharmacol 66, 49–59 (2010). https://doi.org/10.1007/s00228-009-0754-0

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  • DOI: https://doi.org/10.1007/s00228-009-0754-0

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