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Efficacy and safety of secukinumab in active rheumatoid arthritis with an inadequate response to tumor necrosis factor inhibitors: a meta-analysis of phase III randomized controlled trials

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Abstract

Objectives

To address the efficacy and safety of secukinumab in comparison with placebo in active rheumatoid arthritis (RA) patients who had an inadequate response to tumor necrosis factor (TNF) inhibitors.

Methods

Databases of PubMed, Embase, and Web of Science were searched to identify the relevant randomized controlled trials (RCTs). Risk ratio (RR) and 95% confidence interval (95% CI) were calculated with the Mantel–Haenszel random effects method. Statistical heterogeneity was assessed using the Cochran Q and I2 tests.

Results

A total of 1292 patients from three phase III RCT studies were included. Compared with placebo, secukinumab 150 mg was superior at 24 weeks in terms of ACR20 with RR (1.66, 95% CI 1.33, 2.08; P < 0.0001; I2 = 0%), ACR50 (1.88, 95% CI 1.29, 2.72; P = 0.0009; I2 = 0%), and ACR70 (2.15, 95% CI 1.15, 4.02; P = 0.02; I2 = 0%). Consistent effects were also observed in pooled group of 150 mg and 75 mg secukinumab. For secukinumab 75 mg alone, ACR20 response rate was significantly higher compared with placebo (RR 1.62, 95% CI 1.29, 2.03; P < 0.00001; I2 = 0%). Although ACR50 and ACR70 response rates showed a favorable trend to be higher, no statistical difference was observed (RR 1.68, 95% CI 0.99, 2.85, P = 0.05, I2 = 47%; RR 1.81, 95% CI 0.78, 4.21, P = 0.17, I2 = 34%, respectively). Compared with the placebo group, there was no increased risk of adverse effects (AEs) and serious AEs at 16 weeks in the pooled secukinumab group.

Conclusions

In active RA patients with an inadequate response to TNF inhibitors, secukinumab may be a therapeutic option. Secukinumab 150 mg showed significantly better clinical efficacy with no increased risk of AEs and serious AEs compared with placebo.

Trial registration

Clinical Trials.gov identifier: NCT01770379, NCT01350804, NCT01377012

Key Points

• Secukinumab 150 mg showed significantly better clinical efficacy in active RA patients with an inadequate response to TNF inhibitors.

• No increased risk of AEs and serious AEs in secukinumab group compared with placebo.

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Funding

This work was financially supported by the National Natural Science Foundation of China (81771740), the sub-project (2010CB529103) under the National Science Technology Pillar Program of China (973 Program) (2010CB529100), the Capital Health Research and Development of Special Fund Program (2011-4021-03), and the Peking University Clinical Research Program (PUCRP201305).

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Author notes

  1. Yanrong Huang and Yong Fan contributed equally to this work.

Authors and Affiliations

  1. Department of Rheumatology and Clinical Immunology, Peking University First Hospital, No.8, Xishiku Street, West District, Beijing, 100034, China

    Yanrong Huang, Yong Fan, Wenhui Xie & Zhuoli Zhang

  2. Department of Orthopedics, Clinical Sciences, Lund University, 22185, Lund, Sweden

    Yang Liu

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  1. Yanrong Huang
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  2. Yong Fan
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Contributions

ZZL conceived of the work, contributed to its design and coordination, and critically revised the manuscript. HYR and FY had full access to all of the data collection, analysis, interpretation, and drafted the manuscript. LY and XWH were study investigators and contributed to the process of data collection. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Zhuoli Zhang.

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Huang, Y., Fan, Y., Liu, Y. et al. Efficacy and safety of secukinumab in active rheumatoid arthritis with an inadequate response to tumor necrosis factor inhibitors: a meta-analysis of phase III randomized controlled trials. Clin Rheumatol 38, 2765–2776 (2019). https://doi.org/10.1007/s10067-019-04595-1

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