Anti-IL-17 therapy in treatment of rheumatoid arthritis: a systematic literature review and meta-analysis of randomized controlled trials
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IL-17 has a role in inflammation in RA, and its levels in joints correlate with disease severity. Multiple RCTs have been performed to study effects of anti-IL-17 agents. The objective of this study was to perform a systematic review and meta-analysis to analyze the efficacy and safety of anti-IL-17 agents in the management of RA. This work is based on a systematic review of studies retrieved by a sensitive search strategy in PubMed, EMBASE and Cochrane CENTRAL from inception through 9/7/15. Study selection criteria were the following: adult patients (age ≥ 18 years) with RAs, random selection of patients for anti-IL-17 therapy and treatment response compared to placebo. We performed systematic literature review per PRISMA guideline and two investigators independently selected seven randomized clinical trials (RCTs) for meta-analysis. We used random effect model calculating odds ratio (OR) and 95 % confidence interval (CI) to measure the efficacy with ACR20/50/70 responses and the safety with adverse events. Seven studies with total of 1226 patients including 905 in anti-IL-17 group and 321 in placebo were included in the meta-analysis. Anti-IL-17 was effective in achieving ACR20 and ACR50 compared to placebo (OR 2.47, 95 % CI 1.29–4.72, P = 0.006, I 2 77 % and OR 2.94, 95 % CI 1.37–6.28, P = 0.005, I 2 64 %, respectively). Data analysis for ACR70 showed a favorable trend toward anti-IL-17 (OR 2.62, 95 % CI 1–6.89, P = 0.05, I 2 15 %). Subgroup analysis of ACR20 for individual anti-IL-17 agents showed that ixekizumab was more effective than placebo, while secukinumab showed a trend toward achieving the ACR20 response. However, brodalumab was not effective compared to placebo. Safety analysis did not show increased risk of any or serious adverse effects by anti-IL-17 compared to placebo (OR 1.23, 95 % CI 0.94–1.61, P = 0.13, I 2 = 0 % and OR 1.28, 95 % CI 0.57–2.88, P = 0.55, I 2 = 0 %, respectively). This meta-analysis concludes that anti-IL-17 is effective in the treatment of RA without increased risk of any or serious adverse effects; however, the results are limited by significant heterogeneity and small duration of studies.
KeywordsAnti-IL-17 Rheumatoid arthritis Secukinumab Ixekizumab Brodalumab
Dr. Kunwar is guarantor of the study, had full access to all of the data and takes responsibility for the integrity of the data and the accuracy of data analysis. Kunwar, Dahal and Sharma were involved in study concept and design. Kunwar, Dahal and Sharma were involved in data acquisition and analyzed and interpreted the data. Kunwar and Dahal drafted the manuscript. Dahal was involved in statistical analysis. Kunwar and Sharma supervised the study.
Compliance with ethical standards
Conflict of interest
Authors SK, KD and SS declare no conflict of interest.
This article does not contain any studies with animals or human participants performed directly by any of its authors. Authors of the included studies have declared in their published articles that their protocols were approved by institutional review boards or ethics committee at each participating site.
The authors of this article did not directly involve any human subjects; however, the individual studies have declared obtaining informed consent from the patients.
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