Efficacy and safety of monoclonal antibodies targeting interleukin-17 pathway for inflammatory arthritis: a meta-analysis of randomized controlled clinical trials

Abstract

T-helper 17 (Th17) pathway plays an important and distinct role in autoimmunity and inflammation. A growing body of evidence demonstrates that interleukin-17 (IL-17) is also synthesized in inflammatory arthritis tissues and exerts potent proinflammatory and joint-destructive activities. Clinical studies have been performed to evaluate the therapeutic efficacy of antibodies blocking the IL-17 signaling pathway in patients with rheumatoid arthritis (RA). In this study, we performed a meta-analysis to systematically evaluate the clinical effects of IL-17 antibodies in RA patients. By searching PubMed, five randomized, placebo-controlled randomized controlled clinical trials that tested three antibodies against IL-17A (LY2439821 and secukinumab/AIN457) and the IL-17A receptor (brodalumab) were identified. The primary outcomes that were analyzed include American College of Rheumatology (ACR) Improvement Criteria and Disease Activity Score in 28 joints (DAS28). Meanwhile, the safety and adverse effects were also systematically analyzed. The results of the meta-analysis demonstrated that IL-17 antibody is effective in ameliorating the RA symptoms. Specifically, IL-17-blocking antibody significantly reduced ACR20 and ACR50. It also dramatically reduced DAS28, an index that measures tenderness and swelling severity of joints. The side effects of and intolerance to the antibody treatment were higher than those in the placebo control. The analysis result provides evidence-based information for clinical use of these agents in the treatment of inflammatory arthritis.

Keywords: arthritis; clinical trials; interleukin-17A; meta-analysis; rheumatoid arthritis.

Figure 1

Flow diagram for study selection. Abbreviation: RCT, randomized controlled trial.

Figure 2

Forest plot of meta-analysis. Notes: Figure demonstrates the improved scores of ACR20 after antibody treatment, as described in Genovese et al,, Hueber et al, Martin et al, and Patel et al (A), and the increased levels of ACR50 (B) and ACR70 (C) in Genovese et al., Meta-analysis was performed using a fixed model. Abbreviations: ACR, American College of Rheumatology; CI, confidence interval; IL, interleukin; M–H, Mantel–Haenszel method.

Figure 3

Forest plot of studies selected for meta-analysis of adverse effects. Note: Meta-analysis was performed in fixed model. Abbreviations: CI, confidence interval; IL, interleukin; M–H, Mantel–Haenszel method.

Figure 4

Funnel plot of studies selected for meta-analysis of ACR20 (A), ACR50 (B), ACR70 (C), and adverse effects (D). Abbreviations: ACR, American College of Rheumatology; OR, odds ratio; SE, standard error.