Efficacy and safety of interleukin-1 antagonists in rheumatoid arthritis: a systematic review and meta-analysis

Rheumatoid arthritis patients have a high level of pro-inflammatory interleukin-1. Augmenting the blockade of interleukin-1 receptors by external interleukin-1 receptor antagonist modifies the progression of the disease. Therefore, the aim of this study was to evaluate the clinical efficacy and safety of interleukin-1 receptor antagonist (anakinra) in the treatment of rheumatoid arthritis. Clinical trials and extension studies that compared anakinra with placebo or other medications were included. Electronic bibliographic databases: PubMed, Scopus, and Web of Sciences were searched from inception to November 2017. The American College of Rheumatology 20% (ACR20) improvement was the primary efficacy outcome measure. Total number of adverse drug events, serious adverse drug events, total treatment withdrawals, and treatment-related withdrawals were safety outcome measures. Ten studies were included in this review. One study did not fulfil quantitative criteria and was assessed qualitatively. Six clinical trials and three extension studies were included in meta-analysis. Patients treated with anakinra are 42% more likely to have ACR20 response than patients without IL-1Ra (pooled RR 1.42; 95% CI 1.01, 2.00). Patients on 30–150 mg anakinra have lower Health Assessment Questionnaire (HAQ) score than patients without IL-1Ra (SMD − 0.28; 95% CI − 0.53, − 0.03). The inflammatory marker erythrocyte sedimentation rate (ESR) was significantly lower among patients treated with 30–150 mg anakinra (SMD − 0.44; 95% CI − 0.65, − 0.23). Patients on anakinra have a 34% more risk of treatment-related withdrawal than placebo. The other parameters were not found to be statistically significant. Anakinra has a significant improvement in ACR20, HAQ, and ESR. The ACR20 response is maintained after 48 weeks of treatment. Anakinra shows higher episodes of treatment-related withdrawals than placebo.