Association of IL-17 Inhibitors with Hypertension in Patients with Autoimmune Diseases: A Systematic Review and Meta-analysis on Randomized Controlled Trials

Abstract

The influence of IL-17 inhibition on blood pressure in autoimmune disease patients remains inconclusive. Our objective is to examine the risk of hypertension in patients with autoimmune diseases undergoing IL-17 inhibition therapies via meta-analysis of randomized, placebo-controlled trials (RCTs). We obtained integrated data from PubMed, Embase, and ClinicalTrials.gov. Incident hypertension rates were calculated, and hazard ratios (HRs) with 95% confidence intervals (CIs) were analyzed, along with Ι^2 statistics to assess heterogeneity. Sequential analysis ensured conclusion reliability. In 30 RCTs involving 9,909 patients with diverse autoimmune diseases treated with anti-IL-17 agents, our meta-analysis revealed a significant increase in hypertension risk (RR 1.69, CI 1.24-2.31, p=0.001), robustly supported by trial sequential analysis. Among the four agents (secukinumab, ixekizumab, bimekizumab, and brodalumab), only secukinumab exhibited a notable association with hypertension. Patients with various primary autoimmune diseases, particularly those with psoriatic arthritis, had a higher likelihood of developing hypertension; in rheumatic arthritis patient cohorts, anti-IL-17 agents did not elevate hypertension risk. Prolonged treatment duration correlated with an increased hypertension risk. Stratifying by gender, studies with a female predominance demonstrated a higher risk ratio for hypertension compared to male-predominant studies. This highlights that anti-IL-17 treatment escalates hypertension risk, emphasizing the need for extra caution when managing autoimmune disease patients. (Registered by PROSPERO, CRD42016053112).