Urate‐Lowering Drugs and Muscle Injury: A Systematic Review and Network Meta‐Analysis

Abstract

AbstractSeveral urate‐lowering drugs have been linked to muscle injury. This study investigated the association of oral urate‐lowering drugs with the risk of muscle injury by performing a network meta‐analysis of randomized and non‐randomized controlled trials. A systematic search of MEDLINE, via PubMed, the ClinicalTrials.gov website, and the Cochrane Central Register of Controlled Trials was conducted to identify relevant studies with a primary outcome of “all muscle injuries.” A random‐effects model was used to perform a frequentist network meta‐analysis to estimate whether there was significant heterogeneity among the studies. In total, 32 studies including 28,327 participants with 2694 (9.5%) “all muscle injuries” were assessed, and the overall risk of bias was judged to be low to moderate. No statistically significant differences were found between placebo and 6 urate‐lowering therapies: allopurinol (risk ratio, RR, 1.05; 95% confidence interval, 95%CI, 0.63‐1.73), febuxostat (RR 1.10, 95%CI 0.71‐1.70), lesinurad (RR 7.00, 95%CI 0.31‐160.36), lesinurad concomitant with allopurinol (RR 0.85, 95%CI 0.34‐2.11), lesinurad concomitant with febuxostat (RR 1.97, 95%CI 0.55‐7.03), and topiroxostat (RR 0.99, 95%CI 0.37‐2.65). The findings suggest that there is little need to consider the risk of muscle injury when using urate‐lowering drugs in the clinical setting.