Does sex affect the efficacy of systemic pharmacological treatments of pain in knee osteoarthritis? A systematic review

Objective: To determine whether sex influences the analgesic efficacy of systemic pharmacological treatment in patients with knee osteoarthritis. Design: A systematic review, guided by Cochrane methods, sourced studies from Medline, Cochrane Library, Embase, and CINAHL Plus with Full Text as of October 10, 2022. Eligible studies were double-blind RCTs evaluating systemic pharmacological treatments for knee osteoarthritis in adults, with minimum 30-day treatment duration, reporting sex-specific results or mentioning sex subgroup analysis for analgesic efficacy. The risk of bias was assessed using the Cochrane Risk of Bias tool version 2 (RoB 2). Results: 9 studies (5201 participants) met inclusion criteria, analyzing drugs including duloxetine, etoricoxib, tapentadol, naproxcinod, lutikizumab, and rofecoxib. Only one study reported sex-specific results. Review findings suggested no significant sex-based differences in treatment efficacy, however, data were limited due to a lack of sex-specific reporting or inclusion of sex in subgroup analyses. Conclusions: Current evidence does not support the existence of sex differences in the analgesic efficacy of systemic knee osteoarthritis treatments. However, this conclusion is substantially limited by the paucity of sex-specific reporting of results or subgroup analyses in most primary studies, emphasizing the need for future research to report on sex-stratified data to allow for comprehensive, personalized treatment strategies.