Sex-Related Differences in Efficacy and Safety Outcomes in Axial Spondyloarthritis Randomized Clinical Trials: A Systematic Literature Review and Meta-Analysis.

Objective: We aimed to assess differences in baseline characteristics, efficacy, and safety of advanced therapies between male and female patients with axial spondyloarthritis (axSpA) in randomized controlled trials (RCTs).

Methods: We conducted a systematic literature search for RCTs assessing the efficacy of advanced therapies in patients with axSpA until March 19, 2023. We extracted the following outcomes by sex: baseline participant characteristics, Assessment in Spondylarthritis International Society (ASAS) 20/40 criteria, and Axial Spondyloarthritis Disease Activity Score low disease activity or inactive disease (ASDAS-LDA/ID). Random-effects models were used to calculate pooled effects for responses in men versus women for different medication classes.

Results: We included 79 RCTs (n = 23,748 patients, 69.7% male). Only 9 trials (11.4%), 22 trials (28%), and 9 trials (11.4%) reported baseline characteristics, efficacy end points, and safety end points by sex, respectively. At baseline, women were significantly older and had higher pain scores, whereas men had higher C-reactive protein levels. Overall, male patients were more likely to achieve an ASAS40 response compared to female patients for all advanced therapies (odds ratio [OR] 1.88, 95% confidence interval [CI] 1.44-2.46) and for interleukin-17A (IL-17A) inhibitors (IL-17Ai) (OR 1.82) and tumor necrosis factor inhibitor (TNFi) (OR 2.42), and male patients had numerically higher values for IL-17A/Fi. Male patients were also more likely to achieve an ASDAS-LDA/ID (OR 2.19, 95% CI 1.47-3.26) across all advanced therapies and for IL-17Ai (OR 2.08) and TNFi (OR 2.42) individually.

Conclusion: Female patients with axSpA are less likely to achieve efficacy outcomes on advanced therapies compared to their male counterparts, with similar differences across medication classes. Future studies should study the biologic (sex-related) and sociocultural (gender-related) mechanisms underlying these differences.