Male Patients with Axial Spondyloarthritis More Likely to Respond to Advanced Therapies, Meta-analysis Finds
A comprehensive meta-analysis of randomized controlled trials (RCTs) published in Arthritis Care & Research, has found that male patients with axial spondyloarthritis (axSpA) are significantly more likely to achieve key efficacy outcomes from advanced therapies compared to female patients. The findings, drawn from 79 RCTs involving over 23,000 participants, raise critical questions about the influence of sex on therapeutic response and highlight the need for further investigation into underlying biological and sociocultural mechanisms.
The analysis included 23,748 patients, of whom 69.7% were male. Despite this imbalance, few trials reported sex-stratified outcomes: only 11.4% detailed baseline characteristics by sex, 28% reported efficacy outcomes by sex, and 11.4% included sex-specific safety outcomes.
At baseline, notable differences were observed. “Women were significantly older and had higher pain scores, whereas men had higher C-reactive protein levels,” the authors reported, suggesting potential disparities in disease presentation and inflammation markers.
Efficacy differences were consistent across classes of advanced therapies. Male patients were significantly more likely to achieve an ASAS40 response across all therapies (odds ratio [OR] 1.88, 95% CI 1.44–2.46), with individual analysis showing ORs of 1.82 for IL-17A inhibitors and 2.42 for tumor necrosis factor inhibitors (TNFi). Similar trends were observed for the achievement of low disease activity or inactive disease on the Axial Spondyloarthritis Disease Activity Score (ASDAS-LDA/ID), with men again more likely to respond (OR 2.19 overall; OR 2.08 for IL-17Ai and OR 2.42 for TNFi).
“Female patients with axSpA are less likely to achieve efficacy outcomes on advanced therapies compared to their male counterparts,” the authors concluded, noting that this trend was observed across all medication classes.
Safety outcomes were sparsely reported by sex, limiting interpretation in this area. However, the consistent pattern of lower treatment response in women calls for further investigation. The authors emphasized that “future studies should study the biologic (sex-related) and sociocultural (gender-related) mechanisms underlying these differences.”
For practicing rheumatologists, these findings underscore the importance of recognizing sex-based disparities in treatment response.
Clinicians may consider incorporating these data into shared decision-making discussions and monitoring strategies, particularly for female patients who may experience a lower likelihood of achieving standard response thresholds with currently available therapies.
Reference
Gao A, Pardo Pardo J, Dang S, Gensler LS, Mease P, Eder L. Sex-related differences in efficacy and safety outcomes in axial spondyloarthritis randomized clinical trials: a systematic literature review and meta-analysis. Arthritis Care Res (Hoboken). Published online February 24, 2025. doi:10.1002/acr.2551
