Sex differences in axial spondyloarthritis: biological mechanisms, clinical phenotypes, and therapeutic implications - a narrative review

Abstract

Sex differences in axial spondyloarthritis (axSpA) are gaining recognition as clinically significant, but they are still not well incorporated into diagnostic practice and outcome assessment. Although long viewed as a predominantly male disease, axSpA affects women at nearly comparable rates and often follows a distinct phenotype. These differences extend beyond variations in severity and appear to reflect different biological and clinical expressions of disease.

Women with axSpA typically report higher levels of pain, fatigue, and disease activity, frequently alongside lower inflammatory markers and slower radiographic progression. They also experience longer diagnostic delays and more often present with peripheral manifestations or overlapping pain conditions such as fibromyalgia. In contrast, men more commonly exhibit the classical axial phenotype, elevated C-reactive protein, and greater structural damage. This discordance between symptom burden and objective inflammation creates challenges for disease assessment, as conventional tools may not perform equally across sexes. Emerging evidence also indicates sex-related differences in treatment response and drug persistence.

Recognizing sex as a biological determinant of disease expression, rather than merely a covariate for statistical adjustment, offers an opportunity to improve diagnostic precision, refine outcome interpretation, and support more individualized patient care.