Women with spondyloarthritis may experience greater functional deterioration but similar work disability compared with men, according to recent findings from the REGISPON-3 study.
Investigators conducted a longitudinal observational study of 271 men and 140 women with spondyloarthritis from the multicenter Spanish REGISPONSER registry who underwent baseline assessment from 2004 to 2007 and reassessment from 2021 to 2024. All patients met European Spondyloarthropathy Study Group classification criteria at enrollment.
Data were collected during a single visit in each registry period. No prospective intermediate study visits were conducted; clinical information between assessments, including treatment exposure and major clinical events was collected retrospectively through standardized medical record review and structured follow-up interviews.
At baseline, 270 patients met modified New York criteria for ankylosing spondylitis, corresponding to radiographic axial spondyloarthritis under current terminology; 60 were classified with psoriatic arthritis, and 81 had other types of spondyloarthritis.
Bath Ankylosing Spondylitis Functional Index (BASFI) was used to evaluate functional ability and to define change in long-term functional deterioration, with positive values representing deterioration and negative values representing improvement.
The investigators performed sex-stratified univariable logistic regression analyses to identify baseline factors associated with permanent disability and entered statistically significant or clinically relevant variables into multivariable logistic regression models. Sex-specific univariable and multivariable linear regression analyses evaluated factors associated with change in BASFI. They also performed a moderated mediation analysis evaluating C-reactive protein as a mediator of the association between exposure to biologic disease-modifying antirheumatic drugs (DMARD) and change in BASFI, with sex as a moderator. Age and disease duration were included as covariates in the mediation model.
At baseline, men had a longer duration of disease from diagnosis and greater radiographic damage, whereas women had higher disease activity as measured by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and more frequent arthritis and enthesitis. Baseline BASFI scores did not differ statistically between the sexes.
At 17-year follow-up, the mean BASFI and change in BASFI were 4.7 and 1.4 among women and 3.6 and 0.3 among men, respectively, indicating greater functional deterioration among women. Permanent work disability occurred in 27% of women and 32% of men, a difference that was not deemed statistically significant.
Higher baseline BASDAI and total Bath Ankylosing Spondylitis Radiology Index (BASRI) scores were independently associated with permanent disability in both sexes. In multivariable analyses, baseline functional status and disease activity, measured by BASFI and BASDAI, respectively, were associated with change in BASFI in both sexes. Among men, BASRI-total score and occiput-to-wall distance were additional factors associated with functional change, while BASRI-column score was associated with functional change among women.
The moderated mediation analysis found a statistically significant indirect association between biologic DMARD exposure and functional change through C-reactive protein among men but not women. The moderated mediation index indicated that the indirect effect differed significantly between the sexes. The investigators wrote that these findings suggested the relationship between systemic inflammation and long-term functional outcomes may differ by sex.
Study limitations included that multiple spondyloarthritis subtypes may have contributed to clinical heterogeneity, and some instruments used in the registry were developed for axial disease and may have more limited applicability in peripheral-predominant phenotypes. Baseline data did not systematically capture fibromyalgia, depressive symptoms, or other pain-related and psychosocial comorbidities, preventing their inclusion as covariates in the longitudinal analyses. Although clinical information between the assessments was collected retrospectively through standardized medical record review and structured interviews, the absence of prospective intermediate assessments limited the evaluation of changes in disease activity, treatment response, and functional progression during follow-up.
The analysis did not include cumulative biologic exposure, treatment duration, or treatment persistence. The investigators noted that the 17-year follow-up may have introduced attrition or survivor bias because patients who died or were lost to follow-up may have differed from those who were reassessed.
“Our findings suggest that long-term functional outcomes in [spondyloarthritis] should be interpreted with attention to potential sex differences,” wrote lead study author Diana Maria Margareta Moldovan, of the 2nd Internal Medicine Department at the Iuliu Hațieganu University of Medicine and Pharmacy in Romania, and colleagues.
REGISPON-3 received funding from the Instituto de Salud Carlos III through the European Union—NextGenerationEU/PRTR program, with additional financial support from Eli Lilly and Company, UCB, AbbVie, and Novartis. Full disclosures of the study authors can be found in the study.
Source: RMD Open
