Women With Axial Spondyloarthritis Have Higher Disease Burden Than Men

Investigators discovered that women with axial spondyloarthritis (axSpA) have an overall higher disease burden and more peripheral manifestations when compared with men. They further theorized that awareness of these differences and the way the condition presents differently in both sexes may be used to more easily identify axSpA and improve disease management.

Using data from the US-based Corrona Psoriatic Arthritis/Spondyloarthritis (PsA/SpA) Registry, investigators discovered that women with axial spondyloarthritis (axSpA) have an overall higher disease burden and more peripheral manifestations when compared with men, according to a study published in The Journal of Rheumatology.1 Investigators further theorized that awareness of these differences and the way the condition presents differently in both sexes may be used to more easily identify axSpA and improve disease management. As early diagnosis is linked to better patient outcomes, delays in treatment may critically hinder success.

Common symptoms of axSpA are inflammatory back pain (IBP), arthritis, enthesitis, uveitis, psoriasis, and inflammatory bowel disease. A patient’s quality of life (QOL) is greatly affected by pain, stiffness, and fatigue, which increases the risk of developing comorbidities such as cardiovascular disease, osteoporosis, depression, and anxiety.

“In our study population, women with nr-axSpA had worse disease activity and QOL than men, and our results show more pronounced sex differences in patients with nr-axSpA than in patients with ankylosing spondylitis (AS),” stated investigators. “While men and women with AS had comparable swollen joint counts, Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index scores, Ankylosing Spondylitis Disease Activity Score (ASDAS) scores, and patient-reported pain scores for these measures were worse in women than in men with nonradiographic axSpA (nr-axSpA).”

Women have been historically underrepresented in axSpA studies, as it was considered to be a disease that disproportionately affects men. This may be due in part to the classification criteria of AS, which was traditionally focused on axial symptoms and radiographic structural damage, both of which are generally lower in women than men. Further, women are more likely to suffer from peripheral symptoms and extra-articular manifestations, which may lead to misdiagnosis.

Eligible patients were diagnosed with axSpA, aged ≥18 years, and enrolled in the Corrona PsA/SpA Registry between March 2013 and November 2018. Those with a concurrent PsA diagnose were excluded. AxSpA diagnosis was defined using the Assessment of SpondyloArthritis international Society (ASAS) and New York modified classification criteria. It included both radiographic AS (r-axSpA) and nr-axSpA. Information about demographics, clinical characteristics, patient-reported symptoms and outcomes, disease activity, and treatment history was collected via questionnaires completed on enrollment from both patients and rheumatologists. The primary endpoint compared the results between men and women with axSpA. The secondary endpoint involved comparing enrollment characteristics of men and women with AS and men and women with nr-axSpA.

Disease activity was measured using ASDAS; Bath Ankylosing Spondylitis Disease Activity Index (BASDAI); and Bath Ankylosing Spondylitis Functional Index (BASFI). Additional markers of health included PROs, a Health Assessment Questionnaire for the Spondyloarthropathies (HAQ-S; 0-3), mobility measures, and presence of IBP and enthesitis.

Of the 498 patients with axSpA, 307 (61.6%) were men and 191 (38.4%) were women. Most patients in both groups were White and were of comparable age, symptom duration and time from onset to diagnosis. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), ASDAS, and physician global assessment indicated that women had higher disease activity when compared with men. They also had higher tender/swollen joint counts, worse patient-reported symptoms, and higher enthesitis scores. While IBP scores were comparable between women and men (57.6% and 62.2%, respectively), women had greater symptom severity. Additionally, SPARCC Enthesitis Index scores indicated that more women had enthesitis (37.2% vs. 20.2%; P<0.01). While comorbidities were comparable for both men and women, women reported more symptoms of depression (25.7% vs 12.1%; P>0.01) and fibromyalgia (10.5% vs 1.0%; P>0.01).

Investigators believe that genetic differences may account for the disease expression and progression. Central sensitization may also play a role in disease burden, as it is more common in women than in men and symptoms of the condition are similar to inflammatory rheumatic diseases, causing issues in determining disease severity. Disease progression may be impacted by peripheral symptoms, which are more common in women than men. These symptoms are generally treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and prednisone, rather than biologics. Increased prednisone use may indicate a greater probability of misdiagnosis with seronegative peripheral arthritis, especially in the early stages of axSpA. These delays in treatment can cause worse clinical and QOL outcomes. Another difference may be related to differences in work and daily activities between men and women. As women are more likely to care for children or the elderly, perform unpaid labor (in the household or the workplace), and use public transportation, this may result in different psychical and psychological stresses.

A limitation of the study was that patients in the Corrona Registry voluntarily participated, which may not accurately represent US patients with axSpA who are not currently being treated by a rheumatologist. The small sample size of patients with nr-axSpA also limited generalizability and comparison between men and women. As radiographic progression data were not collected, it is difficult to make assumptions between disease burden and radiographic damage. Further, the diagnosis of fibromyalgia and depression symptoms were based on physician judgement, which may have led to over- or underestimation. Lastly, investigators were unable to perform longitudinal analysis to assess disease outcomes over a longer period of time.

“In this US registry of patients with axSpA, women had greater overall disease burden compared with men, including higher disease activity, worse patient-reported symptoms, and greater work productivity impairment,” concluded investigators. “Improved awareness of sex differences in the presentation of axSpA may aid physicians in earlier identification and improved disease management. Further studies are needed to better understand the differences in disease progression and outcomes in men vs women with axSpA.”

Reference:

Mease PJ, McLean RR, Dube B, et al. Comparison of Men and Women With Axial Spondyloarthritis in the US-Based Corrona Psoriatic Arthritis/Spondyloarthritis Registry [published online ahead of print, 2021 Apr 15]. J Rheumatol. 2021;jrheum.201549. doi:10.3899/jrheum.201549