Gender Differences in Axial Spondyloarthritis: Women Are Not So Lucky

Abstract

Purpose of ReviewAnkylosing spondylitis (AS) was historically seen as a predominantly male disease. However, more recent data showed a more homogenous sex prevalence. Unfortunately, in many studies in axial spondyloarthritis (axSpA), the number of women included is low and the analyses are often not stratified for gender distribution. The purpose of this review is to aggregate the existing data on gender differences in axSpA in order to increase the awareness that female axSpA patients are still under-recognized.Recent FindingsSeveral studies considering gender differences revealed that female axSpA patients had different disease manifestations due to different immunological, hormonal, and genetic responses. For instance, allelic frequencies of the AHNK-gene and tissue non-specific alkaline phosphatase (TNAP) haplotypes differed between men and women with ankylosing spondylitis (AS). In addition, different levels of tumor necrosis factor (TNF), interleukins IL-6, IL-17, and IL-18, were found between the two sexes. Furthermore, female patients show a higher diagnostic delay compared to males. Several studies indicate a higher frequency of extra-articular manifestations (EAM) in female axSpA patients, such as enthesitis, psoriasis, and inflammatory bowel disease (IBD), whereas acute anterior uveitis is more prevalent in male patients. Male AS patients more frequently show a higher Bath Ankylosing Spondylitis Radiology Index (BASRI) scores and modified Stoke Ankylosing Spondylitis Spine Scores (mSASSS) than females, which indicates that males have higher radiological damage and radiographic progression. However, disease activity (BASDAI) and quality of life (AsQol) scores are significantly higher in women, and more importantly, they have significantly lower response rates to treatment with TNF inhibitors (TNFi) and a significantly lower drug adherence.SummaryDespite the fact that men with axial SpA have a worse radiologic prognosis, women have a high disease burden, in part because they have a longer delay in diagnosis, higher disease activity, and significantly less responsiveness to treatment with TNFi.

Model‐Based Meta‐Analysis in Ankylosing Spondylitis: A Quantitative Comparison of Biologics and Small Targeted Molecules

“…In addition, female gender was found to experience more improvement in BASDAI and BASFI, which was consistent with the result from a national prospective observational study in the United Kingdom . However, in contrast, most other observational studies suggested that female gender was associated with a significantly lower response . The major difference between our analysis and those observational studies is that our identification of covariate is based on the relative drug effects, which may show different results from that based on the absolute treatment effects .…”

“…a dilemma, and randomized clinical trials that are generated for examining the difference between genders may be required. 23 Compared with the conclusions of previous meta-analyses, this study provided different and more detailed rank-order. The detailed comparison of outcomes is listed in Table S1.…”

“…Besides, our results are based on an aggregation of individual data, but it may not indicate that our results are biased . Overall, gender differences in treatment response are still a dilemma, and randomized clinical trials that are generated for examining the difference between genders may be required …”

“…22 However, in contrast, most other observational studies suggested that female gender was associated with a significantly lower response. 23 The major difference between our analysis and those observational studies is that our identification of covariate is based on the relative drug effects, which may show different results from that based on the absolute treatment effects. 24 Besides, our results are based on an aggregation of individual data, but it may not indicate that our results are biased.…”

Clinical, Economic, and Humanistic Burden Associated With Delayed Diagnosis of Axial Spondyloarthritis: A Systematic Review

“…Thus, early classification criteria that focus primarily on axial symptoms would be less likely to identify female patients with axSpA. The adoption of a broader definition of axSpA that includes peripheral features has revealed that the prevalence of axSpA may be nearly equal between men and women [31,79,80] and that nonradiographic axSpA may be more common in women than men [81]. Based on the available literature, there is limited information on the impact of delayed diagnosis in women or patients with nonradiographic axSpA.…”