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Gender-Based Differences in axSpA: Biology or Study Design?

Op-Med is a collection of original articles contributed by Doximity members.

Gender-based differences in clinical presentation and treatment response in axial spondyloarthritis (axSpA) have gained much attention in the last few years. Several studies have shown that females with axSpA often have high disease activity, functional impairment, poor quality of life, and delayed response to Biologics. At the ACR 2022 convergence meeting, several abstracts focused on gender-based differences in axSpA.

The results from the PROOF study presented at the meeting by D. Poddubny et al. revealed that females with non-radiographic (nr-axSpA) were less likely to achieve inactive disease state (and low disease activity) over time as compared with males. Only 9.6% of females with nr-axSpA compared to 21.7% of males (p=.0013) achieved an inactive disease status at one year. Similarly, 27.1 % of females compared to 46% (p=.0002) of males achieved low disease activity as measured by ASDAS at the end of 1 year. Female gender was independently associated with significantly lower odds of achieving an inactive disease state. These results were independent of treatment effects like the use of tumor necrosis factor inhibitors. However, in patients with radiographic axSpA (r-axSpA), there were no significant differences in attaining inactive or low disease activity status between men and women.

Another abstract presented at the meeting by S. Maguire et al. examined and compared sex-specific relationships between disease activity (as assessed by BASDAI) and quality of life (as assessed by ASQoL) in patients with axSpA. There was a strong correlation between disease activity scores and quality of life, with higher disease activity impairing function and overall quality of life. This correlation was much more robust in men compared to women suggesting that BASDAI may not be capturing the full impact of disease activity on quality of life in females with axSpA. 

An analysis of data from the ASAS-PerSpA study, which is a large international study of more than 4000 patients from 24 countries, presented by D Benavent et al., also revealed that females across the spectrum of spondyloarthritis (axSpA, peripheral SpA, and psoriatic arthritis) had worse outcomes in terms of disease activity, functional status and quality of life compared to men. 

A pilot study presented by C lee et al. examining the difference in immune pathways in men and women with ankylosing spondylitis showed that male and female patients with AS show differential gene expression patterns in IL-17-expressing peripheral blood mononuclear cells. Genes involved in Th17 differentiation, notably BATF, SOCS1, NKD2, and ARID5A, were elevated in men compared to women, while cytokines and receptors known to amplify the IL-17 response were comparable. Instead, TGF-β, PGE2, and S100 proteins, including S100A2, 4, 6, 8, 9, 10, and S100P, were highly upregulated in men. 

It needs to be determined whether these gender-based differences in axSpA patients may be driven by biological differences or could be related to study design and chance alone.

Dr. Magrey is a consultant for Novartis, UCB Pharma, Eli Lilly, Abbvie, Jannsen and Pfizer, and she is currently doing clinical trials with BMS.

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