Regula Neuenschwander 1, Monika Hebeisen1,2, Raphael Micheroli1, Kristina Bürki1, Pascale Exer3, Karin Niedermann4, Michael J. Nissen5, Almut Scherer2 and Adrian Ciurea1* 

Differences between men and women with nonradiographic axial spondyloarthritis: clinical characteristics and treatment effectiveness in a real-life prospective cohort. Arthritis Research & Therapy (2020) 22:233

 

This carefully done observational cohort study provides another piece of the puzzle that examines potential gender differences between men and women with axSpA.  What does it tell us?  The cohort examined is unique since much of the previously proposed gender differences (women have more pain, less radiographic damage, later disease onset, more fibromyalgia, take longer to diagnose, and often respond differently to treatment) have been observed in long standing disease.  This cohort is defined carefully by the (unfortunate) use of the regulatory term non-radiographic ax-SpA (nr-AxSpA), which means in the broadest sense that these are SpA patients whose x-rays do not meet the old NY-classification standard of, at a minimum, bilateral erosions on pelvis x-rays.   All of the above issues were examined in this cohort including a real-world collection of observational data on individual patients' responses to the initiation of their first biologic, a TNFi agent.

They observed that the women with nr-AxSpA, at their baseline evaluation, took longer to diagnose despite having onset of symptoms at similar ages to men.  This finding actually does bridge an important gap - it is likely that diagnostic slant or prejudice created this particular distinction rather than actual age-related disease onset.  It was interesting (and revealing) that self-reported disease activity, fibromyalgia, and presence of enthesitis was reported higher in women, along with a lower proportion of B-27 positivity, but actual arthritis and dactylitis and objective measures of disease activity such as CRP were not different.  Women's BMI were lower than men; how this relates to current theories about body composition causing differences in inflammation and treatment response is not addressed.  Although enthesitis differences have been shown by others in early cohorts to aggregate more to women who have peripheral SpA, some of the more subjective measures of disease activity might be a victim of diagnostic bias.  Finally, the authors suggest, and they might be correct here, that the small B-27+ difference in frequency between men and women in their cohort might reflect misclassification distortion rather than true genotypic differences.

However, the real bottom line of the study (at least from the authors' perspective) is that response to TNFi were significantly lower in women compared to men.  They could not exclude channeling bias (more women would be started on a TNFi if they had a positive B-27) since the proportion of subjects starting TNFi had the same B-27+ proportion between men and women.  Nevertheless, this finding needs further examination and documentation.  Was it really gender, or B-27+, or even the fault of the study design itself that created these differences?  The authors clearly adjusted for all possible confounders and effect modifiers they could find, including a sensitivity analysis of why people stopped their TNFi, and the differences remained.  It is likely real.  From a practical standpoint in the general care of our early disease patients and when we initiate therapy, does this mean we should back-off from TNFi in this subset of patients and use other biologics with different mechanisms of action?  Let us not jump to that conclusion yet, and we should examine this question with more research into why these differences occur in an individual patient as well as on a molecular level.