Despite few differences in patient and disease characteristics being seen between men and women with nonradiographic axial spondyloarthritis (axSpA), women had significantly lower rates of response to tumor necrosis factor (TNF) inhibitors, Swiss researchers reported.
While women were slightly older at the time of enrollment in a national cohort, primarily because of diagnostic delay, there were no baseline differences between the sexes in disease activity, physical function, spinal mobility, or quality of life, according to Adrian Ciurea, MD, of Zurich University Hospital, and colleagues.
However, a 40% improvement on the criteria of the Assessment of SpondyloArthritis International Society (ASAS40) after a year of TNF inhibitor therapy was only achieved by 17% of women compared with 38% of men (OR 0.34, 95% CI 0.12-0.93, P=0.02), the researchers reported online in Arthritis Research & Therapy.
Patients with axSpA today are classified as having nonradiographic or radiographic disease, depending on whether they have evidence of sacroiliac changes visible on x-rays. The radiographic form more often is seen in men, whereas both sexes are affected by nonradiographic axSpA.
In the radiographic group, women typically have higher self-reported disease activity, worse function, lower quality of life, and more peripheral arthritis and enthesitis. In contrast, men typically have higher levels of C-reactive protein (CRP) and more inflammation seen on magnetic resonance imaging. It has not been clear whether similar differences are seen in the nonradiographic group.
To explore the potential sex differences in nonradiographic axSpA, therefore, Ciurea and colleagues analyzed data from the Swiss Clinical Quality Management cohort, identifying 231 men and 264 women with this diagnosis who were enrolled from 2005 to 2018.
At baseline, mean age was 38.2 for women and 36.6 for men, while diagnostic delays were 6 years for women vs 4.7 years for men (P=0.005).
Women had significantly higher scores on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; 5.3 vs 4.6, P=0.003), which is a patient-reported outcome. Women also more often had enthesitis (79.6% vs 64%, P<0.0001) and higher scores on the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES; 3.2 vs 1.9, P<0.001).
Women also were more likely to have concurrent fibromyalgia (13.1% vs 2.7%, P<0.001) and to have a lower body mass index (BMI; 24.3 vs 25.7).
A potential explanation for the observation that women had more enthesitis was that there can be difficulty differentiating enthesitis from the allodynia of fibromyalgia, the researchers suggested. They excluded patients with concurrent fibromyalgia from their treatment response analysis, but some cases may have been overlooked, they noted.
But there were no differences between women and men on various important measures of disease:
- Bath Ankylosing Spondylitis Functional Index, 3.1 for women and 2.8 for men (P=0.16)
- Ankylosing Spondylitis Disease Activity Score, 2.9 for both (P=0.23)
- Bath Ankylosing Spondylitis Spinal Mobility Index, 1.3 for both (P=0.98)
- Quality of life, 59.7 for women and 61.4 for men (P=0.34)
- Median CRP levels, 4 mg/L for both (P=0.86)
- Peripheral arthritis, 39.2 for women and 35.8 for men (P=0.46)
- Dactylitis, 11.4 % of women and 10.9% of men (P=0.89)
Among the overall group of 495 patients enrolled in the cohort, 163 initiated treatment with a TNF inhibitor, and a follow-up visit at 1 year to assess response was available for 120 patients.
After a year of TNF inhibitor treatment, the lower response rate for women on the ASAS40 seen in the unadjusted analysis was even lower after adjustment for baseline differences in diagnostic delay, MASES, BMI, and BASDAI, with an odds ratio of 0.19, 95% CI 0.05-0.62, P=0.009).
Men also were shown to more often achieve remission in a recent open-label phase of a clinical trial of adalimumab (Humira) for nonradiographic axSpA and in a Danish study comparing treatment responses in nonradiographic axSpA and ankylosing spondylitis.
“Our current study therefore adds to available data to support the claim for future randomized controlled trials in axSpA to be sufficiently powered to detect potential sex differences,” the researchers wrote.
A limitation of the study, they said, was the possibility of disease misclassification.
The study was funded by the Stiftung fur Rheumaforschung in Zurich.
The Swiss Clinical Quality Management Foundation is supported by the Swiss Society of Rheumatology, AbbVie, Celgene, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Samsung, Sandoz, Sanofi, UCB, the Arca Foundation, and the Swiss Balgrist Society.
The authors also reported support from AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Merck Sharp & Dohme, Novartis, and Pfizer.