TORONTO — Women with axial spondyloarthritis (axSpA) are less likely than men with the condition to stay on TNF and interleukin-17 (IL-17) inhibitors, but there are no sex differences in continuing on JAK inhibitors, a large new US study has found.
“The results suggest important sex differences in long-term treatment persistence,” lead study author Rachael Stovall, MD, acting assistant professor, Division of Rheumatology, University of Washington, Seattle, told Medscape Medical News.
The findings were presented at the Spondyloarthritis Research and Treatment Network (SPARTAN) 2026 Annual Meeting.
In the past, the prevailing opinion was that axSpA primarily affects men, but recent research has shown its prevalence is similar in women.
Different Presentations
Women may present with different symptoms, though, Stovall said. “They tend to have a longer delay to diagnosis and report higher disease activity and worse outcomes.”
For years, nonsteroidal anti-inflammatory drugs (NSAIDs) and TNF inhibitors were the only treatment options for axSpA, but IL-17 and JAK inhibitors are now available.
Multiple studies have shown women have lower adherence to, and earlier discontinuation of, TNF inhibitors compared with men. However, it has been unclear if sex differences in medication discontinuation extend to newer drug classes.
The current study included 7200 US patients with axSpA from the American College of Rheumatology’s Rheumatology Informatics System for Effectiveness Registry who were under the care of a rheumatologist. The mean age of the sample was 52.7 years; 58% were female, 69% were White, and 25% had Medicare coverage. About 16% had glucocorticoid prescriptions, and 9% had opioid prescriptions.
Patients had to have two of the same prescriptions. “It’s not uncommon for costs to prevent a patient from getting a medication, so with having to have two of the same medications, we felt more confident that patients were receiving that treatment,” Stovall explained.
Patients also were required to have a 6-month washout period where they were not prescribed biologic or targeted synthetic disease-modifying antirheumatic drugs (DMARDs).
The vast majority of study patients (87%) were on a TNF inhibitor, which wasn’t unexpected since the study extended back to 2003 — shortly after these drugs became available. About 10% of patients were on an IL-17 inhibitor, and 3.5% were on a JAK inhibitor.
In terms of median days to discontinuation overall, the study found patients taking an IL-17 inhibitor discontinued the therapy 5 months earlier than those on a TNF inhibitor (274 vs 416 days).
4-Month Sex Difference
Women treated with a TNF inhibitor discontinued this therapy more than 4 months earlier than their male counterparts (363 vs 494 days) and also discontinued IL-17 inhibitors earlier (231 vs 335 days).
There were no statistically significant differences between men and women discontinuing a JAK inhibitor.
The differences persisted after adjusting for confounders (age, race or ethnicity, insurance, BMI, smoking, socioeconomic status, and use of glucocorticoids and opioids). Adjusted hazard ratios were 1.24 (95% CI, 1.16-1.32; P < .001) for TNF inhibitor use, 1.25 (95% CI, 1.01-1.53; P = .038) for IL-17 inhibitors, and 0.89 (95% CI, 0.62-1.27; P = .51) for JAK inhibitors.
Kaplan-Meier curves showed younger women (18-64 years) were less likely to remain on TNF inhibitor therapy than males and older women. The curves also showed women had a lower probability of continuing on IL-17 inhibitors, especially compared to younger men “who are persisting on IL-17 inhibitors the longest,” Stovall said.
There were no differences by age and sex in the probability of JAK inhibitor discontinuation.
Relevant Factors
Several factors might explain why women discontinue treatments earlier than men. For one thing, they’re more likely to have painful axial manifestations like enthesitis, Stovall said. “Patients may perceive a difference in effectiveness and therefore choose to discontinue therapy.”
Women also may have a higher level of noninflammatory pain than men that targeted synthetic DMARDs are unable to treat. This, Stovall said, could give women the sense that they’re not responding to treatment.
Another hypothesis is that women experience more side effects and have a higher rate of antidrug antibodies, perhaps due to hormonal factors, which may necessitate switching therapies. Alternatively, sex differences in therapy discontinuation could reflect socioeconomic disparities or gender differences in care-seeking behavior.
A limitation of the study was the small number of patients taking a JAK inhibitor. Also, researchers couldn’t control for NSAID use because some were purchased over the counter, and the 6-month washout could misclassify some patients as “biologic-naive.”
Future work should further investigate the mechanisms linked to sex differences in therapy discontinuation, Stovall said. “Larger studies are needed to confirm these findings and explore why these differences occur.”
Asked to comment, Virginia Carrizo Abarza, MD, who until recently was a clinical and research fellow in rheumatology at the University of Toronto, Toronto, Ontario, Canada, said the study is important and useful, especially given that experts didn’t pay much attention in the past to sex differences in various areas of rheumatology.
“We thought that women didn’t get these disorders.”
Abarza noted fibromyalgia, which often co-occurs with axSpA, psoriatic arthritis, and rheumatoid arthritis and is more common in women, “wasn’t taken seriously” until relatively recently.
These new study results should be “a warning that we have to pay attention to women” because they are discontinuing biologics 4 or 5 months earlier than men, she said.
Stovall and Abarza reported having no relevant conflicts of interest.
