Dr. van der Horst-Bruinsma notes some clinicians may be less likely to keep axial spondyloarthritis in their differential diagnosis for a young woman with lower back pain because of their preconception the disease occurs mainly in men. Dr. Jovani agrees that limited knowledge of non-rheumatologic health professionals about this group of diseases may contribute to diagnostic delay. She believes it is particularly important primary care physicians be educated that the prevalence of the disease is similar in men and in women, and women more frequently present with enthesitis and peripheral arthritis compared with men.
Differences in Treatment Response
Sex differences appear to be a factor in the response to TNF inhibitors, with women, on average, showing less benefit than men. Dr. van der Horst-Bruinsma points out most randomized, placebo-controlled trials of these drugs were statistically powered to find out whether a drug is more beneficial than a placebo. “But if you look into the gender difference, it doesn’t come out, because in those days the majority of the patients were males, and you had insufficient data on the women,” she states.
When Dr. van der Horst-Bruinsma et al. pooled data from four such studies of etanercept for ankylosing spondylitis, they found, as a group, women had less improvement than men; other data support this idea as well.10,16 Some studies have also shown women tend to switch TNF inhibitors more frequently, possibly signifying decreased treatment response.17 Although it is not clear why women, on average, may respond less strongly to these drugs, higher body fat in women has been proposed as a mediator of poorer efficacy in this group.18 However, Dr. van der Horst-Bruinsma relates she is not less likely to prescribe these drugs to a woman than to a man, because the majority of women do show some positive changes when prescribed TNF inhibitors.
It remains to be seen whether sex may play a role in efficacy of other treatments of axial spondyloarthritis, such as the anti-IL-17 monoclonal antibody secukinumab. Dr. van der Horst-Bruinsma and colleagues are currently preparing data on response to IL-17 inhibitors for axial spondyloarthritis in men compared with women, which they plan to present at the 2019 ACR/ARP Annual Meeting in Atlanta.
Research Challenges
In general, consensus is growing that potential sex differences have not been adequately considered in the process of drug development. This includes basic research, such as with cell lines and mouse models, and continues in the underrepresentation of women in clinical trials.19 “The publication of results with a gender perspective makes the medical community learn the differences and similarities between men and women in different diseases,” Dr. Jovani says. “There is a lack of sex-stratified results in most studies of diagnostic delay in spondyloarthritis, and influences of sex were rarely discussed.” However, she admits that studies without sex-stratified findings are easier to conduct.
