Sex, gender differences matter when treating psoriatic arthritis, axial spondyloarthritis
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Sex and gender differences between patients with psoriatic arthritis and axial spondyloarthritis may explain why women experience longer diagnostic delays, higher burden and lower drug survival in these diseases, noted a speaker here.
“We’ve seen that in axial spondyloarthritis in particular, women have a longer delay in diagnosis. It takes a fair amount of time to get a diagnosis in axSpA anyway — although that does seem to be improving — but it’s clear the women lag behind the men,” Laura Coates, MBChB, PhD, MRCP, of the University of Oxford, told attendees at the 2021 Association of Women in Rheumatology Annual Conference. “In both psoriatic arthritis and axial spondyloarthritis, we see higher levels of disease burden, and, in some particular domains, a higher level of disease activity as well.
“It’s clear in axial spondyloarthritis that women respond less well to biologics,” she added. “That’s not as clear in psoriatic arthritis — I think generally here the response rates are similar. However, that does still translate to a lower chance of achieving disease targets, because of that higher level of baseline disease activity. And across both diagnoses, we see a lower drug survival — thinking about biologic registry data — [among women] in both PsA and [ankylosing spondylitis].”
But why?
According to Coates, this gap can be explained by exploring both the sex and gender differences between patients. In terms of gender — which relates to social aspects and one’s “role in society,” Coates said — providers can expect some psychological differences, as well as differences in social pressures placed on the individual, between men and women. Meanwhile, sex covers the biological differences — including genetics, anatomy and physiology — between male and female patients.
Regarding sex differences, female patients have smaller kidneys and are likely to demonstrate a lower drug elimination, as well as a smaller liver and as such a lower first-pass metabolism for drugs, Coates said. In addition, female patients have a higher pH in their stomach, which may affect oral drugs, as well as a longer gut transit time and a higher body fat percentage, which may be relevant to inflammation, she added.
There are also differences in immune responses between the sexes. According to Coates, female patients are thought to be less vulnerable to infections and demonstrate a higher activity in their immune system. In addition, estrogen will provide a higher antibody production. Female patients also demonstrate a higher risk for autoimmune diseases, compared to males.
In contrast, young male patients can exhibit very high inflammatory responses following infection. However, the presence of testosterone is associated with lower antibody formation and inflammation.
“There is also some nice data looking at the role of testosterone in pain, suggesting that may be an important down-regulator and modulator of pain, which may explain some of the differences in pain scores that we see in men and women,” Coates said.
Regarding the role of gender, Coates stated the pattern of one’s life can greatly impact the management of PsA or axial SpA. Complications can include the patient’s relationship, career and education concerns and considerations.
“It’s really important that we’re proactive in dealing with these questions, proactively addressing these issues around pregnancy, breastfeeding and planning families, so that women can hopefully achieve everything they want in their personal and medical lives,” Coates said.
Providers should consider these factors with regard to treatment in particular, she added. According to Coates, there is often a reason other than efficacy why women opt to discontinue some treatments. For example, a number of medications for these diseases would not be recommended for patients who are pregnant or breastfeeding, she said.
“I think moving forward, it’s clear that this is a hot topic in the field of spondylarthritis,” Coates said. “We’ve seen a great increase in the number of studies looking at this, and the number of studies starting to separate out their data for men and women. So hopefully we will have more data to guide us in the future, but it may be that we need to think about how we treat men and women a little bit differently in terms of what we expect for disease activity, how aggressive we need to be to control disease, and trying to get people to a point where their disease is well controlled, the disease impact is minimized, and they can get back to their normal lives.”
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Coates L. Spondyloarthritis and Sex. Presented at: Association of Women in Rheumatology Annual Conference; August 12-15, 2021, Hilton Head Island, South Carolina (hybrid meeting).
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