Sex Differences Found in nr-axSpA Disease Severity, Treatment Response

Marisa Wexler MS avatar

by Marisa Wexler MS |

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Among people with non-radiographic axial spondyloarthritis (nr-axSpA) — a type of arthritis that mainly affects the joints of the spine — women tend to have more severe disease than men do, as well as a poorer response to treatment, a Swiss study indicates.

This finding may have implications for the design of future clinical trials.

The results were published in the journal Arthritis Research & Therapy, in the study, “Differences between men and women with nonradiographic axial spondyloarthritis: clinical characteristics and treatment effectiveness in a real-life prospective cohort.”

Axial spondyloarthritis is an autoimmune disease that causes arthritis in the spine and pelvis. If there is evidence of spine inflammation on an X-ray, the condition is referred to as ankylosing spondylitis (AS); nr-axSpA refers to symptoms that are similar to AS, but without x-ray evidence of inflammation.

Previous research has suggested the existence of sex-based differences in the symptoms, or clinical manifestations, of the disease, and in the response to treatment among people with AS. However, whether such differences exist among patients with nr-ax-SpA is unclear.

To learn more, a research team using a Swiss database gathered data on 495 people diagnosed with nr-axSpA, of whom 231 were men and 264 were women (age 36.6 vs. 38.2).

“The aim of this study was to compare male and female patients classified as having nr-axSpA with regard to demographics, clinical manifestations and response to tumor necrosis factor inhibitors (TNFi) in a large national observational [group],” the researchers wrote. Of note, TNFi is a group of medications used worldwide to treat inflammatory conditions such as arthritis.

Relative to men, women experienced a significantly longer average diagnostic delay, of six years versus 4.7 years.

Women had more severe disease activity than men, as evidenced by significantly higher mean scores (5.3 vs. 4.6 points) on the Bath Ankylosing Spondylits Disease Activity Index (BASDAI). In addition, significantly more women — 79.6% vs. 64% — had enthesitis, which refers to inflammation sites where tendons or ligaments insert into the bone. Fatigue (6% vs. 4.7%) and co-existing fibromyalgia (13.1% vs. 2.7%) also affected significantly more women than men. Even in analyses where individuals with fibromyalgia were excluded, females still had significantly higher mean BASDAI scores and rates of fatigue and enthesitis than their male counterparts.

The researchers wrote that, apart from fibromyalgia, the sex differences in BASDAI scores “were mainly due to fatigue and enthesitis,” both of which are assessed in the BASDAI.

Of the analyzed patients without co-existing fibromyalgia, 163 initiated treatment with TNFi, therapies which work by blocking inflammatory signals. Medications in this class include Remicade (infliximab), Simponi (golimumab), Enbrel (etanercept), and Humira (adalimumab).

Prior to treatment, patients who were given TNFi showed similar sex differences to the group as a whole — women had a longer diagnostic delay and higher BASDAI scores. For 120 of these individuals, 58 men and 62 women, follow-up data after one year of treatment were available.

Treatment response was primarily evaluated based on the proportion of patients who achieved a 40% or greater improvement on the Assessment of SpondyloArthritis international Society criteria (ASAS40), which includes an improvement of at least 40% in at least three of four categories. The categories are patient global assessment of disease, pain, function, and inflammation.

Among participants with available data, significantly more men than women achieved ASAS40 (38% vs. 17%). This difference was even more pronounced after the researchers made mathematical adjustments to the statistical models to account for the pre-treatment differences in disease activity and other factors.

Additional statistical analyses showed a significant association between treatment response and low body mass index (BMI). Specifically, people who had a lower BMI, which is a ratio of weight to height, were statistically more likely to experience ASAS40.

Finding sex differences in how people with nr-axSpA respond to treatment has important implications for future clinical trials, the investigators noted. When trials are designed, scientists use mathematical models to determine how many participants need to be included to get statistically meaningful results. A trial that has enough participants to get such results is said to be sufficiently “powered.” If some people are more or less likely to respond to treatment, it affects the considerations that must be taken into account for a trial to be found to be adequately powered.

“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.

Among the study’s limitations, according to the team, was the possibility that some cases of fibromyalgia were missed. The fibromyalgia screening was based on the expert opinion of the treating rheumatologist rather than on the fulfillment of classification criteria or the use of a standardized fibromyalgia questionnaire, the researchers noted.

“Despite only few sex differences in baseline characteristics [those at the study’s start] of patients with nr-axSpA, a disease subgroup known for its balanced sex ratio, response to treatment with TNFi was significantly lower in women than in men,” the researchers concluded.