Women Stop Using TNF Inhibitors Earlier and Switch More Often Than Do Men, Dutch Study Reports

Women with ankylosing spondylitis (AS) stay with TNF inhibitor treatment for significantly shorter periods than men, mostly due to ineffectiveness, and they are at higher risk of developing infections while on these biological therapies, according to real-world data from the Netherlands.

The study, “Gender differences in retention rate of tumor necrosis factor alpha inhibitor treatment in ankylosing spondylitis: a retrospective cohort study in daily practice,” was published in the International Journal of Rheumatic Diseases, and led by researchers at VU University Medical Center in Amsterdam.

TNF is a molecule that helps the immune system fight diseases and infections. But its amounts are excessive in AS patients, causing inflammation, pain, and swelling in the joints of the spine.

Therapies such as Enbrel (etanercept), Humira (adalimumab) and infliximab (brand names Remsima and Remicade) act to inhibit, or block, TNF.

Previous studies have shown that over 60% of patients with AS respond to these treatments. Age and gender may be among the reasons the remaining 40% fail to respond, according to the scientists.

A meta-analysis — a statistical assessment — of multiple clinical trials found that women treated with Enbrel had a lower level of response to therapy than did men. More women than men also stopped the treatment.

To assess potential gender differences in long-term survival and side effects in daily practice at a large Dutch hospital, researchers there did a retrospective analysis of AS patients treated with Amgen‘s Enbrel, infliximab, and AbbVie‘s Humira between 2004 and 2014.

The study included 122 patients — 48 women (39.3%) and 74 men (60.7 %) — with a mean age of 43.4. Mean treatment duration was 51 months (4.25 years) and follow-up duration was 5.1 years.

Results showed that more patients were treated with Humira (59.7%) than Enbrel (28.9%) or infliximab (11.3%). Compared to men, significantly more women used infliximab (19.4% vs. 5.4%), while men used Enbrel more frequently (65.2% vs. 52.2%).

In total, 17 patients (17.2%) stopped TNF inhibitor treatment, mainly due to a lack of effectiveness (52.4%) and side effects (47.6%), especially recurrent mild infections in the throat, nose and ears.

Women were treated for significantly less time (33.4 months) than men (44.9 months). Thirty-two (26.2%) patients switched to a different TNF inhibitor, again more frequently women (26.9%) than men (16.3%). Most patients (81.3%) still used this type of treatment after four years.

A total of 38 patients experienced 40 infections, 19 of which were deemed serious and required antibiotics. Women showed a significantly greater risk of developing infections than men (26.1% vs. 18.7%). A similar higher risk was found in older patients, starting at age 41, compared to younger patients.

Overall, “[f]emales stayed on the same TNFi [inhibitor] for a significantly shorter period compared to males (33.4 vs. 44.9 months) and the most important reason to stop or switch the drug was inefficacy. Moreover, females seemed to be more prone to infections during TNFi treatment than males,” the researchers wrote.

“The majority of AS patients (81%) continued TNFi for many years and the most important reason to stop treatment, in both males and females, was inefficacy,” they added.