Men with PsA derive more benefit from MTX+ETN therapy than women

Combination therapy with methotrexate (MTX) plus etanercept (ETN) results in more improved outcomes in men than in women with psoriatic arthritis (PsA) for minimal disease activity (MDA) and Psoriatic Arthritis Disease Activity Score (PASDAS), a study has shown.

In addition, patients with body mass index (BMI) ≤30 kg/m² exhibit better outcomes than those with BMI >30 kg/m², with no clear pattern regarding treatment received.

“These findings suggest that contextual factors such as sex and BMI may affect response to PsA therapy,” said the researchers, led by Philip J Mease, MD, director of rheumatology research at the Swedish Medical Center/Providence St. Joseph Health in Seattle, Washington, US.

Mease and his team performed a post hoc analysis to examine the potential impact of sex and BMI on response in the Study of Etanercept and Methotrexate in Combination or as Monotherapy in Subjects with Psoriatic Arthritis (SEAM-PsA) trial, a 48-week, phase III, randomized controlled trial that compared outcomes with MTX monotherapy, ETN monotherapy, and MTX+ETN combination therapy in patients with PsA who were naïve to MTX and biologics.

The researchers assessed outcomes at week 24 stratified by sex (male vs female) and BMI (≤30 vs >30 kg/m²), including the American College of Rheumatology 20 (ACR20) criteria, MDA, very low disease activity (VLDA), and PASDAS. Data were analysed using descriptive statistics, normal approximation, logistic model, and analysis of covariance.

Overall, 851 patients completed the SEAM-PsA trial. Significantly more men than women who received MTX+ETN combination therapy achieved ACR20 (71.5 percent vs 58.3 percent; p=0.02), MDA (45.8 percent vs 25.2 percent; p=0.0003), and VLDA (19.1 percent vs 9.5 percent; p=0.03). Men also achieved better PASDAS than did women (‒3.0 vs ‒2.3; p=0.0004). [J Rheumatol 2022;49:885-893]

In some treatment arms, patients with BMI ≤30 kg/m² showed better outcomes than those with BMI >30 kg/m² for ACR20, MDA, VLDA, and PASDAS, but no consistent pattern was seen as regards the treatment arm in which the difference was observed.

Biological factors

In an earlier study, women were found to have greater baseline disease severity than men, including higher tender joint count, patient global assessment, PsA pain, enthesitis, and Health Assessment Questionnaire-Disability Index. In addition, treatment with secukinumab for 52 weeks showed higher efficacy in men than in women. [Arthritis Rheumatol 2020;72:0507]

“We observed similar results with MTX+ETN combination therapy in our study, with better outcomes seen in men for some disease measures, including ACR20, MDA, VLDA, and PASDAS,” according to Mease and colleagues. “The results from our study could partly be explained by the fact that women had overall higher disease activity than men at baseline with MTX+ETN combination therapy.”

One of the potential drivers of these differences in disease severity and response to treatment between men and women, including that in sex hormones and their effects on the immune system and inflammatory responses, is biological-based factors. [Front Immunol 2015;6:493]

Estrogens have been shown to enhance immune response, while androgens, progesterone, and glucocorticoids can naturally suppress immune response. A recent study has reported that estrogens may regulate the activity of regulator T cells. [Lupus 2004;13:635-638; Front Immunol 2021;12:619268]

“More work is warranted to understand the factors that drive the differences between men and women in PsA disease severity or in treatment response,” the researchers said.