Sex Disparities in PsA/SpA Save

“Sex is a biologically based construct defining differences between males and females. Gender has sociocultural aspects of being a man, woman, or other AND has effect on social norms and expectations. Both are important to patients and should be to us as their physicians.” – Dr. Lihi Eder

Dr. Eder delivered an illuminating talk at RheumNow Live 2024 on sex differences in psoriatic arthritis; the disease may manifest differently in men and women, and therapeutic responses may differ between the sexes. Men tend to have more aggressive, erosive disease with higher CRP; whereas, women present with greater chronic pain, physical dysfunction, and depression.

She conducted a meta-analysis and systemic review of published randomized controlled trials of different therapeutics  in psoriatic arthritis specifically looking for sex differences in disease activity and responses to treatment (1). She found 17% of studies reported baseline characteristics by sex, 33% reported some endpoints by sex, and only 4% reported safety data by sex. While female patients were less likely to achieve ACR20 responses across all biologic DMARDS; no sex differences were noted for patients on JAK/TYK2 inhibitors. Is this due to the disease being different in men compared to women or is it related to how women may respond to medications differently? She noted placebo rates were similar; hence, the differences in responses between women and men should not be dismissed as psychosomatic causes. 

Dr. Eder’s meta-analysis supported findings of another meta-analysis evaluating gender differences in patients with axial spondyloarthritis (axSpa). Rusman et al. published a meta-analysis in 2018 reporting female patients with axSpa had higher rates of diagnostic delays, greater frequency of extra-articular manifestations, and lower response rates to treatment with TNF inhibitors compared to males counterparts (2). Additionally, disease activity differed between the sexes depending on the tools used to measure the study subjects. The authors noted despite females with axSpa having higher disease burden, the ASDAS did not show differences between sexes but the BASDAI was significantly higher in women than in men*. 

Choosing the right disease measurement tool will affect remission criteria. Remission criteria also have been found to perform differently in men and women. Sex specific strategies to treat and assess patients should be considered in future clinical trials.  Perhaps the effects of sex and gender on disease states and therapeutic responses may be related to immunological, hormonal, genetic, social and cultural differences.

Dr. Eder concluded, “We need to move from a gender-blind to gender-specific approach when treating our patients.”

*Author's note: For our readers, both disease measurement tools include assessments for back pain, peripheral joint pain, and morning stiffness, but the ASDAS also includes the CRP and patient global; whereas the BASDAI includes fatigue and overall discomfort.

References:

1. Lihi Eder et al.  "Sex-related differences in patient characteristics, and efficacy and safety of advanced therapies in randomised clinical trials in psoriatic arthritis: a systematic literature review and meta-analysis" The Lancet Rheumatology, Volume 5, Issue 12, 2023.https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(23)00264-3/fulltext
2. Rusman T, van Vollenhoven RF, van der Horst-Bruinsma IE. Gender Differences in Axial Spondyloarthritis: Women Are Not So Lucky. Curr Rheumatol Rep. 2018 May 12;20(6):35. doi: 10.1007/s11926-018-0744-2