About the PhD thesis

Inflammatory arthritis—including rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis—is commonly treated with biologic agents such as tu-mor necrosis factor inhibitors (TNFi), which target a key inflammatory signal-ing pathway. Sex and gender are important to consider, given known differ-ences in immune function and psychosocial factors.

This dissertation comprises four studies. The first was a register-based study assessing sex- and age-stratified differences in treatment effective-ness and discontinuation among patients with rheumatoid arthritis initiating TNFi therapy. A statistically significant sex effect was observed, driven by greater reductions in CRP and swollen joint count in men. Although the dif-ferences were small, they resulted in a lower proportion of good responders among women. Women also discontinued treatment earlier than men in pa-tients <50 years.

The second register-based study examined patients with rheumatoid arthri-tis starting another biologic or targeted synthetic therapy to determine whether sex differences were drug-specific or general. Similar trends to Study I were observed, though they reached statistical significance only in rituximab-treated patients over 50 years of age.

To explore potential mechanisms, an observational cohort study of 160 pa-tients with rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis evaluated TNFi drug concentrations and anti-drug antibodies, preceded by a methodological validation of the assays used. Men tended to have a greater reduction in DAS28-CRP than women, but similar proportions achieved good response. Overall treatment discontinuation did not differ by sex; how-ever, women more often discontinued due to adverse events, whereas men stopped treatment due to lack of efficacy. These differences were not ex-plained by drug levels or immunogenicity, which were comparable between sexes.

Overall, the observed sex- and gender related differences in treatment re-sponse are modest and of limited clinical relevance. There is no evidence to warrant major concern regarding inferior treatment outcomes in women compared to men receiving TNFi therapy.