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.

Background: Sex-related differences in clinical manifestations and disease outcomes exist in psoriatic arthritis, however, there is limited information on sex-related differences in randomised controlled trials of psoriatic arthritis. We aimed to compare patient characteristics and efficacy and safety of advanced therapies (including biological and targeted synthetic therapies) between male and female patients with psoriatic arthritis participating in randomised controlled trials.

Methods: In this systematic review and meta-analysis, we searched Medline, Embase, and Central databases, and conference abstract archives, from their inception to June 10, 2022, for randomised controlled trials that assessed the efficacy of advanced therapies in psoriatic arthritis. Two reviewers extracted information on participants' characteristics and rates of American College of Rheumatology (ACR) 20 and ACR50 response and minimal disease activity (MDA) by sex. Random-effects models were used to calculate pooled effects of ACR20, ACR50, and MDA in male versus female patients by drug class.

Findings: We included 54 trials (11 514 [50·9%] of 22 621 participants were female and 11 107 [49·1%] were male). Sex-disaggregated results were reported in a minority of studies (nine [17%] of 54 reported baseline characteristics by sex, 18 [33%] reported efficacy by sex, and two [4%] reported safety endpoints by sex). At baseline, male patients had lower baseline tender joint count (mean difference -3·01 [95% CI -3·83 to -2·18], health assessment questionnaire scores (-0·28 [-0·33 to -0·24]), pain scores (-4·58 [-6·86 to -2·30]), patient global assessment (-3·22 [-5·27 to -1·17]), and physician global assessment (-1·34 [-2·08 to -0·08]) than did female patients. Male patients had higher baseline psoriasis area and severity index scores (mean difference 1·95 [95% CI 0·78 to 3·11]) and C-reactive protein concentrations (2·57 [0·40 to 4·74]) than did female patients. ACR20 response by sex varied across drug classes, with higher rates in males than females with interleukin (IL)-17 inhibitors (odds ratio [OR] 1·70 [95% CI 1·38-2·11]), IL-23 inhibitor (1·46 [1·20-1·78]), IL-12 and IL-23 inhibitor (2·67 [1·39-5·09]), and tumour necrosis factor (TNF) inhibitors (1·55 [1·11-2·18]), but no difference with JAK and TYK2 inhibitors (1·10 [0·87-1·38]). Similarly, ACR50 response rates were higher in male patients versus female patients in all drug classes, with exception of JAK and TYK2 inhibitors (TNF inhibitors, OR 2·17 [95% CI 1·62-2·90]; IL-17 inhibitors, 1·93 [1·56-2·38]; IL-23 inhibitor, 1·71 [1·25-2·34]; IL-12 and 23 inhibitor, 2·43 [1·14-5·20]; and JAK and TYK2 inhibitors, 1·09 [0·73-1·62]). Male patients were more likely to reach MDA with most drug classes, including IL-17 inhibitors (OR 1·99 [95% CI 1·50-2·63]), IL-23 inhibitors (1·79 [1·29-2·50]), TNF inhibitors (2·62 [1·54-4·44]), and JAK and TYK2 inhibitors (1·77 [1·15-2·73]). Risk of bias was low for most studies.

Interpretation: Biological sex of patients with psoriatic arthritis influences their response to advanced therapies, but the effect varies by drug class. Selective reporting might have influenced these results. Future trials should report baseline characteristics and endpoint results by sex.

Funding: Canadian Rheumatology Association.