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 center dot 9%] of 22 621 participants were female and 11 107 [49 center dot 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 center dot 01 [95% CI -3 center dot 83 to -2 center dot 18], health assessment questionnaire scores (-0 center dot 28 [-0 center dot 33 to -0 center dot 24]), pain scores (-4 center dot 58 [-6 center dot 86 to -2 center dot 30]), patient global assessment (-3 center dot 22 [-5 center dot 27 to -1 center dot 17]), and physician global assessment (-1 center dot 34 [-2 center dot 08 to -0 center dot 08]) than did female patients. Male patients had higher baseline psoriasis area and severity index scores (mean difference 1 center dot 95 [95% CI 0 center dot 78 to 3 center dot 11]) and C-reactive protein concentrations (2 center dot 57 [0 center dot 40 to 4 center dot 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 center dot 70 [95% CI 1 center dot 38-2 center dot 11]), IL-23 inhibitor (1 center dot 46 [1 center dot 20-1 center dot 78]), IL-12 and IL-23 inhibitor (2 center dot 67 [1 center dot 39-5 center dot 09]), and tumour necrosis factor (TNF) inhibitors (1 center dot 55 [1 center dot 11-2 center dot 18]), but no difference with JAK and TYK2 inhibitors (1 center dot 10 [0 center dot 87-1 center dot 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 center dot 17 [95% CI 1 center dot 62-2 center dot 90]; IL-17 inhibitors, 1 center dot 93 [1 center dot 56-2 center dot 38]; IL-23 inhibitor, 1 center dot 71[1 center dot 25-2 center dot 34]; IL-12 and 23 inhibitor, 2 center dot 43 [1 center dot 14-5 center dot 20]; and JAKand TYK2 inhibitors, 1 center dot 09 [0 center dot 73-1 center dot 62]). Male patients were more likely to reach MDA with most drug classes, including IL-17 inhibitors (OR 1 center dot 99 [95% CI 1 center dot 50-2 center dot 63]), IL-23 inhibitors (1 center dot 79 [1 center dot 29-2 center dot 50]), TNF inhibitors (2 center dot 62 [1 center dot 54-4 center dot 44]), and JAK and TYK2 inhibitors (1 center dot 77 [1 center dot 15-2 center dot 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.Copyright (c) 2023 Elsevier Ltd. All rights reserved.