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.

2021 GRAPPA Trainee Symposium: A Summary of Oral and Poster Presentations.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) held a trainee symposium at its 2021 virtual meeting. Dermatology and rheumatology trainees presented their work on psoriasis and psoriatic arthritis (PsA). This report briefly reviews 5 oral presentations: prediction of cardiovascular events in psoriatic disease (PsD), correlation between spine abnormalities and clinical findings, biomechanical stress as a trigger for PsA, differences in DNA methylation among twins with PsD, and critical proteins associated with induction of PsD. In addition, we highlight 22 posters broadly discussing clinical and molecular implications of PsD.

Trends in mortality and cause-specific mortality among patients with psoriasis and psoriatic arthritis in Ontario, Canada.

BACKGROUND: There is limited information about mortality rates among patients with psoriasis and psoriatic arthritis (PsA) in North America and their change over the past 2 decades. OBJECTIVE: To compare all-cause and cause-specific mortality rates in patients with psoriasis to the general population in Ontario, Canada, from 1996 to 2016. METHODS: We conducted a population-based, retrospective cohort study of adult residents using administrative health data. All-cause and cause-specific standardized mortality rates, standardized mortality ratios, and excess mortality rates were calculated. RESULTS: 176,858 (2,524 deaths) patients with psoriasis and 15,430 (221 deaths) patients with PsA were identified in 2016. Patients with psoriasis and PsA had standardized excess mortality rates of 1.44 and 2.43 per 1000 population, respectively. Standardized mortality rates decreased by approximately 30% over the study period in both disease groups but remained significantly elevated compared to the general population. The leading causes of death in psoriasis and PsA patients were cancer, circulatory disease, and respiratory conditions. LIMITATIONS: We were unable to classify patients according to disease severity. CONCLUSIONS: Despite improvements in psoriasis treatment, the relative excess mortality, which may be related to risk factors for psoriatic disease, remained unchanged, with an average of approximately 1 to 2 extra deaths per 1,000 patients in 2016.

Predictive Utility of Cardiovascular Risk Prediction Algorithms in Inflammatory Rheumatic Diseases: A Systematic Review.

OBJECTIVE: We performed a systematic review of the literature to describe current knowledge of cardiovascular (CV) risk prediction algorithms in rheumatic diseases. METHODS: A systematic search of MEDLINE, EMBASE, and Cochrane Central databases was performed. The search was restricted to original publications in English, had to include clinical CV events as study outcomes, assess the predictive properties of at least 1 CV risk prediction algorithm, and include patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), or psoriasis. By design, only cohort studies that followed participants for CV events were selected. RESULTS: Eleven of 146 identified manuscripts were included. Studies evaluated the predictive performance of the Framingham Risk Score, QRISK2, Systematic Coronary Risk Evaluation (SCORE), Reynolds Risk Score, American College of Cardiology/American Heart Association Pooled Cohort Equations (PCE), Expanded Cardiovascular Risk Prediction Score for Rheumatoid Arthritis (ERS-RA), and the Italian Progetto CUORE score. Approaches to improve predictive performance of general risk algorithms in patients with RA included the use of multipliers, biomarkers, disease-specific variables, or a combination of these to modify or develop an algorithm. In both SLE and PsA patients, multipliers were applied to general risk algorithms. In studies of RA and SLE patients, efforts to include nontraditional risk factors, disease-related variables, multipliers, and biomarkers largely failed to substantially improve risk estimates. CONCLUSION: Our study confirmed that general risk algorithms mostly underestimate and at times overestimate CV risk in rheumatic patients. We did not find studies that evaluated models for psoriasis or AS, which further demonstrates a need for research in these populations.