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At month 3, patients treated with tofacitinib achieved higher rates of ACR20/50, MDA, and PASI75 in both sexes when compared with the placebo. However, female patients were less likely to achieve MDA when compared with males.
Although tofacitinib efficacy surpassed placebo in both men and women with psoriatic arthritis (PsA), females were less likely to achieve minimal disease activity (MDA), according to a study published in Rheumatic and Musculoskeletal Diseases.1 This may be due in part to differences between sexes at baseline.
“PsA affects males and females equally, but differs across sexes in terms of clinical features, disease course and responses to therapy,” wrote a team of investigators led by Lihi Eder, MD, PhD, associated with the Women's College Research Institute at the University of Toronto. “Consistently, female patients are found to have higher disease activity scores at presentation, particularly for predominantly subjective measures (eg, tender joints, entheses, and pain), whereas more objective measures (eg, swollen joint counts (SJCs) and dactylitis) are comparable between sexes.”
Previous observational studies of this patient population indicated that female patients have less favorable outcomes and are less likely to achieve treatment responses and low disease activity (LDA).2 These studies also found that women were also more likely to discontinue treatment earlier due to adverse events and less therapeutic benefits.
Data from phase 3 randomized controlled trials, OPAL Broaden, OPAL Beyond, and OPAL Balance, were utilized to evaluate the efficacy, safety, and time to discontinuation (persistence) in patients with psoriatic arthritis. Patients received tofacitinib 5mg or 10mg twice daily, adalimumab 40 mg every 2 weeks, or placebo.
Outcomes regarding efficacy included MDA, the Psoriasis Area Severity Index (PASI)75, American College of Rheumatology (ACR)20/50/70, and changes from baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient Global Assessment of Disease Activity (PtGA), Short Form-36 (SF-36) Physical (PCS) and Mental (MCS) Component Summary scores, and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). Safety was evaluated to month 12 and persistence was evaluated to month 42 via a long-term extension study.
Of the 816 patients enrolled, 54.3% were female. At baseline, female patients had worse HAQ-DI and FACIT-F, and higher enthesitis scores and tender joint counts. Male patients had a greater presence of dactylitis and PASI.
At month 3, patients treated with tofacitinib achieved higher rates of ACR20/50, MDA and PASI75 in both sexes when compared with the placebo, with similar changes observed in HAQ-DI and FACIT-F. However, female patients were less likely to achieve MDA when compared with males. Male patients in the tofacitinib group achieved higher rates of ACR70 and had greater improvements in SF-36 MCS when compared with placebo.
Both sexes treated with tofacitinib 5mg or 10 mg reported similar proportions of treatment-emergent adverse events (TEAEs). Serious AEs occurred in 3.4% and 6.6% of males and females, respectively, receiving tofacitinib 5mg and 4.0% and 5.9% in the tofacitinib 10mg cohort. Time to discontinuation was similar among both sexes.
Investigators acknowledged several limitations including the small number of patients treated with adalimumab and that sex differences in safety outcomes could not be completely evaluated due to the limited number of patients and short follow-up period. Further, analysis of the time to discontinuation was only conducted in those who had tolerated or were responsive to tofacitinib treatment.
Despite these limitations, the study was strengthened by the avoidance of inherent biases due to the blinded randomized controlled trial design. The long-term extension data allowed investigators to conduct an in-depth analysis of sex differences regarding tofacitinib efficacy.
“Exploratory analyses of clinical trials by sex allow an assessment of potential sex differences in disease expression and responses to advanced therapies,” investigators concluded. “This work underscores the need for further investigation of how sex influences disease phenotype and treatment response, which should result in more personalized and equitable management across men and women with PsA.”