Male, Female Patients With Psoriatic Arthritis Treated With Tofacitinib Show Similar Responses, Key Differences
In a post hoc analysis of pooled data from two phase 3 randomized clinical trials and a long-term extension study, researchers found that treatment with tofacitinib for both male and female patients with psoriatic arthritis (PsA) resulted in greater efficacy compared with those taking placebo at 3 months.
“While males and females entered the studies with differences in several PsA disease activity measures, similar response rates and improvements from baseline following tofacitinib treatment were observed between sexes, although females were less likely to achieve [minimal disease activity (MDA)], a desirable clinical treatment target,” the authors wrote.
The authors noted that this key difference in MDA may be due to sex differences at baseline, where female patients had worse Health Assessment Questionnaire-Disability Index (HAQ-DI) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scores, higher tender joint counts, and higher enthesitis scores. Male patients had greater presence of dactylitis and Psoriasis Area Severity Index (PASI) scores.
Of the 816 study participants, 443 were female (54.3%). The participants either received tofacitinib 5 mg or 10 mg twice daily (n = 474), adalimumab 40 mg every 2 weeks (n = 106), or placebo (n = 236).
To determine efficacy, researchers examined several efficacy endpoints, including MDA, PASI75, American College of Rheumatology (ACR) 20/50/70 scores, and baseline changes in HAQ-DI, Patient Global Assessment of Disease Activity (PtGA), Short Form-36 (SF-36) Physical (PCS) and Mental (MCS) Component Summary, and FACIT-F scores. They also looked at safety to month 12 and evaluated time to discontinuation at month 42 using data from the long-term extension study.
Researchers found that both male and female patients taking tofacitinib reported greater improvements in FACIT-F, HAQ-DI, pain Visual Analogue Scale (VAS), PtGA VAS, and SF-36 PCS scores, compared with patients of the same sex receiving placebo at 3 months.
Regarding safety, at month 12, serious adverse events (AEs) occurred in 3.4% of male patients and 6.6% of female patients receiving 5 mg of tofacitinib. For the 10 mg cohort, serious AEs occurred in 4% of male and 5.9% of female patients.
“Overall, safety and time to discontinuation were generally similar between sexes,” the authors noted.
Digging into the long-term extension data, time to discontinuation was similar for both sexes who received tofacitinib 5 mg two times per day up to month 42.
The authors highlighted several limitations of their study. For example, the authors noted the limited number of patients treated with adalimumab and a short follow-up period for all participants. Additionally, their analysis of patients for time to discontinuation was done on those who were known to be responsive to or tolerate tofacitinib.
Even with these limitations, the authors believe their study’s results could impact future studies.
“Exploratory analyses of clinical trials by sex allow an assessment of potential sex differences in disease expression and responses to advanced therapies,” the authors wrote. “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.”
Eder L, Gladman DD, Mease P, et al. Sex differences in the efficacy, safety and persistence of patients with psoriatic arthritis treated with tofacitinib: a post-hoc analysis of phase 3 trials and long-term extension. RMD Open. 2023;9(1):e002718. doi:10.1136/rmdopen-2022-002718.