Understanding the differences between sexes regarding PsA treatment may change the management of PsA in male and female patients and improve outcomes.
Numerically larger improvements were seen in male patients with psoriatic arthritis (PsA) receiving ixekizumab when compared with females regarding remission, the American College of Rheumatology 20%/50%/70% improvement criteria (ACR20/50/70), minimal disease activity (MDA) or very low disease activity (VLDA), and Disease Activity Index for Psoriatic Arthritis (DAPSA) low disease activity (LDA), according to a study published in Springer.1
“Because of this apparent sex difference in treatment response, it is important to understand whether an effective therapeutic agent for PsA provides consistent responses in both male and female patients,” investigators stated. “Identifying which manifestations and aspects of PsA are responsible for sex differences in treatment response may also support targeting therapies to each individual patient. A more complete knowledge of sex differences could change the management of PsA in male and female patients, which could result in improved outcomes for patients who had prior inadequate response to treatment.”
Data from phase 3, double-blinded, randomized, placebo-controlled randomized clinical trails (RCTs), SPIRIT-P1 and SPIRIT-P2, were used to determine differences between sexes (male and female) in adult patients with active PsA receiving ixekizumab every 2 (Q2W) and 4 (Q4W) weeks. Eligibility included meeting the Classification for Psoriatic Arthritis (CASPAR) criteria for PsA, at least 3 tender and 3 swollen joints at screening and baseline, and either active or documented history of plaque psoriasis. ACR20/50/70, MDA/VLDA, and DAPSA/LDA were used to evaluate efficacy though week 156. Changes in baseline were also assessed throughout the study period.
Within the 2 studies, 679 patients were included, with 224 receiving placebo (104 male, 120 female), 229 receiving ixekizumab Q4W (108 male, 121 female), and 226 receiving ixekizumab Q2W (98 male, 128 female). The mean age was 51.0 years.
Female patients tended to be older, had higher body mass index (BMI), lower C-reactive protein (CRP) levels (P = 0.037), worse tender joint count, worse Health Assessment Questionnaire Disability Index (HAQ-DI) results, (placebo: P < 0.001; ixekizumab Q4W: P = 0.003; ixekizumab Q2W: P = 0.003), and worse Leeds Enthesitis Index scores.
Across treatment groups, females had lower response rates in all measures when compared with males. Further, a significant difference was observed in both ixekizumab treatment arms. Female patients also had smaller changes from baseline in individual components.
The phase 3 data, which was standardized and included both biologic disease-modifying antirheumatic drug (bDMARD)-naïve patients and tumor necrosis factor inhibitor (TNFi)-experienced patients, strengthened the study. Analyses also focused on assessing endpoints that have been validated for measuring the signs and symptoms of PsA. While future studies will be helpful in determining approaches to treatment in different sexes, the results of the study can inform rheumatologists making treatment decisions.
“While composite measures are useful in evaluating treatment response because they assess multiple domains of PsA, male and female patients may perceive or report PsA disease severity differently,” investigators concluded. “Overall, differing response rates in composite measures ultimately reflects the impact of differences among the individual components of these measures. A more complete knowledge of sex and gender differences in PsA could result in improved outcomes for difficult-to-treat patients with prior inadequate response to treatment.”
Eder L, Tony HP, Odhav S, et al. Responses to Ixekizumab in Male and Female Patients with Psoriatic Arthritis: Results from Two Randomized, Phase 3 Clinical Trials [published online ahead of print, 2022 Apr 9]. Rheumatol Ther. 2022;10.1007/s40744-022-00445-w. doi:10.1007/s40744-022-00445-w