Women less likely than men to respond to advanced therapies in psoriatic arthritis
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SAN DIEGO — In patients with psoriatic arthritis, those with female sex are less likely than those with male sex to achieve outcomes in randomized clinical trials for advanced therapies, according to data presented at ACR Convergence 2023.
“There are studies that used real-world data that suggested inferior response to biologic therapies in female patients with PsA,” Lihi Eder, MD, of the Women’s College Research Institute and division of rheumatology at the University of Toronto, told Healio. “However, few studies explored sex differences in randomized controlled trials. Limited information exists on sex differences in newer classes of advanced therapies and whether they differ across drug classes.”
To compare patient characteristics, as well as with efficacy and safety data, between those with male and female sex in PsA trials, Eder and colleagues performed a systematic literature review of the Medline, Embase and Central databases for abstracts published between Jan. 1, 2000, and June 30, 2022. The analysis included 52 trials, representing 21,769 participants. The total assessed study population was comprised of 50.2% with male sex and 49.8% with female sex.
The primary outcome was the proportion of patients who achieved minimal disease activity (MDA) or ACR20 and ACR50 response criteria by sex. Among the included studies, 17.3% of the data sets reported sex-disaggregated baseline characteristics, while 30.7% reported sex-disaggregated efficacy endpoints and 3.8% reported sex-disaggregated safety outcomes.
Baseline data showed that women had significantly higher tender joint counts and Health Assessment Questionnaire (HAQ) Disability Index scores, along with higher physician, patient global assessment and pain scores. Conversely, men demonstrated significantly higher C-reactive protein and psoriasis area and severity index (PASI) scores at baseline.
According to the researchers, patients with male sex were significantly more likely than those with female sex to achieve MDA after treatment with interleukin (IL)-17 inhibitors (OR = 1.99), IL-23 inhibitors (OR = 1.79), TNF inhibitors (OR = 2.62) and Janus kinase (JAK) inhibitors (OR = 1.77).
Those with male sex were also significantly more likely to achieve ACR20 response after treatment with IL-17 (OR = 1.76), IL-23 (OR = 1.46), IL-12/23 (OR = 2.66) and TNF (OR = 1.67) inhibition. However, this trend did not apply to JAK inhibition (OR = 1.10).
A similar trend was observed for ACR50 response. Those with male sex were significantly more likely to reach this endpoint after treatment with IL-17 (OR = 1.95), IL-23 (OR = 1.71), IL-12/23 (OR = 2.43) and TNF (OR = 2.17), but not with JAK inhibition (OR = 1.09).
The two groups experienced comparable ACR20 responses when using placebo (OR = 1.04; 95% CI, 0.86-1.27), according to the findings.
“Our main findings are that female patients with PsA are less likely to respond to advanced therapies, but the magnitude of these differences varies by drug class,” Eder said. “While male patients were more likely to achieve ACR response across all classes of biologics, non-significant sex differences were found in JAK/TYK2 inhibitors. Possibly biological differences in immune profile, pain perception or pharmacokinetics of drug classes may account for the differential effect.
“Future trials should diligently report sex disaggregated data as it will help further explore these differences in new classes of drugs,” she added. “Additionally, studies into the underlying mechanisms of these differences are needed as some of them may be due to gender socio-cultural factors and others are biological sex related mechanisms.”
An additional consideration pertains to the way patients experience their disease, according to Eder.
“Female patients tend to experience more pain and greater physical dysfunction; it is important to address these features of PsA and explore the causes of pain and manage them appropriately,” she said. “The finding of differential response across classes of drugs is interesting. While we need more studies exploring this aspect further, it is possible that sex of the patient may be able to inform selection of drug class in the future.”
Understanding clinical trial design is another component of the discussion, she said. “Female patients with PsA are less likely to achieve optimal treatment outcomes in randomized clinical trials,” Eder said. “These sex differences may be dependent on the class of medications and is more pronounced in biologic therapies.”
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Eder L. Abstract 1687. Presented at: ACR Convergence 2023; Nov. 10-15, 2023; San Diego.
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