Applying a Sex and Gender Lens to Psoriatic Arthritis

We know that sex and gender can impact how a patient responds to their treatment and medication. For those living with psoriatic arthritis (PsA), a type of arthritis linked with psoriasis, research shows that women are less likely to achieve remission, are more likely to experience side effects from advanced therapies and tend to stop treatments earlier than men. Why this is however remains unclear.

To address this gap in knowledge, Women’s College Hospital (WCH) scientist and rheumatologist, Dr. Lihi Eder and team are leading the Sex- And Gender-based analysis of the Effectiveness of advanced therapies in Psoriatic Arthritis (SAGE-PsA Study).

A global study with 40 supporting research sites, SAGE-PsA aims to understand how sex and gender, as well as their intersection with age and ethnicity, influence patient response to advanced therapies for PsA. The study is funded by the Canadian Institutes for Health Research (CIHR) and by the Group for Research and Assessment of Psoriasis and Arthritis (GRAPPA).

To better understand the SAGE-PsA study, Dr Eder tells us about her research and its implications for patient care.

When and why would a Psoriatic Arthritis (PsA) patient be prescribed advanced targeted therapies?

Advanced therapies is a broad term that includesbiologic and targeted synthetic medications used to control arthritis and psoriasis especially in more severe cases and for those who failed first line therapies. About 30 to 50 per cent of patients with PsA require treatment with advanced targeted therapies.

Why examine sex and gender in the treatment of PsA?

Despite the convincing data showing such a difference in response to therapy between male and female patients with PsA, it is surprising that so little attention has been given to understanding which sex- and gender-related factors underlie these notable differences.

These differences could be due to biological, sex-related factors such as differences in immune system or metabolism of drugs or due to gender-related, socio-cultural factors, such as differences in reporting of pain, support systems and patient-physician interaction. Understanding what sex- and gender-related mechanisms explain these differences is the first step in developing approaches to address these disparities.

Has a study of this scale on the impact of sex and gender ever taken place in rheumatology before?

This is the first study of this scale not just in PsA but in rheumatology generally that addresses issues of sex and gender. The study is also unique because it involves approximately 40 international sites including diverse patient populations from four continents representing high- and medium-income countries.

SAGE-PsA includes participants from multiple countries and from diverse backgrounds – how will this impact the study or be demonstrated in it?

While we expect some variability, studies across countries currently show similar gender disparities in response to advanced therapies. We expect similar sex and gender-related mechanisms drive treatment effectiveness across societies. Our goal is to explore common, global underlying mechanisms across different societies and cultures. Nevertheless, we also plan to evaluate whether the effect of sex/gender on treatment response is modified by country level variables, like ethnicity, societal expectations, and norms among others.

How will the study and the information it produces impact treatment for PsA?

We expect that our findings will fill existing knowledge gaps and as a result will inform care and support future research. Specifically, the results could inform selection and prescribing of advanced therapies. For example, where do specific types of targeted therapies work better in women? Should the dose of medication should change by sex?

Better understanding of the unique challenges that men and women with PsA experience could promote the development of gender-specific coping strategies and self-management programs.

Our findings could also inform the design of future clinical trials. For example, randomizing by sex may influence analysis of treatment efficiency. Our findings will also provide patients and clinicians with a better understanding of the effectiveness and risk profile associated with advanced therapies.

Finally, by engaging investigators from different countries, this study will provide a unique opportunity to study the effect of sex and gender across diverse societies and ethnicities. As most published studies have focused on European and North American patients, our study will provide more globally information relevant to patients with PsA.