Obesity, gender, and psoriatic arthritis

Despite a range of new and existing therapies, most patients with psoriatic arthritis (PsA) do not achieve minimal disease activity, the Irish Society for Rheumatology 2026 Autumn Meeting heard. Dr Lihi Eder, Associate Professor of Medicine and Research Chair in Inflammatory Rheumatic Diseases, University of Toronto, Canada, explored the reasons behind this in her talk: ‘Existing gaps in the management of PsA: Can we do better?’

Dr Eder asked why “many patients keep cycling through therapies and biologics”. She explored predictors of poor outcomes in PsA and mechanisms of difficult-to-treat disease, identifying obesity and gender as key drivers.

“We tend to focus on targeting inflammation, but not necessarily metabolic inflammation,” she said.

Data show that higher body mass index (BMI) significantly increases the risk of developing PsA and reduces the likelihood of achieving minimal disease activity. Dr Eder proposed adipose tissue dysfunction as a hypothesis to explain this, noting that hypertrophy of adipocytes leads to issues like hypoxia and changes in angiogenesis, further driving inflamed tissue and increased production of cytokines and adipokines.

“We have fat tissue in our joints,” she added, and presented findings from osteoarthritis research. This showed that, in the context of obesity, inflammation of this fatty tissue is associated with increased synovial inflammation.

“Another potential mechanism that could trigger inflammation is biomechanical stress,” Dr Eder said, adding that obesity can also amplify pain and produce a higher burden of symptoms in PsA. Furthermore, she proposed that dysbiosis of the gut microbiome may also play a role.

Dr Eder discussed evidence for nutritional approaches in PsA, including anti-inflammatory and plant-based diets, as adjunctive therapies. She described her research using the Mediterranean diet in the DIPSA trial, which found that weight loss, rather than a specific dietary pattern, was associated with symptom improvement. “Decreases in weight correlated with reductions in DAPSA [disease activity in PsA score],” she said.

Dr Eder moved on to present an overview of the emerging data investigating incretin-based therapies in PsA. She acknowledged that “indications for GLP-1 [glucagon-like peptide-1] drugs are accumulating”, but that access to them can be “quite challenging”. She presented results from the TOGETHER-PSA trial – a phase 3b randomised trial evaluating the combination of ixekizumab and tirzepatide in 271 adults with active PsA and overweight or obesity.

“Despite the fact that almost 85 per cent of patients lost a substantial amount of weight, only about one-third achieved ACR50 [American College of Rheumatology 50 per cent response criteria], which suggests that in some people, weight may not be the main driver of disease,” Dr Eder said about the results.

“There are a lot of gaps, but signals suggest that GLPs may have an adjunctive effect, especially alongside interleukin (IL)-17 inhibitors…. Is there a direct anti-inflammatory effect from GLPs? We don’t know yet…. If there is, then potentially, these drugs could be used in the context of overweight, not just morbid obesity, or even normal weight with some abnormalities.”

Dr Eder also addressed “questions about safety” around GLP-1 use, “especially sarcopaenia, which is prevalent among patients with arthritis in general, and is a risk in people losing a significant amount of their fat mass”. She promoted “counselling around exercise and a protein-rich diet” for these patients.

Dr Eder cautioned against a “one-size-fits-all” approach to gender in PsA, noting that failure to account for sex and gender differences has been associated with poorer outcomes in other fields. Delegates heard that women tend to enter clinical trials with a greater burden in pain-sensitive domains, including higher pain scores, more enthesitis, and more tender joints. Men, by contrast, tend to have more severe psoriasis, higher C-reactive protein levels, and more dactylitis. Gender differences may also influence treatment response and Dr Eder discussed potential mechanisms for this, such as variations in sex hormones, immune profiles, and inflammatory responses.

The talk concluded with an overview of menopause and PsA, “which has received very little attention,” according to Dr Eder. Symptoms can overlap and DAPSA scores increase during perimenopause, she said. There may also be an increasing PASI [Psoriasis Area and Severity Index] score during what Dr Eder described as a “clinically vulnerable period” for female patients.

“As rheumatologists, we really need to pay attention to women in mid-life,” she concluded.