Exploring the impact of obesity on psoriatic arthritis

During the PsOPsA Hub Steering Committee Meeting on August 24, 2026, key opinion leaders met to discuss the impact of obesity on psoriatic arthritis (PsA). The session opened with a presentation by Laura Coates and included a discussion featuring Paolo Gisondi, Jody Quinn, and Yukari Okubo. The discussion covered accessibility, long-term challenges, and patient experiences with weight loss interventions, and the importance of considering both psoriatic disease- and obesity-related comorbidities during treatment. 

Coates provides an overview of the impact of obesity on psoriatic disease, the current key data in favor of weight reduction as a therapeutic option for psoriatic disease, and a summary of the efficacy and safety data from the phase III TOGETHER-PsA (NCT06588296) trial.¹  

Studies have shown that increases in body mass index (BMI) correlate with a greater risk of developing both psoriasis (PsO) and PsA, and that patients with an elevated BMI experience greater levels of skin and joint disease activity (Figure 1).^2-5 Subsequently, concomitant weight loss and pharmacological interventions for the management of psoriatic disease activity are of increasing interest.¹ 

TOGETHER-PsA was conducted to evaluate ixekizumab + tirzepatide vs ixekizumab alone in patients with overweight/obesity and PsA.¹ Patients were randomized to receive either ixekizumab + individualized counseling for healthy diet and exercise or ixekizumab + tirzepatide + individualized counseling for healthy diet and exercise (Figure 2).¹ The primary endpoint was simultaneous achievement of ≥50% improvement in American College of Rheumatology response criteria (ACR50) and ≥10% weight loss at Week 36; key secondary endpoints included achievement of ACR50, ≥10% weight loss, and simultaneous achievement of ACR20 and ≥5% weight reduction.¹  

Key points 

• Obesity is a complex, multifactorial disease that is influenced by psychological, lifestyle and behavioral, environmental and social, and biological factors.^6,7 
• Studies indicate that obesity is associated with an increased prevalence of PsO, increased disease severity, and a greater risk of developing both PsO and PsA.^{2–5, 8–10}  
• Weight loss interventions, including dietary interventions, have been shown to improve disease activity in both PsO and PsA.^11–14  
• The European Alliance of Associations for Rheumatology (EULAR) and Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) recommendations for the treatment of PsA emphasize consideration and management of comorbidities, including obesity.^15,16 
• In the randomized, multicenter, open-label phase IIIb TOGETHER-PsA trial, a greater proportion of patients receiving ixekizumab + tirzepatide met the primary endpoint of simultaneous ACR50 and ≥10% weight loss at Week 36 vs ixekizumab alone (31.7% vs 0.8%; p < 0.001).¹ 
• Significantly greater rates of ACR50 and percentage change in body weight were observed in the ixekizumab + tirzepatide vs ixekizumab alone group from Week 4 onwards.¹ 
• A greater proportion of patients receiving ixekizumab + tirzepatide vs ixekizumab alone also met the secondary endpoints of ACR50 (33.5% vs 20.4% p < 0.05), ≥10% weight loss (84.5% vs 4.5%; p < 0.001), minimal disease activity (26.3% vs 15.3%; p < 0.05), ≥90% reduction from baseline in Psoriasis Area and Severity Index (PASI90; 52.2% vs 35.6%; p < 0.05), and Disease Activity in Psoriatic Arthritis (DAPSA) low disease activity/remission (39.9% vs 26.1%; p < 0.05).¹ 
• The safety profile of ixekizumab + tirzepatide was consistent with the established profiles of the individual drugs, with no new safety concerns reported.¹ 
• The most frequently reported adverse events (AEs) in the ixekizumab + tirzepatide group were nausea (29.7%), diarrhea (18.1%), constipation (16.7%), injection site reactions (15.2%), and vomiting (10.9%).¹ 
• Gastrointestinal AEs were more frequent in the ixekizumab + tirzepatide group vs the ixekizumab alone group.¹ 
• Together, the panel discussed the importance of individualized weight-loss interventions for psoriatic disease, emphasizing the importance of long-term consideration of treatment preferences, dietary and exercise education for both patient and physicians, and the effects of treatment on comorbidities. 

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