Adding Tirzepatide Improves PsA Control in Obesity: Philip Mease, MD

Adding tirzepatide (Zepbound) to ixekizumab (Taltz) improved psoriatic arthritis (PsA) disease control and weight in patients with obesity or overweight in the phase 3b TOGETHER-PsA trial.¹˒² Philip J. Mease, MD, director of rheumatology research at Providence Swedish Medical Center and clinical professor at the University of Washington School of Medicine, said addressing excess weight is becoming a core part of PsA management.

Mease, a coauthor, discussed the data presented at ACR Convergence 2026, held November 6-11, 2026, in Orlando, Florida. TOGETHER-PsA (NCT06588296) randomized adults with active PsA and a body mass index above 30, or 27 to under 30 with a weight-related comorbidity, to open-label ixekizumab plus tirzepatide (n = 138) or ixekizumab alone (n = 133), with dietary and exercise counseling in both arms.¹˒² Mease estimated 40% to 50% of patients with PsA have obesity and another 20% to 30% are overweight.

“So I think what is happening is that it is now becoming an imperative for us to engage with patients respectfully, ask permission to have a conversation about the role of excess weight in driving inflammation, driving disease severity, and then addressing it either with diet and exercise alone, or possibly with use of a pharmacotherapy,” Mease said.

At week 36, 31.7% of patients receiving combination therapy achieved the primary composite of ACR50 plus at least 10% weight reduction versus 0.8% with ixekizumab alone (P < .001), with significantly greater Disease Activity in Psoriatic Arthritis improvement from week 12 onward.¹ At week 52, ACR50 response reached 43.7% versus 15.7% (difference, 28.0%; 95% CI, 17.1%–38.9%; nominal P < .001), with nominal improvements in minimal disease activity, high-sensitivity C-reactive protein, physical function, weight, systolic blood pressure, triglycerides, and total cholesterol.²

Adverse events were mostly mild to moderate and consistent with each drug’s known profile, led by nausea, diarrhea, constipation, and injection-site reactions, with comparable discontinuation rates between arms.¹˒² Mease said rheumatologists can evaluate and treat obesity themselves or build teams with primary care, metabolic, and weight loss specialists, adding few patients take offense when the topic is raised respectfully. The trial was open label, and these congress data have not been peer reviewed.

Relevant disclosures include AbbVie, Acelyrin, Amgen, BMS, Century, Cullinan, Eli Lilly and Company, Inmagene, Johnson & Johnson Innovative Medicine, Moonlake, Novartis, Pfizer, Sana, Spyre, Takeda, and UCB.

References

1. Coates L, Mease P, Merola J, et al. Ixekizumab and concomitant tirzepatide achieved early disease control in adults with psoriatic arthritis and obesity/overweight: phase 3b TOGETHER-PsA trial. Abstract 2297. Presented at: ACR Convergence 2026; November 6-11, 2026; Orlando, FL.

2. Merola J, Kartman C, Fischer P, et al. Ixekizumab plus tirzepatide demonstrated greater disease control at 52 weeks versus ixekizumab alone with incremental improvement from week 36 in adults with psoriatic arthritis and overweight or obesity: results from a randomised clinical trial. Abstract 2942. Presented at: ACR Convergence 2026; November 6-11, 2026; Orlando, FL.