Durable and Additive Disease Control at 52 Weeks With Ixekizumab Plus Tirzepatide Versus Ixekizumab Alone in Adults With Psoriatic Arthritis and Obesity or Overweight: Additional Results From a Randomized Clinical Trial

OBJECTIVE: Obesity or overweight occurs in 72% to 82% of individuals with psoriatic arthritis (PsA). Previous data revealed greater disease control with concomitant ixekizumab (IXE) and tirzepatide (TZP) versus IXE alone in adults with active PsA and obesity or overweight with at least one weight-related comorbidity at the week 36 primary end point. The objective of this report is to evaluate the effect of IXE+TZP versus IXE on psoriatic disease control and safety measures up to week 52. METHODS: TOGETHER-PsA (ClinicalTrials.gov ID NCT06588296) is a phase 3b, randomized, open-label, assessor-blinded 52-week trial. Participants were randomized 1:1 to IXE+TZP or IXE using US-approved doses. Week 52 outcomes were prespecified, non-multiplicity-controlled, and exploratory. Outcomes included 50% improvement in American College of Rheumatology response criteria (ACR50) and rheumatologic, dermatologic, patient-reported, metabolic, and safety outcomes. RESULTS: A total of 271 participants were randomized (IXE+TZP, n = 138; IXE, n = 133). The proportion achieving the primary outcome of simultaneous ACR50 and ≥10% weight reduction continued to increase from week 36 through week 52 for IXE+TZP (39.2%) versus IXE (1.7%) (Δ37.5%; P < 0.001). ACR50 continued to diverge after week 36, with a clinically meaningful difference at week 52 for IXE+TZP (43.7%) versus IXE (15.7%) (Δ 28.0%; P < 0.001). IXE+TZP demonstrated significant improvements in ACR20, minimal disease activity, Disease Activity Index for Psoriatic Arthritis, patient-reported outcomes, and metabolic outcomes versus IXE alone. Safety profiles were consistent with previous studies for each drug. CONCLUSION: Comprehensive improvements in disease activity, including ACR50, quality of life, weight, and metabolic outcomes, continued through week 52 and were greater with IXE+TZP than IXE alone, with no new safety concerns. These findings support concomitant IXE+TZP in patients with active PsA and immunometabolic disease.