Ixekizumab With Tirzepatide Achieved Greater Disease Control Than Ixekizumab Alone in Adults With Psoriatic Arthritis and Overweight or Obesity: Results From a Randomized Clinical Trial

Journal article

Objective: Overweight or obesity is prevalent in 72% to 82% of individuals with psoriatic arthritis (PsA). We assessed the efficacy and safety of ixekizumab (IXE) concomitantly administered with tirzepatide (TZP) compared with IXE alone in adult participants with active PsA and overweight with at least one weight‐related comorbidity or obesity. Methods: TOGETHER‐PsA (ClinicalTrials.gov identifier: NCT06588296) is a phase 3b, randomized, 52‐week trial in adults with active PsA and overweight (body mass index [BMI] ≥27 to <30) with at least one weight‐related comorbidity or obesity (BMI ≥30) using US‐approved doses for IXE and TZP. The primary end point was simultaneous achievement of 50% improvement in American College of Rheumatology response criteria (ACR50) and ≥10% weight reduction at 36 weeks. Key secondary outcomes included ACR50. Additional secondary outcomes and patient‐reported outcomes (PROs) were assessed. Safety was assessed as adverse events (AEs), treatment‐emergent AEs, and serious AEs. Results: A total of 271 participants were randomized (IXE + TZP, n = 138; IXE, n = 133). The primary end point was achieved with significant improvements in the IXE + TZP arm (31.7%) compared to IXE alone (0.8%) (P < 0.001). Greater improvements in ACR50 were demonstrated in IXE + TZP (33.5%) versus IXE alone (20.4%) (P = 0.02), with significant early separation at week 4 (nominal P < 0.05). IXE + TZP demonstrated nominally significant improvements in ACR20 (P < 0.001), minimal disease activity (P < 0.05), and absolute Psoriasis Area and Severity Index score (P < 0.01) compared to IXE alone. IXE + TZP demonstrated significant improvements in PROs, including Health Assessment Questionnaire–Disability Index (∆ −0.2; nominal P < 0.001) and Functional Assessment of Chronic Illness Therapy–Fatigue (improvement of 3.8; nominal P < 0.01) compared to IXE alone. Safety profiles were consistent with previous studies for each drug. Conclusion: Participants with active PsA and complex inflammatory‐metabolic disease achieved clinically meaningful improvement of PsA, physical function, weight reduction, and quality of life when treated with IXE + TZP compared to IXE alone, with no new safety concerns. image

Authors: Merola, JF; Mease, P; Kivitz, A; Sattar, N; Coates, LC

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wiley
• Journal: Arthritis & Rheumatology
• Article number: art.70134
• Publication date: 2026-03-28
• Acceptance date: 2026-03-13
• DOI: 10.1002/art.70134
• EISSN: 2326-5205
• ISSN: 2326-5191
• Language: English