26 | CONCOMITANT THERAPY WITH IXEKIZUMAB PLUS TIRZEPATIDE IN ADULTS WITH PSORIATIC ARTHRITIS AND OVERWEIGHT OR OBESITY DEMONSTRATED SUPERIOR DISEASE CONTROL COMPARED TO IXEKIZUMAB ALONE: RESULTS FROM THE PH3B TOGETHER-PSA TRIAL

E. Filippi¹, J. F. Merola², P. Mease³, A. Kivitz⁴, N. Sattar⁵, L. C. Coates⁶, C. E. Kartman⁷, P. Fischer⁷, L. Sun⁷, A. Cardoso⁷, M. C. Genovese⁷, A. Ogdie⁸ | ¹Eli Lilly Italia S.p.A, Florence, Italy; ²Department of Dermatology and Department of Medicine, Division of Rheumatology, UT Southwestern Medical Center and O’Donnell School of Public Health, Dallas, TX, USA; ³Providence Swedish Medical Center, Seattle, WA, USA; ⁴Altoona Center for Clinical Research, Duncansville, PA, USA; ⁵School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK; ⁶Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK; ⁷Eli Lilly and Company, Indianapolis, IN, USA; ⁸Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

Background. Overweight and obesity occurs in 72-82%[1,2] of patients with psoriatic arthritis (PsA) and is associated with worse clinical outcomes and increased comorbidities[3]. We evaluated efficacy and safety of ixekizumab and tirzepatide (IXE+TZP) compared to ixekizumab (IXE) in adults with active PsA and overweight (BMI>27-<30 kg/m2) with ≥1 weight-related comorbidity or obesity (BMI≥30 kg/m2). Type of Study: TOGETHER-PsA (NCT06588296) is a Phase 3b, randomized, 52-week trial.
Methods. Participants were randomized 1:1 to IXE+TZP or IXE (open-label) using FDA-approved doses. Primary outcome was week 36 simultaneous achievement of ACR50 and ≥10% weight reduction. Key secondaries included ACR50.
Results. Of participants on IXE+TZP (n=138) and IXE (n=133), mean age was 55.0 years, 69.7% were female, BMI was 37.6 kg/m2, 71.6% had psoriasis, and 18.8% had failed ≥2 classes of advanced therapies. 31.7% participants achieved primary outcome with IXE+TZP versus 0.8% for IXE (p<0.001). A meaningful difference in ACR50 was observed in IXE+TZP (33.5%) versus IXE alone (20.4%) (multiplicity-controlled p=0.020) with a significant improvement (p<0.05) seen as early as week 4. Improvements were demonstrated in PASI 75/90/100 for IXE+TZP and IXE alone, with IXE+TZP demonstrating a significant difference in absolute PASI change from baseline (p<0.01). Significant improvements were observed in physical function (HAQ-DI; p<0.001), FACIT-fatigue (p<0.01), SF-36 MCS (p<0.05) and PCS (p<0.001). Adverse events (AEs) aligned with established drug profiles. Treatment discontinuations due to AEs were comparable among treatment groups.
Conclusions. Significant comprehensive improvement in disease activity was demonstrated with IXE+TZP compared to IXE alone in active PsA, with no new safety concerns.