Eli Lilly: Taltz plus Zepbound show broader immunometabolic biomarker changes in TOGETHER‑PsO
- 482 vs 140 differentially expressed proteins by Week 36 with Taltz+Zepbound vs Taltz alone.
- 467 vs 16 differentially expressed genes by Week 36 with combination therapy vs Taltz alone.
- 274 participants randomized 1:1 in the 52-week Phase 3b TOGETHER‑PsO trial; primary endpoint was PASI100 plus ≥10% weight loss at Week 36.
- Biomarker changes appeared as early as Week 12 and neutrophil-associated markers mediated part of the additional PASI response with combination therapy.
Overview
TOGETHER‑PsO is a 52‑week Phase 3b, randomized, multicenter, assessor‑blinded, open‑label trial in adults with moderate‑to‑severe plaque psoriasis and obesity or overweight plus at least one weight‑related comorbidity. A total of 274 participants were randomized 1:1 to receive Taltz (ixekizumab) alone or concomitantly with Zepbound (tirzepatide); both arms received lifestyle counseling. The trial’s primary endpoint was the proportion achieving PASI100 and ≥10% weight reduction at Week 36.
Biomarker and immune‑metabolic findings
Prespecified exploratory analyses of circulating proteins and blood gene expression showed broader changes with the combination vs Taltz monotherapy. By Week 36, the combination arm had 482 differentially expressed proteins versus 140 with Taltz alone, and 467 differentially expressed genes versus 16. Differences were evident as early as Week 12. The combination produced greater reductions in inflammatory immune activity, including changes related to neutrophils, and a subset of neutrophil‑associated markers mediated part of the additional PASI benefit.
Clinical context and implications
These biomarker shifts align with previously reported TOGETHER‑PsO clinical results showing superior skin clearance and meaningful weight reduction with the combination at Week 36, maintained or improved through Week 52. Investigators interpret the data as evidence of a connected immune and metabolic biology in patients with psoriasis and obesity and as rationale for further immunometabolic research and integrated treatment approaches.
Source: Lilly