TOGETHER-PsO: Combination Therapy Shows Expanded Molecular Response by Week 12
Key Takeaways
TOGETHER-PsO data showed broader immune and metabolic biomarker changes with ixekizumab plus tirzepatide vs ixekizumab alone in adults with plaque psoriasis and obesity or overweight with a weight-related comorbidity.
At Week 36, combination treatment was associated with changes in 482 proteins and 467 genes, compared with 140 proteins and 16 genes with ixekizumab monotherapy.
Changes in neutrophil-associated inflammatory markers partially mediated the additional improvement in Psoriasis Area and Severity Index (PASI) response observed with combination therapy.
Eli Lilly and Company announced Phase 3 data from the TOGETHER-PsO trial indicating broader immune and metabolic biomarker changes with concomitant ixekizumab (Taltz) and tirzepatide (Zepbound) compared with ixekizumab alone in adults with moderate-to-severe plaque psoriasis and obesity or overweight with at least one weight-related comorbidity.
The prespecified analysis, presented at the 2026 Fall Clinical Dermatology Conference in Las Vegas, examined circulating proteins and blood gene expression to investigate potential connections between inflammatory and metabolic pathways in psoriasis.
Combination Therapy Associated With Broader Molecular Responses
At Week 36, combination therapy was associated with 482 differentially expressed proteins compared with 140 with ixekizumab monotherapy. Investigators also identified 467 differentially expressed genes in the combination group versus 16 in the monotherapy group. Broader biomarker responses were detectable as early as Week 12.
According to the manufacturer, the analysis additionally identified greater reductions in inflammatory immune activity with combination treatment, including changes involving neutrophil-associated pathways. According to Lilly, changes in a subset of these markers partially mediated the additional PASI response observed with combination therapy.
Previously reported TOGETHER-PsO findings showed superior skin clearance and weight reduction with combination treatment versus ixekizumab alone at Week 36. Improvements were maintained or increased through Week 52, with safety findings consistent with the known profiles of the individual medications.
The exploratory analysis did not establish a causal relationship between specific biomarker changes and clinical outcomes. Detailed statistical results and independent peer-reviewed validation were not provided in the announcement.
"These data at the intersection of psoriasis and obesity highlight immunometabolic health as an important area for continued scientific research," said James G. Krueger, MD, PhD, professor and laboratory head at The Rockefeller University, in the press release.
Source
Lilly press release. October 9, 2026.