TOGETHER-PsO Biomarker Analysis Examines Ixekizumab and Tirzepatide in Psoriasis With Obesity
Key Takeaways
- In TOGETHER-PsO, concomitant ixekizumab and tirzepatide treatment was associated with changes in more circulating proteins and blood-expressed genes than ixekizumab alone.
- At week 36, investigators identified 482 versus 140 differentially expressed proteins and 467 versus 16 differentially expressed genes in the combination and monotherapy groups, respectively.
- Exploratory analyses linked changes in neutrophil-associated markers to part of the additional PASI response; these associations do not establish causation.a
A prespecified exploratory analysis of the phase 3b TOGETHER-PsO trial found broader changes in circulating proteins and blood gene expression among adults receiving concomitant ixekizumab (Taltz; Eli Lilly) and tirzepatide (Zepbound; Eli Lilly) than among those receiving ixekizumab alone, according to findings presented at the 2026 Fall Clinical Dermatology Conference.1
The 52-week, randomized, multicenter, open-label, assessor-blinded study enrolled 274 adults with moderate-to-severe plaque psoriasis and obesity, or overweight with at least one additional weight-related comorbidity. Participants were assigned 1:1 to subcutaneous ixekizumab alone or ixekizumab plus tirzepatide. Both groups received dietary and physical activity counseling. The primary endpoint was the proportion achieving complete skin clearance (PASI 100) and at least 10% weight reduction at week 36.
Broader Molecular Changes Observed With Combination Treatment
According to the company, differences in molecular responses emerged by week 12. At week 36, investigators identified 482 differentially expressed proteins with concomitant treatment versus 140 with ixekizumab alone, along with 467 versus 16 differentially expressed genes, respectively. The analysis also found greater reductions in markers of inflammatory immune activity, including neutrophil-associated pathways, in the concomitant-treatment group.
An exploratory mediation analysis associated changes in a subset of neutrophil-related markers with a portion of the additional Psoriasis Area and Severity Index response observed with concomitant therapy. Previously reported trial findings favored concomitant treatment for the composite skin-clearance and weight-loss endpoint, with outcomes reportedly maintained or improved through week 52.
- Eli Lilly and Company. New Phase 3b data on Lilly’s Taltz (ixekizumab) and Zepbound (tirzepatide) advance understanding of the interconnected immune and metabolic biology in adults with psoriasis and obesity. Published October 9, 2026. Accessed October 14, 2026. https://investor.lilly.com/news-releases/news-release-details/new-phase-3b-data-lillys-taltz-ixekizumab-and-zepbound-0