Lilly's Taltz and Zepbound combo shows broader biomarker changes

Eli Lilly and Company (NYSE: LLY) presented exploratory data from its TOGETHER-PsO Phase 3b clinical trial at the 2026 Fall Clinical Dermatology Conference in Las Vegas, showing that combining Taltz (ixekizumab) and Zepbound (tirzepatide) produced broader biomarker changes compared with Taltz alone in adults with moderate-to-severe plaque psoriasis and obesity.

The prespecified analysis examined circulating proteins and gene expression in the blood of patients treated with both drugs versus Taltz monotherapy. By Week 36, the combination was associated with changes in 482 differentially expressed proteins and 467 differentially expressed genes, compared with 140 proteins and 16 genes for Taltz alone. These differences were observed as early as Week 12.

The analysis also showed greater reductions in inflammatory immune activity with the combination, including changes related to neutrophils. Changes in a subset of neutrophil-associated markers were found to mediate a portion of the additional Psoriasis Area and Severity Index response seen with the combination versus Taltz alone.

"The broader biomarker changes observed with Taltz and Zepbound, including those associated with skin clearance, may point to a meaningful relationship between immune and metabolic biology," said Mark Genovese, M.D., senior vice president of Lilly Immunology development.

James G. Krueger, M.D., Ph.D., professor and laboratory head at Rockefeller University, said the findings identified differences in inflammatory pathways when patients received concomitant treatment, calling immunometabolic health "an important area for continued scientific research."

The TOGETHER-PsO trial enrolled 274 participants randomized 1:1 to receive Taltz alone or combined with Zepbound, both administered subcutaneously. Previously reported results from the trial showed the combination delivered superior skin clearance and clinically meaningful weight reduction compared with Taltz alone at the Week 36 primary endpoint, with improvements maintained or further improved through Week 52.

According to data cited in the press release, approximately 61% of people with psoriasis in the U.S. also have obesity or overweight with at least one weight-related comorbidity.

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