Ixekizumab, Tirzepatide Broaden Biomarker Effects in Psoriasis, Obesity

Concomitant treatment with ixekizumab (Taltz) and tirzepatide (Zepbound) was associated with broader changes in psoriasis-associated, immune, and metabolic biomarkers compared with ixekizumab alone in adults with psoriasis and obesity, according to new exploratory data from the phase 3b TOGETHER-PsO trial. The prespecified analysis was presented at the 2026 Fall Clinical Dermatology Conference in Las Vegas and announced by Eli Lilly and Company on October 9, 2026.

According to Lilly, approximately 61% of people with psoriasis in the US also have obesity or overweight with at least 1 weight-related comorbidity. The company stated the findings suggest an immunometabolic relationship between the 2 conditions, which are often managed through separate treatment approaches.

The new analysis builds on previously reported TOGETHER-PsO results. In those data, concomitant ixekizumab and tirzepatide delivered superior skin clearance and clinically meaningful weight reduction versus ixekizumab alone at the Week 36 primary endpoint, with improvements maintained or further improved through Week 52.

What Did the TOGETHER-PsO Biomarker Analysis Show?

TOGETHER-PsO (NCT06588283) is a 52-week, randomized, multicenter, assessor-blinded, open-label phase 3b study. The trial enrolled adults with moderate-to-severe plaque psoriasis and either obesity (body mass index [BMI] of 30 kg/m² or higher) or overweight (BMI of 27 to less than 30 kg/m²) with at least 1 additional weight-related comorbid condition. A total of 274 participants were randomized 1:1 to subcutaneous ixekizumab alone or in combination with tirzepatide, and patients in both arms received counseling on a reduced-calorie diet and increased physical activity. The primary endpoint was the proportion of participants achieving both Psoriasis Area and Severity Index (PASI) 100 and at least 10% weight reduction at Week 36.

The exploratory analysis evaluated circulating proteins and blood gene expression to characterize biological changes in each arm. At Week 36, changes in psoriasis-specific, immune, and metabolic biomarkers in both arms were consistent with the known effects of each medication in their approved indications.

Combination therapy was associated with broader biomarker responses beginning as early as Week 12, according to Lilly. By Week 36, 482 proteins were differentially expressed with the combination versus 140 with ixekizumab alone, and 467 genes were differentially expressed versus 16, respectively.

How Might Neutrophil Activity Explain Added Skin Clearance?

The analysis also showed greater reductions in inflammatory immune activity with combination therapy compared with ixekizumab monotherapy, including changes in neutrophil-related markers. Changes in a subset of neutrophil-associated markers mediated a portion of the additional PASI response observed with the combination versus ixekizumab alone.

James G. Krueger, MD, PhD, professor and laboratory head at The Rockefeller University, said the analysis offers new insight into the potentially connected immune and metabolic biology of psoriasis and obesity. He noted the most compelling finding was the identification of differences in inflammatory pathways when patients received concomitant treatment for both conditions, and highlighted immunometabolic health as an important area for continued research.

Mark Genovese, MD, senior vice president of Lilly Immunology development, said the broader biomarker changes, including those associated with skin clearance, may point to a meaningful relationship between immune and metabolic biology. Together with prior clinical outcomes, he said, the findings support a more comprehensive approach to psoriasis care addressing obesity in patients with both conditions.

Safety in the earlier TOGETHER-PsO results was consistent with the known profiles of each medication, according to Lilly.

Editor’s note: This summary has been edited for grammar and clarity using artificial intelligence tools.

References

1. 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 9, 2026. https://investor.lilly.com/news-releases/news-release-details/new-phase-3b-data-lillys-taltz-ixekizumab-and-zepbound-0.

2. A study of ixekizumab (LY2439821) and tirzepatide (LY3298176) in adults with moderate-to-severe plaque psoriasis and obesity or overweight (TOGETHER-PsO). ClinicalTrials.gov identifier: NCT06588283. Updated 2026. Accessed October 9, 2026. https://clinicaltrials.gov/study/NCT06588283.