Lilly says Taltz plus Zepbound shifted more biomarkers than Taltz alone in psoriasis-obesity trial

Eli Lilly said an exploratory analysis from its TOGETHER-PsO Phase 3b trial found that Taltz (ixekizumab) plus Zepbound (tirzepatide) changed more blood proteins and genes than Taltz alone in adults with moderate-to-severe plaque psoriasis and obesity or overweight ^[1]. The data were presented October 9, 2026, at the Fall Clinical Dermatology Conference in Las Vegas ^[1][3].

By week 36, the combination was associated with changes in 482 differentially expressed proteins, compared with 140 for Taltz alone, and 467 differentially expressed genes, compared with 16 for Taltz alone ^[1][2]. Lilly said the broader biomarker responses appeared as early as week 12 ^[1]. The analysis examined circulating proteins and gene expression in the blood ^[1].

The release said reductions in inflammatory immune activity were greater with the combination than with Taltz alone, including changes related to neutrophils, a type of immune cell involved in inflammation ^[1]. Changes in a subset of neutrophil-associated markers "mediated a portion of" the additional Psoriasis Area and Severity Index (PASI) response seen with the combination, according to the release ^[1]. PASI is a scale used to measure the severity and extent of psoriasis.

"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 ^[1].

James G. Krueger, M.D., Ph.D., of The Rockefeller University, said in the release that the findings "identified differences in inflammatory pathways when patients received concomitant treatment with Taltz plus Zepbound for both conditions" ^[1].

The new analysis did not report clinical symptom outcomes for the comparison. It focused on biomarkers, and Lilly said the changes seen in both treatment arms were consistent with the known biological effects of each medicine when used for its approved indications ^[1]. The release referred to previously reported TOGETHER-PsO results, which Lilly said showed superior skin clearance and clinically meaningful weight reduction with the combination compared with Taltz alone at the week 36 primary endpoint, maintained or further improved through week 52, with safety consistent with the known profile of each medicine ^[1]. Specific numbers from those earlier clinical results were not included in this release.

TOGETHER-PsO (NCT06588283) is a 52-week, randomized, multicenter, assessor-blinded, open-label Phase 3b study ^[1][2]. A total of 274 participants were randomized 1:1 to receive Taltz alone or Taltz with Zepbound, both given as subcutaneous injections, and patients in both arms received counseling on a reduced-calorie diet and increased physical activity ^[1]. Participants had moderate-to-severe plaque psoriasis plus obesity or overweight (BMI of 30 or higher, or 27 to under 30 with at least one additional weight-related condition) ^[1]. The primary endpoint is the proportion of participants achieving both PASI 100 and at least 10% weight reduction at week 36 ^[1]. Lilly said about 61% of people with psoriasis in the U.S. also have obesity or overweight with at least one weight-related comorbidity ^[1].

Why it matters for patients

Taltz is approved to treat moderate-to-severe plaque psoriasis in people 6 and older, active psoriatic arthritis, active ankylosing spondylitis, and active non-radiographic axial spondyloarthritis with objective signs of inflammation ^[1]. Zepbound is approved for adults with obesity or some adults with overweight plus a weight-related medical problem, and for moderate-to-severe obstructive sleep apnea with obesity ^[1][2]. Whether the two drugs will be reviewed or approved as a combined regimen for psoriasis and obesity has not been reported.

Biomarker changes are laboratory measurements of proteins and gene activity, not measures of how patients feel or how their skin looks. This analysis did not report new symptom or skin-clearance outcomes, so it does not show whether people on the combination did better on those measures than people on Taltz alone ^[1].

Both medicines carry warnings. Taltz affects the immune system and may raise the risk of infections, including tuberculosis; serious skin reactions and new or worsening Crohn's disease or ulcerative colitis can also occur ^[1]. Zepbound carries a boxed warning about thyroid C-cell tumors in animals and warnings that include severe stomach problems, gallbladder problems, pancreatitis, and low blood sugar when used with insulin or a sulfonylurea ^[2]. Lilly said safety in the trial was consistent with the known profile of each medicine ^[1].

What happens next

TOGETHER-PsO is a 52-week study ^[1]. Lilly cited week 52 results as previously reported, but has not disclosed whether it plans to seek approval for Taltz and Zepbound used together, and no filing or regulatory decision dates have been announced ^[1]. The biomarker analysis was prespecified and described as exploratory ^[1].