Eli Lilly and Company has reported new exploratory data from the Phase 3b TOGETHER-PsO clinical trial evaluating the combined use of Taltz (ixekizumab) and Zepbound (tirzepatide) in adults with moderate-to-severe plaque psoriasis and obesity or overweight with at least one additional weight-related comorbidity. The findings suggest a potential relationship between immune and metabolic pathways in people living with both conditions.

It compared changes in circulating proteins and blood gene expression in patients receiving Taltz and Zepbound together with those receiving Taltz alone. The results showed broader changes in psoriasis-associated, immune and metabolic biomarkers with the combination treatment.

By Week 36, the combination group showed changes in 482 differentially expressed proteins and 467 differentially expressed genes, compared with 140 proteins and 16 genes in the Taltz monotherapy group. Differences in biomarker responses were observed as early as Week 12.

The analysis also identified greater reductions in inflammatory immune activity among patients receiving both medicines, including changes in pathways associated with neutrophils, immune cells involved in inflammation. Changes in a subset of neutrophil-associated markers accounted for part of the additional Psoriasis Area and Severity Index (PASI) response observed with the combination compared with Taltz alone.

According to Lilly, the findings provide further insights into the potential interaction between immune and metabolic biology in people with psoriasis and obesity. Mark Genovese, Senior Vice President of Lilly Immunology Development, said the broader biomarker changes, including those associated with skin clearance, could indicate a relationship between immune and metabolic processes.

The latest analysis follows previously reported TOGETHER-PsO results showing that the combination of Taltz and Zepbound achieved superior skin clearance and clinically meaningful weight reduction compared with Taltz alone at the Week 36 primary endpoint. Improvements were maintained or further improved through Week 52, while the safety profile remained consistent with the known profiles of the individual medicines.

TOGETHER-PsO (NCT06588283) is a 52-week, randomised, multicentre, assessor-blinded, open-label Phase 3b study involving 274 adults with moderate-to-severe plaque psoriasis and obesity, or overweight with at least one additional weight-related comorbidity. Participants were randomised in a 1:1 ratio to receive Taltz alone or Taltz alongside Zepbound. Both treatments were administered subcutaneously, and participants in both groups received counselling on a reduced-calorie diet and increased physical activity.

The primary endpoint assessed the proportion of participants achieving complete skin clearance, defined as PASI 100, alongside at least 10 percent weight reduction at Week 36.

The findings highlight immunometabolic health as an area for further research into the management of psoriasis and obesity. The reported biomarker results are exploratory and provide additional biological insights alongside the previously reported clinical outcomes.