Lilly's Zepbound enhances Taltz efficacy in psoriasis study

A study has shown that the efficacy of Eli Lilly's psoriasis therapy Taltz is improved when it is given in combination with the company's blockbuster weight-loss therapy Zepbound.

The first-of-its-kind TOGETHER-PsO study tested anti-IL-17 antibody Taltz (ixekizumab) with GIP/GLP-1 agonist Zepbound (tirzepatide) in adults with moderate-to-severe plaque psoriasis and obesity or overweight and at least one weight-related comorbid condition.

The results showed that when the two drugs were used together, a higher proportion of patients saw improvements in psoriasis disease-associated and metabolic biomarkers compared to those treated with Taltz alone, which Lilly said further supports the hypothesis of "an immunometabolic relationship between psoriasis and obesity."

In the US, approximately 61% of people with psoriasis also have obesity or are overweight with at least one weight-related comorbidity, according to Lilly. Some researchers think that the two conditions have a shared, low-grade chronic inflammatory state and endocrine dysfunction within fat tissue. Meanwhile, a higher body mass index (BMI) has been associated with reduced response rates to biologic therapies for psoriasis.

Earlier this year, Lilly reported other results from TOGETHER-PsO, which showed that the combination regimen was more effective than Taltz alone at reaching 100% skin clearance (a PASI 100 response) and a 10% reduction in body weight.

At 36 weeks, 27.1% of subjects treated with Taltz and Zepbound achieved those objectives, compared to 5.8% of the Taltz monotherapy group.

The new readout lends weight to the rationale of simultaneously targeting skin inflammation and obesity in psoriasis in order to improve clinical outcomes, providing evidence of a shift in the underlying disease process.

The latest analysis examined circulating proteins and gene expression in the blood to better understand the biological changes associated with dual treatment, including psoriasis-specific, immune, and metabolic biomarkers, and levels of certain immune cells (neutrophils).

"This analysis provides new insights into the potential connected immune and metabolic biology in people with psoriasis and obesity," said James Krueger, professor and laboratory head at The Rockefeller University.

"What is most compelling is these findings identified differences in inflammatory pathways when patients received concomitant treatment with Taltz plus Zepbound for both conditions," he added. "[This] data at the intersection of psoriasis and obesity highlight[s] immunometabolic health as an important area for continued scientific research."

Lilly said that the findings "support a more comprehensive approach to psoriasis care that also addresses obesity for people managing both conditions."