In a first-of-its-kind clinical trial, Eli Lilly and Company has announced that combining Taltz (ixekizumab) and Zepbound (tirzepatide) dramatically outperformed Taltz alone for adults with moderate-to-severe plaque psoriasis who are also overweight or obese.

 

At 36 weeks, the TOGETHER-PsO Phase 3b trial hit its primary endpoint: 27.1% of patients on the combination therapy achieved complete skin clearance and ≥10% weight loss, compared to just 5.8% with Taltz alone.

 

On a key secondary measure, the combination made patients 40% more likely to reach PASI 100, with 40.6% hitting full skin clearance versus 29.0% for Taltz monotherapy.

 

“Psoriasis and obesity can profoundly impact how people feel, how they are seen, and how they live,” said Adrienne Brown, executive vice president and president, Lilly Immunology. 

 

“For people living at the intersection of these chronic inflammatory diseases, these PASI 100 results represent far more than a clinical milestone—they demonstrate what becomes possible when we address both simultaneously. Taltz has a decade of proven efficacy in psoriasis, and the superior outcomes achieved when Zepbound was used concomitantly for obesity signal a potential advance in treatment for patients who deserve nothing less.”

 

The trial targeted a patient population with high BMI and extensive skin involvement, averaging over 39 kg/m², with nearly all participants affected in high-impact areas such as the face, scalp, or genitals.

 

“Psoriasis and obesity share underlying inflammatory pathways, yet they are too often treated in silos despite psoriasis treatment guidelines calling for obesity management,” said Mark Lebwohl, Dean for Clinical Therapeutics at the Icahn School of Medicine at Mount Sinai, and TOGETHER-PsO principal investigator. 

 

“This study involved patients with particularly high BMI and difficult-to-treat psoriasis, making the PASI 100 results with Taltz plus Zepbound especially remarkable. The findings show that treating psoriasis and obesity or overweight at the same time significantly improved outcomes, reinforcing psoriasis as an obesity-related condition and supporting a potential comprehensive approach to care.”

 

Adverse events were mostly mild to moderate and aligned with known profiles of each drug. The most common effects with combination therapy included nausea, diarrhea, constipation, injection site reactions, and dizziness.