Eli Lilly's Taltz-Zepbound Combo Improves Psoriasis, Arthritis, and Obesity Outcomes in Two Phase 3b Trials

Eli Lilly and Company announced results from two pivotal Phase 3b clinical trials demonstrating that the combination of Taltz (ixekizumab) and Zepbound (tirzepatide) significantly improved outcomes in patients with moderate-to-severe plaque psoriasis or active psoriatic arthritis and obesity, compared to Taltz alone.

In the TOGETHER-PsO open-label trial evaluating the concomitant use of Taltz and Zepbound versus Taltz alone for plaque psoriasis and obesity, 27.1% of patients in the combination arm achieved complete skin clearance (PASI 100) and at least 10% weight loss, compared to 5.8% in the monotherapy arm, meeting the primary endpoint. The combination therapy also yielded a 40% relative increase over Taltz alone in the proportion of patients achieving PASI 100 (40.6% vs. 29%).

In the TOGETHER-PsA trial, presented as a late-breaking study at the 2026 American Academy of Dermatology Annual Meeting and published in Arthritis & Rheumatology, the combination met the primary endpoint and all key secondary endpoints at 36 weeks, showing statistically significant superiority over Taltz monotherapy. A greater reduction in psoriatic arthritis disease activity (ACR50) was observed as early as Week 4 in the combination arm, before clinically meaningful weight loss occurred. The combination also led to a significant increase in patients achieving Minimal Disease Activity (MDA), along with improvements in fatigue, physical function, mental health-related quality of life, cardiometabolic health, and inflammation. Additional nominally significant improvements were seen in BMI, body weight, systolic blood pressure, glucose, HbA1c, triglycerides, and total cholesterol compared to Taltz alone.

The most common adverse events reported in the TOGETHER-PsO trial for the combination included nausea, diarrhea, constipation, injection site reaction, dosing error, vomiting, and dizziness; in the Taltz monotherapy arm, common events were injection site reaction, dosing error, and nasopharyngitis.

The TOGETHER-PsA trial targeted a patient population with a high disease burden: an average BMI of 37.6 kg/m², elevated psoriatic arthritis activity, impaired physical function, and over 60% having prior experience with advanced therapies. About 65% of adults with PsA in the U.S. also have obesity or overweight with at least one additional weight-related comorbidity, underscoring the need for integrated treatment strategies. 'In TOGETHER-PsA, treating PsA and obesity concurrently with Taltz and Zepbound yielded meaningful, broad improvements in PsA disease activity, inflammation, and outcomes that can impact patients' daily lives, such as fatigue, disability and quality of life,' said the lead investigator, who serves as Director of Rheumatology Research at Swedish Medical Center and Clinical Professor at the University of Washington, Seattle. 'These two chronic inflammatory diseases are often intertwined, with patients managing a substantial disease burden that remains difficult to treat. This clinical evidence supports a potential transformation in how we approach treatment for this patient population.'