Eli Lilly and Company announced positive topline results from the landmark TOGETHER-PsO open-label Phase 3b clinical trial evaluating the concomitant use of Taltz (ixekizumab) and Zepbound (tirzepatide) compared to Taltz alone in adults with moderate-to-severe plaque psoriasis and obesity or overweight with at least one additional weight-related comorbid condition. At 36 weeks, treatment with Taltz and Zepbound met the primary and all key secondary endpoints, delivering superior skin clearance and weight loss versus Taltz monotherapy. In the U.S., approximately 61% of people with psoriasis also have obesity or overweight with at least one weight-related comorbidity, highlighting a need for comprehensive treatment approaches that address the full burden of their diseases.
In the first-of-its-kind TOGETHER-PsO study, 27.1% of participants receiving Taltz and Zepbound reached complete skin clearance (Psoriasis Area Severity Index (PASI) 100) and at least 10% weight loss, compared to 5.8% of patients treated with Taltz alone, meeting the primary endpoint (p<0.001). In a key secondary endpoint, Taltz plus Zepbound delivered a 40% relative increase over Taltz monotherapy in the proportion of patients who achieved PASI 100 (40.6% of patients vs. 29.0%, respectively, p<0.05), demonstrating that treatment of obesity or overweight with Zepbound reduced the burden of psoriasis.
The study enrolled a population with a very high burden of disease that is often associated with poorer treatment outcomes, with an average BMI of more than 39 kg/m2 across both treatment arms. This reflects a mean BMI of approximately 9-10 kg/m2 higher than any population studied to date in Phase 3 pivotal trials of a psoriasis biologic. An increase in BMI has been shown to reduce the odds of reaching skin clearance across multiple psoriasis studies. Most patients in the TOGETHER-PsO trial had extensive skin involvement, with approximately 25% of their body surface area affected, and nearly all (97%) had psoriasis affecting high-impact body areas linked to significant morbidity, itch, and skin pain, such as the face, scalp or genitals.
"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."
Adverse events in participants treated with concomitant administration of Taltz and Zepbound were generally mild to moderate, and the types of adverse events were generally consistent with the known safety profile of each medicine. The most common adverse events occurring in ≥5% of participants were nausea, diarrhea, constipation, injection site reaction, dosing error, vomiting, and dizziness in the Taltz and Zepbound concomitant treatment arm, and injection site reaction, dosing error, and nasopharyngitis in the Taltz monotherapy arm.
"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, M.D., Dean for Clinical Therapeutics, and Professor and Chairman Emeritus of the Department of Dermatology 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."
Taltz is a monoclonal antibody that selectively binds with interleukin 17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. Building on positive topline data from the TOGETHER-PsA study, it is now the only biologic with data supporting a comprehensive treatment approach alongside an incretin therapy for people with psoriasis or psoriatic arthritis who also have obesity or overweight. Zepbound is the only FDA-approved dual GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptor agonist obesity management medication.
Detailed 36-week results from TOGETHER-PsO will be published in a peer-reviewed journal and discussed with regulators.
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