Taltz and Zepbound Combination Achieves Superior Results in Psoriasis and Obesity Trial

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 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 randomized, open-label TOGETHER-PsO study (ClinicalTrials.gov Identifier: NCT06588283) compared the safety and efficacy of ixekizumab administered concomitantly with tirzepatide vs ixekizumab alone in adults with moderate to severe plaque psoriasis and obesity or overweight with at least 1 weight-related comorbid condition. A total of 274 participants were randomized 1:1 to receive either Taltz alone or concomitantly with Zepbound, both administered subcutaneously. Patients in both arms received counseling on a reduced-calorie diet and increased physical activity.

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.

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.

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.

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.

Ixekizumab is approved under the brand name Taltz for the treatment of adults with moderate to severe plaque psoriasis. Tirzepatide, a glucose-dependent insulinotropic polypeptide receptor and glucagon-like peptide-1 receptor agonist, is marketed under the brand name Zepbound for use in combination with a reduced-calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in adults with obesity or adults with overweight in the presence of at least 1 weight-related comorbid condition.

The TOGETHER-PsO study results complement the findings recently reported in the TOGETHER-PsA study (ClinicalTrials.gov Identifier: NCT06588296), which showed that the concomitant use of ixekizumab and tirzepatide significantly improved outcomes in patients with psoriatic arthritis and obesity. Detailed 36-week results from TOGETHER-PsO will be published in a peer-reviewed journal and discussed with regulators.