Lilly’s Zepbound shows combo promise with Taltz in psoriasis

Eli Lilly and Co., announced positive results from the Phase IIIb TOGETHER-PsO study evaluating the co-administration of the IL-17A inhibitor Taltz (ixekizumab) and the dual GIP/GLP-1 receptor agonist Zepbound (tirzepatide) in patients with both moderate-to-severe plaque psoriasis and obesity. The trial met its primary endpoint, demonstrating that the combination therapy significantly improved skin clearance compared to Taltz alone, suggesting that treating metabolic comorbidities alongside the primary inflammatory condition may enhance clinical outcomes.

The TOGETHER-PsO study was a 52-week, randomized, multicenter, assessor-blinded, open-label Phase IIIb trial. The patient population consisted of 274 adults with moderate-to-severe plaque psoriasis and a high body mass index (BMI), with a mean baseline BMI exceeding 39 kg/m². Participants were randomized 1:1 to receive either Taltz alone or Taltz concomitantly with Zepbound, with both medications administered via subcutaneous injection. The primary endpoint was a composite measure requiring patients to achieve both complete skin clearance, defined as 100% improvement in the Psoriasis Area and Severity Index (PASI 100), and at least 10% weight reduction at week 36.

Data at the 36-week mark showed that 27.1% of participants in the combination arm met the dual primary endpoint, compared to only 5.8% in the Taltz monotherapy arm. In a key secondary analysis, 40.6% of patients receiving the combination reached PASI 100, representing a 40% relative increase over the 29.0% who achieved complete clearance with Taltz alone. Safety results were reported as consistent with the established profiles of both therapies.

Lilly stated that these results, alongside earlier positive data from the TOGETHER-PsA trial in psoriatic arthritis, position Taltz as the first biologic with data supporting a comprehensive treatment approach alongside an incretin therapy. Adrienne Brown, president of Lilly Immunology, remarked that the outcomes signal a “potential advance in treatment” for patients at the intersection of these diseases. The company intends to present full data at upcoming medical congresses and submit the findings to global regulatory authorities for discussion.

Research context

Psoriasis is a chronic immune-mediated inflammatory disease that is increasingly recognized as systemic in nature. Obesity is a common comorbidity and has been associated with greater disease severity and reduced responsiveness to biologic therapies.

Taltz is a monoclonal antibody targeting interleukin-17A (IL-17A), a key cytokine in the inflammatory cascade driving psoriasis. Zepbound acts as a dual agonist of the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, regulating appetite, metabolic function, and weight. Both drugs are approved by the US FDA for their respective primary indications of plaque psoriasis and chronic weight management.

Lilly is continuing to explore the broader cardiometabolic–immunology intersection across its pipeline, positioning tirzepatide not only as a weight-management therapy but as a potential disease-modifying adjunct in inflammatory conditions. If replicated and sustained in longer-term studies, these latest findings could influence future treatment algorithms, particularly for patients who fail to achieve complete skin clearance on biologic monotherapy.