Ixekizumab, Tirzepatide Effective Together for Psoriasis and Obesity or Overweight

New findings suggest, for adults with moderate-to-severe plaque psoriasis and obesity or overweight, combined ixekizumab (Taltz) and tirzepatide (Zepbound) treatment delivers significantly greater improvements in both skin clearance and weight reduction versus ixekizumab alone.1

This new release by Eli Lilly and Company on February 18 pointed to positive topline findings from the phase 3b TOGETHER-PsO trial, an open-label analysis evaluating the combined use of ixekizumab and tirzepatide versus ixekizumab alone. The data were seen as significant, as in the US, roughly 61% of those with psoriasis are impacted by obesity or overweight, accompanied by at least a single related comorbidity.2

"Psoriasis and obesity share underlying inflammatory pathways, yet they are too often treated in silos despite psoriasis treatment guidelines calling for obesity management," Mark Lebwohl, MD, dean for Clinical Therapeutics, professor and Chairman Emeritus of the Department of Dermatology at the Icahn School of Medicine at Mount Sinai, and TOGETHER-PsO principal investigator, said in a statement.1

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist indicated for those in need of chronic weight management. The medication promotes weight loss by diminishing one’s appetite and caloric intake and is US Food and Drug Administration (FDA) approved for use alongside a reduced-calorie diet and increased physical activity in adults with obesity, or in those who are overweight with at least a single weight-related comorbidity.

Ixekizumab is a monoclonal antibody designed to target interleukin (IL)-17A, blocking its interaction with the IL-17 receptor to diminish the inflammatory signaling seen in psoriasis. Building on prior positive data from the TOGETHER-PsA study, this medication is currently the only biologic supported by clinical research assessing its implementation in combination with an incretin-based therapy for those with psoriasis or psoriatic arthritis (PsA) who also have obesity or overweight.

In the TOGETHER-PsO study (NCT06588283), a 52-week, randomized, multicenter, assessor-blinded, open-label phase 3b analysis, investigators involved a total of 274 adults. These patients were randomized 1:1 to receive subcutaneous ixekizumab either alone or in combination with tirzepatide. All of those recruited were given guidance on calorie restriction and physical activity.

A body mass index (BMI) of at least 30 kg/m², or 27 to less than 30 kg/m² was required for eligibility, along with at least 1 weight-related comorbidity. The study’s main endpoint looked at the proportion of participants achieving complete skin clearance. The latter would be defined as Psoriasis Area and Severity Index (PASI) 100, together with at least 10% weight loss at the 36-week mark.

By the 36-week mark, the investigative team found 27.1% of patients on combination therapy were successful in attaining both PASI 100 and a minimum 10% reduction in weight.1 This was compared with only 5.8% of those treated with ixekizumab alone (P < .001), meeting the study’s primary endpoint. In a key secondary analysis, the team noted 40.6% of subjects in the combination cohort attained PASI 100 versus 29.0% in the monotherapy cohort, reflecting a 40% relative increase (P < .05).

Adverse events (AEs) with combination therapy were generally shown to be mild to moderate.1 They also aligned with the known safety profiles of each of these medications. AEs were observed in at least 5% of participants on both therapies included diarrhea, nausea, constipation, injection site reactions, vomiting, dosing errors, and dizziness. In the ixekizumab-only arm, the most frequent AEs were shown to be errors in dosing, injection site reactions, and nasopharyngitis.

In this release, Lilly noted the 36-week findings are expected to be published in a peer-reviewed journal and shared with regulatory authorities.

"This study involved patients with particularly high BMI and difficult-to-treat psoriasis, making the PASI 100 results with Taltz plus Zepbound especially remarkable,” Lebwohl said in his statement.1 “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."

References

1. Lilly's Taltz (ixekizumab) and Zepbound (tirzepatide) used together delivered superior efficacy in first-of-its-kind Phase 3b trial for adults with psoriasis and obesity or overweight. Eli Lilly. February 18, 2026. https://investor.lilly.com/news-releases/news-release-details/lillys-taltz-ixekizumab-and-zepbound-tirzepatide-used-together-0.

2. Armstrong et al, Addressing the Obesity-Psoriasis Connection: Prevalence, Incidence, and Comorbidity Insights from a Large US Population of 19.9 Million (2018-2024). Presented at Maui Derm, 2026.