Phase 3b Data on Ixekizumab, Tirzepatide for Psoriasis and Overweight, With Mark Lebwohl, MD

New findings from the phase 3b TOGETHER-PsO trial suggest combining ixekizumab (Taltz) with tirzepatide (Zepbound) may significantly improve outcomes for patients with moderate-to-severe plaque psoriasis and obesity or overweight, according to Mark Lebwohl, MD, of the Icahn School of Medicine at Mount Sinai.1,2

The 52-week, randomized phase 3b TOGETHER-PsO trial evaluated ixekizumab alone versus ixekizumab combined with tirzepatide in 274 adults with psoriasis and obesity or overweight. By Week 36, investigators found 27.1% of patients receiving combination therapy achieved both complete skin clearance, defined as Psoriasis Area and Severity Index (PASI) 100, and at least 10% weight loss, compared with 5.8% of patients treated with ixekizumab alone (P < .001). Investigators also observed a 40% relative increase in PASI 100 responses with the combination regimen.

In an interview with HCPLive, Lebwohl said the findings reinforce growing recognition that psoriasis and obesity should not be managed separately, given their overlapping inflammatory pathways.

“We know that [for] obesity, the fat cells of obesity secrete cytokines that make psoriasis worse,” Lebwohl explained, noting patients with obesity often respond less effectively to biologic medications by themselves. According to Lebwohl, adding weight management therapy can improve biologic efficacy while simultaneously addressing broader health risks associated with obesity.

Lebwohl suggested the study may also influence dermatology practice patterns, predicting dermatologists will become increasingly comfortable prescribing anti-obesity medications directly for patients with inflammatory skin disease. He described monitoring requirements for incretin-based therapies as relatively straightforward and emphasized their potential benefits beyond weight reduction, including improvements in blood pressure, cholesterol, diabetes risk, and overall quality of life.

Lebwohl also pointed to related findings from the TOGETHER-PsA trial in psoriatic arthritis, where combination treatment similarly demonstrated stronger outcomes than biologic therapy alone. He noted weight loss interventions have increasingly become a core strategy when biologic treatments appear less effective in patients with obesity.

Overall, Lebwohl described the combination approach in his interview as a potentially important advancement in comprehensive psoriasis care, particularly for patients with obesity or overweight whose inflammatory disease may be amplified by metabolic dysfunction.

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. Accessed May 24, 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. Accessed May 24, 2026.