Ixekizumab-Tirzepatide Sustains 1-Year Gains in Psoriatic Disease, Obesity

Eli Lilly and Company has reported 52-week results from the phase 3b TOGETHER-PsO and TOGETHER-PsA trials, showing sustained or further improved psoriasis and psoriatic arthritis (PsA) disease activity, systemic inflammation and metabolic outcomes with concomitant ixekizumab (Taltz) and tirzepatide (Zepbound) versus ixekizumab alone in adults with psoriatic disease and obesity or overweight.¹

The 52-week data build on the Week 36 primary endpoint results, when the combination showed statistically superior improvements in disease activity and metabolic outcomes versus ixekizumab alone in both trials.¹ Obesity or overweight with an additional weight-related comorbidity affects an estimated 61% of people with psoriasis and 65% of people with PsA and is independently associated with poorer response to biologic therapy.¹,² Baseline body mass index (BMI) averaged 39.2 in TOGETHER-PsO and 37.6 in TOGETHER-PsA.¹

"The primary results from these first-of-their-kind studies were already remarkable, showing that Taltz and Zepbound used together improved outcomes for patients with psoriatic disease and obesity," Mark Genovese, MD, senior vice president of Lilly Immunology development, said in a statement.¹ "What's especially exciting now is seeing those improvements further deepened or sustained at one year, across disease activity, inflammation and metabolic outcomes."

Ixekizumab-Tirzepatide Efficacy in TOGETHER-PsO and TOGETHER-PsA

TOGETHER-PsO (NCT06588283) and TOGETHER-PsA (NCT06588296) are 52-week, phase 3b, randomized, multicenter, assessor-blinded, open-label trials comparing concomitant ixekizumab and tirzepatide with ixekizumab alone in adults with psoriatic disease and obesity or overweight plus at least 1 weight-related comorbidity.¹ TOGETHER-PsO enrolled 274 adults with moderate-to-severe plaque psoriasis and TOGETHER-PsA enrolled 271 adults with active PsA.¹ Participants were randomized 1:1 to subcutaneous ixekizumab alone or combined with subcutaneous tirzepatide, alongside counseling on a reduced-calorie diet and increased physical activity, and enrollment required a BMI of 30 kg/m² or higher, or 27 kg/m² to less than 30 kg/m² with 1 additional weight-related comorbidity.¹

At Week 52, ixekizumab plus tirzepatide produced the primary multi-component outcome of PASI 100 plus at least 10% weight loss in 30.6% of patients with psoriasis, versus 4.4% with ixekizumab alone.¹ In TOGETHER-PsA, 39.2% of patients receiving combination treatment achieved the primary outcome of ACR50 plus at least 10% weight loss at Week 52, versus 1.7% with ixekizumab monotherapy.¹ Both results improved from the Week 36 primary analysis, when the combination already showed statistically superior outcomes versus ixekizumab alone in each trial.¹

Ixekizumab-Tirzepatide Secondary Endpoints and Safety Profile

Complete skin clearance (PASI 100) was maintained in 40.5% of patients receiving ixekizumab plus tirzepatide in TOGETHER-PsO at Week 52, versus 29.1% with ixekizumab alone.¹ In TOGETHER-PsA, the proportion of patients achieving ACR50 with combination treatment increased to 43.7% at Week 52, versus 15.7% with ixekizumab monotherapy, building on separation seen as early as Week 4, before clinically meaningful weight loss occurred.¹ Combination treatment also produced deeper improvements in systemic inflammation over time in both trials, as measured by high-sensitivity C-reactive protein (hsCRP).¹

Improvements in BMI, blood pressure, glucose, HbA1c, triglycerides and total cholesterol with ixekizumab plus tirzepatide versus ixekizumab alone were sustained or further improved through 1 year.¹ Lilly reported adverse events with combination treatment were generally mild to moderate and consistent with the known safety profile of each medicine, with no new safety concerns identified.¹ In the concomitant treatment arm of both trials, adverse events reported in 5% or more of participants included nausea, diarrhea, constipation, injection site reactions, vomiting, dizziness and headache.¹

"Psoriatic disease is often accompanied by obesity or overweight, which can make treatment goals related to the skin and joints harder to reach," Joseph F. Merola, MD, MMSc, dermatologist and rheumatologist, president of the Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network, co-president of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis, and president of the Rheumatology-Dermatology Society, said in a statement.¹ "In PsA, the greater improvements in disease activity seen with Taltz and Zepbound in the first month, before clinically meaningful weight loss occurred, continued through one year. In psoriasis, the durability of complete skin clearance at one year represents real, lasting progress for patients."

Detailed 52-week results from TOGETHER-PsO and TOGETHER-PsA are expected to be presented at future medical meetings and published in peer-reviewed journals, according to Lilly.¹ Ixekizumab is separately approved for adults with active PsA and for adults and children 6 years and older with moderate-to-severe plaque psoriasis, while tirzepatide is approved for chronic weight management and, separately, for moderate-to-severe obstructive sleep apnea with obesity.¹

References

1. Eli Lilly and Company. New Phase 3b data on Lilly's Taltz (ixekizumab) and Zepbound (tirzepatide) used together showed improved and durable efficacy at one year in adults with psoriatic disease and obesity. Published August 31, 2026. Accessed September 3, 2026. https://www.prnewswire.com/news-releases/new-phase-3b-data-on-lillys-taltz-ixekizumab-and-zepbound-tirzepatide-used-together-showed-improved-and-durable-efficacy-at-one-year-in-adults-with-psoriatic-disease-and-obesity-302864391.html.

2. Enos CW, et al. Comorbid obesity and history of diabetes are independently associated with poorer treatment response to biologics at 6 months: a prospective analysis in Corrona Psoriasis Registry. J Am Acad Dermatol. 2022;86(1):68-76.