Ixekizumab (Taltz) Plus Tirzepatide (Zepbound) Sustains Benefit at 1 Year in Psoriatic Disease

Eli Lilly and Company announced 52-week results from the phase 3b TOGETHER-PsO and TOGETHER-PsA trials showing that concomitant use of ixekizumab (Taltz) and tirzepatide (Zepbound) maintained or further improved disease activity, systemic inflammation, and metabolic outcomes compared with ixekizumab alone in adults with psoriatic disease and obesity, the company announced August 31, 2026.¹ At the week 36 primary endpoint reported previously, the combination showed statistically superior improvements in disease activity and metabolic outcomes compared with ixekizumab alone in both trials, and no new safety concerns were identified through week 52.¹

"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," said Mark Genovese, MD, senior vice president of Lilly Immunology Development, in a company press release.¹ "What's especially exciting now is seeing those improvements further deepened or sustained at one year, across disease activity, inflammation, and metabolic outcomes."

What did the week 52 data show?

In the TOGETHER-PsO (NCT06588283) trial, the primary outcome of complete skin clearance (Psoriasis Area Severity Index [PASI] 100) plus at least 10% weight loss was achieved by 30.6% of patients receiving ixekizumab and tirzepatide at week 52, compared with 4.4% receiving ixekizumab alone. Complete skin clearance alone was maintained in 40.5% of combination-treated patients versus 29.1% with ixekizumab alone.¹,²

In the TOGETHER-PsA (NCT06588296) trial, the primary outcome of at least 50% reduction in disease activity (American College of Rheumatology [ACR] 50) plus at least 10% weight loss was achieved by 39.2% of patients on the combination versus 1.7% on ixekizumab alone, and ACR50 response alone further increased to 43.7% with the combination compared with 15.7% for monotherapy.¹ Adverse events with the combination were generally mild to moderate and consistent with each medicine's known safety profile; those reported in at least 5% of participants included nausea, diarrhea, constipation, injection site reactions, vomiting, dizziness, and headache.¹

Why does obesity matter for psoriatic disease treatment?

In the United States, approximately 61% of people with psoriasis and 65% of people with psoriatic arthritis also have obesity or overweight with at least one weight-related comorbidity, which is often associated with poorer treatment outcomes.¹ Independent research has shown that obesity in psoriatic disease is linked to lower rates of remission and poorer treatment response, driven in part by proinflammatory properties of adipose tissue.³ At baseline, mean body mass index among trial participants was 39.2 in TOGETHER-PsO and 37.6 in TOGETHER-PsA.¹

What did the trials evaluate, and what did an outside expert say?

TOGETHER-PsO enrolled 274 adults with moderate-to-severe plaque psoriasis and TOGETHER-PsA enrolled 271 adults with active psoriatic arthritis. Both were 52-week, randomized, assessor-blinded, open-label phase 3b trials in which participants were randomized 1:1 to ixekizumab alone or concomitantly with tirzepatide, alongside counseling on a reduced-calorie diet and increased physical activity.¹

"In psoriatic arthritis, 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," said Joseph F. Merola, MD, MMSc, dermatologist, rheumatologist, president of the Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network (PPACMAN), co-president of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), and president of the Rheumatology-Dermatology Society, in the release.¹ "In psoriasis, the durability of complete skin clearance at one year represents real, lasting progress for patients."

What are the limitations?

Week 52 analyses were prespecified but exploratory, without multiplicity control, and comparisons between timepoints appear descriptive rather than formally tested. Detailed results have not yet been peer-reviewed or published, and both trials were open-label rather than blinded to treatment assignment.

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. Press release. Published August 31, 2026. Accessed August 31, 2026. https://investor.lilly.com/news-releases/news-release-details/new-phase-3b-data-lillys-taltz-ixekizumab-and-zepbound
2. ClinicalTrials.gov. Ixekizumab concomitantly administered with tirzepatide in adults with moderate-to-severe plaque psoriasis and obesity or overweight (TOGETHER-PsO). NCT06588283. Updated June 17, 2026. Accessed August 31, 2026. https://clinicaltrials.gov/study/NCT06588283
3. Haberman RH, Ogdie A, Merola JF, Scher JU, Eder L.. The obesity-inflammation axis in psoriatic disease: mechanisms and therapeutic strategies. Nat Rev Rheumatol. 2026;22(3):151-164. doi:10.1038/s41584-025-01326-6