Taltz Plus Zepbound Show Durable Year-One Efficacy in Psoriatic Disease

Eli Lilly and Company reported 52-week results from 2 phase 3b trials evaluating ixekizumab (Taltz; Eli Lilly) plus tirzepatide (Zepbound; Eli Lilly) (NCT06588283) compared with ixekizumab alone in adults with psoriatic disease and obesity or overweight (NCT06588296). In TOGETHER-PsO, 30.6% of patients receiving the combination achieved complete skin clearance plus at least 10% weight loss at week 52, compared with 4.4% receiving ixekizumab alone. In TOGETHER-PsA, 39.2% of combination-treated patients achieved an ACR50 response plus at least 10% weight loss, compared with 1.7% receiving monotherapy.¹

The findings build on statistically superior week 36 primary results previously reported from both trials. At week 52, improvements in disease activity and metabolic outcomes were maintained or further improved in prespecified exploratory analyses. According to Lilly, ixekizumab is the only biologic with data supporting a potential comprehensive treatment approach alongside an incretin therapy for patients with psoriasis or psoriatic arthritis and obesity or overweight. Tirzepatide is the only FDA-approved dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist obesity medication.¹

Approximately 61% of people with psoriasis and 65% of those with psoriatic arthritis also have obesity or overweight with at least 1 weight-related comorbidity, according to data cited by Lilly. Obesity and metabolic dysfunction may complicate treatment outcomes in patients with psoriatic disease.^1,2

TOGETHER-PsO and TOGETHER-PsA Trial Design

TOGETHER-PsO (NCT06588283) and TOGETHER-PsA (NCT06588296) are 52-week, randomized, multicenter, assessor-blinded, open-label phase 3b trials comparing concomitant ixekizumab and tirzepatide with ixekizumab alone.³,⁴ TOGETHER-PsO enrolled 274 adults with moderate to severe plaque psoriasis, and TOGETHER-PsA enrolled 271 adults with active psoriatic arthritis. Participants were randomized 1:1 to receive ixekizumab alone or ixekizumab plus tirzepatide, with all participants receiving counseling on a reduced-calorie diet and increased physical activity.

Eligible participants had a BMI of 30 kg/m² or greater, or a BMI of 27 kg/m² to less than 30 kg/m² with at least 1 weight-related comorbidity. Mean baseline BMI was 39.2 kg/m² in TOGETHER-PsO and 37.6 kg/m² in TOGETHER-PsA.

Week 52 Responses Build on Primary Results

At the week 36 primary endpoint, combination treatment demonstrated statistically superior improvements in disease activity and metabolic outcomes compared with ixekizumab alone in both trials. These improvements were maintained or further improved through week 52 in prespecified exploratory analyses conducted without multiplicity control.¹

At week 52 in TOGETHER-PsO, 30.6% of patients receiving combination treatment achieved PASI 100 plus at least 10% weight loss, compared with 4.4% receiving ixekizumab alone. In TOGETHER-PsA, 39.2% of combination-treated patients achieved ACR50 plus at least 10% weight loss, compared with 1.7% receiving ixekizumab alone.¹

Skin, Joint, and Metabolic Outcomes at One Year

Key secondary disease activity outcomes also favored combination treatment. In TOGETHER-PsO, 40.5% of patients receiving ixekizumab plus tirzepatide achieved complete skin clearance (PASI 100) at week 52, compared with 29.1% receiving ixekizumab alone. In TOGETHER-PsA, 43.7% of patients receiving combination treatment achieved ACR50 at week 52, compared with 15.7% receiving ixekizumab alone. Lilly noted that improvements in ACR50 were observed as early as week 4, before clinically meaningful weight loss occurred.¹

Combination treatment also led to deeper improvements in systemic inflammation over time in both trials, as measured by high-sensitivity C-reactive protein (hsCRP). Improvements in BMI, blood pressure, glucose, HbA1c, triglycerides, and total cholesterol with combination treatment compared with ixekizumab alone were sustained or further improved through week 52.¹

No New Safety Concerns Through Week 52

No new safety concerns were identified through 52 weeks. Adverse events with combination treatment were generally mild to moderate and consistent with the known safety profiles of each therapy. Adverse events reported in at least 5% of combination-treated participants in both trials included nausea, diarrhea, constipation, injection-site reactions, vomiting, dizziness, and headache.¹

Joseph F. Merola, MD, MMSc, dermatologist and rheumatologist and president of the Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network, said, “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.”¹

Merola added that the durability of complete skin clearance in psoriasis at 1 year, paired with continued metabolic improvements, demonstrates the potential of treating psoriatic disease and obesity concurrently.

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.¹

References

1. 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. News release. Eli Lilly and Company. 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. Armstrong A, 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.
3. A study of ixekizumab in combination with tirzepatide in participants with plaque psoriasis and obesity or overweight (TOGETHER-PsO). ClinicalTrials.gov. NCT06588283. Accessed August 31, 2026. https://clinicaltrials.gov/study/NCT06588283
4. A study of ixekizumab in combination with tirzepatide in participants with psoriatic arthritis and obesity or overweight (TOGETHER-PsA). ClinicalTrials.gov. NCT06588296. Accessed August 31, 2026. https://clinicaltrials.gov/study/NCT06588296