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Jump to Key Points At the 1-year mark, patients with moderate-to-severe psoriasis or psoriatic arthritis (PsA) treated with a combination of ixekizumab (Taltz), an interleukin-17A inhibitor, and tirzepatide (Zepbound), a GLP-1 inhibitor, showed marked improvements in disease activity compared to those who took ixekizumab alone in two phase 3b trials.
The 52-week results were announced on August 31 by Eli Lilly, the manufacturer of ixekizumab and tirzepatide (Zepbound), the GLP-1 inhibitor in the studies. The new data built on favorable results at 36 weeks reported earlier this year.
The two open-label, phase 3b clinical trials — TOGETHER-PsO and TOGETHER-PsA — evaluated the concomitant use of ixekizumab and tirzepatide compared with ixekizumab monotherapy. In addition to having psoriasis or PsA, adults in the trials also had obesity or overweight and had at least one additional weight-related comorbidity.
After 1 year, according to a press release from Eli Lilly, 30.6% of the patients with psoriasis in TOGETHER-PsO who took ixekizumab and tirzepatide achieved the primary outcome of 100% improvement in the Psoriasis Area Severity Index plus at least 10% weight loss compared with 4.4% among those on ixekizumab alone. In TOGETHER-PsA, 39.2% of patients with PsA taking the combination therapy achieved at least a 50% improvement in American College of Rheumatology response criteria plus at least 10% weight loss compared with 1.7% among those on ixekizumab monotherapy.
- 52-week combo: higher psoriasis/PsA response vs ixekizumab alone.
- PsO: 30.6% achieved PASI100 + ≥10% weight loss vs 4.4% monotherapy.
- PsA: 39.2% achieved ACR50 + ≥10% weight loss vs 1.7% monotherapy.
- Combo improved hs-CRP, BMI, BP, glucose, A1c, TG, total cholesterol.
- AEs mostly mild-moderate; nausea, diarrhea, constipation, injection-site reactions common.
In both trials, according to Eli Lilly, the combination therapy had beneficial effects on systemic inflammation as measured by high-sensitivity C-reactive protein, as well as improvements in BMI, blood pressure, glucose, A1c, triglycerides, and total cholesterol compared with ixekizumab monotherapy.
TOGETHER-PsA researchers enrolled 271 patients — 138 taking the combination therapy and 133 taking ixekizumab alone. Doses of ixekizumab were 80 mg monthly after a starting dose of 180 mg, and the tirzepatide dose was increased over time from 2.5 mg to 15 mg weekly.
TOGETHER-PsO enrolled 274 participants, who were randomly assigned in a 1:1 ratio to receive either ixekizumab alone or with tirzepatide. All participants received nutritional and physical activity counseling.
Adverse events in participants treated with ixekizumab and tirzepatide together were generally mild to moderate, according to the Eli Lilly release, and were consistent with known safety profiles. In the concomitant treatment arm in both trials, adverse events reported in ≥ 5% of participants included nausea, diarrhea, constipation, injection-site reactions, vomiting, dizziness, and headache.
TOGETHER-PsA’s 36-week results were reported in March, at the American Academy of Dermatology (AAD) 2026 Annual Meeting, by Joseph F. Merola, MD, professor and chair of dermatology, UT Southwestern Medical Center, Dallas. At the meeting, he said, “This represents an important paradigm shift as we think about how other combination therapies have not made a major dent in our ability to move [American College of Rheumatology 50] and other endpoints. We’re seeing clear improvement here.”
The studies were funded by Eli Lilly, which makes both tirzepatide and ixekizumab. Merola disclosed relationships with Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, AbbVie, Dermavant, Eli Lilly, Moonlake, Novartis, Janssen, Oruka, UCB, Sanofi, Regeneron, Sun Pharma, Galderma, and Pfizer.
Scott Harris has been covering dermatology and rheumatology for more than a decade. He lives near Washington, DC.
