Ixekizumab + Tirzepatide Improves Psoriasis, Reduces Weight in Those with Obesity

Concomitant use of ixekizumab and tirzepatide significantly improves rates of complete skin clearance in addition to meaningful weight loss in adults with moderate-to-severe plaque psoriasis and overweight or obesity, new data suggest, compared with ixekizumab alone.1

These data, published in JAMA and resulting from a phase 3b clinical trial conducted across 72 US sites, were authored by investigators such as Mark Lebwohl, MD, from the Icahn School of Medicine at Mount Sinai. The randomized, multicenter, open-label study included blinded assessors for psoriasis-specific evaluations.

Previous clinical trial data on patients with psoriatic arthritis (PsA) and overweight or obesity suggested concomitant ixekizumab and tirzepatide led to joint disease and quality of life improvements along with weight reductions.2

“In this article, we describe the TOGETHER-PsO trial, which evaluated the efficacy and safety of [ixekizumab] as concomitantly administered with [tirzepatide] compared with [ixekizumab] alone in participants with moderate to severe psoriasis and overweight or obesity,” Lebwohl and colleagues wrote.1

Trial Design and Findings on Ixekizumab + Tirzepatide

Investigators initiated the trial in September 2024, with the primary endpoint assessed at the 36-week mark on January 8, 2026. The team’s full 52-week analysis is slated to end in May 2026. Lebwohl et al set out to assess the combination regimen’s efficacy and safety in adult patients living with longstanding moderate-to-severe plaque psoriasis.

In order to qualify, those included were required to have had psoriasis for at least 6 months, showing a Static Physician Global Assessment (sPGA) score of at least 3. Additionally, they would be required to have a Psoriasis Area and Severity Index (PASI) score of 12 or more and involvement of1 0% body surface area (BSA) at minimum. They also had to meet criteria for either overweight or obesity, including those with body mass index (BMI) values between 27 - 30 accompanied by at least 1 weight-related comorbidity, or a BMI of 30 or greater.

Lebwohl and coauthors randomly assigned approved participants in a 1:1 ratio to be treated either with a subcutaneous ixekizumab injection plus tirzepatide or ixekizumab as a monotherapy. Their randomization of these individuals was stratified according to sex, previous exposure to advanced psoriasis medications, and BMI category.

Ixekizumab dosing consisted of 160 mg at baseline followed by 80 mg on an every-2-week basis through Week 12 and every 4 weeks thereafter. Tirzepatide use began at 2.5 mg weekly for the first month, with dose escalation taking place every 4 weeks in 2.5-mg increments until those evaluated saw a tolerated maintenance dose of 5 mg, 10 mg, or 15 mg by the 32-week mark.

In total, the investigative team randomized 274 participants. The cohort had a mean age of 45.6 years, and nearly 45% were women. Participants had a mean BMI of 39.2 and an average psoriasis disease duration of approximately 15 years. Mean baseline PASI score was 19.7. By week 36, 84.3% of enrolled participants had completed treatment.

In Lebwohl and coauthors’ primary endpoint analysis, they found 27.1% of subjects on the ixekizumab-tirzepatide combination treatment simultaneously saw complete skin clearance (PASI 100) and at least 10% dip in body weight. In contrast, only 5.8% of subjects treated with only ixekizumab met the same combined endpoint, representing a statistically significant difference.

Higher rates of PASI 100 attainment were seen in the combination arm overall, with the investigators noting 40.6% achieved complete clearance compared and 29.0% in the monotherapy arm. Additionally, Lebwohl et al found nearly 80% of patients on combination therapy saw PASI 75 scores alongside at least 5% reductions in weight. This was compared with fewer than 20% in the ixekizumab-only cohort. Rates of at least 10% weight loss were also shown to be significantly higher with the addition of tirzepatide.

The study’s safety results aligned with the established profiles of both medications, with gastrointestinal adverse events (AEs) and injection-site reactions found to be the most commonly reported treatment-emergent AEs. Lebwohl and colleagues noted gastrointestinal effects appeared more frequently in those treated with the combination regimen.

“Combined, the findings from this trial support the multifaceted health benefits of concomitant therapy with IXE and TZP for treating psoriasis and management of comorbidities and may help to inform future clinical practice and guideline recommendations for these patients,” they wrote.1

References

1. Lebwohl M, Blauvelt A, Kartman CE, et al. Ixekizumab With or Without Tirzepatide in Adults With Psoriasis and Overweight or Obesity: A Phase 3b Randomized Clinical Trial. JAMA Dermatol. Published online May 15, 2026. doi:10.1001/jamadermatol.2026.1753.

2. Garvey WT, Frias JP, Zhang XM, et al. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2023 Aug 19;402(10402):613-626. doi: 10.1016/S0140-6736(23)01200-X. Epub 2023 Jun 26. PMID: 37385275.