Ixekizumab Plus Tirzepatide Improves PASI and Weight Loss in Psoriasis Study

Key Takeaways

• In a phase 3b trial, ixekizumab plus tirzepatide significantly improved simultaneous complete skin clearance and weight reduction compared with ixekizumab alone in adults with psoriasis and overweight or obesity.
• More than one-quarter of patients receiving combination therapy achieved both PASI 100 and at least 10% weight loss at week 36.
• Safety findings were consistent with known profiles of both agents, although gastrointestinal adverse events were more common with tirzepatide-containing therapy.

New research published online in JAMA Dermatology found that combining ixekizumab with tirzepatide significantly improved both psoriasis clearance and weight reduction in adults with moderate-to-severe plaque psoriasis and overweight or obesity.

The 52-week, open-label study enrolled 274 adults across 72 US sites. Participants had moderate-to-severe plaque psoriasis and either overweight with at least 1 weight-related comorbidity or obesity. Patients were randomized 1:1 to receive ixekizumab plus tirzepatide or ixekizumab alone, with both groups also receiving diet and exercise counseling.

At week 36, 27.1% of participants receiving combination therapy simultaneously achieved complete skin clearance, defined as a Psoriasis Area and Severity Index (PASI) 100 response, and at least 10% weight reduction, compared with 5.8% of those receiving ixekizumab alone (risk difference [RD], 21.2%; 95% CI, 12.8%-29.7%; P < 0.001).

Tirzepatide Combination Demonstrates Dual Benefit in Psoriasis and Weight Reduction

Investigators also reported higher PASI 100 response rates in the combination arm versus ixekizumab monotherapy (40.6% vs 29.0%; RD, 11.6%; 95% CI, 0.3%-22.9%; P = 0.04). In addition, 69.2% of patients receiving tirzepatide achieved at least 10% weight loss compared with 9.1% in the ixekizumab-alone group (RD, 60.0%; 95% CI, 50.4%-69.7%; P < 0.001).

The study population had a mean age of 45.6 years, a mean body mass index of 39.2, and mean psoriasis duration of 14.6 years. Overall, 84.3% of participants completed treatment through week 36.

Adverse events were consistent with established safety profiles for both therapies. The most frequently reported events included gastrointestinal adverse events and injection-site reactions, with gastrointestinal events occurring more commonly in the combo-treatment arm.

“The trial results suggest that concomitant ixekizumab and tirzepatide produced clinically meaningful, statistically significant improvements in skin clearance and reductions in weight in participants with moderate to severe psoriasis, with no new safety concerns,” the authors wrote.

Source

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