Taking ixekizumab and tirzepatide together results in higher rates of skin clearance and weight loss compared with ixekizumab alone in patients with psoriasis and overweight or obesity, who represent a population that is difficult to treat, according to the phase IIIb TOGETHER-PsO trial.
At week 36, 27.1 percent of patients who received ixekizumab plus tirzepatide simultaneously achieved complete skin clearance (Psoriasis Activity and Severity Index [PASI] 100) and a ≥10-percent weight reduction—the primary endpoint—as opposed to only 5.8 percent of those who received ixekizumab alone (risk difference [RD], 21.2 percent, 95 percent confidence interval [CI], 12.8–29.7; p<0.001). [JAMA Dermatol 2026;doi:10.1001/jamadermatol.2026.1753]
Similarly, more patients treated with ixekizumab plus tirzepatide vs ixekizumab alone met the clinically meaningful response of a ≥75-percent improvement in PASI and ≥5-percent weight reduction (79.9 percent vs 17.9 percent; RD, 62 percent, 95 percent CI, 51.7–72.2; p<0.001), achieved complete skin clearance (40.6 percent vs 29 percent; RD, 11.6 percent, 95 percent CI, 0.3–22.9; p=0.04), and experienced ≥10-percent weight loss (69.2 percent vs 9.1 percent; RD, 60 percent, 95 percent CI, 50.4–69.7; p<0.001).
The therapeutic advantage of concomitant ixekizumab and tirzepatide use over ixekizumab monotherapy in terms of achieving complete skin clearance occurred as early as week 24, noted the investigators. Furthermore, ixekizumab plus tirzepatide was associated with significant weight reduction through week 36 and improvements in cardiometabolic parameters, such as systolic and diastolic blood pressure, total cholesterol levels, triglyceride levels, and haemoglobin A1c levels.
A higher proportion of patients in the ixekizumab plus tirzepatide arm than in the ixekizumab arm had Static Physician Global Assessment (sPGA) and Dermatology Life Quality Index (DLQI) scores of 0-1.
As for safety, “adverse events were generally consistent with established drug safety profiles, the most common being gastrointestinal tract events and injection site reactions. Gastrointestinal tract events occurred more frequently with ixekizumab plus tirzepatide vs ixekizumab,” according to the investigators.
“Collectively, these findings support elevating the standard of care from treating psoriasis in isolation to a therapeutic approach that addresses the immunologic and metabolic (especially obesity) components of psoriasis-associated inflammation with ixekizumab plus tirzepatide,” they said.
The data complement the findings from the TOGETHER-PsA trial, which showed clinically meaningful improvements in psoriatic arthritis, physical function, and quality of life, as well as substantial reductions in weight with ixekizumab plus tirzepatide vs ixekizumab alone. [Arthritis Rheumatol 2026;doi:10.1002/art.70134]
“In the context of current guidelines, to our knowledge, TOGETHER-PsO and TOGETHER-PsA provide the first randomized clinical evidence to further support addressing comorbidities, such as overweight or obesity, in treating psoriatic disease, providing benefits on metabolic and inflammatory disease outcomes,” the investigators said.
Conducted at 72 sites in the US, TOGETHER-PsO included 274 adult patients (mean age 45.6 years, 44.9 percent female) with moderate to severe plaque psoriasis who had overweight with ≥1 weight-related comorbidities or obesity. These patients were randomly assigned to receive treatment with ixekizumab plus tirzepatide (n=138) or ixekizumab alone (n=136) as adjunct to diet and exercise.
The mean BMI at baseline was 39.2 kg/m2, and the mean duration of psoriasis was 14.6 years. A total of 231 patients (84.3 percent) completed the treatment through week 36.