A PHASE 3b randomised clinical trial has demonstrated that combining ixekizumab with tirzepatide significantly improves both skin clearance and weight reduction in adults with moderate-to-severe plaque psoriasis and overweight or obesity. The findings support a more integrated therapeutic approach targeting both inflammatory skin disease and metabolic comorbidity.
Psoriasis is closely associated with obesity, with previous estimates suggesting that 60–78% of patients are overweight or obese. Excess adiposity has been linked to increased disease severity, poorer treatment response, and worse cardiometabolic outcomes. Despite this, few clinical trials have explored simultaneous management of psoriasis and obesity.
In this multicentre, open-label Phase 3b study, 274 adults from 72 sites across the USA were randomised 1:1 to receive either ixekizumab plus tirzepatide or ixekizumab alone, alongside diet and exercise counselling. Participants had moderate-to-severe plaque psoriasis with either obesity or overweight plus at least one weight-related comorbidity. The primary endpoint at Week 36 was simultaneous achievement of complete skin clearance, defined as Psoriasis Area and Severity Index (PASI) 100, and ≥10% body weight reduction.
Significant Weight Loss Observed with Tirzepatide
The combination regimen met the primary endpoint with a marked advantage over ixekizumab monotherapy. At Week 36, 27.1% of participants receiving ixekizumab plus tirzepatide achieved both PASI 100 and ≥10% weight loss, compared with 5.8% in the ixekizumab-alone arm. Complete skin clearance alone was also higher in the combination group, achieved by 40.6% versus 29.0%, respectively.
Weight outcomes were particularly notable. A ≥10% reduction in body weight was observed in 69.2% of patients receiving tirzepatide in combination therapy, compared with 9.1% of those receiving ixekizumab alone. Additionally, nearly 80% of participants in the combination arm achieved PASI 75 alongside ≥5% weight loss.
Safety findings were consistent with the established profiles of both agents. Gastrointestinal adverse events occurred more frequently in the combination group, reflecting the known effects of tirzepatide, while injection-site reactions were also commonly reported. No new safety signals emerged.
Findings Support a New Approach to Difficult-to-Treat Psoriasis
The authors concluded that concomitant treatment with ixekizumab and tirzepatide may represent a promising strategy for difficult-to-treat psoriasis in patients with obesity, potentially improving dermatological and cardiometabolic outcomes simultaneously.
Reference
Lebwohl M et al. Ixekizumab with or without tirzepatide in adults with psoriasis and overweight or obesity: a phase 3b randomized clinical trial. JAMA Dermatol. 2026;DOI: 10.1001/jamadermatol.2026.1753.
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