TOGETHER-PsO phase IIIb: Ixekizumab ± tirzepatide in adults with PsO and overweight/obesity

Results from the phase IIIb, randomized, open-label TOGETHER-PsO (NCT06588283) trial, evaluating ixekizumab ± tirzepatide in 274 adults with moderate-to-severe plaque psoriasis (PsO) and overweight or obesity, were published in JAMA Dermatology by Lebwohl et al. The primary endpoint was simultaneous achievement of 100% improvement from baseline in Psoriasis Activity and Severity Index (PASI100) and ≥10% weight reduction from baseline at Week 36. Key secondary endpoints included PASI100 rates, simultaneous achievement of 75% improvement from baseline in Psoriasis Activity and Severity Index (PASI75) and ≥5% weight reduction, and rates of ≥10% weight reduction at Week 36. 

Key data: At Week 36, 27.1% of patients receiving ixekizumab + tirzepatide (n = 138) vs 5.8% receiving ixekizumab alone (n = 136) simultaneously achieved PASI100 and ≥10% weight reduction (risk difference [RD], 21.2%; 95% confidence interval [CI], 12.8–29.7; p < 0.001). PASI100 was achieved by 40.6% vs 29.0% of patients receiving ixekizumab + tirzepatide vs ixekizumab alone (p = 0.04). Rates of simultaneous achievement of PASI75 and ≥5% weight reduction from baseline were 79.9% with ixekizumab + tirzepatide vs 17.9% with ixekizumab alone (p < 0.001), and 69.2% vs 9.1% experienced ≥10% weight reduction from baseline, respectively (p < 0.001). The most common adverse events (AEs) were gastrointestinal (GI) tract events and injection site reactions; GI AEs were more frequent with combination therapy. 

Key learning: In adults with moderate-to-severe psoriasis and overweight or obesity, ixekizumab + tirzepatide led to significant improvements in skin clearance and weight reduction, supporting integrated management of psoriasis and obesity as a potential new treatment approach.