A first-of-its-kind Phase 3b study has shown that combining Eli Lilly’s Taltz (ixekizumab) with Zepbound (tirzepatide) delivers superior benefits for adults living with both active psoriatic arthritis (PsA) and obesity or overweight, compared with Taltz alone, announced Lilly last month.
The TOGETHER-PsA trial evaluated whether simultaneously treating joint inflammation and excess weight could meaningfully improve PsA outcomes. The 52-week, randomized, multicenter, assessor-blinded, open-label study enrolled 271 adults with active PsA and either obesity (BMI ≥30 kg/m²) or overweight (BMI 27–29.9 kg/m²) plus at least one weight-related comorbidity. Participants were randomized 1:1 to Taltz monotherapy or Taltz plus Zepbound; all received counseling on a reduced-calorie diet and increased physical activity.
At week 36, the combination arm met the primary endpoint: 31.7% of patients on Taltz plus Zepbound achieved both a 50% improvement in PsA signs and symptoms (ACR50) and at least 10% weight loss, versus just 0.8% on Taltz alone (p<.001). This dual-response endpoint underscores the trial’s focus on addressing PsA and obesity together rather than as separate conditions.
A key secondary endpoint further highlighted the clinical impact on joint disease. The combination regimen produced a 64% relative increase in the proportion of patients achieving ACR50 compared with Taltz monotherapy (33.5% vs. 20.4%, p<.05), supporting the concept that actively treating obesity with Zepbound can reduce PsA disease burden. The study population had high baseline disease activity and functional impairment, with an average BMI of 37.6 kg/m² and more than 60% having failed at least one advanced therapy, reflecting a difficult-to-treat cohort.
Safety findings were consistent with the known profiles of both agents. In the combination arm, adverse events were generally mild to moderate, most commonly nausea, diarrhea, constipation and injection site reactions. In the Taltz-only arm, injection site reactions and upper respiratory tract infections were most frequent.
Taltz, an IL-17A–blocking monoclonal antibody, is an established treatment for PsA and several spondyloarthritides, as well as plaque psoriasis. Zepbound, a dual GIP/GLP-1 receptor agonist, is approved for obesity management and for obesity-associated obstructive sleep apnea. TOGETHER-PsA is the first controlled pharmacologic study to show that targeted obesity treatment can improve PsA measures when added to a biologic.
Investigators and Lilly leaders describe the results as a potential paradigm shift toward integrated therapy for patients who live with both PsA and excess weight. Detailed 36-week data will be presented at an upcoming medical meeting, and related work is ongoing in TOGETHER-PsO, which is testing the same combination in adults with moderate to severe plaque psoriasis and obesity or overweight.
