Eli Lilly and Company has reported positive topline results from its novel TOGETHER-PsA Phase 3b trial, demonstrating that the concomitant use of Taltz (ixekizumab) and Zepbound (tirzepatide) delivered superior outcomes compared with Taltz alone in adults with active psoriatic arthritis (PsA) who also have obesity or are overweight with at least one weight-related condition. The findings highlight the potential of an integrated treatment strategy that addresses both inflammatory disease and metabolic burden.
The open-label TOGETHER-PsA study is the first controlled clinical trial to evaluate an incretin-based therapy used alongside a biologic treatment for PsA. At 36 weeks, the combination of Taltz and Zepbound met the primary endpoint and all key secondary endpoints for superiority over Taltz monotherapy. The results are particularly significant given that an estimated 65% of adults with PsA in the United States also live with obesity or overweight, conditions known to worsen disease severity and complicate treatment outcomes.
In the primary endpoint analysis, 31.7% of patients receiving the combination therapy achieved both a 50% improvement in PsA disease activity, as measured by the American College of Rheumatology 50 (ACR50), and a weight reduction of at least 10%. In contrast, only 0.8% of patients treated with Taltz alone reached this combined outcome, a difference that was statistically significant (p<0.001). A key secondary endpoint showed that 33.5% of patients in the combination arm achieved ACR50, compared with 20.4% in the monotherapy arm, representing a 64% relative increase (p<0.05).
The trial enrolled patients with a high disease burden, including an average body mass index of 37.6 kg/m² and significant functional impairment at baseline. More than 60% of participants had previously been treated with one or more advanced therapies, underscoring the difficult-to-treat nature of the population.
Mark Genovese, M.D., senior vice president of Lilly Immunology development, said the study represents a major step forward in addressing the cumulative burden of PsA and obesity. He noted that the results demonstrate, for the first time in a controlled pharmacologic study, that treating obesity can meaningfully improve PsA disease measures when combined with a biologic therapy.
Safety findings were consistent with the known profiles of both medicines. Adverse events with the combination were generally mild to moderate, with the most common including nausea, diarrhea, constipation, and injection site reactions.
Experts believe the findings could signal a shift in PsA management. Joseph F. Merola, M.D., of UT Southwestern Medical Center, said the results suggest PsA may be an obesity-related condition for many patients, and that integrated therapy could lead to better outcomes.
Detailed data from the TOGETHER-PsA trial will be presented at an upcoming medical meeting, while results from the related TOGETHER-PsO psoriasis study are expected in the first half of 2026.