As evidence of tirzepatide’s efficacy mounts across a range of cardiometabolic conditions, Eli Lilly has shown that taking the incretin medicine alongside another of its drugs, Taltz, could lead to better outcomes for patients living with both psoriatic arthritis (PsA) and obesity.
In an open-label phase 3b trial, the co-administration of Lilly’s IL-17A antagonist Taltz (ixekizumab) and dual GIP/GLP-1 receptor agonist Zepbound (tirzepatide) helped more patients achieve improvements in PsA activity and lose a certain percentage of body weight than Taltz alone, the company reported Thursday.
The trial, which enrolled adults with active PsA and obesity or overweight with at least one weight-related condition, met its primary and all secondary endpoints, Lilly said in a Jan. 8 press release. Detailed results from the trial will be presented at an upcoming medical meeting and shared with regulators, the company added.
The Indianapolis drugmaker estimates that 65% of adults with PsA in the U.S. also have obesity or are overweight with at least one weight-related comorbidity, demonstrating the “need for integrated treatment approaches that address the full burden of their diseases.”
After 36 weeks in Lilly’s Together-PsA study, 31.7% of patients receiving Taltz plus Zepbound achieved a 50% improvement in PsA activity on the American College of Rheumatology 50 (ACR50) clinical benchmark and lost at least 10% of their body weight, compared to just 0.8% of patients who received Taltz alone.
Apart from that primary endpoint win, Taltz plus Zepbound also charted a 64% relative increase over solo Taltz in the proportion of patients who achieved ACR50, Lilly said—this suggests that treatment with Zepbound for obesity or overweight “reduced the burden of PsA,” according to Lilly.
Adverse events recorded in the study’s Taltz and Zepbound arm were generally mild to moderate and on par with the known safety profile of each drug, Lilly said.
The company noted that patients enrolled in the trial had a high disease burden at baseline and that more than 60% had prior experience with one or more advanced therapies, reflecting difficulties in treating this particular patient population.
The study, which is set to run for a full year, enrolled 271 patients who were randomized 1:1 to receive either Taltz plus Zepbound or Taltz as a monotherapy. Patients in both arms of the trial also received counseling on adopting low-calorie diets and increasing physical activity.
“While treatment guidelines for psoriatic arthritis recommend management of obesity, the reality is these two chronic diseases are often addressed separately, and moving the needle in psoriatic arthritis has remained challenging,” UT Southwestern Medical Center’s Joseph Merola, M.D., said in Lilly’s announcement.
“The observed benefit with treatment using Taltz and Zepbound appears to meaningfully impact psoriatic disease activity, indicating that for many patients, PsA is an obesity-related condition,” he continued. “This integrated therapy approach represents a potential paradigm shift and could lead to better outcomes for those living with both diseases.”
Zepbound has done gangbusters for Lilly, especially in the U.S., where the company overtook its chief metabolic rival, Novo Nordisk, in terms of obesity market share last year. And while Lilly is increasingly focused on promising potential future assets in cardiometabolic disease—such as orforglipron and retatrutide—the company has continued efforts to expand Zepbound’s reach in parallel.
Following its initial obesity approval in late 2023, Zepbound in Dec. 2024 picked up its second indication in severe obstructive sleep apnea.
Separately, Lilly has turned out impressive data on the molecule in areas such as heart failure and metabolic dysfunction-associated steatohepatitis (MASH). Plus, the company expects to share topline results from its separate Together-PsO trial, looking at Zepbound plus Taltz in patients with obesity and plaque psoriasis, in the first half of 2026.
Elsewhere on the obesity front, Lilly is expecting the FDA to weigh in on its oral GLP-1 prospect orforglipron in 2026’s first quarter.