Eli Lilly Trial Shows Superior Outcomes with Ixekizumab and Tirzepatide in Patients with PsA and Obesity

Eli Lilly and Company has announced positive topline results from the TOGETHER-PsA trial, a first-of-its-kind phase 3b study evaluating the concomitant use of the IL-17A inhibitor ixekizumab (Taltz) and the dual GIP/GLP-1 receptor agonist tirzepatide (Zepbound) in adults with active psoriatic arthritis (PsA) who also have obesity or overweight with at least 1 weight-related comorbidity.¹ These new results suggest that an integrated pharmacologic approach targeting both inflammatory disease activity and excess body weight can deliver superior clinical outcomes compared with biologic therapy alone.

Background

Psoriatic arthritis is a chronic, immune-mediated inflammatory disease associated with progressive joint damage, functional impairment, and a substantial burden of comorbidities. Obesity is highly prevalent among patients with PsA, affecting an estimated 65% of adults in the United States, and is increasingly recognized as a modifier of disease severity, treatment response, and long-term outcomes.² Despite guideline recommendations to address obesity in PsA management, weight reduction and inflammatory control are typically treated separately in clinical practice.

Ixekizumab is a monoclonal antibody that selectively inhibits interleukin-17A, a key cytokine involved in psoriatic inflammation, and is approved for the treatment of PsA, plaque psoriasis, and axial spondyloarthritis. Tirzepatide is the only FDA-approved dual GIP and GLP-1 receptor agonist for obesity management and has demonstrated robust and sustained weight loss across multiple clinical programs.

Study Design

TOGETHER-PsA was designed to directly test whether concomitant pharmacologic treatment of obesity could enhance PsA outcomes. The 52-week, randomized, multicenter, assessor-blinded, open-label study enrolled 271 adult patients with active PsA and a body mass index (BMI) ≥30 kg/m², or BMI 27–29.9 kg/m² with at least 1 weight-related comorbidity. Participants were randomized 1:1 to receive subcutaneous ixekizumab alone or in combination with tirzepatide. All patients received standardized counseling on a reduced-calorie diet and increased physical activity, ensuring that observed differences reflected pharmacologic effects.

Results

At the 36-week analysis, the study met its primary endpoint, defined as the proportion of participants achieving both a 50% improvement in PsA disease activity, measured by the American College of Rheumatology 50 (ACR50) response, and at least 10% body weight reduction. In the combination arm, 31.7% of patients met this composite endpoint, compared with only 0.8% of patients treated with ixekizumab monotherapy (p < 0.001).

Key secondary endpoints further supported the superiority of the combination regimen. Notably, 33.5% of patients receiving ixekizumab plus tirzepatide achieved an ACR50 response at week 36, compared with 20.4% in the ixekizumab arm, representing a 64% relative increase in response rate (p < 0.05). This improvement in joint and systemic inflammation occurred in a population with high baseline disease burden, including high disease activity, meaningful functional impairment, and an average BMI of 37.6 kg/m². More than 60% of participants had previously been treated with one or more advanced therapies, underscoring the refractory nature of the study population.

Safety Profile

Safety outcomes in TOGETHER-PsA were consistent with the known profiles of both agents. Adverse events in the combination arm were generally mild to moderate. The most common events occurring in at least 5% of patients included gastrointestinal symptoms such as nausea, diarrhea, and constipation, as well as injection site reactions. In the ixekizumab monotherapy arm, injection site reactions and upper respiratory tract infections were most commonly reported. No new safety signals were identified with concomitant use.

Clinical Implications

From a dermatologic perspective, these findings are particularly relevant, as skin disease and systemic inflammation in psoriatic disease are closely linked to metabolic dysfunction. The findings suggest that obesity may act not only as a comorbidity but also as a modifiable driver of inflammatory disease activity in PsA. Detailed results will be presented at an upcoming medical meeting, and regulatory discussions are planned.

"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," said Joseph F. Merola, MD, Professor and Chair of the Department of Dermatology and Professor of Internal Medicine in the Division of Rheumatic Diseases at UT Southwestern Medical Center. "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. This integrated therapy approach represents a potential paradigm shift and could lead to better outcomes for those living with both diseases."¹

References

1. Lilly's Taltz (ixekizumab) and Zepbound (tirzepatide) used together delivered superior efficacy in first-of-its-kind Phase 3b trial for adults with active psoriatic arthritis and obesity or overweight. News release. Eli Lilly and Company. Published January 8, 2026. Accessed January 8, 2026. https://investor.lilly.com/news-releases/news-release-details/lillys-taltz-ixekizumab-and-zepbound-tirzepatide-used-together

2. Kumthekar A, Ogdie A. Obesity and Psoriatic Arthritis: A Narrative Review. Rheumatol Ther. 2020;7(3):447-456. doi:10.1007/s40744-020-00215-6