Tirzepatide Boosts Izekizumab Efficacy for PsA and Obesity Disease Control

Ixekizumab (Taltz) and tirzepatide (Zepbound) used together demonstrated superior efficacy to izekizumab alone in adults with active psoriatic arthritis (PsA) and obesity or overweight with at least one weight-related condition, achieving high rates of disease control and weight reduction.1

"While treatment guidelines for PsA recommend management of obesity, the reality is these 2 chronic diseases are often addressed separately and moving the needle in psoriatic arthritis has remained challenging," Joseph F. Merola, MD, Professor and Chair, Department of Dermatology and Professor of Internal Medicine in the Division of Rheumatic Diseases, UT Southwestern Medical Center, said in a statement.1 "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."

These findings are from the phase 3b TOGETHER-PsA study, the first controlled study to evaluate the combination of incretin therapy with a biologic for PsA. Ixekizumab is an IL-17a inhibitor and tirzepatide is the only US Food and Drug Administration-approved dual GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptor agonist.2

The study population represents an area with high unmet need, as an estimated 65% of adults with PsA in the United States also have obesity or overweight with at least 1 additional weight-related comorbidity. Study participants had a high disease burden at baseline and an average BMI of 37.6 kg/m2 across both arms. They represented a difficult-to-treat population, with over 60% having received 1 or more advanced therapies prior to the study.1

Investigators found that, at 36 weeks, 31.7% participants receiving concomitant ixekizumab and tirzepatide in TOGETHER-PsA met the primary and all key secondary endpoints for superiority to Taltz monotherapy. The primary endpoint was a 50% improvement in PsA activity, based on American College of Rheumatology 50 (ACR50), and weight reduction of at least 10%, compared to 0.8% of patients on Taltz monotherapy, (P <.001).The study met a key secondary endpoint, with the combination yielding a 64% relative increase in ACR50 achievement (33.5%) over ixekizumab alone (20.4%); P <.05).1

"TOGETHER-PsA represents a pioneering first step leveraging Lilly's leadership in incretin science to deliver a major advance in disease outcomes for people living with the cumulative burden of psoriatic arthritis and obesity or overweight," Mark Genovese, MD, senior vice president of Lilly Immunology development, added.1 "This is the first controlled pharmacologic study to demonstrate that treatment of obesity improved PsA disease measures, and we are particularly impressed with the findings showing significant improvement in PsA disease activity with Zepbound used alongside Taltz, an already rapid-acting and durable PsA treatment. These results demonstrate how an integrated treatment approach has the potential to improve the standard of care in a compelling and comprehensive way."

In terms of safety, adverse events (AEs) were generally mild to moderate and consistent with the known safety profiles of the individual therapies. The most common AEs included nausea, diarrhea, constipation and injection site reactions in the concomitant treatment arm, and injection site reactions and upper respiratory tract infections in the izekizumab monotherapy arm.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. Lilly. January 8, 2026. https://investor.lilly.com/news-releases/news-release-details/lillys-taltz-ixekizumab-and-zepbound-tirzepatide-used-together

2. Campbell P. FDA Approves Tirzepatide (Zepbound) for Chronic Weight Management. Article. HCPLive. November 8, 2023. https://www.hcplive.com/view/fda-approves-tirzepatide-zepbound-chronic-weight-management