Ixekizumab and Tirzepatide combo Improves PsA Control and Weight Loss, suggests study
The TOGETHER-PsA study shows that combining ixekizumab with tirzepatide leads to significantly better psoriatic arthritis disease control and greater weight reduction compared with ixekizumab alone in patients with PsA and obesity.
This is the first controlled trial to evaluate incretin therapy alongside a biologic in PsA, suggesting a potential paradigm shift in managing PsA with comorbid obesity.
At 36 weeks, treatment with concomitant Taltz and Zepbound met the primary and all key secondary endpoints for superiority to Taltz monotherapy. TOGETHER-PsA is the first controlled study to evaluate an incretin therapy used with a PsA biologic. An estimated 65% of adults with PsA in the U.S. also have obesity (BMI ≥30 kg/m²) or overweight (BMI 27-29.9 kg/m²) with at least one additional weight-related comorbidity,1 highlighting a need for integrated treatment approaches that address the full burden of their diseases.
In the study, 31.7% of patients in the Taltz plus Zepbound treatment arm achieved 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, meeting the primary endpoint (p<.001). In a key secondary endpoint, Taltz plus Zepbound delivered a 64% relative increase over Taltz monotherapy in the proportion of patients who achieved ACR50 (33.5% of patients vs. 20.4%, respectively, p<.05), demonstrating that treatment of obesity or overweight with Zepbound reduced the burden of PsA.2,3 The study population included patients with a high disease burden at baseline and an average BMI of 37.6 kg/m2 across both arms. Patients had high disease activity and meaningful functional impairment.4 More than 60% had prior experience with one or more advanced therapies, reflecting a difficult-to-treat patient population.
"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," said Mark Genovese, M.D., senior vice president of Lilly Immunology development. "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."
Adverse events in participants treated with concomitant administration of Taltz and Zepbound were generally mild to moderate, and the types of adverse events were consistent with the known safety profile of each medicine. The most common adverse events occurring in ≥5% of participants were nausea, diarrhea, constipation and injection site reactions in the concomitant treatment arm, and injection site reactions and upper respiratory tract infections in the Taltz monotherapy arm.
Taltz is a monoclonal antibody that selectively binds with interleukin 17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. Zepbound is the only FDA-approved dual GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptor agonist obesity management medication.
"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, M.D., Professor and Chair, Department of Dermatology and Professor of Internal Medicine in the Division of Rheumatic Diseases, 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."
Detailed 36-week results from the TOGETHER-PsA trial will be presented at an upcoming medical meeting and discussed with regulators. Topline results from the ongoing TOGETHER-PsO trial, investigating the efficacy and safety of treating adults who have moderate-to-severe plaque psoriasis and obesity or overweight with concomitant Taltz and Zepbound compared to Taltz monotherapy, are also expected in the first half of 2026.
About the TOGETHER-PsA Trial
TOGETHER-PsA (NCT06588296) is a 52-week Phase 3b, randomized, multicenter, assessor-blinded, open-label study assessing the efficacy and safety of concomitant administration of Taltz and Zepbound compared with Taltz alone in adult participants with active psoriatic arthritis and obesity or overweight. A total of 271 participants were randomized 1:1 to receive either Taltz alone or concomitantly with Zepbound, both administered subcutaneously. Patients in both arms received counseling on a reduced-calorie diet and increased physical activity. The primary objective of the study is to assess the proportion of participants achieving both an ACR50 response and ≥10% weight reduction at Week 36. Participants must have a BMI ≥30 kg/m², or ≥27 to <30 kg/m² with at least one weight-related comorbidity.
About Taltz (ixekizumab)
Taltz is a monoclonal antibody that selectively binds with interleukin 17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Taltz inhibits the release of pro-inflammatory cytokines and chemokines. Taltz is approved to treat adults with active psoriatic arthritis. Additionally, Taltz is approved for adults and children 6 years and older with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy, adults with active ankylosing spondylitis, and adults with active non-radiographic axial spondyloarthritis with objective signs of inflammation.
About Zepbound (tirzepatide) injection
Zepbound is a GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptor agonist obesity medication. Zepbound lowers body weight by decreasing calorie intake and appetite. Zepbound is indicated in combination with a reduced-calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction in adults with obesity, or adults with overweight in the presence of at least one weight-related comorbid condition. Additionally, Zepbound is FDA-approved to treat adults with moderate-to-severe obstructive sleep apnea and obesity in combination with a reduced-calorie diet and increased physical activity. Zepbound contains tirzepatide and should not be used with other tirzepatide-containing products or any GLP-1 receptor agonist medicines. It is not known if Zepbound is safe and effective for use in children.
