Concomitant Use of Tirzepatide, Ixekizumab Improves PsA Disease Activity and Promotes Weight Reduction

Positive topline results from the novel TOGETHER-PsA (NCT06588296) phase 3b clinical trial demonstrate that the concomitant use of tirzepatide (Zepbound; Eli Lilly) and ixekizumab (Taltz; Eli Lilly) compared with ixekizumab alone met all primary end points when treating adults with active psoriatic arthritis (PsA) and obesity or overweight with at least 1 weight-related condition.^1,2

Associations Between Obesity and PsA

According to research published in Joint Bone Spine, nearly 1 in 2 individuals with PsA are living with obesity. Obesity is associated with increased risks of developing PsA, worsening disease activity, pain and fatigue, impaired response to treatments, and amplified risk of other cardiometabolic comorbidities already more prevalent in PsA.³

Although evidence for the pathogenic role of obesity in PsA is increasing, current treatment focuses on immune-mediated therapies, with limited attention to tackling excess adiposity. Because residual pain and disease activity in PsA can adversely impact physical activity, this can lead to a cycle of further weight gain and worse disease activity.³

According to a news release from Eli Lilly, there are an estimated 65% of adults with PsA in the US who also have obesity (body mass index [BMI]: 30 or higher) or overweight (BMI: 27–29.9) with at least 1 additional weight-related comorbidity, emphasizing a need for integrated treatment approaches that address the full burden of their diseases.¹

About Tirzepatide and Ixekizumab

Tirzepatide is a glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist medication that lowers body weight by decreasing calorie intake and appetite. Currently, tirzepatide is indicated under the name brand Zepbound when used 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 with overweight in the presence of at least 1 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. ¹

Ixekizumab is a monoclonal antibody that selectively binds with the IL-17A cytokine—a naturally occurring cytokine that is involved in normal inflammatory and immune responses—and inhibits its interaction with the IL-17 receptor by preventing the release of proinflammatory cytokines and chemokines. Ixekizumab is approved under the brand name Taltz to treat adults with active PsA, 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 nonradiographic axial spondyloarthritis with objective signs of inflammation.¹

What is the TOGETHER-PsA Clinical Trial?

TOGETHER-PsA is a randomized, multicenter, assessor-blinded, open-label phase 3b clinical trial assessing the efficacy and safety of concomitant administration of tirzepatide and ixekizumab compared with ixekizumab alone over a 52-week duration in adults with active PsA and overweight or obesity.²

A total of 271 patients were randomly assigned to receive either the concomitant regimen or ixekizumab alone, both of which were administered subcutaneously. Regardless of their assigned treatment, all patients received counseling on a reduced-calorie diet and increased physical activity. The trial’s primary objective was to assess the proportion of participants achieving both a 50% improvement in PsA activity—assessed by American College of Rheumatology 50 (ACR50) response—and at least a 10% reduction in weight at week 36.^1,2

What Did the Findings Show?

According to the findings, treatment with concomitant ixekizumab and tirzepatide met the primary and key secondary end points for superiority to ixekizumab monotherapy.¹

Specifically, approximately 31.7% of patients in the concomitant treatment arm achieved a 50% improvement in PsA activity and weight reduction of at least 10%, compared with only 0.8% of patients on ixekizumab alone (p < .001). In a key secondary end point, ixekizumab plus tirzepatide delivered a 64% relative increase over ixekizumab monotherapy in the number of patients who achieved ACR50 (33.5% vs 20.4%, respectively; p < .05), showing that treatment of obesity or overweight with tirzepatide reduced the burden of PsA.

Further, the study population included patients with a high disease burden at baseline and an average BMI of about 37.6 across both arms. Patients had high disease activity and meaningful functional impairment. Over 60% also had prior experience with 1 or more advanced therapies, reflecting a difficult-to-treat patient population.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 of the Department of Dermatology and professor of internal medicine in the Division of Rheumatic Diseases at the University of Texas Southwestern Medical Center, said in the news release. “The observed benefit with treatment using [ixekizumab] and [tirzepatide] 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

Adverse Events

The adverse events (AEs) observed in participants treated with concomitant administration of tirzepatide and ixekizumab were generally mild to moderate in severity, and the types of AEs were consistent with the known safety profile of each medicine. The most common AEs, which occurred in 5% or more 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 ixekizumab monotherapy arm.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 PsA and obesity or overweight,” Mark Genovese, MD, senior vice president of Lilly Immunology development, said in the news release. “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 [tirzepatide] used alongside [ixekizumab], 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.”¹

REFERENCES

1. Eli Lilly. 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. January 8, 2026. Accessed January 9, 2026. https://investor.lilly.com/news-releases/news-release-details/lillys-taltz-ixekizumab-and-zepbound-tirzepatide-used-together

2. Ixekizumab Concomitantly Administered With Tirzepatide in Adults With Psoriatic Arthritis and Obesity or Overweight (TOGETHER-PsA). ClinicalTrials.gov identifier: NCT06588296. Updated November 24, 2025. Accessed January 9, 2026. https://clinicaltrials.gov/study/NCT06588296

3. Siebert S, Sattar N, Ferguson LD. Weighing in on obesity and psoriatic arthritis – Time to move beyond association to robust randomised trials. Joint Bone Spine. 2025;92(5):105904. doi:10.1016/j.jbspin.2025.105904