Lilly reports Phase 3b TOGETHER-PsA results showing improved disease activity, greater weight loss and sustained benefits with Taltz and Zepbound at Week 52.
Written By: Aasritha Thippavajjala, PharmD
Reviewed By: Pharmacally Editorial Team
Eli Lilly has reported 52-week results from its Phase 3b TOGETHER-PsA trial, showing that combining the interleukin-17A (IL-17A) inhibitor Taltz (ixekizumab) with the dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist Zepbound (tirzepatide) was associated with sustained improvements in psoriatic arthritis (PsA) disease activity, body weight, and patient-reported outcomes in adults with PsA and obesity or overweight. The combination was compared with Taltz alone, and the findings were presented at ACR Convergence 2026 and simultaneously published in Arthritis & Rheumatology.
Approximately 65% of adults living with PsA in the United States also have obesity or overweight alongside at least one weight-related comorbidity, creating an overlapping clinical burden that can complicate disease management. The new 52-week findings extend previously reported Week 36 results, when the combination demonstrated statistically significant superiority over Taltz monotherapy across the primary and key secondary endpoints. The one-year analyses indicate that improvements across multiple disease activity, functional, and cardiometabolic measures were maintained or further improved through 52 weeks.
TOGETHER-PsA Trial Design and Participant Characteristics
TOGETHER-PsA (NCT06588296) was a 52-week, randomized, multicenter, assessor-blinded, open-label Phase 3b study evaluating 271 adults with active PsA and obesity or overweight with at least one additional weight-related comorbidity. Participants were eligible with a body mass index (BMI) of at least 30 kg/m² or a BMI of 27 to less than 30 kg/m² with an additional weight-related condition. The enrolled cohort reflected a population with substantial disease and metabolic burden, featuring a mean baseline BMI of 37.6 kg/m² and over 60% reporting prior exposure to at least one advanced therapy.
Participants were randomized in a 1:1 ratio to receive subcutaneous Taltz alone or Taltz in combination with subcutaneous Zepbound, with both therapies administered at their U.S.-approved doses. Both treatment groups also received counseling on following a reduced-calorie diet and increasing physical activity throughout the study.
Week 36 Primary Endpoint Results
The primary endpoint assessed the proportion of participants achieving both an American College of Rheumatology 50% response (ACR50) and at least 10% body-weight reduction at Week 36. The combination achieved this composite primary endpoint in 31.7% of participants compared with 0.8% of those receiving Taltz alone. ACR50 responses were also higher with combination therapy (33.5% versus 20.4%), while 84.5% achieved at least 10% weight reduction compared with 4.5% in the monotherapy group. These results established the clinical basis for evaluating whether the observed benefits persisted through Week 52.
Sustained Efficacy Outcomes at Week 52
At Week 52, 43.7% of participants receiving Taltz and Zepbound achieved an ACR50 response, compared with 15.7% of those receiving Taltz alone. The combined outcome of ACR50 and at least 10% body-weight reduction was achieved by 39.2% versus 1.7% of participants, respectively. Weight reduction remained substantially greater with combination therapy, with 85.7% of participants achieving at least 10% weight loss compared with 6.7% in the Taltz-alone group.
Additional measures of psoriatic arthritis disease activity similarly favored combination therapy at one year. Minimal disease activity (MDA) was achieved by 28.2% of participants receiving the combination and 13.6% receiving monotherapy. The mean change from baseline in the Disease Activity Index for Psoriatic Arthritis (DAPSA) was -32.2 and -20.3, respectively.
Patient-Reported Outcomes and Cardiometabolic Improvements
Clinically meaningful improvements were observed across physical function, fatigue, and mental health measures through Week 52. The mean change in the Health Assessment Questionnaire-Disability Index (HAQ-DI) was -0.6 with combination therapy compared with -0.3 with Taltz alone. Fatigue, measured using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale, improved by 9.7 points versus 4.8 points, while the mean change in the SF-36 mental component score was +3.4 versus +0.2.
Combination therapy was also associated with greater reductions in high-sensitivity C-reactive protein (hsCRP), a biomarker of systemic inflammation, showing a mean change of -2.2 mg/L compared with -0.4 mg/L with Taltz alone. Additional cardiometabolic improvements were reported across BMI, total body weight, systolic blood pressure, fasting glucose, HbA1c, triglycerides, and total cholesterol.
Safety Profile
The overall safety findings were consistent with the established profiles of both medicines, with no new safety signals identified through 52 weeks. Most adverse events observed with combination therapy were mild to moderate in severity. Commonly reported events in the combination arm included nausea, diarrhea, constipation, injection-site reactions, vomiting, urinary tract infections, sinusitis, dizziness, and headache. In the Taltz monotherapy arm, commonly reported events included injection-site reactions, upper respiratory tract infections, arthralgia, and diarrhea.
Clinical Interpretation and Development Outlook
The TOGETHER-PsA findings underscore the potential clinical value of addressing excess body weight alongside targeted anti-inflammatory therapy in adults living with PsA and obesity or overweight. Notably, a greater proportion of participants receiving combination therapy achieved ACR50 responses as early as Week 4, prior to clinically meaningful weight loss. However, this early separation does not establish whether the improvement in joint disease activity occurred independently of weight reduction or reflects another pharmacodynamic interaction between IL-17A inhibition and dual GIP/GLP-1 receptor agonism.
An important methodological limitation is that the Week 52 analyses were prespecified exploratory objectives without multiplicity control. Comparisons across time points were descriptive and were neither statistically tested nor adjusted for multiple comparisons. Consequently, the one-year outcomes should be interpreted as exploratory evidence of maintained or further improved efficacy rather than confirmatory proof of between-group superiority at Week 52. Longer-term research will be important to establish the durability, clinical significance, and broader applicability of combining ixekizumab and tirzepatide in routine practice.
References
New Phase 3b data on Lilly’s Taltz (ixekizumab) and Zepbound (tirzepatide) used together showed improved and durable efficacy, patient-reported and metabolic outcomes at one year in adults with psoriatic arthritis and obesity, Eli Lilly and Company, November 11, 2026.
Merola JF, Mease P, Kivitz A, et al. Ixekizumab with Tirzepatide Achieved Greater Disease Control Than Ixekizumab Alone in Adults with Psoriatic Arthritis and Overweight or Obesity: Results from a Randomized Clinical Trial. Arthritis Rheumatol. 2026;78(10):2089–2101. doi:10.1002/art.70134
Ixekizumab Concomitantly Administered with Tirzepatide in Adults with Psoriatic Arthritis and Obesity or Overweight (TOGETHER-PsA), ClinicalTrials.gov ID NCT0658829
About the Writer
Aasritha Thippavajjala (Linkedin) is a pharm D student and aspiring medical writer with medical writing, clinical training experience and a strong interest in clinical research and patient safety She has hands-on exposure to clinical pharmacy activities including medication profile assessment, clinical case review, identification of potential drug-related problems, ADR awareness, patient counselling, and clinical documentation. She has also gained experience in medical literature review, evidence synthesis, and scientific communication through her published review article on digital twin-based patient simulation and her poster presentation at the 74th Indian Pharmaceutical Congress. Certified in ICH Good Clinical Practice (E6(R3)) and Scientific Writing in Health Research, she is passionate about applying her clinical knowledge and research skills to medical writing ,clinical research and contributing to accurate, evidence-based healthcare.