Lilly’s TOGETHER-PsA Phase 3b trial showed 31.7% of patients on Taltz plus Zepbound achieved both ACR50 and ≥10% weight loss at 36 weeks, supporting an integrated treatment approach for psoriatic arthritis and obesity
Written By: Pharmacally Medical News Desk
Eli Lilly and Company has reported positive topline results from the TOGETHER-PsA Phase 3b clinical trial evaluating the combined use of Taltz (ixekizumab) and Zepbound (tirzepatide) in adults living with active psoriatic arthritis (PsA) who were also obese or overweight with at least one weight-related condition.
This first-of-its-kind study showed that adding Zepbound to Taltz delivered better clinical outcomes than Taltz alone, particularly when addressing both inflammatory disease and excess body weight.
Mark Genovese, senior vice president of Immunology development at Lilly, said the TOGETHER-PsA study marks a first-of-its-kind advance showing that treating obesity can directly improve psoriatic arthritis outcomes. He highlighted that adding Zepbound to Taltz led to meaningful improvements in PsA disease activity, even though Taltz is already a fast and durable therapy. Overall, he emphasized that this integrated approach, combining metabolic and immunologic treatment, has the potential to raise the standard of care for patients living with both PsA and obesity.
Trial Design and Participant Profile
The TOGETHER-PsA trial (NCT06588296) was a 52-week, randomized, open-label, multicenter study that enrolled 271 adults with active PsA and a body mass index (BMI) of ≥30 kg/m² or BMI 27–29.9 kg/m² with a weight-related comorbidity. Participants were randomly assigned to receive either:
- Taltz (ixekizumab) alone
- Taltz in combination with Zepbound (tirzepatide)
All patients received standard lifestyle counseling, including dietary guidance and increased physical activity recommendations.
Primary and Secondary Endpoints Met
At 36 weeks, the study met its primary endpoint. A composite measure defined success as achieving both:
At least 50% improvement in PsA disease activity (American College of Rheumatology 50 response, ACR50)
At least 10% reduction in body weight
Results:
31.7% of participants receiving the combo therapy met this primary composite endpoint
Only 0.8% of those on Taltz alone achieved the same benchmark.
In key secondary analyses, the combination therapy also showed a 64% relative increase in the proportion of patients achieving ACR50 compared with Taltz monotherapy (33.5% vs. 20.4%, respectively). These results highlight the potential benefit of tackling both systemic inflammation and obesity in psoriatic arthritis management.
Safety Profile
The safety findings were consistent with the known profiles of the individual medicines. Most adverse events in the combination group were mild to moderate and included nausea, diarrhea, constipation and injection site reactions. Participants on Taltz alone experienced common events like injection site reactions and upper respiratory infections. No new safety signals emerged.
How both drugs work
Taltz (ixekizumab) is a monoclonal antibody targeting interleukin-17A (IL-17A), a pro-inflammatory cytokine involved in psoriatic disease pathways. It is already approved for PsA and other related inflammatory conditions.
Zepbound (tirzepatide) is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that has shown strong efficacy in weight management and metabolic disorders.
By combining the anti-inflammatory action of ixekizumab with the metabolic and weight-loss effects of tirzepatide, the trial tested a strategy that could address two major drivers of disease burden in PsA patients who struggle with overweight or obesity.
Joseph F. Merola, Professor and Chair of Dermatology and Professor of Internal Medicine at UT Southwestern Medical Center, said that although guidelines recognize obesity as important in psoriatic arthritis, it is usually treated separately from joint disease, which has limited progress in PsA outcomes. He noted that the benefits seen with Taltz plus Zepbound suggest PsA may be closely linked to obesity in many patients, and that addressing both together could represent a paradigm shift with the potential to deliver better, more meaningful outcomes for people living with both conditions.
Implications and Future Directions
The TOGETHER-PsA results support a potential shift in treatment strategy for psoriatic arthritis patients with obesity. Rather than treating inflammation and weight issues separately, combining targeted immunologic therapy with a metabolic agent may yield better overall outcomes. Detailed data from the full 36-week analysis will be presented at upcoming scientific meetings and shared with regulatory authorities.
Lilly is also conducting a TOGETHER-PsO trial, exploring the effect of Taltz and Zepbound in adults with moderate-to-severe plaque psoriasis and obesity, with topline results expected in the first half of 2026.
About PsA
Psoriatic arthritis is a chronic immune-mediated condition that causes joint pain, swelling, and functional impairment. Obesity is common in this population and is linked to greater disease severity and poorer treatment response. An integrated therapy that simultaneously targets inflammatory disease activity and weight may improve patient quality of life more than standard biologic therapy alone.
References
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, 08 January 2026, 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 | Eli Lilly and Company
Ixekizumab Concomitantly Administered with Tirzepatide in Adults with Psoriatic Arthritis and Obesity or Overweight (TOGETHER-PsA), ClinicalTrials.gov ID NCT06588296, https://clinicaltrials.gov/study/NCT06588296
Ixekizumab Concomitantly Administered with Tirzepatide in Adults with Moderate-to-Severe Plaque Psoriasis and Obesity or Overweight (TOGETHER-PsO), ClinicalTrials.gov ID NCT06588283, https://clinicaltrials.gov/study/NCT06588283