Eli Lilly has reported positive topline results from the Phase 3b TOGETHER-PsA trial, marking a first-of-its-kind integrated treatment approach for psoriatic arthritis (PsA).
The study evaluated Taltz (ixekizumab) used alongside Zepbound (tirzepatide) versus Taltz alone in adults with active PsA and obesity or overweight.
A First for PsA: Treating Inflammation and Obesity Together
Psoriatic arthritis and obesity often coexist.
- Around 65% of adults with PsA in the US also have obesity or overweight with related comorbidities.
- Despite guideline recommendations, these conditions are usually treated separately.
- TOGETHER-PsA is the first controlled study to test an incretin therapy with a PsA biologic.
The results suggest this separation may no longer make sense.
Primary Endpoint Met at 36 Weeks
The trial met its primary endpoint with strong statistical significance.
At Week 36:
- 31.7% of patients on Taltz + Zepbound achieved:
- ACR50 (50% improvement in PsA activity)
- ≥10% weight reduction - Only 0.8% of patients on Taltz alone achieved both outcomes
- p < 0.001
This confirms superiority over biologic monotherapy.
Key Secondary Endpoint: Better PsA Control
The combination therapy also delivered clear disease activity benefits.
- 33.5% of patients on Taltz + Zepbound achieved ACR50
- 20.4% of patients on Taltz alone achieved ACR50
- This represents a 64% relative increase
- p < 0.05
Treating obesity meaningfully reduced the burden of PsA.
A Difficult-to-Treat Patient Population
This was not a low-risk cohort.
Key baseline characteristics:
- Average BMI: 37.6 kg/m²
- High PsA disease activity and functional impairment
- Over 60% had prior exposure to advanced therapies
Despite this, combination therapy delivered superior outcomes.
Safety Profile Remained Consistent
Adverse events were generally mild to moderate. Most common events:
- Combination arm: nausea, diarrhea, constipation, injection site reactions
- Taltz alone: injection site reactions, upper respiratory infections
No new safety signals were identified beyond known profiles.
Why This Matters Clinically?
According to investigators, these results may redefine PsA care.
- Obesity appears to directly influence PsA disease activity
- Addressing metabolic drivers improves inflammatory outcomes
- PsA may be partly an obesity-related condition for many patients
This opens the door to more holistic treatment strategies.
What Makes This Approach Different?
Taltz
- IL-17A monoclonal antibody
- Rapid-acting, durable PsA biologic
Zepbound
- Dual GIP/GLP-1 receptor agonist
- FDA-approved for obesity management
- Addresses appetite, caloric intake, and metabolic inflammation
Together, they target both immune and metabolic pathways.
What’s Next for the TOGETHER Program?
- Detailed 36-week data will be presented at an upcoming medical meeting
- Results will be discussed with regulators
- TOGETHER-PsO, studying plaque psoriasis with obesity, is ongoing
- Topline PsO data are expected in H1 2026
The Big Picture
Taltz is now the first biologic in PsA with data supporting use alongside an incretin therapy.
The TOGETHER-PsA trial shows that:
- Treating obesity improves arthritis outcomes
- Integrated therapy can outperform biologic monotherapy
- A paradigm shift in PsA management may be underway
For patients living with both PsA and obesity, this could change the standard of care.
