New year-long data show Taltz and Zepbound combination sustains gains in psoriatic disease and obesity

Eli Lilly has released 52 week findings from TOGETHER-PsO and TOGETHER-PsA, a pair of open-label Phase 3b trials testing whether combining Taltz (ixekizumab) with Zepbound (tirzepatide) outperforms Taltz alone in adults who have moderate to severe plaque psoriasis or active psoriatic arthritis alongside obesity or overweight with at least one related health condition. The trials had already shown statistically superior results for the combination over Taltz monotherapy at the Week 36 primary endpoint, covering both disease activity and metabolic measures. The new data show those gains held steady or grew further by Week 52, with no new safety issues emerging.

Mark Genovese, senior vice president of Lilly Immunology development, said the one-year results build on findings that were already striking at the primary endpoint, with disease activity, inflammation and metabolic markers continuing to improve or holding firm a year in. He said patients dealing with both psoriatic disease and obesity are frequently managed through separate, uncoordinated treatments, and argued that the durability seen across multiple measures supports treating the two conditions together as a matter of immunometabolic health.

Obesity and metabolic dysfunction commonly accompany psoriasis and psoriatic arthritis, both immune-driven conditions. Roughly 61% of people with psoriasis and 65% of those with psoriatic arthritis in the US also have obesity or overweight paired with a weight-related comorbidity, a combination generally linked to weaker treatment results. Trial participants had an average BMI of 39.2 in TOGETHER-PsO and 37.6 in TOGETHER-PsA at the outset.

Joseph Merola, a dermatologist and rheumatologist who leads PPACMAN and serves as co-president of GRAPPA and president of the Rheumatology-Dermatology Society, said obesity and overweight often stand in the way of hitting skin and joint treatment targets in psoriatic disease. He noted that in the arthritis trial, the combination’s edge over Taltz alone showed up within the first month, before patients had lost enough weight for that alone to explain the difference, and that advantage persisted to one year. In the psoriasis trial, he pointed to the durability of complete skin clearance at 12 months as meaningful progress, and said the combined metabolic gains point to what treating both conditions at once could achieve.

At Week 52, exploratory analyses (pre-specified but not adjusted for multiplicity, with between-timepoint comparisons treated as descriptive) showed:

• Primary outcome: Both trials’ composite endpoints kept improving through Week 52. In TOGETHER-PsO, that meant complete skin clearance (PASI 100) combined with at least 10% weight loss, reached by 30.6% of patients on the combination versus 4.4% on Taltz alone. In TOGETHER-PsA, it meant at least a 50% reduction in disease activity (ACR50) plus 10% weight loss, achieved by 39.2% on the combination versus 1.7% on monotherapy.
• Psoriasis skin clearance: The share of combination-treated patients hitting PASI 100 held at 40.5% by Week 52, compared with 29.1% for Taltz alone.
• Psoriatic arthritis response: ACR50 response with the combination climbed further to 43.7% at Week 52, versus 15.7% for monotherapy, extending an advantage that had already appeared by Week 4, ahead of any meaningful weight loss.
• Systemic inflammation: hsCRP levels, a marker of systemic inflammation, showed deeper improvement over time with the combination in both trials.
• Metabolic measures: Gains in BMI, blood pressure, glucose, HbA1c, triglycerides and total cholesterol seen with the combination versus Taltz alone were maintained or extended.

Side effects among patients on both drugs together were mostly mild to moderate and matched what’s already known about each medicine individually. Nausea, diarrhea, constipation, injection site reactions, vomiting, dizziness and headache each occurred in at least 5% of participants in the combination arm across both trials.

Taltz works by binding to the IL-17A cytokine and blocking its interaction with the IL-17 receptor; Lilly describes it as the only biologic with data behind pairing it with an incretin therapy for psoriatic disease patients who also have obesity or overweight. Zepbound remains the only FDA-approved weight management drug that targets both the GIP and GLP-1 receptors. Full 52-week results are expected at upcoming medical conferences and in peer-reviewed publications.

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Related Topics and Keywords

Eli Lilly, obesity, psoriatic disease, Taltz, Zepbound™