Lilly's Taltz Plus Zepbound Shows Durable One-Year Benefits in Psoriatic Disease and Obesity
核心洞察
At Week 52, Taltz (ixekizumab) combined with Zepbound (tirzepatide) maintained or further improved psoriasis and psoriatic arthritis (搜索) disease activity compared with Taltz alone in the TOGETHER-PsO and TOGETHER-PsA trials.
In TOGETHER-PsO, 30.6% of patients on combination therapy achieved PASI 100 plus at least 10% weight loss versus 4.4% on Taltz monotherapy; in TOGETHER-PsA, 39.2% achieved ACR50 plus at least 10% weight loss versus 1.7%.
Systemic inflammation (hsCRP) and metabolic outcomes including BMI, blood pressure, glucose, HbA1c, triglycerides, and total cholesterol were sustained or further improved through one year.
Eli Lilly and Company announced 52-week results from TOGETHER-PsO and TOGETHER-PsA, two novel open-label Phase 3b clinical trials evaluating the concomitant use of Taltz (ixekizumab) and Zepbound (tirzepatide) compared to Taltz alone in adults with moderate-to-severe plaque psoriasis (搜索) (PsO) or active psoriatic arthritis (搜索) (PsA), respectively, and obesity (搜索) or overweight with at least one additional weight-related comorbid condition. At the previously reported Week 36 primary endpoint, Taltz and Zepbound showed statistically superior improvements in disease activity and metabolic outcomes compared to Taltz alone in both trials. The new data show these improvements were maintained or further improved through Week 52, with no new safety concerns identified.
"The primary results from these first-of-their-kind studies were already remarkable, showing that Taltz and Zepbound used together improved outcomes for patients with psoriatic disease and obesity (搜索). What's especially exciting now is seeing those improvements further deepened or sustained at one year, across disease activity, inflammation and metabolic outcomes," said Mark Genovese, M.D., senior vice president of Lilly Immunology development.
Durable Efficacy Across Skin, Joint, and Metabolic Measures
At Week 52, the primary multi-component outcome continued to improve through Week 52 in each trial. In TOGETHER-PsO, the primary outcome was Psoriasis Area Severity Index (PASI) 100 plus at least 10% weight loss, achieved by 30.6% of patients with Taltz plus Zepbound at Week 52 versus 4.4% for Taltz alone. In TOGETHER-PsA, the primary outcome was an at least 50% reduction in PsA disease activity based on American College of Rheumatology 50 (ACR50) plus at least 10% weight loss, achieved by 39.2% of patients with Taltz and Zepbound at Week 52 versus 1.7% for monotherapy.
In TOGETHER-PsO, the percentage of patients receiving Taltz and Zepbound who achieved the highest bar of complete skin clearance (PASI 100) was maintained at 40.5% at Week 52 versus 29.1% for Taltz monotherapy. In TOGETHER-PsA, the proportion of patients achieving ACR50 with Taltz and Zepbound further increased to 43.7% at Week 52 versus 15.7% for Taltz monotherapy. This builds on the ACR50 improvements with Taltz and Zepbound compared to Taltz alone seen as early as Week 4, before clinically meaningful weight loss was observed.
Systemic Inflammation and Metabolic Outcomes
Treatment with Taltz and Zepbound also led to deeper improvements in systemic inflammation over time in both trials, as measured by high-sensitivity C-reactive protein (hsCRP). Improvements in BMI, blood pressure, glucose, HbA1c, triglycerides, and total cholesterol with Taltz and Zepbound compared to Taltz monotherapy were sustained or further improved.
"In psoriatic arthritis (搜索), the greater improvements in disease activity seen with Taltz and Zepbound in the first month, before clinically meaningful weight loss occurred, continued through one year. In psoriasis, the durability of complete skin clearance at one year represents real, lasting progress for patients. Paired with continued metabolic improvements, these findings show what may be possible when treating psoriatic disease and obesity (搜索) concurrently," said Joseph F. Merola, M.D. MMSc, President of the Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network (PPACMAN).
Disease Burden and Clinical Context
Psoriasis and psoriatic arthritis (搜索) are immune-mediated diseases that are often linked with metabolic dysfunction, including obesity (搜索). In the U.S., approximately 61% of people with psoriasis and 65% of people with psoriatic arthritis also have obesity or overweight with at least one weight-related comorbidity, which is often associated with poorer treatment outcomes. At baseline, the mean body mass index (BMI) of participants was 39.2 in TOGETHER-PsO and 37.6 in TOGETHER-PsA.
"People living with the cumulative burden of psoriatic disease and obesity (搜索) are too often treated with separate, disconnected approaches. These data showing durable results across multiple measures support a comprehensive approach that can potentially address immunometabolic health for patients living with these chronic diseases," said Genovese.
Safety Profile
Adverse events in participants treated with Taltz and Zepbound together were generally mild to moderate, and the types of adverse events were consistent with the known safety profile of each medicine. In the concomitant treatment arm in both trials, the adverse events reported in at least 5% of participants were nausea, diarrhea, constipation, injection site reactions, vomiting, dizziness and headache.
Trial Design
TOGETHER-PsO (NCT06588283) and TOGETHER-PsA (NCT06588296) are 52-week Phase 3b, randomized, multicenter, assessor-blinded, open-label studies assessing the efficacy and safety of concomitant administration of Taltz and Zepbound compared with Taltz alone. TOGETHER-PsO enrolled 274 adults with moderate-to-severe plaque psoriasis (搜索), and TOGETHER-PsA enrolled 271 adults with active psoriatic arthritis (搜索). Participants were randomized 1:1 to receive either Taltz alone or concomitantly with Zepbound, both administered subcutaneously, and received counseling on a reduced-calorie diet and increased physical activity. Participants were required to have a BMI of at least 30 kg/m², or 27 to less than 30 kg/m² with at least one weight-related comorbidity.
Taltz is a monoclonal antibody that selectively binds with interleukin 17A (IL-17A (搜索)) cytokine and inhibits its interaction with the IL-17 receptor. Zepbound is the only FDA-approved dual GIP (搜索) (glucose-dependent insulinotropic polypeptide) and GLP-1 (搜索) (glucagon-like peptide-1) receptor agonist obesity (搜索) management medication. Detailed 52-week results from TOGETHER-PsO and TOGETHER-PsA will be presented at future medical meetings and published in peer-reviewed journals.