Ixekizumab, Tirzepatide Maintains Efficacy in Psoriatic Disease

Eli Lilly and Company announced new phase 3b data, showing that combining ixekizumab (Taltz) with tirzepatide (Zepbound) produced improved and durable efficacy at 1 year in adults with psoriatic disease and obesity.¹

The data come from two concurrent 52-week trials, TOGETHER-PsO (NCT06588283) and TOGETHER-PsA (NCT06588296), which enrolled adults with moderate to severe plaque psoriasis or active psoriatic arthritis who also had obesity or were overweight with at least one weight-related comorbidity. Participants in each trial were randomized 1:1 to receive ixekizumab alone or ixekizumab plus tirzepatide administered concomitantly.¹

"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," Mark Genovese, MD, senior vice president of Lilly Immunology Development, said in a news release.¹

Trial Design and Baseline Characteristics

TOGETHER-PsO enrolled 274 adults, and TOGETHER-PsA enrolled 271 adults in randomized, multicenter, assessor-blinded, open-label phase 3b trials lasting 52 weeks. The mean body mass index (BMI) at baseline was 39.2 in TOGETHER-PsO and 37.6 in TOGETHER-PsA.¹

Eligible participants in TOGETHER-PsA had active psoriatic arthritis with a BMI of 30 or higher or a BMI of 27 to 29.9 with at least 1 weight-related comorbidity. All participants also received counseling on a reduced-calorie diet and increased physical activity alongside their assigned treatment.²

Lilly first announced primary results from TOGETHER-PsA on January 8, 2026, when the trial met its week 36 primary end point. The results showed that 31.7% of participants receiving ixekizumab plus tirzepatide achieved both an American College of Rheumatology 50 (ACR50) response and at least 10% weight reduction compared with 0.8% of those receiving ixekizumab alone (P < .001).²

Those results were subsequently published in Arthritis & Rheumatology, where investigators reported that ACR50 alone was achieved by 33.5% of the combination group compared with 20.4% of the ixekizumab-alone group (P = .02), with separation between the arms emerging as early as week 4. The same analysis found nominally significant improvements with the combination in ACR20 (P < .001), minimal disease activity (P < .05), and absolute Psoriasis Area and Severity Index (PASI) score (P < .01), along with improvements in the Health Assessment Questionnaire-Disability Index and the Functional Assessment of Chronic Illness Therapy-Fatigue scale.³

Efficacy Results at 1 Year

At week 52, the combination continued to outperform ixekizumab alone across both trials. In TOGETHER-PsO, 30.6% of participants receiving ixekizumab plus tirzepatide achieved both complete skin clearance, defined as PASI 100, and at least 10% weight loss, compared with 4.4% of those on ixekizumab alone. Complete skin clearance on its own was reached by 40.5% of the combination group versus 29.1% of the monotherapy group.¹

In TOGETHER-PsA, 39.2% of participants receiving the combination achieved both an ACR50 response and at least 10% weight loss at week 52, compared with 1.7% of those on ixekizumab alone. Further, ACR50 alone was achieved by 43.7% of the combination group versus 15.7% of the monotherapy group.¹

"In psoriatic arthritis, the greater improvements in disease activity seen with Taltz and Zepbound in the first month, before clinically meaningful weight loss occurred, continued through 1 year," Joseph F. Merola, MD, MMSc, a dermatologist and rheumatologist who serves as president of the Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network (PPACMAN), said in a news release.¹

Metabolic and Safety Findings

The combination also produced deeper reductions in high-sensitivity C-reactive protein, a marker of systemic inflammation, than ixekizumab alone across both trials. Participants receiving ixekizumab plus tirzepatide had sustained or further improved BMI, blood pressure, glucose, glycated hemoglobin, triglycerides, and total cholesterol compared with those on ixekizumab alone.¹

Adverse events reported in at least 5% of participants receiving the combination at week 52 included nausea, diarrhea, constipation, injection site reactions, vomiting, dizziness, and headache. The safety profile was consistent with the known profiles of each medicine, and no new safety concerns were identified.¹

In the earlier week 36 readout from TOGETHER-PsA, events occurring in at least 5% of the combination group included nausea, diarrhea, constipation, and injection site reactions, and injection site reactions and upper respiratory tract infections were most common with ixekizumab alone. Investigators described those events as generally mild to moderate.²

What This Means for Pharmacists

Psoriasis and psoriatic arthritis frequently coexist with obesity. Lilly cited data showing that approximately 61% of people with psoriasis and approximately 65% of people with psoriatic arthritis have obesity or are overweight with at least 1 weight-related comorbidity.¹

Ixekizumab is a humanized IgG monoclonal antibody that selectively binds interleukin-17A (IL-17A), blocking its interaction with the IL-17 receptor and interrupting the inflammatory cascade involved in psoriasis and psoriatic arthritis. It is approved for moderate to severe plaque psoriasis in patients 6 years and older who are candidates for phototherapy or other systemic therapy, active psoriatic arthritis, active ankylosing spondylitis, and active nonradiographic axial spondyloarthritis with objective signs of inflammation.^4,5

Standard adult dosing for plaque psoriasis is 160 mg, given as two 80-mg injections, at week 0, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks. Dosing for psoriatic arthritis and ankylosing spondylitis is 160 mg at week 0 followed by 80 mg every 4 weeks. It is supplied as 80 mg/mL, 40 mg/0.5 mL, and 20 mg/0.25 mL injections.^1,5

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist given by weekly subcutaneous injection alongside a reduced-calorie diet and increased physical activity, supplied in 6 dose strengths from 2.5 mg to 15 mg. It is approved for adults who are obese or overweight and have at least 1 weight-related medical condition and separately for moderate to severe obstructive sleep apnea with obesity.¹

For pharmacists, these results add to a small but growing evidence base on combining an IL-17A inhibitor with an incretin therapy in patients with overlapping inflammatory and metabolic disease, relevant to counseling on injection technique, adherence, and monitoring as more patients are prescribed both drug classes at once.¹

REFERENCES

1. Eli Lilly and Company. New Phase 3b data on Lilly's Taltz (ixekizumab) and Zepbound (tirzepatide) used together showed improved and durable efficacy at one year in adults with psoriatic disease and obesity. News release. Eli Lilly and Company. August 31, 2026. Accessed August 31, 2026. https://investor.lilly.com/news-releases/news-release-details/new-phase-3b-data-lillys-taltz-ixekizumab-and-zepbound

2. Eli Lilly and Company. 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. News release. Eli Lilly and Company. January 8, 2026. Accessed August 31, 2026. https://investor.lilly.com/news-releases/news-release-details/lillys-taltz-ixekizumab-and-zepbound-tirzepatide-used-together

3. 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. Published online March 28, 2026. doi:10.1002/art.70134

4. Preuss CV, Quick J. Ixekizumab. In: StatPearls. StatPearls Publishing. Updated July 6, 2025. Accessed August 31, 2026. https://www.ncbi.nlm.nih.gov/books/NBK431088/

5. Mayo Clinic. Ixekizumab (subcutaneous route). Mayo Clinic. Updated February 1, 2026. Accessed August 31, 2026. https://www.mayoclinic.org/drugs-supplements/ixekizumab-subcutaneous-route/description/drg-20311588