Together-PsA: Ixekizumab + Tirzepatide Deliver Superior Efficacy Over Biologic Monotherapy, With Joseph Merola, MD

TOGETHER-PsA, the first controlled trial to evaluate a GLP-1/GIP receptor agonist in combination with a psoriatic arthritis (PsA) biologic has demonstrated that co-treating obesity alongside active PsA produces meaningful gains in joint outcomes beyond what biologic therapy alone can achieve — with early separation suggesting the benefit may extend beyond weight loss to direct modulation of systemic inflammation.

To discuss the findings, we spoke with Joseph F. Merola, MD, MMSc, FAAD, Professor and Chair of the Department of Dermatology and Professor of Internal Medicine in the Division of Rheumatic Diseases and in the Peter O'Donnell Jr. School of Public Health at UT Southwestern Medical Center in Dallas, following his late-breaking presentation at the 2026 American Academy of Dermatology (AAD) Annual Meeting held in Denver, Colorado, from March 27-31.. The results were simultaneously published in Arthritis & Rheumatology.

TOGETHER-PsA (NCT06588296) was a 52-week, randomized, open-label, assessor-blinded phase 3b trial enrolling 271 adults with active PsA and obesity (BMI ≥30 kg/m²) or overweight (BMI 27–29.9 kg/m²) with at least 1 weight-related comorbidity — a population reflecting the reality that an estimated 65–82% of patients with PsA in the United States meet overweight or obese criteria. Participants had a mean age of 55.0 years (SD 11.9), mean baseline weight of 106.1 kg (SD 24.8), and mean BMI of 37.6 kg/m² (SD 7.6); over 60% had previously received at least 1 advanced therapy for PsA. Both arms received diet and exercise counseling. Patients were randomized 1:1 to ixekizumab (Taltz) plus tirzepatide (Zepbound) or ixekizumab alone.

The composite primary endpoint — simultaneous achievement of ACR50 and ≥10% weight reduction at week 36 — was met by 31.7% of combination-arm patients versus 0.8% on ixekizumab monotherapy (P <.001). On ACR50 alone, combination therapy achieved 33.5% versus 20.4% (P = .02), with separation between groups observed as early as week 4 — before clinically meaningful weight loss had accrued — a finding Merola flagged as mechanistically provocative. The implication, he noted, is that tirzepatide may be acting not only through weight reduction but through direct modulation of the adipokine and cytokine milieu that drives psoriatic inflammation, hitting the disease on 2 fronts simultaneously. Consistent improvements were observed across PsA domains including joint inflammation, pain, physical function, and health-related quality of life.

Merola also previewed early data from the companion TOGETHER-PsO trial, noting encouraging signals on stringent skin endpoints including PASI 100 and a composite of PASI 100 with ≥10% weight loss. Week 52 data from both trials are forthcoming, and Merola expressed optimism that longer follow-up — combined with planned mechanistic substudies — will further unpack the biological basis for the synergy observed and potentially extend the paradigm to osteoarthritis, cardiovascular outcomes, and other obesity-driven comorbidities prevalent in this population.

“I think this holistic approach to the patient that comes out of this study is hopefully paradigm shifting for us. The idea that we're going to do better by them in joints and skin, that we're going to ultimately improve their quality of life dramatically, and maybe lengthen their lives and improve cardiovascular endpoints is just very, very compelling,” Merola said.

Merola’s disclosures include Amgen, Astra-Zeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Abbvie, Dermavant, Eli Lilly, Moonlake, Novartis, Janssen, Oruka, UCB, Sanofi, Regeneron, Sun Pharma, Galderma, Biogen and Pfizer.

References

1. Merola JF, 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. 2026. doi:10.1002/art.70134.

2. Eli Lilly and Company. Phase 3b data presented at AAD Annual Meeting show Lilly's Taltz (ixekizumab) plus Zepbound (tirzepatide) delivered superior efficacy for adults with psoriatic arthritis and obesity. Press release. March 28, 2026. https://investor.lilly.com/news-releases/news-release-details/phase-3b-data-presented-aad-annual-meeting-show-lillys-taltz. Accessed March 28, 2026.