Combination of ixekizumab and tirzepatide boosts psoriatic arthritis outcomes

In patients with psoriatic arthritis (PsA) and coexisting overweight or obesity, adding the glucagon-like peptide-1 (GLP-1) agonist tirzepatide to the interleukin-17A (IL-17A) inhibitor ixekizumab substantially improved both articular and metabolic outcomes. In a phase 3 randomised trial, nearly one-third of patients receiving the combination achieved a composite endpoint of the American College of Rheumatology 50% improvement criteria (ACR50) plus ≥10% weight loss at week 36, compared with fewer than 1% of patients receiving ixekizumab monotherapy.

Approximately half of adults with PsA are affected by obesity [1]. This burden is increasingly recognised as contributing to reduced response to biologic therapy [2], increasing cardiometabolic risk, and impaired patient-reported outcomes. Against this background, dual targeting of inflammatory disease activity and adiposity has emerged as a rational therapeutic strategy. This approach was evaluated in the phase 3b TOGETHER-PsA head-to-head trial (NCT06588296), presented by Prof. Joseph Merola (UT Southwestern Medical Center, TX, USA) [3].

Adults with PsA and overweight or obesity, along with at least 1 weight-related comorbidity (n=271), were randomised to receive ixekizumab plus tirzepatide or ixekizumab alone and were followed for 36 weeks. The primary composite endpoint required achievement of both ACR50 and ≥10% body-weight reduction. At week 36, this endpoint was met by 31.7% of patients in the combination arm, compared with fewer than 1% of the ixekizumab monotherapy arm.

Hierarchical secondary analyses supported the primary findings. The proportions of patients achieving ACR50 (33.5% vs 20.4%; P<0.05), ≥10% weight loss (84.5% vs 4.5%; P<0.001), or the alternative composite of ACR20 plus ≥5% weight reduction (69.7% vs. 10.3%; P<0.001) were all significantly higher with combination therapy. Additional articular outcomes and patient-reported measures, including overall symptom burden and quality of life, also consistently favoured the dual-therapy approach.

According to Prof. Merola, the early and statistically robust separation in ACR50 was particularly notable and may signal a potential paradigm shift. He further emphasised that effective management of obesity as a core comorbidity is likely to translate into long-term improvements in quality of life and potentially survival in this population.

For dermatologists managing PsA in patients with overweight or obesity, the combination of ixekizumab and tirzepatide may offer meaningful benefits for skin-joint disease activity and cardiometabolic health, supporting an integrated treatment approach.

Siebert S, et al. Joint Bone Spine 2025;92(5):105904.
Di Minno M, et al. Arthritis Care Res (Hoboken) 2013:65(1):141-147.
Merola JF. Ixekizumab plus tirzepatide in patients with psoriatic arthritis and overweight or obesity: a phase III randomised trial. S034: Late-breaking Research Session 2. AAD 2026, 27–31 March, Denver, CO, USA.