April 27, 2026
2 min read
Key takeaways:
- Ixekizumab plus tirzepatide yielded significant improvement over ixekizumab alone in ACR50 response in patients with PsA and obesity.
- No new safety signals were observed.
Treatment with ixekizumab plus tirzepatide achieves greater disease control, physical function and weight loss vs. monotherapy in patients with psoriatic arthritis and obesity, according to data published in Arthritis Care & Research.
“Overweight or obesity is disproportionately prevalent in PsA compared with the general population, with estimates ranging from 72% to 82%,” Joseph F. Merola, MD, of the University of Texas Southwestern Medical Center and O’Donnell School of Public Health, and colleagues wrote. “… Obesity promotes a chronic, low-grade inflammatory state through adipokine release and up-regulation of cytokines such as tumor necrosis factor (TNF), interleukin-17 (IL-17), and IL-6, while mechanical stress at entheseal sites and reduced physical activity exacerbate musculoskeletal symptoms.
“Given the interplay between obesity, systemic inflammation, and PsA disease activity, use of an IL-17A inhibitor with an effective weight loss therapy may offer additive clinical benefits,” they added.
In the TOGETHER-PsA trial, Merola and colleagues assessed the efficacy and safety of combination therapy with ixekizumab (Taltz, Eli Lilly) plus tirzepatide (Mounjaro, Zepbound; Eli Lilly), compared with ixekizumab alone in a cohort of 271 adults with active PsA and overweight or obesity. Eligibility criteria included at least one comorbidity associated with overweight or obesity.
A 50% improvement in ACR50 response, along with a weight reduction of 10% or greater at 36 weeks served as the primary outcome measure. Other endpoints included ACR50 alone and patient-reported outcomes. The final analysis included 138 participants in the combination therapy group and 133 in the ixekizumab alone group.
According to the researchers, the primary endpoint was met by 31.7% of participants in the ixekizumab plus tirzepatide arm, compared with 0.8% of those in the monotherapy arm (P < .001). Similarly, 33.5% of participants in the combination arm achieved ACR50, compared with 20.4% of those who received ixekizumab alone (P = .02). Significant early separation between the two groups was observed at week 4 (nominal P < .05), according to the findings.
Nominally significant improvements were also observed in the combination arm vs. the monotherapy arm for ACR20 response (P<.001), minimal disease activity (P< .05), and absolute Psoriasis Area and Severity Index score (P<.01). Regarding patient-reported outcomes, ixekizumab plus tirzepatide bested ixekizumab alone as assessed by Health Assessment Questionnaire-Disability Index ( = 0.2; nominal P<.001) and Functional Assessment of Chronic Illness Therapy-Fatigue (improvement of 3.8; nominal P<.01).
No new safety findings were observed for either medication, according to the researchers.
“This is the first randomized controlled trial of [tirzepatide] and [ixekizumab] in patients with PsA and overweight or obesity that addresses the comprehensive management needs of this patient population, with a positive meaningful impact in multiple domains of PsA disease, including disease control and its comorbidities,” Merola and colleagues wrote. “These data strengthen the EULAR and GRAPPA treatment guidelines, which recommend that clinicians consider comorbidities in the patient’s treatment approach to achieve low disease activity or remission.”
Sources/Disclosures
Source:
Merola JF, et al. Arthritis Care Res. 2026;doi:10.1002/art.70134.
Disclosures:
This study was sponsored by Eli Lilly and Co. Merola reports receiving consultant fees from AbbVie, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Incyte, Janssen, Leo Pharma, MoonLake Immunotherapeutics, Novartis, Pfizer, Sanofi-Regeneron and UCB; and grant or research support from Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, MoonLake Immunotherapeutics, Sanofi-Regeneron, Sun Pharma and UCB. Please see the full study for additional researchers’ disclosures.
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