AgAIN: Secukinumab Outperforms Ustekinumab in Post-TNFi Psoriatic Arthritis, With Frank Behrens, MD

Secukinumab (Cosentyx; Novartis) has demonstrated superior efficacy compared with ustekinumab (Stelara; Janssen) in patients with psoriatic arthritis (PsA) who had previously failed or were intolerant to TNF inhibitor (TNFi) therapy, according to results from the AgAIN study (NCT04632927)—the first randomized, double-blind, active-controlled, multicenter head-to-head trial comparing the 2 biologics in this difficult-to-treat population.

Findings from AgAIN were presented at the American College of Rheumatology (ACR) Convergence 2025, held October 24–29 in Chicago, Illinois, by Frank Behrens, MD, Professor and Head of Translational Rheumatology, Immunology, and Inflammation Medicine and Head of the Inflammation Clinic at Goethe-University Frankfurt.

The phase 3b study enrolled 119 adults with active PsA across 28 centers in Germany, all of whom met CASPAR criteria and had prior exposure to TNFi therapy, most commonly adalimumab (68.9%). Participants were randomized to receive secukinumab 300 mg once weekly for the first 4 weeks, then every 4 weeks thereafter, or ustekinumab 45 mg (90 mg for patients >100 kg) at baseline and week 4, followed by every 12 weeks.

At week 28, 57.1% of patients treated with secukinumab achieved a HAQ-DI response (≥0.35-point improvement) compared with 27.0% in the ustekinumab group (OR 3.647; 95% CI, 1.601–8.311; P = .002), nearly doubling response rates with IL-17 inhibition over IL12/IL23 inhibition. Secukinumab also outperformed ustekinumab across all key secondary and exploratory endpoints, including joint counts, ACR responses, pain, skin outcomes, and enthesitis resolution. Improvements were observed as early as week 2 and were sustained through week 28.

Treatment discontinuations were notably higher in the ustekinumab arm (25.4% vs 3.6%), primarily due to loss of efficacy. No new safety signals were identified, and the overall rates of adverse events (AEs) were similar between groups—occurring in 76.8% (SEC) versus 81.0% (UST)—with serious AEs in 8.9% and 3.2%, respectively.

HCPLive spoke with Behrens to learn more about the significance of these findings, the implications for post-TNFi treatment sequencing, and how the AgAIN trial may guide clinicians in choosing the next best step for PsA patients with inadequate TNFi response.

Behrens' disclosures include Abbvie, Acelyrin, Amgen, Boehringer-Ingelheim, Bristol-Myers Squibb, Lilly, GSK, Janssen, MoonLake Immunotherapeutics, Novartis, Pfizer, Sandoz, and UCB Pharma.

Reference

Behrens F, Sternad P, Krueger K, et al. AgAIN Study: First Head-to-Head Trial of Secukinumab vs. Ustekinumab in TNFα Inhibitor-Experienced Psoriatic Arthritis Patients Reveals Better Efficacy Across Multiple Domains. Presented at: ACR Convergence 2025; October 24-29; Chicago, Illinois. Poster #LB06.