Journal Article

Ustekinumab Intravenous Reinduction after Secondary Loss of Response in Patients with Crohn’s Disease

Nazar, Maciej, Lee, Scott D, Gasink, Christopher, Schnoy, Elisabeth, Salzberg, Bruce, Borghorst, Stephan, Wolf, Douglas C, Baker, Thomas, Godwin, Bridget, Feagan, Brian G, Schreiber, Stefan, Busse, Christopher, Adedokun, Omoniyi J, van der Woude, C Janneke, Marín-Jiménez, Ignacio, Ma, Tony

2025

Overview

Abstract Background The POWER study (NCT03782376) evaluated efficacy and safety of a single ustekinumab intravenous (IV) reinduction dose versus placebo under continued ustekinumab subcutaneous (SC) treatment in adult patients with moderately to severely active Crohn’s disease who demonstrated a secondary loss of response to ustekinumab every 8 weeks (q8w) maintenance therapy. Methods Patients were randomly assigned 1:1 at Week 0 to ustekinumab IV reinduction (ustekinumab ∼6 mg/kg and SC placebo) or continuous maintenance (IV placebo and SC ustekinumab 90 mg q8w). Clinical and biomarker assessments occurred at Weeks 0, 8, 16, and 24 with optional ileocolonoscopy at Weeks 0 and16. The primary endpoint was clinical response (≥100-point decrease from baseline Crohn’s Disease Activity Index [CDAI] score or CDAI <150) at Week 16. Safety events were analyzed through Week 36 and serum samples were collected for pharmacokinetic analyses and anti-ustekinumab antibody detection. Results Overall, 215 patients were randomized: 108 to the IV reinduction group and 107 to the SC group. In the IV reinduction group, 49.1% achieved clinical response at Week 16 versus 37.4% in the SC group (adjusted treatment difference 11.5% [95% CI: −1.5%, 24.5%; P = .089]). Proportions of patients with endoscopic remission and improvement, normalization of inflammatory biomarkers, and improvement in IBDQ score were greater in the IV reinduction group vs the SC group. No new safety signals were identified. Conclusions Although the primary endpoint of clinical response was not met at Week 16, ustekinumab IV reinduction showed numerical improvements in objective endpoints including inflammatory biomarkers and endoscopic outcomes compared with SC maintenance therapy. Safety and immunogenicity results were consistent with the established profile of ustekinumab. Lay Summary Some patients with Crohn’s disease who respond to biologic treatment may lose response over time. The POWER study evaluated the efficacy and safety of receiving an additional intravenous dose of ustekinumab in patients who initially lost response to ustekinumab. Graphical abstract Graphical Abstract

• Publisher: Oxford University Press
• Subject: Administration, Intravenous / Adult / Biomarkers / Crohn Disease - drug therapy / Crohn Disease - pathology / Crohn's disease / Double-Blind Method / Endoscopy / Female / Humans / Male / Middle Aged / Remission Induction / Safety / Severity of Illness Index / Treatment Outcome / Ustekinumab - administration & dosage / Ustekinumab - pharmacokinetics / Ustekinumab - therapeutic use / Young Adult