BACKGROUND: STARDUST, a phase 3b randomised trial, compared ustekinumab therapeutic strategies in patients with Crohn's disease (CD) using early endoscopic assessment and treat-to-target (T2T) versus standard of care (SoC). AIM: To assess the efficacy of ustekinumab extended treatment in a long-term extension (LTE) of up to 104 weeks with dosing adapted according to clinical, biomarker and endoscopy outcomes. METHODS: Adults with moderately-to-severely active CD received intravenous ustekinumab approximating 6 mg/kg at Week 0 and subcutaneous ustekinumab 90 mg at Week 8. At Week 16, 440 ≥70-point responders were randomised to T2T or SoC and 323 entered the LTE. At Week 48, a unified, protocol-defined ustekinumab dose frequency escalation/de-escalation was applied based on achieving endoscopic remission and corticosteroid-free clinical remission. Achieving corticosteroid-free clinical remission and biomarker remission at consecutive visits determined ustekinumab dosing frequency. Dichotomous variables were analysed using non-responder imputation. RESULTS: Among patients who entered the LTE, 7.7%, 48.6% and 43.7% received doses every 4, 8 and 12 weeks, respectively. Ustekinumab dose frequency was escalated in 23.5% and de-escalated in 19.7%. Endoscopic response and remission rates were 28.9% and 10.73% (all randomised) and 39.3% and 14.6% (patients entering the LTE), respectively, at Week 104. Clinical remissiona rates at week 104 were 50.2% (all randomised) and 68.4% (patients entering the LTE). There were no new safety signals. CONCLUSION: STARDUST LTE is the first interventional ustekinumab efficacy study to show a favourable benefit-risk profile with preservation of clinical and endoscopic outcomes through Week 104 using flexible, algorithm-driven dose adjustment including de-escalation.

Amsterdam University Medical Centre University of Amsterdam Amsterdam The Netherlands

Clinical Center ISCARE Clinical and Research Center for Inflammatory Bowel Diseases Prague Czech Republic

Department of Biomedical Sciences Humanitas University Milan Italy

Department of Gastroenterology and Hepatology University Hospitals Leuven Leuven Belgium

Department of Gastroenterology Glasgow Royal Infirmary Glasgow UK

Department of Gastroenterology Hospital Clinic of Barcelona IDIBAPS CIBERehd Barcelona Spain

Department of Gastroenterology Hospital de São João Porto Portugal

Department of Medicine 1 Agaplesion Markus Hospital Frankfurt Main Germany

Department of Pharmacology and Therapeutics Institute for Molecular and Cell Biology Faculty of Medicine University of Porto Porto Portugal

Faculty of Medicine of the University of Porto DEPARTAMENTO Porto Portugal

Gastroenterology and Endoscopy IRCCS Ospedale San Raffaele and University Vita Salute San Raffaele Milan Italy

Groupe Hospitalier privé Ambroise Paré Hartmann Paris IBD Center Neuilly sur Seine France

IBD Center IRCCS Humanitas Research Hospital Milan Italy

Janssen Cilag B 5 Breda The Netherlands

Janssen Cilag Issy les Moulineaux France

Janssen Cilag Milan Italy

Janssen Cilag Moscow Russian Federation

Janssen Cilag Polska Sp z o o Warsaw Poland

University of Lorraine INSERM NGERE Nancy France

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