Clinical trial: Clinical and endoscopic outcomes with ustekinumab in patients with Crohn's disease: Results from the long-term extension period of STARDUST.

Autor: Peyrin-Biroulet L; University of Lorraine, INSERM, NGERE, Nancy, France.; Groupe Hospitalier privé Ambroise Paré-Hartmann, Paris IBD Center, Neuilly sur Seine, France., Vermeire S; Department of Gastroenterology & Hepatology, University Hospitals Leuven, Leuven, Belgium., D'Haens G; Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, The Netherlands., Panés J; Department of Gastroenterology, Hospital Clinic of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain., Dignass A; Department of Medicine I, Agaplesion Markus Hospital, Frankfurt/Main, Germany., Magro F; Department of Pharmacology & Therapeutics, Institute for Molecular and Cell Biology, Faculty of Medicine, University of Porto, Porto, Portugal.; Department of Gastroenterology, Hospital de São João, Porto, Portugal., Nazar M; Janssen-Cilag, Polska Sp. z o.o, Warsaw, Poland., Le Bars M; Janssen-Cilag, Issy-les-Moulineaux, France., Lahaye M; Janssen-Cilag, B.V, Breda, The Netherlands., Ni L; Janssen-Cilag, Moscow, Russian Federation., Bravatà I; Janssen-Cilag, Milan, Italy., Lavie F; Janssen-Cilag, Issy-les-Moulineaux, France., Daperno M; Faculty of Medicine of the University of Porto, CINTESIS@RISE, DEPARTAMENTO, Porto, Portugal., Lukáš M; Clinical Center ISCARE, Clinical and Research Center for Inflammatory Bowel Diseases, Prague, Czech Republic., Armuzzi A; IBD Center, IRCCS Humanitas Research Hospital, Milan, Italy.; Department of Biomedical Sciences, Humanitas University, Milan, Italy., Löwenberg M; Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, The Netherlands., Gaya DR; Department of Gastroenterology, Glasgow Royal Infirmary, Glasgow, UK., Danese S; Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy.
Jazyk: angličtina
Zdroj: Alimentary pharmacology & therapeutics [Aliment Pharmacol Ther] 2024 Jan; Vol. 59 (2), pp. 175-185. Date of Electronic Publication: 2023 Nov 30.
DOI: 10.1111/apt.17751
Abstrakt: 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 remission a 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.
(© 2023 Janssen Pharmaceuticals and The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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