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

Data de publicação: 01/01/2024 Data Ahead of Print: 01/11/2023

Autores da FMUP

Fernando José Magro Dias

Autor

Participantes de fora da FMUP

Peyrin-Biroulet, Laurent
Vermeire, Severine
D'Haens, Geert
Panes, Julian
Dignass, Axel
Nazar, Maciej
Le Bars, Manuela
Lahaye, Marjolein
Ni, Lioudmila
Bravata, Ivana
Lavie, Frederic
Daperno, Marco
Lukas, Milan
Armuzzi, Alessandro
Loewenberg, Mark
Gaya, Daniel R.
Danese, Silvio

Unidades de investigação

Biomedicina
Laboratório Associado RISE- Rede de Investigação em Saúde

Investigador

Fernando Carlos De Landér Schmitt
RISE-Health

Investigador

Fernando Carlos De Landér Schmitt

Abstract

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.

Dados da publicação

ISSN/ISSNe:: 0269-2813, 1365-2036
Tipo:: Article
Páginas:: 175-185
DOI:: 10.1111/apt.17751
Link para outro recurso:: www.scopus.com

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Adult; Biomarkers; Crohn Disease; Endoscopy, Gastrointestinal; Humans; Remission Induction; Treatment Outcome; Ustekinumab; adalimumab; azathioprine; beclomethasone dipropionate; biological marker; budesonide; calgranulin; certolizumab pegol; infliximab; new drug; ustekinumab; biological marker; ustekinumab; abdominal pain; adult; adverse drug reaction; arthralgia; Article; backache; clinical outcome; colonoscopy; controlled study; Crohn disease; demographics; drug blood level; drug dose escalation; drug efficacy; drug response; drug safety; drug withdrawal; feces level; female; fever; headache; health care quality; human; immunogenicity; infection; injection site reaction; long term care; major clinical study; male; malignant neoplasm; methodology; remission; rhinopharyngitis; statistical analysis; treat to target; treatment outcome; clinical trial; Crohn disease; gastrointestinal endoscopy; phase 3 clinical trial