TY - JOUR
T1 - Clinical trial
T2 - Clinical and endoscopic outcomes with ustekinumab in patients with Crohn's disease: Results from the long-term extension period of STARDUST
AU - Peyrin-Biroulet, Laurent
AU - Vermeire, S. verine
AU - D'Haens, Geert
AU - Panés, Julian
AU - Dignass, Axel
AU - Magro, Fernando
AU - Nazar, Maciej
AU - le Bars, Manuela
AU - Lahaye, Marjolein
AU - Ni, Lioudmila
AU - Bravatà, Ivana
AU - Lavie, Frederic
AU - Daperno, Marco
AU - Lukáš, Milan
AU - Armuzzi, Alessandro
AU - Löwenberg, Mark
AU - Gaya, Daniel R.
AU - Danese, Silvio
N1 - Publisher Copyright: © 2023 Janssen Pharmaceuticals and The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.
PY - 2024/1/1
Y1 - 2024/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85178393995&partnerID=8YFLogxK
U2 - 10.1111/apt.17751
DO - 10.1111/apt.17751
M3 - Article
C2 - 38036946
SN - 0269-2813
VL - 59
SP - 175
EP - 185
JO - Alimentary Pharmacology and Therapeutics
JF - Alimentary Pharmacology and Therapeutics
IS - 2
ER -