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

Summary 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.