Ustekinumab in Paediatric Patients with Moderately to Severely Active Crohn's Disease: Pharmacokinetics, Safety, and Efficacy Results from UniStar, a Phase 1 Study

摘要

Background and Aims: The objective was to evaluate the pharmacokinetics, safety/tolerability, and efficacy of ustekinumab in children with moderately to severely active Crohn's disease. Methods: In this Phase 1, multicentre, 16-week, double-blind, induction dose-ranging study NCT02968108, patients aged 2-= 10 kg were randomised 1:1 to one of two weight range-based intravenous induction doses: 130 mg vs 390 mg in patients >= 40kg and 3 mg/kg vs 9 mg/kg in patients = 40kg or 2 mg/kg in patients = 40 kg and the reference Phase 3 adult population. Through Week 16, 73 of patients reported >= 1 adverse event 82.6 lower vs 62 higher dose; two discontinued due to adverse events one in each group. Serious adverse events occurred in 16 26 lower, 5 higher dose, with Crohn's disease exacerbation being the most frequent. At Week 16, 22/29 lower/higher dose achieved clinical remission Paediatric Crohn's Disease Activity Index <= 10. Conclusions: The pharmacokinetics/safety profiles were generally consistent with those observed in adults with Crohn's disease. These results suggest a different dosing regimen may be required for patients <40 kg from that employed in this study; additional pharmacokinetic analyses may be needed in this population.