Ustekinumab in paediatric patients with moderately to severely active Crohn's disease: UniStar study long-term
Dan Turner1, Joel R Rosh2, Stanley A Cohen3
1The Juliet Keidan Institute of Paediatirc Gastroenterology and Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel.
Insights
Ustekinumab demonstrated comparable efficacy, safety, and immunogenicity in pediatric Crohn's disease patients over 240 weeks, mirroring adult study findings. Pharmacokinetics were also assessed, showing consistent levels and lower concentrations in younger patients.
Area of Science:
- Pediatric Gastroenterology
- Immunology
- Pharmacology
Background:
- Crohn's disease (CD) is a chronic inflammatory condition affecting children.
- Limited long-term data exists for ustekinumab in pediatric CD patients.
Purpose of the Study:
- To evaluate the long-term efficacy, safety, immunogenicity, and pharmacokinetics of ustekinumab in pediatric CD patients.
- Assess treatment outcomes up to 240 weeks in the UniStar trial's long-term extension (LTE).
Main Methods:
- Paediatric patients with moderately to severely active CD received intravenous ustekinumab, followed by subcutaneous maintenance doses.
- Patients entered the LTE and continued maintenance dosing every 8 weeks up to 240 weeks.
- Stratification by body weight (<40 or ≥40 kg) guided dosing.
Main Results:
- 41.2% of patients achieved clinical remission at Week 48.
- CRP normalization was observed in 29.2% of patients with elevated baseline CRP at Week 48.
- Common adverse events included infections and gastrointestinal disorders; worsening of CD was the most common serious adverse event.
- Antibodies to ustekinumab were detected in only one patient.
- Median serum ustekinumab concentrations remained consistent and were detectable through Week 224.
Conclusions:
- Ustekinumab treatment in pediatric CD patients showed efficacy and pharmacokinetic profiles comparable to adult data.
- Safety and immunogenicity through 4 years were also consistent with previous adult findings.
- The study provides valuable long-term data for ustekinumab use in pediatric CD.
Objectives:
To assess the efficacy, safety, immunogenicity, and pharmacokinetics through 240 weeks of ustekinumab treatment in paediatric patients from the long-term extension (LTE) of the phase 1, double-blind UniStar trial.
Methods:
Paediatric patients with moderately to severely active Crohn's disease (CD) were randomised 1:1 and stratified by body weight (<40 or ≥40 kg) to low- or high-dose intravenous ustekinumab followed by a subcutaneous maintenance dose at Week 8. At Week 16, patients were eligible to enter the LTE at the discretion of the investigator and continued maintenance dosing every 8 weeks up to Week 240.
Results:
Of the 34 patients who entered the LTE, 25 patients with evaluable data completed Week 48, and 41.2% (14/34) achieved clinical remission at Week 48. Among the 24 patients with Week-0 C-reactive protein (CRP) levels ≥3 mg/L, 29.2% (7/24) achieved normalisation of CRP at Week 48, while imputing missing data as failures. Through Week 240, the most common adverse events were infections (n = 28) and gastrointestinal disorders (n = 26). The most common serious adverse event was worsening of CD (n = 6). Only one patient had detectable antibodies to ustekinumab. Median serum ustekinumab concentrations remained consistent through Week 48, were detectable through Week 224, and trended lower in patients <40 kg.
Conclusions:
Efficacy and pharmacokinetics through 1 year and safety and immunogenicity through 4 years of ustekinumab treatment in paediatric patients with CD were generally comparable to those previously reported in adults.
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