Growth Improvement with Adalimumab Treatment in Children with Moderately to Severely Active Crohn's Disease
Thomas D Walters1, William A Faubion, Anne M Griffiths
1*Department of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada; †Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN; ‡Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA; §Department of Pediatric Gastroenterology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands; ‖Department of Pediatrics, Pediatric Gastroenterology, Universite Sorbonne Paris-Cite, Hospital Necker-Enfants Malades, Paris, France; ¶Division of Digestive Diseases, Hepatology and Nutrition, Connecticut Children's Medical Center, Hartford, CT; **AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany; and ††AbbVie Inc., North Chicago, IL.
Insights
Adalimumab (ADA) treatment normalized growth rates in children with Crohn's disease and growth impairment. This study shows adalimumab (ADA) is effective for pediatric Crohn's disease growth failure.
Area of Science:
- Pediatric Gastroenterology
- Inflammatory Bowel Disease Research
- Clinical Trial Analysis
Background:
- Growth failure is a significant complication in pediatric Crohn's disease.
- Adalimumab (ADA), a TNF antagonist, is investigated for its impact on linear growth.
- The IMAgINE 1 trial specifically assessed ADA's effect on height velocity in children with baseline growth impairment.
Purpose of the Study:
- To evaluate the efficacy of adalimumab (ADA) in improving height velocity in pediatric Crohn's disease patients with baseline growth impairment.
- To compare growth rates between patients with and without baseline growth impairment during ADA therapy.
- To assess the impact of induction therapy response on subsequent growth outcomes.
Main Methods:
- Analysis of pediatric patients with growth potential and active Crohn's disease refractory to conventional therapy.
- Administration of open-label adalimumab (ADA) induction followed by double-blind, randomized maintenance therapy.
- Height velocity z-scores were measured at baseline, week 26, and week 52, stratified by baseline growth status.
Main Results:
- Adalimumab (ADA) significantly improved and normalized growth rates in patients with baseline growth impairment by weeks 26 and 52 (P < 0.001).
- No significant growth rate changes were observed in patients with normal baseline growth.
- Early responders to ADA induction showed significantly greater growth improvement by week 26 compared to non-responders (P = 0.02).
Conclusions:
- Adalimumab (ADA) treatment effectively normalizes growth rates in children with moderate to severe Crohn's disease and growth impairment.
- Growth normalization can be achieved as early as 26 weeks of adalimumab (ADA) therapy.
- The findings support adalimumab's (ADA) role in managing growth failure associated with pediatric Crohn's disease.
Background:
Growth failure is common in children with Crohn's disease. The effect of adalimumab (ADA), a fully human antitumor necrosis factor antagonist, on height velocity in pediatric patients with baseline (BL) linear growth impairment in the IMAgINE 1 trial is presented.
Methods:
This analysis included female and male patients with growth potential (bone age ≤13 and ≤14 yr, respectively), with BL Pediatric Crohn's disease Activity Index >30, and who failed or were intolerant to conventional therapy. Patients received open-label induction ADA at weeks 0 and 2 by body weight (≥40 kg, 160 and 80 mg and <40 kg, 80 and 40 mg). At week 4, patients were randomized to double-blind high (40 or 20 mg for ≥40 kg or <40 kg) or low dose (20 or 10 mg for ≥40 kg or <40 kg) every other week ADA to week 52. Height velocity z-score was summarized at BL, week 26, and week 52 by patients with BL growth impairment (z-score ≤-1.0) or normal growth (z-score >-1.0).
Results:
ADA therapy significantly improved and normalized growth rate at weeks 26 and 52 in patients with BL growth impairment (median z-score, BL, -3.25; week 26, -0.34; and week 52, 0.21; P < 0.001 versus BL for both), but not in patients with normal growth. Growth improvement was significantly greater at week 26 in week 4 responders to induction therapy compared with nonresponders (median z-score 0.09 versus -2.92; P = 0.02).
Conclusions:
ADA treatment resulted in growth rate normalization as early as week 26 in children with moderately to severely active Crohn's disease and growth impairment.
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