Thomas D Walters1, William A Faubion, Anne M Griffiths, Robert N Baldassano, Johanna Escher, Frank M Ruemmele, Jeffrey S Hyams, Andreas Lazar, Samantha Eichner, Bidan Huang, Yao Li, Roopal B Thakkar. 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.
Abstract
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.
RCT Entities:
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.
Authors: David R Mack; Eric I Benchimol; Jeff Critch; Jennifer deBruyn; Frances Tse; Paul Moayyedi; Peter Church; Colette Deslandres; Wael El-Matary; Hien Huynh; Prévost Jantchou; Sally Lawrence; Anthony Otley; Mary Sherlock; Thomas Walters; Michael D Kappelman; Dan Sadowski; John K Marshall; Anne Griffiths Journal: J Can Assoc Gastroenterol Date: 2018-07-10