title: Efficacy and Safety of Escalation of Adalimumab Therapy to Weekly Dosing in Pediatric Patients with Crohn's Disease.
abstract: BACKGROUND
  The efficacy of adalimumab in inducing and maintaining remission in children with moderately to severely active Crohn's disease was shown in the IMAgINE 1 trial (NCT00409682). As per protocol, nonresponders or patients experiencing flare(s) on every other week (EOW) maintenance dosing could escalate to weekly dosing; we aimed to determine the therapeutic benefits of weekly dose escalation in this subpopulation.
  
  
  METHODS
  Week 52 remission and response rates were assessed in patients who escalated to weekly dosing from their previous EOW schedule, which was according to randomized treatment dose (higher dose [HD] adalimumab [≥40 kg, 40 mg EOW; <40 kg, 20 mg EOW] or lower dose [LD; ≥40 kg, 20 mg EOW; <40 kg, 10 mg EOW]). Adverse events were reported for patients remaining on EOW dosing and patients receiving weekly dosing.
  
  
  RESULTS
  Escalation to weekly dosing occurred in 48/95 (50.5%) patients randomized to LD and 35/93 (37.6%) patients randomized to HD adalimumab (P = 0.076). Week 52 remission and response rates were 18.8% and 47.9% for patients receiving LD adalimumab weekly and 31.4% and 57.1% for patients receiving HD adalimumab weekly, respectively (LD versus HD, P = 0.19 for remission; P = 0.41 for response). Adverse event rates were similar for patients receiving EOW and weekly adalimumab.
  
  
  CONCLUSIONS
  Weekly adalimumab dosing was clinically beneficial for children with Crohn's disease who experienced nonresponse or flare on EOW dosing. No increased safety risks were observed with weekly dosing.
authors.affiliation: *Pediatric Gastroenterology and Hepatology, Icahn School of Medicine at Mount Sinai, New York, New York; †Division of Gastroenterology and Nutrition, Goryeb Children's Hospital/Atlantic Health, Morristown, New Jersey; ‡Gastroentrology and Hepatology, Mayo Clinic, Rochester, Minnesota; §Department of Gastroenterology, Hepatology and Feeding Disorders, Children's Memorial Health Institute, Warsaw, Poland; ‖Faculté de Médecine, Universite Paris Descartes, Sorbonne Paris-Cite and Department of Paediatric Gastroenterology, APHP Hopital Necker-Enfants Malades, Paris, France; ¶Digestive Diseases, Hepatology and Nutrition, Connecticut Children's Medical Center, Hartford, Connecticut; **US Medical Affairs, AbbVie Inc., North Chicago, Illinois; ††Data and Statistical Sciences, AbbVie Inc., North Chicago, Illinois; ‡‡Clinical Pharmacology & Pharmacometrics, AbbVie Inc., North Chicago, Illinois; §§AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany; and ‖‖Global Regulatory Affairs, AbbVie Inc., North Chicago, Illinois.
authors.forename: Marla C
authors.initials: MC
authors.lastname: Dubinsky
authors.forename: Joel
authors.initials: J
authors.lastname: Rosh
authors.forename: William A
authors.initials: WA
authors.lastname: Faubion
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Kierkus
authors.forename: Frank
authors.initials: F
authors.lastname: Ruemmele
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Hyams
authors.forename: Samantha
authors.initials: S
authors.lastname: Eichner
authors.forename: Yao
authors.initials: Y
authors.lastname: Li
authors.forename: Bidan
authors.initials: B
authors.lastname: Huang
authors.forename: Nael M
authors.initials: NM
authors.lastname: Mostafa
authors.forename: Andreas
authors.initials: A
authors.lastname: Lazar
authors.forename: Roopal B
authors.initials: RB
authors.lastname: Thakkar
mesh_terms: D000068879:Adalimumab / Q000627:therapeutic use*; D000293:Adolescent; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002648:Child; D003424:Crohn Disease / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D011379:Prognosis; D012449:Safety
chemical_list: D000893:Anti-Inflammatory Agents; D000068879:Adalimumab