title: Safety and efficacy of adalimumab for moderate to severe Crohn's disease in children.
abstract: OBJECTIVE
  The IMAgINE 1 study (NCT00409682) evaluated the safety and efficacy of adalimumab double-blind maintenance dosing regimens following open-label induction for pediatric patients with moderate to severe Crohn's disease (CD).
  
  
  METHODS
  We studied 192 patients with Pediatric Crohn's Disease Activity Index (PCDAI) scores >30 for whom conventional treatment was unsuccessful. Patients received open-label induction therapy with subcutaneous adalimumab at weeks 0 and 2 (160 mg and 80 mg, or 80 mg and 40 mg, for body weight ≥40 kg or <40 kg). At week 4, 188 patients were assigned to groups based on achievement of clinical response (defined as decrease in PCDAI ≥15 points from baseline; 155/188 [82.4%]) and prior exposure to infliximab (82/188 [43.6%]). Groups were given double-blind maintenance therapy with adalimumab at high (40 mg or 20 mg for body weight ≥40 kg or <40 kg; n = 93) or low doses (20 mg or 10 mg for body weight ≥40 kg or <40 kg; n = 95) every other week for 48 weeks. Clinical remission (PCDAI ≤10) at week 26 (the primary end point) was compared between groups using the Cochran-Mantel-Haenszel test, adjusting for strata, with nonresponder imputation. Adverse events were monitored to evaluate safety.
  
  
  RESULTS
  A total of 152 of 188 patients (80.9%) completed all 26 weeks of the study. At week 26, 63 patients (33.5%) were in clinical remission, with no significant difference between high- and low-dose groups (36/93 [38.7%] vs 27/95 [28.4%]; P = .075). No new safety signals were detected.
  
  
  CONCLUSIONS
  Adalimumab induced and maintained clinical remission of children with CD, with a safety profile comparable to that of adult patients with CD. More children who received high compared with low dose were in remission at week 26, but the difference between dose groups was not statistically significant.
authors.affiliation: Connecticut Children's Medical Center, Hartford, CT, USA. jhyams@ccmckids.org
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Hyams
authors.forename: Anne
authors.initials: A
authors.lastname: Griffiths
authors.forename: James
authors.initials: J
authors.lastname: Markowitz
authors.forename: Robert N
authors.initials: RN
authors.lastname: Baldassano
authors.forename: William A
authors.initials: WA
authors.lastname: Faubion
authors.forename: Richard B
authors.initials: RB
authors.lastname: Colletti
authors.forename: Marla
authors.initials: M
authors.lastname: Dubinsky
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Kierkus
authors.forename: Joel
authors.initials: J
authors.lastname: Rosh
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Wang
authors.forename: Bidan
authors.initials: B
authors.lastname: Huang
authors.forename: Barry
authors.initials: B
authors.lastname: Bittle
authors.forename: Michael
authors.initials: M
authors.lastname: Marshall
authors.forename: Andreas
authors.initials: A
authors.lastname: Lazar
mesh_terms: D000068879:Adalimumab; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D003424:Crohn Disease / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D060828:Induction Chemotherapy; D060046:Maintenance Chemotherapy; D008297:Male; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D000068879:Adalimumab