Safety and efficacy of adalimumab for moderate to severe Crohn's disease in children

Gastroenterology. 2012 Aug;143(2):365-74.e2. doi: 10.1053/j.gastro.2012.04.046. Epub 2012 May 2.

Abstract

Background & aims: 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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab
  • Adolescent
  • Adrenal Cortex Hormones / therapeutic use
  • Anti-Inflammatory Agents / pharmacokinetics
  • Anti-Inflammatory Agents / therapeutic use*
  • Antibodies, Monoclonal, Humanized / pharmacokinetics
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Child
  • Crohn Disease / drug therapy*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Induction Chemotherapy
  • Maintenance Chemotherapy*
  • Male
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Adrenal Cortex Hormones
  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal, Humanized
  • Immunosuppressive Agents
  • Adalimumab

Supplementary concepts

  • Pediatric Crohn's disease

Associated data

  • ClinicalTrials.gov/NCT00409682