Mucosal Healing in Paediatric Patients with Moderate-to-Severe Luminal Crohn's Disease Under Combined Immunosuppression: Escalation versus Early Treatment

J Crohns Colitis. 2016 Nov;10(11):1279-1286. doi: 10.1093/ecco-jcc/jjw086. Epub 2016 Apr 19.

Abstract

Background and aims: We aimed to compare the efficacy of combined immunosuppression in terms of mucosal healing in paediatric patients with moderate-to-severe luminal Crohn's disease receiving infliximab according to either an 'escalated combined immunosuppression' or an 'early combined immunosuppression' strategy.

Methods: In this prospective observational study, the efficacy of combined immunosuppression was evaluated in terms of mucosal healing at weeks 14 and 54 from baseline infliximab infusion. Comparison was performed between the escalated combined immunosuppression group [group A] and the early combined immunosuppression group [group B]. Factors associated with mucosal healing at weeks 14 and 54 from baseline infliximab infusion were also investigated.

Results: Seventy-six patients initiated infliximab with concomitant azathioprine [group A = 28; group B = 48]. Comparison of baseline characteristics revealed a significantly longer duration from initial diagnosis to infliximab infusion in group A [median 8.1 vs. 0.7 months; p < 0.001]. Mucosal healing was achieved in 32% of patients in group A and 51% in group B at week 14 [p = 0.121], and in 42% in group A and 74% in group B at week 54 [p = 0.007]. Group B was also positively associated with mucosal healing at week 54 on multivariate logistic regression [odds ratio = 6.216, 95% confidence interval = 1.782-21.686, p = 0.004].

Conclusions: Mucosal healing during combined immunosuppression is more effectively achieved by treatment with an early combined immunosuppression strategy without corticosteroid induction administered within 1 month rather than escalating to receive combination therapy later during the course. The therapeutic window of opportunity in early Crohn's disease may be shorter than generally thought, especially in children.

Keywords: combined immunosuppression; mucosal healing; paediatric Crohn’s disease.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Azathioprine / administration & dosage
  • Azathioprine / therapeutic use
  • Child
  • Crohn Disease / drug therapy*
  • Crohn Disease / pathology
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / therapeutic use*
  • Infliximab / administration & dosage
  • Infliximab / therapeutic use*
  • Intestinal Mucosa / pathology*
  • Male
  • Mesalamine / administration & dosage
  • Mesalamine / therapeutic use
  • Prospective Studies
  • Treatment Outcome

Substances

  • Immunosuppressive Agents
  • Mesalamine
  • Infliximab
  • Azathioprine

Supplementary concepts

  • Pediatric Crohn's disease