Infliximab dependency in children with Crohn's disease

Aliment Pharmacol Ther. 2009 Apr 1;29(7):792-9. doi: 10.1111/j.1365-2036.2009.03926.x. Epub 2009 Jan 13.

Abstract

Background: Recently, infliximab dependency has been described.

Aim: To assess frequency of ID in 82 consecutive Crohn's disease children treated with infliximab 2000-2006 and to describe clinical and genetic predictors of long-term infliximab response.

Methods: A phenotype model of infliximab dependency was used to assess treatment response: 'immediate outcome' (30 days after infliximab start)--complete/partial/no response. 'Long-term outcome': (i) prolonged response: maintenance of complete/partial response; (ii) infliximab dependency: relapse < or = 90 days after intended infliximab cessation requiring repeated infusions to regain complete/partial response or need of infliximab >12 months to sustain response. Polymorphisms TNF-308 A>G, TNF-857 C>T, Casp9 93 C>T, FasL-844 C>T, LTA 252 C>T and CARD15 (R702W, G908R, 1007fs) were analysed.

Results: Ninety-four per cent of children obtained complete/partial response. In long-term outcome, 22% maintained prolonged response, 12% had no response, while 66% became infliximab dependent. Perianal disease and no previous surgery were associated with infliximab dependency (OR 5.34, 95% CI: 1.24-22.55; OR 6.7, 95% CI: 1.67-26.61). No association was found with studied polymorphisms. The cumulative probability of surgery 50 months after starting infliximab was 10% in infliximab dependency, 30% in prolonged responders and 70% in nonresponders (P = 0.0002).

Conclusions: Sixty-six per cent of children became infliximab dependent. Perianal disease and no surgery prior to infliximab were associated with infliximab dependency phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects*
  • Child
  • Crohn Disease / complications
  • Crohn Disease / drug therapy*
  • Crohn Disease / genetics
  • Dose-Response Relationship, Drug
  • Female
  • Gastrointestinal Agents / administration & dosage
  • Gastrointestinal Agents / adverse effects*
  • Humans
  • Infliximab
  • Male
  • Phenotype
  • Remission Induction
  • Retrospective Studies
  • Substance-Related Disorders* / genetics
  • Time Factors
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Gastrointestinal Agents
  • Infliximab