title: A prospective study of the efficacy and tolerance of a chimeric antibody to tumor necrosis factors (remicade) in severe pediatric crohn disease.
abstract: OBJECTIVE
  To evaluate the efficacy and toxicity of infliximab in children with severe Crohn disease (CD), the authors prospectively monitored 21 children aged 15 +/- 2 years with severe CD who they treated with infliximab (5 mg/kg) on days 0, 15, and 45. One patient received only one injection. Eighteen patients were corticosteroid dependent, and 6 were receiving parenteral nutrition. Three patients were corticoid resistant (1 mg/kg/d >15 days). Sixteen had perianal disease.
  
  
  RESULTS
  The Harvey-Bradshaw index (HB) decreased from 8 +/- 3 on day 0 to 1 +/- 2 on day 45 (P = 0.001). The inflammation factors decreased (P = 0.001), and albumin increased (P = 0.002). Nineteen children were in complete remission (HB < 4) on day 45, and 2 had improved (HB = -6 points). Tumor necrosis factor-alpha (TNFalpha) in the stools (n = 16) decreased (P = 0.04). All perianal fistulas (n = 12) were closed by day 90. Fourteen of 21 patients had stopped taking steroids at 3 months, and all had stopped parenteral nutrition. Growth velocity was significantly greater after infliximab administration (Z score, +0.5) than before (-0.45; P = 0.004). Nineteen of 21 patients had relapsed (90%) at 1 year despite continued immunosuppressors. Seven had surgery because of an uncontrolled relapse ( 5), stenosis ( 1), or fistula ( 1). Six patients developed antinuclear antibodies (1/40-1/640e), and two had anti-DNA antibodies. Epstein-Barr virus (EBV) polymerase chain reaction (PCR) values increased (>100-fold) in eight patients. One child developed an anaphylactic reaction to the medication, and one had a catheter-related sepsis.
  
  
  CONCLUSIONS
  Infliximab produces spectacular results for children with severe CD and is well tolerated. However, its effect is transitory for many (90%), with frequent relapses despite continued immunosuppressors. Long-term management with infliximab should be tested despite its worrying side effects.
authors.affiliation: Pediatric Gastroenterology Unit, Hôpital Robert Debré, dagger Pediatric Gastroenterology Unit, Hôpital Necker Enfants Malades, and double dagger Laboratory of Coprology, Hôpital Pitié Salpétrière, Paris, France. pierre.cezard@rdb.ap-hop-paris.fr
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Cezard
authors.forename: Nizar
authors.initials: N
authors.lastname: Nouaili
authors.forename: Cécile
authors.initials: C
authors.lastname: Talbotec
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hugot
authors.forename: Jean-Gérard
authors.initials: JG
authors.lastname: Gobert
authors.forename: Jacques
authors.initials: J
authors.lastname: Schmitz
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Mougenot
authors.forename: Corinne
authors.initials: C
authors.lastname: Alberti
authors.forename: Olivier
authors.initials: O
authors.lastname: Goulet
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D003424:Crohn Disease / Q000601:surgery / Q000628:therapy* / Q000821:virology; D005243:Feces / Q000737:chemistry; D005260:Female; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D000069285:Infliximab; D008297:Male; D011446:Prospective Studies; D012008:Recurrence; D012074:Remission Induction; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology*
chemical_list: D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab