ORIGINAL ARTICLE Efficacy and Tolerance of Infliximab in Children and Adolescents with Crohn’s Disease Thierry Lamireau, Jean-Pierre Cézard, Alain Dabadie, Olivier Goulet, Alain Lachaux, Dominique Turck, Chantal Maurage, Alain Morali, Etienne Sokal, Dominique Belli, Joaquim Stoller, Samy Cadranel, Jean-Louis Ginies, Sheila Viola, Frédéric Huet, Jane Languepin, Catherine Lenaerts, Françoise Bury, Jacques Sarles, and the French-Speaking Group for Pediatric Gastroenterology and Nutrition Abstract: Infliximab, a monoclonal antibody against tumor necrosis factor-alpha, has been shown to be effective for the treatment of re- fractory Crohn’s disease in adult patients, but experience in pediatrics is limited. This retrospective study included 88 children and adoles- cents, 39 girls and 49 boys, with a median age of 14 years (range 3.3–17.9). Infliximab was indicated for active disease (66%) and/or fistulas (42%) that were refractory to corticosteroids (70%), and/or other immunosuppressive (82%) agents, and/or parenteral nutrition (20%). Patients received 1 to 17 infusions (median 4) of 5 mg/kg (range 3.8–7.3) of infliximab during a median time period of 4 months (1–17 months). Infusion reaction was noted in 13 patients (15%), with a total of 16 reactions in 450 infusions (4%). At Day 90 after the first infusion of infliximab, symptoms improved in 49% of patients, whereas 29% of patients were in remission and 13% of patients re- lapsed. From Day 0 to Day 90, Harvey–Bradshaw score decreased from 7.5 to 2.8 (P < 0.001), C-reactive protein from 36 to 16 mg/L (P < 0.01), and 1-hour erythrocyte sedimentation rate from 35 to 17 mm (P < 0.01). Dosage of corticosteroids decreased from to 0.59 to 0.17 mg/kg/d (P < 0.001); 53% of patients could be weaned of corticoste- roids and 92% of parenteral nutrition. Treatment with infliximab is well tolerated and effective in most children and adolescents with Crohn’s disease that is refractory to conventional immunosuppressive therapy. Nevertheless, long-term efficacy remains to be shown, and further studies are urgently needed to precisely determine the best modality of continuing treatment. Key Words: Crohn’s disease, children, infliximab (Inflamm Bowel Dis 2004;10:745–750) C rohn’s disease (CD) is a chronic inflammatory bowel dis- ease of unknown cause that is characterized by transmural inflammation involving any portion of the gastrointestinal tract. Corticosteroids are effective for inducing remission in adults 1 but are associated with a high prevalence of side effects and lead to altered growth when given for prolonged periods in children. 2,3 Nutritional therapy has been used as an alternative treatment, with efficacy rates ranging from 50% to 82%, espe- cially in children and adolescents with growth failure and/or delayed puberty. 3 Among adult patients receiving corticoste- roids, 20% have corticosteroid-refractory disease, and 36% of those with an initial response develop corticosteroid depen- dence within 1 year, 4 requiring the use of immunomodulatory agents, such as azathioprine or 6-mercaptopurine, methotrex- ate, mycophenolate mofetil, or cyclosporine. 5 Tumor necrosis factor (TNF)- has been identified as a key mediator of inflammation in CD. TNF- production is in- creased in the intestinal mucosa, 6,7 and the fecal concentration of this cytokine is increased in CD patients. 8 Infliximab, a chi- meric (75% human and 25% mouse) monoclonal antibody against TNF-, 9 binds both the soluble subunit and mem- brane-bound precursor of TNF- and inhibits a broad range of its biologic activities. 10 It may also cause lysis of cells that produce TNF-. 11 The use of infliximab has been well docu- mented in adult CD patients 2,12–15 but pediatric experience is mostly from retrospective, short-term series with a limited number of patients. 16–20 We report herein the experience of the French Speaking Group of Pediatric Gastroenterology, Hepa- tology and Nutrition through a large series of pediatric patients treated with infliximab for refractory CD. MATERIAL AND METHODS A multicentric retrospective review of CD patients younger than 18 years of age who were treated with infliximab (Remicade; Shering-Plough, Malvern, PA) was undertaken under the direction of the French-Speaking Group for Pediatric Gastroenterology, Hepatology and Nutrition review board. University Hospital Medical Centers who participated in the Received for publication July 20, 2003; accepted July 26, 2004. From Unité de Gastroentérologie Pédiatrique, Hôpital des Enfants, Place Amélie Raba Léon, Cedex, France. Support for data collection and statistical analysis was provided by Shering- Plough. Reprints: Dr Thierry Lamireau, Unité de Gastroentérologie Pédiatrique, Hôpi- tal des Enfants, Place Amélie Raba Léon, 33077, Bordeaux, Cedex, France (e-mail: thierry.lamireau@chu-bordeaux.fr). Copyright © 2004 by Lippincott Williams & Wilkins Inflamm Bowel Dis • Volume 10, Number 6, November 2004 745 Downloaded from https://academic.oup.com/ibdjournal/article/10/6/745/4718190 by guest on 12 December 2023