Outcome of Infliximab Therapy in Children with Refractory Crohnʼs Disease

Abstract

Purpose: Crohn's disease (CD) is a chronic inflammatory bowel disorder that can affect children and adults. Treatments include anti-inflammatory and immunomodulator drugs. Due to the potential side effects of impaired growth and osteoporosis due to chronic corticosteroid therapy, steroid-sparing agents are often utilized for treatment of refractory CD. Inflimixab, a monoclonal antibody to TNFα has been increasingly used for treatment of CD refractory to treatment with other medications. Methods: The medical records of pediatric patients with Crohn's disease treated with infliximab were reviewed. Demographic characteristics, concomitant medication use, Pediatric Crohn's Disease Activity Index (PCDAI), and the presence/absence of extraintestinal manifestations were analyzed. All patients received induction therapy with intravenous infliximab 5 mg/kg over 2 hours at 0, 2, and 6 weeks. Treatment efficacy was determined by the change in PCDAI, where < 10 is in remission and >30 is moderate to severe disease. Results: The medical records of fifteen patients, age 13.8 ± 2.8 yr, x ± SD, range 8–18 yr, 40% male) with CD who were treated with infliximab were reviewed. There were 9 patients with inflammatory disease and 6 with fistulizing disease with a distribution of 12 with ileocolonic, 2 ileal, and 1 jejunal disease. Concomitant medications at baseline included antibiotics (n = 13), azathioprine (n = 11), 5-aminosalicylates (5-ASA, n = 10), methotrexate (n = 2), and nonsteroidal anti-inflammatory drugs (n = 5). The PCDAI score significantly decreased after infliximab therapy (40.1 ± 13.3 vs. 10.9 ± 8.2, pre- and post- infliximab, respectively, p = 0.0000025). The PCDAI score decreased in all patients and 10 of 15 patients were in remission as defined by a PCDAI of ≤ 10. Corticosteroids were used an average of 11.5 months prior to infliximab therapy and were able to be discontinued in 13 of 15 patients. Eleven patients continue to receive infliximab every 8 weeks for maintenance therapy (duration of therapy 26.7 ± 8.7 months, range 15 – 44 mo.) while infliximab was discontinued in 4 patients after fistula closure was achieved. Four patients underwent surgery (2 for fistulae, 2 for resection). Conclusions: Infliximab significantly reduced the PCDAI and improved symptoms of CD in children with refractory disease. Infliximab can be effective therapy for pediatric patients with refractory Crohn's disease.