Decrease in symptom severity linked to infliximab Crohn’s treatment [Pediatrics Classics Series]

Classics Series, Landmark Trials in Medicine

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1. The severity of Crohn’s disease as assessed by the Pediatric Crohn’s Disease Activity Index in patients recruited from 3 pediatric specialty centers decreased significantly over the course of a 12-week treatment regimen with infliximab.

2. All patients were on corticosteroids at the start of the study; however, steroid administration decreased significantly over the course of the investigation.

Original Date of Publication: August 2000

Study Rundown: Crohn’s disease is an inflammatory bowel disease (IBD) often diagnosed in adolescence and young adulthood and results from an immune-mediated, inflammatory process with the potential to affect any portion of the gastrointestinal tract. Knowing that tumor necrosis factor –α (TNF-α), a cytokine involved in the modulation of the inflammatory responses, is increased in patients with Crohn’s and that the drug infliximab (Remicade) acts to neutralize TNF-α, this study built upon encouraging research in adult patients in investigating the potential utility of infliximab in the pediatric population. In this study, 19 patients with poor response to other therapies were started on varying infliximab dosing schedules. All patients were on daily prednisone at baseline. Crohn’s disease symptom status was assessed at baseline, 1 month, and 3 months into the study through physician assessment and use of the Pediatric Crohn’s Disease Activity Index (PCDAI). Over the study period, the severity of Crohn’s symptoms by PCDAI score and the doses of steroids used to treat disease decreased significantly. This study was limited by the variation in infliximab dosing schedules, lack of a control group, and small sample size. However, it stands as one of the first studies to investigate the use of infliximab in a pediatric population with Crohn’s and indicated many potential positive outcomes.

Following Food and Drug Administration approval in 2006, infliximab was and still is used in pediatric patients with moderate to severe Crohn’s who have not responded adequately to other therapies. While only 3 of the 19 patients in this study experienced any type of adverse reactions, adverse effects from long-term use, including lymphoma, are of major concern in patients. The risk of malignancy along with other severe reactions continues to be investigated. In addition, many patients with Crohn’s are on combined therapies, the efficacy and adverse effects of these regimens are also under investigation.

Click to read the study in The Journal of Pediatrics

In-Depth [prospective cohort study]: Pediatric patients with Crohn’s disease, treated at 3 IBD specialty centers, and who had responded poorly or not at all to previously treatment strategies or depended entirely on corticosteroids, were eligible to participate. A total of 19 patients were recruited (average age 14.4 years, with a mean 3.5 years since diagnosis) to receive infliximab administered intravenously at a dose of 5 mg/kg over 2 hours. The number of treatments varied among participants. Treatment outcomes were assessed by physician assessment and the PCDAI, a physician-completed health evaluation, filled out prior to infliximab treatment and then 4 and 12 weeks after initiation. Patients were followed for an additional 3 to 9 months following the 12-week evaluation. At the time of treatment initiation, all patients had moderate to severe disease as measured by the evaluation tool and all were on daily corticosteroids with 14 participants on an additional agent.

Over the course of treatment, all patients experienced symptomatic improvement. After 4 weeks of therapy, 9 patients were asymptomatic and PCDAI values significantly decreased from 42.1 + 13.7 to 10.0 + 5.6 (p < 0.0001). Over the 12 week study period, patients became increasingly symptomatic, but the 12-week PCDAI still remained significantly lower than the score at the time of treatment initiation at 26.8 + 16.4 (p < 0.01). Prednisone dosing decreased over the course of the study with doses at both 4 weeks and 12 weeks significantly lower than at baseline (28 + 14 mg at baseline v. 20 + 12 mg at 4 weeks and 8 + 12 mg at 12 weeks, p < 0.01) and 9 participants on no corticosteroids at the study’s conclusion. At final follow-up, 3 patients had inactive disease, 9 had mild disease, and 4 had moderate disease. 3 patients experienced adverse reactions such as dyspnea and rash which were controlled in 2 who received pretreatment with diphenhydramine prior to administration of infliximab.

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