Treatment of Inflammatory Bowel Disease with Biologics by Adam S. Cheifetz & Joseph D. Feuerstein

Author:Adam S. Cheifetz & Joseph D. Feuerstein
Language: eng
Format: epub
Publisher: Springer International Publishing, Cham

Infliximab for Pediatric Ulcerative Colitis

Infliximab was FDA approved for the treatment of moderate to severe p ediatric ulcerative colitis in 2011; however, similar to pediatric CD, this medication was used off-label for pediatric patients with refractory colitis for several years prior to approval based on adult data and smaller pediatric case series demonstrating efficacy of this therapy. A preliminary case series by Mamula et al. showed that seven of nine patients (77%) with moderate to severe UC that was refractory to traditional therapy had a clinical response to infliximab as measured by the PGA, with six of these patients having inactive disease 2 weeks after the infusion [19]. A steroid-sparing effect was seen and 66% of these patients were able to discontinue corticosteroid therapy. Nine patients in this cohort were reevaluated after a minimum of 2 years of follow-up, and 73% of these patients were considered to be responders to the initial dose [20]. Two of these patients lost response within 9 months, and the remaining five responders had a sustained response, three of whom were doing well without ongoing infliximab therapy. A clinical response rate of 88% was seen in an additional eight patients with refractory UC treated with infliximab [20]. In total, 14 of 17 patients (82%) developed a short-term response, and 10 patients (63%) developed a long-term response to infliximab therapy. Another retrospective single-center study evaluated the response to infliximab in 12 pediatric patients with UC, 3 with fulminant colitis, 3 with an acute relapse of disease, 5 with steroid-dependent colitis, and 1 with corticosteroid-refractory colitis [21]. Nine patients (75%) developed a complete short-term response, two had a partial response, and eight patients had a long-term response to infliximab (median follow-up 10.4 months). In this small study, long-term response to infliximab therapy was more likely in patients who were receiving concomitant mercaptopurine. A larger single-center retrospective series by McGinnis et al. evaluated the short- and long-term response to infliximab induction in 40 pediatric UC patients with steroid-dependent or steroid-resistant disease [22]. Twenty-eight patients (70%) had a clinical response to infliximab, including 9 of 12 patients with steroid-dependent disease and 18 or 27 with steroid-refractory disease. Over the study period, 20% of responders had undergone colectomy compared to 82% of nonresponders. A multicenter cohort, inception cohort study of 332 pediatric patients with UC prospectively evaluated outcomes of 52 patients who received continuous maintenance therap y or episodic treatment with infliximab [23]. Approximately 35% of these patients had corticosteroid-free inactive or mild disease at 3-, 6-, 12-, and 24-month assessments, and 61% were colectomy-free at 24 months. Looking at the subset of patients receiving continuous maintenance therapy, approximately 50% of the patients had inactive or mild disease across these time points, and the likelihood of being colectomy-free was 74% at 24 months, suggesting additional benefit on maintenance dosing. These remission rates were lower than previously reported; however, 50% of this cohort was hospitalized at initiation of infliximab, perhaps suggesting more severe or chronic disease.

Patients with chronic ulcerative colitis refractory

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