Health Canada approval Remicade® for treatment of pediatric ulcerative colitis

Young Canadians living with the debilitating inflammatory bowel disease ulcerative colitis (UC) will now have access to a new treatment option with Health Canada’s approval of REMICADE® (infliximab) for use in pediatric patients (age six to 17 years). REMICADE® has been approved for the treatment of UC in adults in Canada since 2006.

With this Health Canada approval, REMICADE® represents the first biologic approved for the treatment of pediatric UC. REMICADE® is indicated for the reduction of signs and symptoms, induction and maintenance of clinical remission and induction of mucosal healing, in pediatric patients with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy (i.e., aminosalicylate and/or corticosteroid and/or an immunosuppressant). The safety and efficacy of REMICADE® have not been established in UC patients less than six years of age.[1]

Ulcerative colitis is a chronic inflammatory bowel disease affecting an estimated 88,500 Canadians, including an estimated 1,758 children under 20.[2,3] While the overall clinical features, clinical course of disease and response to treatment are comparable in pediatric and adult populations with UC, pediatric disease is often more extensive and severe. Despite this, there are few approved therapeutic options for pediatric UC.[4,5,6,7]

“Pediatric ulcerative colitis can be a serious condition. The approval of biologic therapy that can help in managing ulcerative colitis in children and adolescents is welcome news,” said Dr. David Mack, Chief of Pediatric Gastroenterology, Hepatology & Nutrition at the Children’s Hospital of Eastern Ontario in Ottawa. “REMICADE® has demonstrated efficacy in the treatment of pediatric UC as evidenced by the clinical trial results and has been used in the treatment of inflammatory bowel disease including adult and pediatric Crohn’s disease for years.”

The approval of REMICADE® for pediatric UC was supported by data from a pivotal Phase 3, randomized, open-label trial that assessed its safety and efficacy in 60 patients age six through 17 with moderately to severely active UC. Eligible patients had an inadequate response to treatment with conventional therapy (i.e. aminosalicylate and/or corticosteroid and/or an immunosuppressant.[8]

In the clinical study, patients were administered REMICADE® 5 mg/kg at weeks 0, 2, and 6. REMICADE® induced a clinical response after eight weeks in 73.3 per cent of the pediatric patients with UC according to the Mayo score, a 12-point clinical assessment and colonoscopy-based measure of disease activity, and the definition of induced clinical remission was met by 40 per cent of patients. Also after eight weeks, 68.3 per cent of patients enrolled in the study achieved mucosal healing and one third (33.3 per cent) had normal or inactive disease as measured by the Mayo endoscopy subscore.[8]

Patients who achieved clinical response at eight weeks (n=45) were randomized to REMICADE® maintenance therapy at two different levels; 5 mg/kg every eight weeks or every 12 weeks. At week 54, 38.1 per cent (8/21) of those in the eight week group and 18.2 per cent (4/22) in the 12 week group were in remission, as measured by the Pediatric UC Activity Index (PUCAI).[8]

REMICADE® was generally well tolerated by the 60 pediatric patients in the study and the safety profile was consistent with that reported in other studies with REMICADE®. No deaths, malignancies, serious neurologic events, opportunistic infections, tuberculosis, serious infusion reactions, delayed hypersensitivity reactions or anaphylactic reactions were reported.[8]

“REMICADE® fills an important need for children and adolescents with ulcerative colitis, which is a very difficult disease for anyone, but particularly for young people,” added Dr. Mack. “It provides a medical option for some who have not responded to other medical therapies and, as such, is an important and effective therapeutic option.”

References

1. REMICADE® Product Monograph, Janssen Inc., 2011.
2. Crohn’s and Colitis Foundation of Canada. The Burden of Inflammatory Bowel Disease (IBD) in Canada: Final Report and Recommendations. 2008: 34, 19-20. Available at:http://www.ccfc.ca/site/c.ajIRK4NLLhJ0E/b.6431205/k.884D/The_Burden_of_IBD_in_Canada.htm. Last accessed: August 22, 2011.
3. Fedorak RN, Wong K, and Bridges R. Canadian Digestive Health Foundation Public Impact Series.  Inflammatory bowel disease in Canada: Incidence, prevalence, and direct and indirect economic impact.  Can J Gastroenterol. 2010 Nov;24(11):65 1-5.
4. Langholz E, Munkholm P, Krasilnikoff PA, Binder V. Inflammatory bowel diseases with onset in childhood. Clinical features, morbidity, and mortality in a regional cohort. Scand J Gastroenterol. 1997;32(2):139-147.
5. Hyams J, Markowitz J, Lerer T, et al. The natural history of corticosteroid therapy for ulcerative colitis in children. Clin Gastroenterol Hepatol. 2006;4(9):1118-1123.
6. Sauer CG, Kugathasan S. Pediatric Inflammatory Bowel Disease: Highlighting pediatric differences in IBD. Gastroenterol Clin N Am.2009:38:611-628.
7. Van Limbergen J, Russell RK, Drummond HE, et al. Definition of phenotypic characteristics of childhood-onset inflammatory bowel disease. Gastroenterology. 2008;135(4):1114-1122.
8. Hyams et al. A Randomized, multicentre, open-label phase III study to evaluate the safety and efficacy of infliximab in pediatric patients with moderate to severe ulcerative colitis.  Presented at the Digestive Disease Week, 7-11 May 2011, Chicago, IL, USA.