Response to Induction Therapy in a Pediatric Population of Inflammatory Bowel Disease

Zusammenfassung

Die Crohn-Krankheit (Morbus Crohn) und die Colitis ulcerosa sind 2 entzündliche Darmerkrankungen, charakterisiert durch eine chronische intestinale Entzündung. In dieser Studie wurden die klinischen Charakteristika einer Gruppe pädiatrischer Patienten mit entzündlicher Darmerkrankung überprüft und ihre Reaktionen auf die Induktionstherapie beurteilt. Für 43 Patienten (20 mit Morbus Crohn und 23 mit Colitis ulcerosa) wurde, gestützt auf die initiale Aktivität, mittels PCDAI und PUCAI die Heftigkeit der Erkrankung bestimmt und die Therapie eingeleitet. Anschließend wurde die Aktivität 6 Monate nach der ersten Diagnose noch einmal überprüft. Die Patienten beider Gruppen litten unter milder bis schwerer Erkrankung. Die durchschnittlichen PCDAI- und PUCAI-Werte betrugen 60,62 ± 16,48 und 50,95 ± 9,35, jeweils für Morbus-Crohn- bzw. Colitis-ulcerosa-Patienten. Die meisten Patienten (83,7 %) reagierten auf Standardbehandlungen mit signifikanter Reduktion der PCDAI- und PUCAI-Ergebnisse des Ausgangspunkts (p-Wert < 0,001). Am ursprünglichen Endpunkt von 24 Wochen waren 54 % aller Patienten in klinischer Remission; 16 von 23 in der Colitis-ulcerosa-Gruppe (70 %) und 6 von 20 in der Morbus-Crohn-Gruppe (30 %). Die Ergebnisse dieser Studie geben Klarheit darüber, dass die Einteilung pädiatrischer Patienten mit chronisch entzündlicher Darmerkrankung in unterschiedliche klinische Phänotypen, basierend auf der Aktivität der anfänglichen Symptomatik, Anhalt für ein besseres Management dieser Gruppe liefern und die Nebenwirkungen unnötiger Therapien reduzieren könnte.

Abstract

Crohn’s disease (CD) and ulcerative colitis (UC) are two inflammatory bowel diseases (IBD) characterized by chronic intestinal inflammation. In this study, the clinical characteristics of a cohort of pediatric patients with IBD are reviewed and their responses to induction therapy are evaluated. The severity of disease for 43 patients (20 with CD and 23 with UC) was determined using the PCDAI and PUCAI and based on the initial severity, before treatment was started. Following treatment, the severity of disease was re-evaluated at 6 months after the initial diagnosis. The patients in both groups had mild-to-severe disease. The mean PCDAI and PUCAI values were 60.62 ± 16.48 and 50.95 ± 9.35, for CD and UC patients, respectively. Most patients (83.7 %) responded to standard treatments with a significant reduction in the PCDAI and PUCAI scores from baseline (p value < 0.001). At the primary endpoint of 24 weeks, 54 % of all patients were in clinical remission; 16 of 23 in the UC group (70 %) and 6 of 20 in the CD group (30 %). The results of this study provide evidence that subgrouping pediatric patients with IBD into distinct clinical phenotypes based on severity of the initial presentation may provide better means of management of this group. This approach can result in a better response to treatment and reduce the side effects of unnecessary therapy.

Schlüsselwörter

Crohn-Krankheit (Morbus Crohn) - Colitis ulcerosa - entzündliche Darmerkrankung - Heftigkeit - Behandlung

Key words

Crohn’s disease - ulcerative colitis - inflammatory bowel diseases - severity - treatment

References

• 1 Baldassano R N, Piccoli D A. Inflammatory bowel disease in pediatric and adolescent patients.  Gastroenterol Clin North Am. 1999;  28 445-458
• 2 Bernstein C N, Blanchard J F. The epidemiology of Crohn’s disease.  Gastroenterology. 1999;  116 1503-1504
• 3 Farrokhyar F, Swarbrick E R. A critical review of epidemiological studies in inflammatory bowel disease.  Scand J Gastroenterol. 2001;  36 2-15
• 4 Kugathasan S, Judd R H, Hoffmann R G. et al . Wisconsin Pediatric Inflammatory Bowel Disease Alliance. Epidemiologic and clinical characteristics of children with newly diagnosed inflammatory bowel disease in Wisconsin: a statewide population based study.  J Pediatr. 2003;  143 525-531
• 5 Polito 2nd  J M, Childs B, Mellits E D. et al . Crohn’s disease: influence of age at diagnosis on site and clinical type of disease.  Gastroenterology. 1996;  111 580-586
• 6 Farmer R G, Michener W M. Prognosis of Crohn’s disease with onset in childhood or adolescence.  Dig Dis Sci. 1979;  24 752-757
• 7 Louis E, Peeters M, Franchimont D. et al . Tumour necrosis factor (TNF) gene polymorphism in Crohn’s disease (CD): influence on disease behaviour?.  Clin Exp Immunol. 2000;  119 64-68
• 8 Davies G, Evans C M, Shand W S. et al . Surgery for Crohn’s disease in childhood: influence of site of disease and operative procedure on outcome.  Br J Surg. 1990;  77 891-894
• 9 Rufo P A, Bousvaros A. Current therapy of inflammatory bowel disease in children.  Paediatr Drugs. 2006;  8 279-302
• 10 Hyams J, Markowitz J, Otley A. et al . Evaluation of the pediatric crohn disease activity index: a prospective multicenter experience. Pediatric Inflammatory Bowel Disease Collaborative Research Group.  J Pediatr Gastroenterol Nutr. 2005;  41 416-421
• 11 Hyams J S, Ferry G D, Mandel F S. et al . Development and validation of a pediatric Crohn’s disease activity index.  J Pediatr Gastroenterol Nutr. 1991;  12 439-447
• 12 Turner D, Otley A R, Mack D. et al . Development, validation, and evaluation of a pediatric ulcerative colitis activity index: a prospective multicenter study.  Gastroenterology. 2007;  133 423-432
• 13 Fallahi G H, Moazzami K, Tabatabaeiyan M. et al . Clinical characteristics of Iranian pediatric patients with inflammatory bowel disease.  Act Gastroenterol Belg. 2009;  72 230-234
• 14 Bousvaros A, Leichtner A. Overview of the management of Crohn’s disease in children and adolescents (online). Available from URL: http://www.upto-date.com (Accessed 2006 Sep 27)
• 15 Gremse D A, Crissinger K D. Ulcerative colitis in children: medical management.  Paediatr Drugs. 2002;  4 807-815
• 16 Hyams J S, Davis P, Grancher K. et al . Clinical outcome of ulcerative colitis in children.  J Pediatr. 1996;  129 81-88
• 17 Ferry G D, Kirschner B S, Grand R J. et al . Olsalazine versus sulfasalazine in mild to moderate childhood ulcerative colitis: results of the Pediatric Gastroenterology Collaborative Research Group Clinical Trial.  J Pediatr Gastroenterol Nutr. 1993;  17 32-38
• 18 Singleton J W, Hanauer S B, Gitnick G L. et al . Mesalamine capsules for the treatment of active Crohn’s disease: results of a 16-week trial. Pentasa Crohn’s Disease Study Group.  Gastroenterology. 1993;  104 1293-1301
• 19 Summers R W, Switz D M, Sessions J T. et al . National Co-operative Crohn’s Disease Study: results of drug treatment.  Gastroenterology. 1979;  77 847-869
• 20 Malchow Jr H, Ewe K, Brandes J W. et al . European Co-operative Crohn’s Disease Study (ECCDS): results of drug treatment.  Gastroenterology. 1984;  86 249-266
• 21 Hyams J, Markowitz J, Lerer T. et al . Pediatric Inflammatory Bowel Disease Collaborative Research Group. The natural history of corticosteroid therapy for ulcerative colitis in children.  Clin Gastroenterol Hepatol. 2006;  4 1118-1123
• 22 Levine A, Milo T, Buller H. et al . Consensus and controversy in the management of pediatric Crohn disease: an international survey.  J Pediatr Gastroenterol Nutr. 2003;  36 464-469
• 23 Herzog D, Bishop N, Glorieux F. et al . Interpretation of bone mineral density values in pediatric Crohn’s disease.  Inflamm Bowel Dis. 1998;  4 261-267
• 24 Sandborn W, Sutherland L, Pearson D. et al . Azathioprine or 6-mercaptopurine for inducing remission of Crohn’s disease.  Cochrane Database Syst Rev. 2000;  CD000545
• 25 Pearson D C, May G R, Fick G. et al . Azathioprine for maintaining remission of Crohn’s disease.  Cochrane Database Syst Rev. 2000;  CD000067
• 26 Kozuch P L, Hanauer S B. Treatment of inflammatory bowel disease: a review of medical therapy.  World J Gastroenterol. 2008;  14 354-377
• 27 Markowitz J, Grancher K, Kohn N. et al . A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn’s disease.  Gastroenterology. 2000;  119 895-902
• 28 Rosenberg J L, Wall A J, Levin B. et al . A controlled trial of azathioprine in the management of chronic ulcerative colitis.  Gastroenterology. 1975;  69 96-99
• 29 Kirk A P, Lennard-Jones J E. Controlled trial of azathioprine in chronic ulcerative colitis.  Br Med J (Clin Res Ed). 1982;  284 1291-1292
• 30 Boot A M, Bouquet J, Krenning E P. et al . Bone mineral density and nutritional status in children with chronic inflammatory bowel disease.  Gut. 1998;  42 188-194