Comparative Effectiveness of Nutritional and Biological Therapy in North American Children with Active Crohn's Disease

Background:Therapeutic targets in pediatric Crohn's disease include symptoms, quality of life (QOL), and mucosal healing. Although partial enteral nutrition (PEN), exclusive enteral nutritional (EEN), and anti-tumor necrosis factor alpha (anti-TNF) therapy all improve symptoms, the comparative effectiveness of these approaches to improve QOL and achieve mucosal healing has not been assessed prospectively. Methods:In a prospective study of children initiating PEN, EEN, or anti-TNF therapy for Crohn's disease, we compared clinical outcomes using the Pediatric Crohn's Disease Activity Index (PCDAI), QOL (IMPACT score), and mucosal healing as estimated by fecal calprotectin (FCP). PCDAI, IMPACT, FCP, and diet (prompted 24-h recall) were measured at baseline and after 8 weeks of therapy. Results:We enrolled 90 children with active Crohn's disease (PCDAI, 33.7 ± 13.7; and FCP, 976 ± 754), of whom 52 were treated with anti-TNF, 22 with EEN, and 16 with PEN plus ad lib diet. Clinical response (PCDAI reduction ≥15 or final PCDAI ⩽10) was achieved by 64% on PEN, 88% EEN, and 84% anti-TNF (test for trend P = 0.08). FCP ⩽250 &;g/g was achieved with PEN in 14%, EEN 45%, and anti-TNF 62% (test for trend P = 0.001). Improvement in overall QOL was not statistically significantly different between the 3 groups (P = 0.86). However, QOL improvement was the greatest with EEN in the body image (P = 0.03) domain and with anti-TNF in the emotional domain (P = 0.04). Conclusions:Although PEN improved clinical symptoms, EEN and anti-TNF were more effective for decreasing mucosal inflammation and improving specific aspects of QOL.

[1]  K. Lindor,et al.  A randomized prospective trial comparing a defined formula diet, corticosteroids, and a defined formula diet plus corticosteroids in active Crohn's disease. , 1992, Mayo Clinic proceedings.

[2]  S. Kuriyama,et al.  Effectiveness of an ‘half elemental diet’ as maintenance therapy for Crohn's disease: a randomized‐controlled trial , 2006, Alimentary pharmacology & therapeutics.

[3]  J. Fell,et al.  Improvement in quality of life of children with acute Crohn's disease does not parallel mucosal healing after treatment with exclusive enteral nutrition , 2004, Alimentary pharmacology & therapeutics.

[4]  M. Färkkilä,et al.  Fecal calprotectin concentration predicts outcome in inflammatory bowel disease after induction therapy with TNF&agr; blocking agents , 2012, Inflammatory bowel diseases.

[5]  S. Vermeire,et al.  Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease , 2012, Inflammatory bowel diseases.

[6]  B. Jiang,et al.  Meta-analysis: Fecal Calprotectin for Assessment of Inflammatory Bowel Disease Activity , 2014, Inflammatory bowel diseases.

[7]  P. Rutgeerts,et al.  Infliximab, azathioprine, or combination therapy for Crohn's disease. , 2010, The New England journal of medicine.

[8]  R. Reifen,et al.  Dietary iron affects inflammatory status in a rat model of colitis. , 2004, The Journal of nutrition.

[9]  A. Day,et al.  Effect of exclusive enteral nutrition on bone turnover in children with Crohn’s disease , 2010, Journal of Gastroenterology.

[10]  S. Uccini,et al.  Polymeric diet alone versus corticosteroids in the treatment of active pediatric Crohn's disease: a randomized controlled open-label trial. , 2006, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[11]  M. Färkkilä,et al.  Correlation of faecal calprotectin and lactoferrin with an endoscopic score for Crohn’s disease and histological findings , 2008, Alimentary pharmacology & therapeutics.

[12]  A. Griffiths,et al.  Health‐related quality of life in the first year after a diagnosis of pediatric inflammatory bowel disease , 2006, Inflammatory bowel diseases.

[13]  M. Kamm,et al.  Mucosal Healing in Crohn's Disease: A Systematic Review , 2013, Inflammatory bowel diseases.

[14]  K. Ewe,et al.  Feasibility and effectiveness of a defined-formula diet regimen in treating active Crohn's disease. European Cooperative Crohn's Disease Study III. , 1990, Scandinavian journal of gastroenterology.

[15]  J. Lewis The utility of biomarkers in the diagnosis and therapy of inflammatory bowel disease. , 2011, Gastroenterology.

[16]  Til Stürmer,et al.  Confounder summary scores when comparing the effects of multiple drug exposures , 2010, Pharmacoepidemiology and drug safety.

[17]  M. Boaz,et al.  Partial Enteral Nutrition with a Crohn's Disease Exclusion Diet Is Effective for Induction of Remission in Children and Young Adults with Crohn's Disease , 2014, Inflammatory bowel diseases.

[18]  A. Day,et al.  Systematic review: nutritional therapy in paediatric Crohn’s disease , 2007, Alimentary pharmacology & therapeutics.

[19]  A. Amiot,et al.  Negative Screening Does Not Rule Out the Risk of Tuberculosis in Patients with Inflammatory Bowel Disease Undergoing Anti-TNF Treatment: A Descriptive Study on the GETAID Cohort. , 2016, Journal of Crohn's & colitis.

[20]  A. Griffiths,et al.  Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn's disease. , 2014, Journal of Crohn's & colitis.

[21]  D. Shreeve,et al.  Faecal calprotectin: a marker of inflammation throughout the intestinal tract , 2002, European journal of gastroenterology & hepatology.

[22]  C. Clar,et al.  Faecal calprotectin testing for differentiating amongst inflammatory and non-inflammatory bowel diseases: systematic review and economic evaluation. , 2013, Health technology assessment.

[23]  S. Koletzko,et al.  Influence of Exclusive Enteral Nutrition Therapy on Bone Density and Geometry in Newly Diagnosed Pediatric Crohn's Disease Patients , 2013, Annals of Nutrition and Metabolism.

[24]  Melissa S. Murphy,et al.  Treatment of active Crohn’s disease in children using partial enteral nutrition with liquid formula: a randomised controlled trial , 2005, Gut.

[25]  A. Schoepfer,et al.  Fecal Calprotectin Correlates More Closely With the Simple Endoscopic Score for Crohn's Disease (SES-CD) than CRP, Blood Leukocytes, and the CDAI , 2010, The American Journal of Gastroenterology.

[26]  A. Griffiths,et al.  The IMPACT Questionnaire: A Valid Measure of Health-Related Quality of Life in Pediatric Inflammatory Bowel Disease , 2002, Journal of pediatric gastroenterology and nutrition.

[27]  P. Rutgeerts,et al.  Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn's disease. , 2010, Gastroenterology.

[28]  A. Griffiths,et al.  Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn's disease in children. , 2007, Gastroenterology.

[29]  A. Griffiths,et al.  Outcome measures for clinical trials in paediatric IBD: an evidence-based, expert-driven practical statement paper of the paediatric ECCO committee , 2014, Gut.

[30]  Gaëlle Favé,et al.  Measurement of dietary exposure: a challenging problem which may be overcome thanks to metabolomics? , 2009, Genes & Nutrition.