Top-down therapy for IBD: rationale and requisite evidence
- 1 February 2010
- journal article
- review article
- Published by Springer Science and Business Media LLC in Nature Reviews Gastroenterology & Hepatology
- Vol. 7 (2), 86-92
- https://doi.org/10.1038/nrgastro.2009.222
Abstract
Early treatment of Crohn's disease with immunomodulators and anti-TNF agents is associated with better clinical outcomes than standard therapy, but these drugs may have serious adverse effects and are not suitable for all patients. The author reviews current clinical evidence and proposes a strategy for adequate selection of patients for top-down therapy of IBD. Several trials have shown that early treatment of Crohn's disease with immunomodulators and anti-TNF agents leads to a superior clinical outcome, including healing of the mucosa, compared with standard therapy alone. Mounting evidence indicates that mucosal healing is associated with a reduced risk of complications, and a reduced need for surgeries and hospitalizations. In the SONIC trial, a combination of the standard azathioprine immunomodulator therapy and infliximab, an anti-TNF agent, had more potent anti-inflammatory effects than either drug alone in patients with Crohn's disease who had evidence of active inflammation. These findings and those from rheumatoid arthritis trials have prompted the investigation of early initiation of immunomodulator (standard or anti-TNF) therapy for Crohn's disease, in suitable patients, which has led to substantial improvements in disease management. Careful selection of patients is, however, essential given the potential risk of toxic effects from these therapies and the fact that some patients with IBD will have a favorable disease course without them. Identification of suitable patients, however, remains a challenge, as genetic, phenotypic and environmental factors have not yet been identified that can be used for routine assessment and selection is mainly based on clinical criteria.This publication has 60 references indexed in Scilit:
- Safety Profile of IBD: Lymphoma RisksGastroenterology Clinics of North America, 2009
- Adalimumab for the treatment of fistulas in patients with Crohn's diseaseGut, 2009
- Mucosal T-cell immunoregulation varies in early and late inflammatory bowel diseaseGut, 2007
- Histologic Inflammation Is a Risk Factor for Progression to Colorectal Neoplasia in Ulcerative Colitis: A Cohort StudyGastroenterology, 2007
- New serological markers in inflammatory bowel disease are associated with complicated disease behaviourGut, 2007
- Mucosal Healing in Inflammatory Bowel Disease: Results From a Norwegian Population-Based CohortGastroenterology, 2007
- Risks and benefits of biologic therapy for inflammatory bowel diseasesGut, 2007
- Slipping the barrier: how variants in CARD15 could alter permeability of the intestinal wall and population healthGut, 2006
- Infliximab Maintenance Therapy for Fistulizing Crohn's DiseaseThe New England Journal of Medicine, 2004
- Clinical pattern of corticosteroid dependent Crohnʼs diseaseEuropean Journal of Gastroenterology & Hepatology, 1998