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Role of genetics in prediction of disease course and response to therapy

World Journal of Gastroenterology 2010年第21期16卷 2609-2615页

作者： Severine Vermeire Gert Van Assche paul rutgeerts Department of Gastroenterology University Hospital Gasthuisberg and Catholic University LeuvenB-3000 LeuvenBelgium

The clinical course of Crohn's disease and ulcerative colitis is highly variable between patients,and this has therapeutic implications.A number of clinical features have been identified,which predict a mild or more severe ***,several of these are subjective and/or not persistent over *** the progress in genetics research in inflammatory bowel disease(IBD),genetic markers are increasingly being proposed to improve stratification of *** have the major advantage of being stable over time and not prone to subjective ***,none of the genetic variants associated with particular outcomes have shown sufficient sensitivity or specificity to have been implemented in daily *** the same line of thinking,pharmacogenetics or the study of association between variability in drug response and genetic variation has also received more attention as part of the endeavor for personalized *** ultimate goal in this area of medicine is to adapt medication to a patient's specific genetic background and therefore improve on efficacy and safety *** pharmacogenetic studies have been performed for all classes of drugs applied in IBD,few have generated consistent findings or have been *** only genetic test approved for clinical practice is thiopurine S-methyltransferase testing prior to starting treatment with thiopurine *** other reported associations have suffered from lack of confirmation or still need replication ***,the importance and necessity of pharmacogenetic studies will increase further as more therapeutic classes are being developed.

关键词： Genetics Inflammatory bowel diseases Pharmacogenetics

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Pharmacogenetics in inflammatory bowel disease

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World Journal of Gastroenterology 2006年第23期12卷 3657-3667页

作者： Marie Pierik paul rutgeerts Robert Vlietinck Severine Vermeire Department of Gastroenterology University Hospital GasthuisbergLeuvenBelgium Department of Epidemiology and Human Genetics Katholieke Universiteit LeuvenLeuvenBelgium

Pharmacogenetics is the study of the association between variability in drug response and （or） drug toxicity and polymorphisms in genes. The goal of this field of science is to adapt drugs to a patient＇s specific genetic background and therefore make them more efficacious and safe. In this article we describe the variants in genes that influence either the efficacy or toxicity of common drugs used in the treatment of inflammatory bowel diseases （IBD）, ulcerative colitis （UC）, and Crohn＇s disease （CD） including sulfasalazine and mesalazine, azathioprine （AZA） and 6-mercaptopurine （6-MP）, methotrexate （MTX）, glucocorticosteroids （CSs） and infliximab. Furthermore, difficulties with pharmacogenetic studies in general and more specifically in IBD are described. Although pharmacogenetics is a promising field that already contributed to a better understanding of some of the underlying mechanisms of action of drugs used in IBD, the only discovery translated until now into daily practice is the relation between thiopurine S-methyltransferase （TPMT） gene polymorphisms and hematological toxicity of thiopurine treatment. In the future it is necessary to organize studies in well characterized patient cohorts who have been uniformly treated and systematically evaluated in order to quantitate drug response more objectively. An effort should be made to collect genomic DNA from all patients enrolled in clinical drug trials after appropriate informed consent for pharmacogenetic studies.

关键词： Inflammatory bowel disease Pharmaco-genetics Crohn's disease Ulcerative colitis

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Treatment of severe steroid refractory ulcerative colitis

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World Journal of Gastroenterology 2008年第36期14卷 5508-5511页

作者： Gert Van Assche Séverine Vermeire paul rutgeerts Division of Gastroen-terology University of Leuven Hospitals Herestraat 49 B-3000 Leuven Belgium Division of Gastroenterology University of Leuven Hospitals Herestraat 49 B-3000 Leuven Belgium

Although systemic steroids are highly efficacious in ulcerative colitis (UC), failure to respond to steroids still poses an important challenge to the surgeon and physician alike. Even if the life time risk of a fulminant UC flare is only 20%, this condition is potentially life threatening and should be managed in hospital. If patients fail 3 to 5 d of intravenous corticosteroids and optimal supportive care, they should be considered for any of three options: intravenous cyclosporine (2 mg/kg for 7 d, and serum level controlled), infliximab (5 mg/kg Ⅳ, 0-2-6 wk) or total colectomy. The choice between these three options is a medical- surgical decision based on clinical signs, radiological and endoscopic findings and blood analysis (CRP, serum albumin). Between 65 and 85% of patients will initially respond to cyclosporine and avoid colectomy on the short term. Over 5 years only 50% of initial responders avoid colectomy and outcomes are better in patients naive to azathioprine (bridging strategy). The data on infliximab as a medical rescue in fulminant colitis are more limited although the efficacy of this anti tumor necrosis factor (TNF) monoclonal antibody has been demonstrated in a controlled trial. Controlled data on the comparative efficacy of cyclosporine and infliximab are not available at this moment. Both drugs are immunosuppressants and are used in combination with steroids and azathioprine, which infers a risk of serious, even fatal, opportunistic infections. Therefore, patients not responding to these agents within 5-7 d should be considered for colectomy and responders should be closely monitored for infections.

关键词： Ulcerative colitis Steroids Corticosteroids Azathioprine Cyclosporine Infliximab Imrnunosuppressants

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