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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 outcome.However,several of these are subjective and/or not persistent over time.With the progress in genetics research in inflammatory bowel disease(IBD),genetic markers are increasingly being proposed to improve stratification of patients.Genetics have the major advantage of being stable over time and not prone to subjective interpretation.Nevertheless,none of the genetic variants associated with particular outcomes have shown sufficient sensitivity or specificity to have been implemented in daily management.Along 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 medicine.The 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 rates.Although pharmacogenetic studies have been performed for all classes of drugs applied in IBD,few have generated consistent findings or have been replicated.The only genetic test approved for clinical practice is thiopurine S-methyltransferase testing prior to starting treatment with thiopurine analogues.The other reported associations have suffered from lack of confirmation or still need replication efforts.Nevertheless,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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Withdrawal of anti-tumour necrosis factor α therapy in inflammatory bowel disease

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World Journal of Gastroenterology 2015年第16期21卷 4773-4778页

作者： Konstantinos Papamichael severine vermeire Department of Clinical and Experimental Medicine Translational Research Center for Gastrointestinal Disorders

Anti-tumour necrosis factor α(anti-TNFα) therapy is an established treatment in inflammatory bowel disease.However, this treatment is associated with high costs and the possibility of severe adverse events representing a true challenge for patients, clinicians and health care systems.Consequently, a crucial question is raised namely if therapy can be stopped once remission is achieved and if so, how and in whom.Additionally, in a real-life clinical setting, discontinuation may also be considered for other reasons such as the patient's preference, pregnancy, social reasons as moving to countries or continents with less access, or different local policy or reimbursement.In contrast to initiation of anti-TNFα therapy guidelines regarding stopping of this treatment are missing.As a result, the decision of discontinuation is still a challenging aspect in the use of anti-TNFα therapy.Currently this is typically based on an estimated, case-by-case, benefit-risk ratio.This editorial is intended to provide an overview of recent data on this topic and shed light on the proposed drug withdrawal strategies.

关键词： Inflammatory bowel disease Anti-tumournecrosis factor α therapy Withdrawal Remission Infliximab

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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

遗传药理学是在在药反应的可变性之间的协会的学习并且(或) 在基因的药毒性和多型性。科学的这个领域的目标是使药适应一个病人的特定的基因背景因此使他们更有效、安全。在这篇文章，我们在影响的基因描述变体在煽动性的肠疾病( IBD )... 详细信息

遗传药理学是在在药反应的可变性之间的协会的学习并且(或) 在基因的药毒性和多型性。科学的这个领域的目标是使药适应一个病人的特定的基因背景因此使他们更有效、安全。在这篇文章，我们在影响的基因描述变体在煽动性的肠疾病( IBD )的治疗使用的普通的药的功效或毒性， ulcerative ( UC )，和 Crohn 包括 sulfasalazine 和 mesalazine 是疾病( CD )， azathioprine ( AZA )和 6-mercaptopurine ( 6-MP )， methotrexate ( MTX )， glucocorticosteroids ( CS )和 infliximab 。而且， pharmacogenetic 研究的困难一般来说并且更明确地在 IBD 被描述。尽管遗传药理学是已经贡献了一些药的行动的内在的机制的更好的理解的一个有希望的领域，在 IBD 使用，翻译直到现在成每日的实践的唯一的发现是在 thiopurine S-methyltransferase (TPMT ) 基因多型性和 thiopurine 治疗的 hematological 毒性之间的关系。在未来，在很好描绘的耐心的队组织研究是必要的谁一致地被对待并且系统地评估了以便测定药反应更客观地。一个努力应该被作从为 pharmacogenetic 研究在适当知情同意以后在临床的药试用注册的所有病人收集 genomic DNA。

关键词：药物反应遗传学肠炎溃疡毒力学

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