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Clinical impact of immunomonitoring in the treatment of inflammatory bowel disease

World Journal of Gastroenterology 2017年第3期23卷 414-425页

作者： donal tighe Deirdre Mc Namara Department of Gastroenterology Adelaide and Meath Incorporating the National Children’s Hospital TallaghtSchool of Clinical MedicineTrinity College DublinTrinity Academic Gastroenterology Group24 DublinIreland

Despite improvement in outcomes, loss of response(LOR) to tumor necrosis factor-alpha (TNFα) therapies is a big concern in the management of inflammatory bowel disease. LOR is associated with flares of disease, increased hospitalisation rates, need for surgical interventions, and decline in quality of life. LOR may be multifactorial, but immunogenicity makes a significant contribution. Traditionally doses of anti-TNFα have been adjusted based on clinical response, using a standard approach. Immunomonitoring involves the measurement of anti-TNFα trough and antibody levels. It takes into account the underlying pharmacokinetics of anti-TNFα therapies. Expanding on this a treat to target approach may be used, where doses are intensified, or tailored to the individual based on the measurement of anti-TNFα trough and antibody levels. This review looks at the history, evolution, and clinical impact that immunomonitoring is having in the treatment of inflammatory bowel disease. It will focus on the role of immunomonitoring in helping to achieve long lasting deep remission and mucosal healing. It will explore the different options in terms of best measuring trough and antibody levels, explore possible advantages of immunomonitoring, and discuss its role in best optimising response, at induction, during the maintenance phase of treatment, as well as a role in withdrawing or switching therapy.

关键词： Inflammatory bowel disease Ulcerative colitis Immunomonitoring loss of response AntiTNFα trough and antibody levels Crohn’s disease immunogenicity

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Molecular detection of Helicobacter pylori antibiotic resistance in stool vs biopsy samples

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World Journal of Gastroenterology 2016年第41期22卷 9214-9221页

作者： Denise E Brennan Joseph Omorogbe Mary Hussey donal tighe.grainne.holle.an Colm O'Morain Sinéad M Smith Deirdre McNamara Department of Clinical Medicine School of Medicine Trinity College Dublin School of Pharmacy and Pharmaceutical Sciences Trinity College Dublin

AIM To compare(1) demographics in urea breath test(UBT) vs endoscopy patients; and(2) the molecular detection of antibiotic resistance in stool vs biopsy *** Six hundred and sixteen adult patients undergoing endoscopy or a UBT were prospectively recruited to the study. The Geno Type Helico DR assay was used to detect Helicobacter pylori(H. pylori) and antibiotic resistance using biopsy and/or stool samples from CLOpositive endoscopy patients and stool samples from UBT-positive patients. RESULTS Infection rates were significantly higher in patients referred for a UBT than endoscopy(overall rates: 33% vs 19%; treatment-na?ve patients: 33% vs 14.7%, respectively). H. pylori-infected UBT patients were younger than H. pylori-infected endoscopy patients(41.4 vs 48.4 years, respectively, P < 0.005), with a higher percentage of H. pylori-infected males in the endoscopy-compared to the UBT-cohort(52.6% vs 33.3%, P = 0.03). The Geno Type Helico DR assay was more accurate at detecting H. pylori infection using biopsy samples than stool samples [98.2%(n = 54/55) vs 80.3%(n =53/66), P < 0.005]. Subset analysis using stool and biopsy samples from CLO-positive endoscopy patients revealed a higher detection rate ofresistance-associated mutations using stool samples compared to biopsies. The concordance rates between stool and biopsy samples for the detection of H. pylori DNA, clarithromycin and fluoroquinolone resistance were just 85%, 53% and 35%, respectively. CONCLUSION Differences between endoscopy and UBT patients provide a rationale for non-invasive detection of H. pylori antibiotic resistance. However, the Geno Type Helico DR assay is an unsuitable approach.

关键词： Helicobacter pylori Antibiotic resistance Clarithromycin Fluoroquinolone Molecular methods

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