Lichtenstein Gary R, Hanauer Stephen B, Sandborn William J
Director, Center for Inflammatory Bowel Diseases Professor of Medicine University of Pennsylvania Philadelphia, Pennsylvania.
Professor of Medicine and Clinical Pharmacology Director, Section of Gastroenterology and Nutrition University of Chicago Chicago, Illinois.
Gastroenterol Hepatol (N Y). 2012 Nov;8(11 Suppl 8):1-20.
For treatment of moderate-to-severe active Crohn's disease, clinicians generally rely on immunosuppressants (including azathioprine and 6-mercaptopurine), corticosteroids, and antibodies against tumor necrosis factor α. However, a significant proportion of patients do not respond to these therapies, lose response over time, or are intolerant to these therapies. In such cases, one of the only remaining pharmacologic treatment options is natalizumab, an α4 integrin-targeted antibody. Unfortunately, 3 cases of progressive multifocal leukoencephalopathy (PML) were reported in natalizumab-treated patients in 2005, shortly after natalizumab's approval by the US Food and Drug Administration (FDA). Natalizumab was subsequently withdrawn from the market but was then reintroduced in 2006 under close supervision by the FDA. Careful review of postmarketing data revealed 3 major risk factors for the development of natalizumab-associated PML, the most significant of which is prior exposure to the JC virus (JCV). To help identify patients who may be at higher risk for developing natalizumab-associated PML, a JCV antibody assay was developed that can detect anti-JCV antibodies in patients' blood. Clinicians can now consider a patient's anti-JCV antibody status together with the other major risk factors for natalizumab-associated PML-duration of natalizumab therapy and prior immunosuppressant use-to more accurately gauge the risks and benefits of natalizumab therapy in a particular patient.
对于中重度活动性克罗恩病的治疗，临床医生通常依赖免疫抑制剂（包括硫唑嘌呤和6-巯基嘌呤）、皮质类固醇以及抗肿瘤坏死因子α抗体。然而，相当一部分患者对这些疗法无反应、随着时间推移失去反应或对这些疗法不耐受。在这种情况下，仅存的药物治疗选择之一是那他珠单抗，一种靶向α4整合素的抗体。不幸的是，2005年，在美国食品药品监督管理局（FDA）批准那他珠单抗后不久，有3例接受那他珠单抗治疗的患者报告发生了进行性多灶性白质脑病（PML）。那他珠单抗随后被撤出市场，但于2006年在FDA的密切监督下重新引入。对上市后数据的仔细审查揭示了与那他珠单抗相关的PML发生的3个主要风险因素，其中最显著的是既往接触过JC病毒（JCV）。为了帮助识别可能发生那他珠单抗相关PML风险较高的患者，开发了一种JCV抗体检测方法，可检测患者血液中的抗JCV抗体。临床医生现在可以将患者的抗JCV抗体状态与那他珠单抗相关PML的其他主要风险因素——那他珠单抗治疗持续时间和既往免疫抑制剂使用情况——一起考虑，以更准确地评估特定患者接受那他珠单抗治疗的风险和益处。
