ST LOUIS (MD Consult) - On October 23, 2009, the US Food and Drug Administration (FDA) announced that Genentech has notified health care professionals about new safety information regarding Rituxan (rituximab) and the risk of progressive multifocal leukoencephalopathy (PML). A third case of PML has been reported in a patient with rheumatoid arthritis (RA) who was treated with Rituxan.
Progressive multifocal leukoencephalopathy is a rare, progressive, demyelinating disease of the central nervous system that usually leads to death or severe disability. The disease is caused by activation of the JC virus.
This new case of PML occurred in a 73-year-old woman with a diagnosis of seronegative rheumatoid arthritis (RA) of 3 years' duration. The patient's concomitant and/or prior treatments for RA included leflunomide, hydroxychloroquine, and prednisone. Her other medical history included hypertension, hypothyroidism, osteoporosis, recurrent bronchitis, and stroke. In February 2009, she received 1 course of Rituxan (1000 mg given 2 weeks apart). She experienced dysesthesias and ataxia 4 to 6 months after her treatment with Rituxan. Progressive multifocal leukoencephalopathy was diagnosed on the basis of her clinical symptoms, magnetic resonance imaging (MRI) findings, and detection of JC viral DNA (using polymerase chain reaction testing) in her cerebrospinal fluid.
This is the first reported case of PML in a patient with RA treated with Rituxan who has not previously received treatment with a tumor-necrosis–factor antagonist. Previously, 2 fatal cases of confirmed PML have been reported in patients with RA treated with Rituxan. These cases involved a 51-year-old woman and a 73-year-old woman with possible risk factors for the development of PML, including oropharyngeal malignancy treated with chemotherapy and radiation therapy and/or long-standing lymphopenia present before and during Rituxan treatment.
Physicians should consider a diagnosis of PML in any patient being treated with Rituxan who presents with new-onset neurologic manifestations. Neurology consultation, brain MRI, and lumbar puncture would be considered clinically indicated interventions. In patients who are diagnosed with PML, Rituxan should be discontinued.
Health care professionals should report any serious adverse events suspected to be associated with the use of Rituxan to Genentech at 1-888-835-2555. Alternatively, this information may be reported to the FDA's MedWatch reporting system online, by telephone (1 800-FDA-1088), by fax (1-800-FDA-0178), or by mail using the MedWatch Form FDA 3500 and sending the completed form to FDA Medical Products Reporting Program, 5600 Fishers Lane, Rockville, MD 20852-9787.
圣路易斯(MD Consult)——2009年10月23日，美国食品药品管理局(FDA)宣布，基因泰克公司已向医护人员通告了有关Rituxan的最新安全性信息及其诱发进行性多灶性白质脑病(PML)的风险。据报告，又有1例接受Rituxan治疗的类风湿性关节炎(RA)患者发生PML，迄今为止已达3例。
进行性多灶性白质脑病是一种发生于中枢神经系统的罕见进行性脱髓鞘疾病，常可致死或致重度残疾。此病系JC病毒激活所致。
这例PML新发病例是一位73岁、诊断为血清阴性的RA且病程达3年的女性。该患者接受的RA联合治疗和/或既往治疗包括来氟米特、羟化氯喹及强的松。她的其他医疗史包括高血压、甲状腺功能低下、骨质疏松、复发性支气管炎及卒中。2009年2月，她接受了1个疗程的Rituxan治疗(1,000 mg，间隔2周服用1次)。该患者在Rituxan治疗后出现了感觉迟钝和共济失调。诊断她患进行性多灶性白质脑病的依据为临床症状、磁共振成像(MRI)检查结果以及其脑脊液中JC病毒DNA的检出(采用多聚酶链反应检测)。
这是所报告的首例既往无肿瘤坏死因子阻断剂治疗史的患者接受Rituxan治疗RA后出现PML。先前已报告，接受Rituxan治疗RA的患者中2例确诊为PML的致死病例。其中包括1位51岁女性和1位73岁女性，两者均存在发生PML的潜在危险因素，其中包括以化疗法和放疗法治疗口咽恶性肿瘤和/或Rituxan治疗前和治疗期间存在长期性淋巴细胞减少症。
接受Rituxan治疗的任何患者一旦出现新发的神经学表现时，医生均应考虑到PML诊断。在这种情况下，临床上应实施神经科会诊、脑MRI以及腰椎穿刺等干预手段。诊断为PML的患者应停用Rituxan。
医护人员应将任何怀疑与使用Rituxan有关的严重不良事件报告至基因泰克公司，电话：1-888-835-2555。或者将该信息在线报告至FDA MedWatch 报告系统，亦可致电1 800-FDA-1088报告，或传真至1-800-FDA-0178，或将MedWatch FDA 3500表填写完整后邮寄至FDA Medical Products Reporting Program, 5600 Fishers Lane, Rockville, MD 20852-9787。
