Nottingham City Hospital, Hucknall Road, Nottingham, United Kingdom.
Takeda Pharmaceutical Company Ltd, Cambridge, Massachusetts, USA.
Inflamm Bowel Dis. 2018 Apr 23;24(5):953-959. doi: 10.1093/ibd/izx097.
Progressive multifocal leukoencephalopathy is a serious condition linked to certain diseases and immunosuppressant therapies, including the α4 integrin antagonist natalizumab. No cases have been reported to date with vedolizumab, a selective antagonist of the α4β7 integrin expressed on gut-homing lymphocytes. This analysis aimed to describe the current and future expected occurrence of progressive multifocal leukoencephalopathy with vedolizumab use, were the risk the same as in other populations in which this disease has been studied.
The expected number of vedolizumab-associated progressive multifocal leukoencephalopathy cases was estimated up to May 19, 2016, and modeled up to 2034. These estimates were based on the cumulative exposure to the drug, assuming an equivalent risk to that of patients treated with natalizumab or those from other reference populations where progressive multifocal leukoencephalopathy has been examined. Future cases were modeled based on similar risks and projected sales.
The cumulative vedolizumab exposure was estimated at 54,619 patient-years, with a 95% confidence interval of 0.0 to 6.75 cases per 100,000 patient-years. An estimated 30.2 (95% confidence interval, 19.4-40.9) cases of progressive multifocal leukoencephalopathy would have occurred if vedolizumab had the same risk as that of natalizumab. There would be a 50% chance of the first case occurring by 2018, assuming an equivalent risk to the general population.
These analyses indicate that the risk of progressive multifocal leukoencephalopathy with vedolizumab is small, and unlikely to be above 6.75 cases per 100,000 patient-years.
进行性多灶性白质脑病是一种严重的疾病，与某些疾病和免疫抑制剂治疗有关，包括α4 整合素拮抗剂那他珠单抗。迄今为止，尚未报道与 vedolizumab 相关的病例，后者是一种选择性的α4β7 整合素拮抗剂，表达于肠道归巢淋巴细胞上。本分析旨在描述 vedolizumab 使用时进行性多灶性白质脑病的当前和未来预期发生率，如果这种疾病在其他研究人群中进行了研究，其风险是否与其他人群相同。
截至 2016 年 5 月 19 日，估计了 vedolizumab 相关进行性多灶性白质脑病病例的预期数量，并对 2034 年进行了建模。这些估计是基于药物的累积暴露量，假设风险与接受那他珠单抗治疗的患者或其他研究过进行性多灶性白质脑病的参考人群中的患者相当。根据类似的风险和预测的销售额对未来的病例进行建模。
累积 vedolizumab 暴露量估计为 54619 患者年，95%置信区间为 0.0 至 6.75 例/100000 患者年。如果 vedolizumab 的风险与那他珠单抗相同，则预计会发生 30.2 例（95%置信区间，19.4-40.9）进行性多灶性白质脑病病例。如果风险与普通人群相当，则首次发病的概率为 50%，预计首次发病将在 2018 年发生。
这些分析表明，vedolizumab 发生进行性多灶性白质脑病的风险很小，不太可能超过 6.75 例/100000 患者年。
