Abstract：
The use of immune checkpoint inhibitors (ICIs) for oncologic indications is associated with immune-related adverse events (irAEs). Patients with pre-existing autoimmune diseases are at increased risk of irAEs and have largely been excluded from clinical trials of ICIs. Therefore, there is limited data on the safety of safety of ICIs in patients with pre-existing neurologic autoimmune diseases (nAIDs) such as myasthenia gravis and multiple sclerosis. This review aims to synthesize the literature on the post-marketing experience with ICI in patients with pre-existing nAID and to discuss possible strategies for mitigating the risk of post-ICI nAID relapses.
Patients with pre-existing myasthenia gravis (MG), myositis, and paraneoplastic encephalitis appear highly susceptible to neurologic relapses of their underlying neurologic disorder following ICI initiation; these relapses can cause considerable morbidity and mortality. In patients with multiple sclerosis (MS), the risk and severity of MS relapses following ICI appears to be relatively lower compared to MG. Preliminary evidence suggests that older MS patients with no recent focal neuroinflammatory activity may be safely treated with ICI. Among the several case reports of ICI in patients with a history of Guillain-Barre syndrome (GBS), neurologic worsening was only recorded in one patient who was in the acute phase of GBS at the time of ICI start. Initiating an ICI in a patient with pre-existing nAID involves a complex risk-benefit discussion between the patient, their oncologist, and neurologist. Relevant issues to consider before ICI include the choice of disease-modifying therapy for nAID (if any) and strategies for promptly identifying and managing nAID relapses should they occur. Currently, the literature consists mainly of case reports and case series, subject to publication bias. Prospective studies of ICI in patients with nAID are needed to improve the level of evidence.
Patients with pre-existing myasthenia gravis (MG), myositis, and paraneoplastic encephalitis appear highly susceptible to neurologic relapses of their underlying neurologic disorder following ICI initiation; these relapses can cause considerable morbidity and mortality. In patients with multiple sclerosis (MS), the risk and severity of MS relapses following ICI appears to be relatively lower compared to MG. Preliminary evidence suggests that older MS patients with no recent focal neuroinflammatory activity may be safely treated with ICI. Among the several case reports of ICI in patients with a history of Guillain-Barre syndrome (GBS), neurologic worsening was only recorded in one patient who was in the acute phase of GBS at the time of ICI start. Initiating an ICI in a patient with pre-existing nAID involves a complex risk-benefit discussion between the patient, their oncologist, and neurologist. Relevant issues to consider before ICI include the choice of disease-modifying therapy for nAID (if any) and strategies for promptly identifying and managing nAID relapses should they occur. Currently, the literature consists mainly of case reports and case series, subject to publication bias. Prospective studies of ICI in patients with nAID are needed to improve the level of evidence.
摘要：
目的：在肿瘤适应症中使用免疫检查点抑制剂（ICIs）与免疫相关不良事件（irAEs）相关。预先存在自身免疫性疾病的患者发生irAE的风险增加，并且在很大程度上被排除在ICIs的临床试验之外。因此,关于ICIs在已有神经自身免疫性疾病(nAIDs)如重症肌无力和多发性硬化患者中安全性的安全性数据有限.这篇综述旨在综合有关先前存在nAID的患者的ICI上市后经验的文献，并讨论减轻ICI后nAID复发风险的可能策略。
结果：已存在重症肌无力（MG）的患者，肌炎,副肿瘤性脑炎在ICI开始后似乎对其潜在神经系统疾病的神经系统复发高度敏感;这些复发可导致相当高的发病率和死亡率。在多发性硬化症（MS）患者中，与MG相比,ICI后MS复发的风险和严重程度似乎相对较低.初步证据表明，近期没有局灶性神经炎症活动的老年MS患者可以安全地接受ICI治疗。在几例有格林-巴利综合征（GBS）病史的ICI患者中，仅在ICI开始时处于GBS急性期的1例患者中记录到神经系统恶化.在预先存在nAID的患者中启动ICI涉及患者之间复杂的风险收益讨论，他们的肿瘤学家，和神经科医生.在ICI之前需要考虑的相关问题包括选择nAID的疾病改善疗法（如果有的话）以及在发生nAID复发时及时识别和管理nAID复发的策略。目前,文献主要包括病例报告和病例系列，受到出版偏见的影响。需要对nAID患者进行ICI的前瞻性研究以提高证据水平。
结果：已存在重症肌无力（MG）的患者，肌炎,副肿瘤性脑炎在ICI开始后似乎对其潜在神经系统疾病的神经系统复发高度敏感;这些复发可导致相当高的发病率和死亡率。在多发性硬化症（MS）患者中，与MG相比,ICI后MS复发的风险和严重程度似乎相对较低.初步证据表明，近期没有局灶性神经炎症活动的老年MS患者可以安全地接受ICI治疗。在几例有格林-巴利综合征（GBS）病史的ICI患者中，仅在ICI开始时处于GBS急性期的1例患者中记录到神经系统恶化.在预先存在nAID的患者中启动ICI涉及患者之间复杂的风险收益讨论，他们的肿瘤学家，和神经科医生.在ICI之前需要考虑的相关问题包括选择nAID的疾病改善疗法（如果有的话）以及在发生nAID复发时及时识别和管理nAID复发的策略。目前,文献主要包括病例报告和病例系列，受到出版偏见的影响。需要对nAID患者进行ICI的前瞻性研究以提高证据水平。
