PDF(Pubmed)
Abstract：
Drug-induced liver injury (DILI) is a potential adverse event of disease-modifying therapies (DMTs) for the treatment of multiple sclerosis (MS), as well as of methylprednisolone pulsed therapy used in case of MS relapse. DILI may be induced by different mechanisms, including idiosyncratic reaction, autoimmune hepatitis or viral reactivation. In patients receiving the humanized anti-CD20 monoclonal antibody (mAb) ocrelizumab, DILI has been rarely reported and was mostly associated with hepatitis B virus (HBV) reactivation. Here we present the case of a woman with highly active relapsing-remitting MS who had experienced two episodes of DILI while receiving different DMTs, and was successfully switched to ofatumumab, a fully human anti-CD20 mAb, after a further event associated with ocrelizumab treatment and unrelated to HBV reactivation. Despite sharing the mechanism of action, differences in structure, pharmacokinetic/pharmacodynamic profile, and use of ancillary drugs (only needed for ocrelizumab) may have accounted for the successful switch. To our knowledge, this is the first report of a successful switch from ocrelizumab to ofatumumab due to DILI. Ofatumumab may therefore represent a valid therapeutic option for patients experiencing DMTs- and ocrelizumab-induced liver injury, providing that HBV reactivation has been ruled out.
摘要：
药物诱导的肝损伤（DILI）是用于治疗多发性硬化症（MS）的疾病修饰疗法（DMT）的潜在不良事件，以及用于MS复发的甲基强的松龙脉冲疗法。DILI可能由不同的机制诱导，包括特殊反应，自身免疫性肝炎或病毒再激活。在接受人源化抗CD20单克隆抗体（mAb）ocrelizumab的患者中，DILI很少报道，主要与乙型肝炎病毒（HBV）再激活有关。在这里，我们介绍了一名患有高度活跃的复发缓解型MS的女性，该女性在接受不同的DMT时经历了两次DILI发作，并且成功地切换到了Ofatumumab,一种完全人类的抗CD20单克隆抗体，在发生与ocrelizumab治疗相关且与HBV再激活无关的进一步事件后.尽管分享了行动机制，结构差异，药代动力学/药效学，和辅助药物的使用(仅奥克瑞珠单抗需要)可能是成功转换的原因.据我们所知,这是因DILI而成功从奥克瑞珠单抗转换为奥伐珠单抗的第一份报告.因此，Ofatumumab可能是一种有效的治疗方案，适用于DMT和奥利珠单抗诱导的肝损伤患者。前提是HBV再激活已被排除。
