Mariottini Alice, Barilaro Alessandro, Lotti Antonio, Marra Fabio, Massacesi Luca
Department of Neurosciences, Drug and Child Health, University of Florence, Florence, Italy.
Department of Neurology 2 and Tuscan Region Multiple Sclerosis Referral Centre, Careggi University Hospital, Florence, Italy.
Front Neurol. 2024 Feb 29;15:1363493. doi: 10.3389/fneur.2024.1363493. eCollection 2024.
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.
药物性肝损伤(DILI)是用于治疗多发性硬化症(MS)的疾病修饰疗法(DMTs)以及MS复发时使用的甲基强的松龙脉冲疗法的潜在不良事件。DILI可能由不同机制诱发,包括特异反应、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)奥瑞珠单抗治疗的患者中,DILI鲜有报道,且大多与乙型肝炎病毒(HBV)再激活有关。在此,我们报告一例高度活动性复发缓解型MS女性患者的病例,该患者在接受不同DMTs治疗期间经历了两次DILI发作,在与奥瑞珠单抗治疗相关且与HBV再激活无关的又一次事件后,成功换用了全人源抗CD20 mAb奥法木单抗。尽管作用机制相同,但结构、药代动力学/药效学特征以及辅助药物使用(仅奥瑞珠单抗需要)的差异可能是成功换药的原因。据我们所知,这是首例因DILI而成功从奥瑞珠单抗换用奥法木单抗的报告。因此,在排除HBV再激活的情况下,奥法木单抗可能是经历DMTs和奥瑞珠单抗诱发肝损伤患者的有效治疗选择。