Department of Medicine, Universitat Autònoma de Barcelona (UAB), Bellaterra, Spain.
Liver Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
J Neurol. 2024 Jan;271(1):134-140. doi: 10.1007/s00415-023-11973-y. Epub 2023 Sep 11.
Prospective data on the risk of hepatitis B reactivation (HBVr) among patients with resolved HBV infection undergoing anti-CD20 antibodies monotherapy is scarce. We aimed to assess the risk of HBVr in patients with resolved HBV infection treated with rituximab or ocrelizumab in monotherapy for multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD) without antiviral prophylaxis.
HEBEM is a prospective study that included all consecutive adults HBsAg-negative/anti-HBc-positive who initiated anti-CD20 antibodies for MS or NMOSD at Cemcat. Inclusion criteria encompassed undetectable HBV-DNA, absence of other immunosuppressants or antiviral therapy. Every 6 months HBsAg, ALT and HBV-DNA were performed to rule out HBVr (defined by 2-log increase in HBV-DNA or seroconversion to HBsAg+).
From August/2019 to August/2022, 540 subjects initiated anti-CD20 antibodies, 28 (5.2%) were anti-HBc-positive and were included. Twenty-two received rituximab and 6 ocrelizumab. The majority (89.3%) had previously received ≥ 1 immunomodulatory drug, with corticosteroids (82.1%) and interferon (42.9%) as the most common. At inclusion, all presented normal transaminases and undetectable HBV-DNA. Median anti-HBs levels were 105.5 mIU/mL (IQR 0-609). Median follow-up was 3.1 years (2.1-4.0). Median number of cycles of anti-CD20 antibodies was 6 (3-7), with a cumulative dose of 8.5 g (5.8-11.2) of rituximab and 3 g (1.8-3.8) of ocrelizumab. Neither cases of HBVr nor changes in anti-HBs titers were observed per 83.6 patient-years treated with monotherapy with anti-CD20 antibodies.
In this cohort of patients with MS or NMOSD and resolved HBV infection, anti-CD20 monotherapy was not associated with detectable risk of HBV reactivation despite the lack of antiviral prophylaxis.
在接受抗 CD20 抗体单药治疗的已治愈乙型肝炎病毒（HBV）感染患者中，关于 HBV 再激活（HBVr）风险的前瞻性数据很少。我们旨在评估在未接受抗病毒预防的情况下，接受利妥昔单抗或奥瑞珠单抗单药治疗多发性硬化症（MS）或视神经脊髓炎谱系障碍（NMOSD）的已治愈 HBV 感染患者中发生 HBVr 的风险。
HEBEM 是一项前瞻性研究，纳入了所有在 Cemcat 开始接受抗 CD20 抗体治疗 MS 或 NMOSD 的连续 HBsAg 阴性/抗 HBc 阳性的成年患者。纳入标准包括 HBV-DNA 不可检测、无其他免疫抑制剂或抗病毒治疗。每 6 个月进行 HBsAg、ALT 和 HBV-DNA 检测以排除 HBVr（定义为 HBV-DNA 增加 2 个对数或 HBsAg 血清转换阳性）。
自 2019 年 8 月至 2022 年 8 月，540 例患者开始接受抗 CD20 抗体治疗，其中 28 例（5.2%）抗 HBc 阳性并被纳入研究。22 例接受利妥昔单抗治疗，6 例接受奥瑞珠单抗治疗。大多数患者（89.3%）此前接受过≥1 种免疫调节剂，最常见的药物为皮质类固醇（82.1%）和干扰素（42.9%）。入组时，所有患者的转氨酶均正常且 HBV-DNA 不可检测。中位抗 HBs 水平为 105.5 mIU/mL（IQR 0-609）。中位随访时间为 3.1 年（2.1-4.0）。接受抗 CD20 抗体治疗的中位周期数为 6（3-7）个，利妥昔单抗累积剂量为 8.5g（5.8-11.2），奥瑞珠单抗累积剂量为 3g（1.8-3.8）。在接受抗 CD20 抗体单药治疗的 83.6 患者年中，未观察到 HBVr 病例或抗 HBs 滴度变化。
在本队列中，MS 或 NMOSD 合并已治愈 HBV 感染患者接受抗 CD20 单药治疗，未发现有明显的 HBV 再激活风险，尽管未进行抗病毒预防。
