完成利妥昔单抗治疗后 6 或 12 个月内进行抗病毒预防对乙型肝炎缓解患者的疗效：一项多中心、随机研究。
Efficacy of Antiviral Prophylaxis up to 6 or 12 Months From Completion of Rituximab in Resolved Hepatitis B Patients: A Multicenter, Randomized Study.
机构信息
Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Korea.
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
出版信息
J Korean Med Sci. 2023 Jul 17;38(28):e216. doi: 10.3346/jkms.2023.38.e216.
BACKGROUND
Rituximab occasionally induces reactivation of hepatitis B virus (HBV) in patients with resolved HBV, at times with fatal consequences. The optimal duration of prophylactic antiviral therapy in this situation is unclear. We aimed to investigate the difference in HBV reactivation according to the duration of prophylactic tenofovir disoproxil fumarate (TDF) in patients with resolved HBV and receiving rituximab.
METHODS
A multicenter, randomized, open-label, prospective study was conducted in hepatitis B surface antigen-negative and anti-HBc-positive non-Hodgkin's lymphoma patients treated with rituximab-based chemotherapy. A total of 90 patients were randomized and received prophylactic TDF from the initiation of rituximab until 6 months (the 6-month group) or 12 months (the 12-month group) after the completion of rituximab. The primary outcome was the difference in HBV reactivation and the secondary outcomes were the difference in hepatitis flare and adverse events between the two groups.
RESULTS
In an intention to treat (ITT) analysis, HBV reactivation occurred in 1 of 43 patients (2.3%; 95% confidence interval [CI], 0.41-12%) at a median of 13.3 months in the 6-month group and 2 of 41 patients (4.9%; 95% CI, 1.4-16%) at a median of 13.7 months in the 12-month group. In a per protocol (PP) analysis, HBV reactivation occurred in 1 of 18 patients (5.6%; 95% CI, 0.99-26%) at 13.3 months in the 6-month group and 1 of 13 patients (7.7%; 95% CI, 1.4-33%) at 9.7 months in the 12-month group. The cumulative incidence of HBV reactivation was not significantly different between the two groups in ITT and PP analyses ( = 0.502 and 0.795, respectively). The occurrence of adverse events was not significantly different between the two groups in ITT (9.3% in the 6-month group, 22.0% in the 12-month group, = 0.193) and PP analyses (5.6% in the 6-month group, 7.7% in the 12-month group, > 0.999).
CONCLUSION
Prophylactic TDF up to 6 months after completion of rituximab-based chemotherapy is sufficient in terms of the efficacy and safety of reducing HBV reactivation in patients with resolved HBV.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02585947.
背景
利妥昔单抗偶尔会在已治愈乙型肝炎病毒（HBV）的患者中引发 HBV 再激活，有时会导致致命后果。在这种情况下，预防性抗病毒治疗的最佳持续时间尚不清楚。我们旨在研究在接受利妥昔单抗治疗的已治愈 HBV 且接受利妥昔单抗治疗的患者中，根据预防性替诺福韦酯（TDF）持续时间的不同，HBV 再激活的差异。
方法
一项多中心、随机、开放标签、前瞻性研究在接受基于利妥昔单抗的化疗的乙型肝炎表面抗原阴性和抗 HBc 阳性非霍奇金淋巴瘤患者中进行。共有 90 名患者被随机分配，并在开始利妥昔单抗治疗后至 6 个月（6 个月组）或完成利妥昔单抗治疗后 12 个月（12 个月组）接受预防性 TDF。主要结局是 HBV 再激活的差异，次要结局是两组之间肝炎发作和不良事件的差异。
结果
在意向治疗（ITT）分析中，6 个月组的中位时间为 13.3 个月时，43 名患者中有 1 名（2.3%；95%置信区间 [CI]，0.41-12%）发生 HBV 再激活，12 个月组的中位时间为 13.7 个月时，41 名患者中有 2 名（4.9%；95% CI，1.4-16%）发生 HBV 再激活。在方案（PP）分析中，6 个月组的中位时间为 13.3 个月时，18 名患者中有 1 名（5.6%；95% CI，0.99-26%）发生 HBV 再激活，12 个月组的中位时间为 9.7 个月时，13 名患者中有 1 名（7.7%；95% CI，1.4-33%）发生 HBV 再激活。两组在 ITT 和 PP 分析中 HBV 再激活的累积发生率无显著差异（ = 0.502 和 0.795）。两组在 ITT（6 个月组为 9.3%，12 个月组为 22.0%， = 0.193）和 PP（6 个月组为 5.6%，12 个月组为 7.7%， > 0.999）分析中的不良事件发生率无显著差异。
结论
在已治愈 HBV 的患者中，完成利妥昔单抗治疗后 6 个月内预防性使用 TDF 可有效且安全地降低 HBV 再激活。
试验注册
ClinicalTrials.gov 标识符：NCT02585947。
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