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Abstract：
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 (P = 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, P = 0.193) and PP analyses (5.6% in the 6-month group, 7.7% in the 12-month group, P > 0.999).
CONCLUSIONS: 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.
BACKGROUND: ClinicalTrials.gov Identifier: NCT02585947.
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 (P = 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, P = 0.193) and PP analyses (5.6% in the 6-month group, 7.7% in the 12-month group, P > 0.999).
CONCLUSIONS: 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.
BACKGROUND: ClinicalTrials.gov Identifier: NCT02585947.
摘要：
背景：利妥昔单抗偶尔诱导乙型肝炎病毒（HBV）的患者的乙型肝炎病毒（HBV）的再激活，有时会带来致命的后果。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。我们的目的是调查HBV再激活的差异，根据预防性替诺福韦酯富马酸酯（TDF）的持续时间，患者已解决的HBV和接受利妥昔单抗。
方法：多中心，随机化，开放标签，前瞻性研究是在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的，这些患者接受基于利妥昔单抗的化疗。共有90名患者被随机分配，并从利妥昔单抗开始到完成利妥昔单抗后6个月（6个月组）或12个月（12个月组）接受预防性TDF。主要结果是HBV再激活的差异，次要结果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，HBV再激活发生在43例患者中的1例（2.3％;95％置信区间[CI]，0.41-12％），6个月组的中位数为13.3个月，41名患者中有2名（4.9％；95％CI，1.4-16％），12个月组的中位数为13.7个月。在每个协议(PP)分析中，HBV再激活发生在18例患者中的1例（5.6％;95％CI，0.99-26％）在6个月组13.3个月和13例患者中的1例（7.7％;95％CI，1.4-33％）在9.7个月在12个月组。在ITT和PP分析中，两组之间HBV再激活的累积发生率没有显着差异（分别为P=0.502和0.795）。不良事件的发生率在ITT中两组之间没有显着差异（6个月组中为9.3％，12个月组的22.0%，P=0.193）和PP分析（6个月组中为5.6％，12个月组的7.7%，P>0.999)。
结论：在完成基于利妥昔单抗的化疗后长达6个月的预防性TDF在减少HBV复发患者的HBV再激活的疗效和安全性方面是足够的。
背景：ClinicalTrials.gov标识符：NCT02585947。
方法：多中心，随机化，开放标签，前瞻性研究是在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的，这些患者接受基于利妥昔单抗的化疗。共有90名患者被随机分配，并从利妥昔单抗开始到完成利妥昔单抗后6个月（6个月组）或12个月（12个月组）接受预防性TDF。主要结果是HBV再激活的差异，次要结果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，HBV再激活发生在43例患者中的1例（2.3％;95％置信区间[CI]，0.41-12％），6个月组的中位数为13.3个月，41名患者中有2名（4.9％；95％CI，1.4-16％），12个月组的中位数为13.7个月。在每个协议(PP)分析中，HBV再激活发生在18例患者中的1例（5.6％;95％CI，0.99-26％）在6个月组13.3个月和13例患者中的1例（7.7％;95％CI，1.4-33％）在9.7个月在12个月组。在ITT和PP分析中，两组之间HBV再激活的累积发生率没有显着差异（分别为P=0.502和0.795）。不良事件的发生率在ITT中两组之间没有显着差异（6个月组中为9.3％，12个月组的22.0%，P=0.193）和PP分析（6个月组中为5.6％，12个月组的7.7%，P>0.999)。
结论：在完成基于利妥昔单抗的化疗后长达6个月的预防性TDF在减少HBV复发患者的HBV再激活的疗效和安全性方面是足够的。
背景：ClinicalTrials.gov标识符：NCT02585947。
