Rituximab-associated hepatitis B virus (HBV) reactivation in lymphoproliferative diseases: meta-analysis and examination of FDA safety reports
Rituximab-associated hepatitis B virus (HBV) reactivation in lymphoproliferative diseases: meta-analysis and examination of FDA safety reports
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DOI：
10.1093/annonc/mdq583
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发表时间：
2011-05-01
影响因子：
50.5
通讯作者：
Kuo, C. -Y.
中科院分区：
文献类型：
--
作者：
Evens, A. M.;Jovanovic, B. D.;Kuo, C. -Y.
背景：利妥昔单抗与B型肝炎病毒再激活（HBV-R）有关。然而，这种关联的特点和范围仍然在很大程度上undefined.Methods：我们完成了全面的文献检索所有已发表的利妥昔单抗相关的HBV-R的情况下，从美国食品和药物管理局（FDA）不良事件报告系统（AERS）MedWatch数据库。文献和FDA的情况下进行比较的完整性，和荟萃分析completed.Results：183个独特的情况下，利妥昔单抗相关的HBV-R从文献中确定（n=27例病例报告，n=156例病例系列）。从最后一次利妥昔单抗到再激活的时间为3个月（范围0-12），尽管29%发生在最后一次利妥昔单抗后> 6个月。在FDA数据（n=118例病例）中，利妥昔单抗相关HBV-R存在强信号[比例报告比= 28. 5，95%置信区间（CI）23. 9 - 34. 1;经验贝叶斯几何平均值= 26. 4，95% CI 21. 4 - 31. 1]。然而，FDA报告中数据的完整性明显低于文献病例（P < 0.0001）。在HBV核心抗体（HBcAb（+））系列中，与非利妥昔单抗治疗的患者相比，利妥昔单抗治疗的合并效应显示HBV-R风险显著增加（OR 5.73，95% CI 2.01-16.33; Z = 3.33，P = 0.0009）无异质性（χ 2 = 2.12，P = 0.5473）。然而，基于文献的病例提供了更为完整的描述。此外，HBcAb（+）系列的荟萃分析确定利妥昔单抗相关HBV-R的发生率增加了5倍以上。
Background: Rituximab has been associated with hepatitis B virus reactivation (HBV-R). However, the characteristics and scope of this association remain largely undefined.Methods: We completed a comprehensive literature search of all published rituximab-associated HBV-R cases and from the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) MedWatch database. Literature and FDA cases were compared for completeness, and a meta-analysis was completed.Results: One hundred and eighty-three unique cases of rituximab-associated HBV-R were identified from the literature (n=27 case reports, n=156 case series). The time from last rituximab to reactivation was 3 months (range 0-12), although 29% occurred > 6 months after last rituximab. Within FDA data (n=118 cases), there was a strong signal for rituximab-associated HBV-R [proportional reporting ratio = 28.5, 95% confidence interval (CI) 23.9-34.1; Empiric Bayes Geometric Mean = 26.4, 95% CI 21.4-31.1]. However, the completeness of data in FDA reports was significantly inferior compared with literature cases (P < 0.0001). Among HBV core antibody (HBcAb(+)) series, the pooled effect of rituximab-based therapy showed a significantly increased risk of HBV-R compared with nonrituximab-treated patients (odds ratio 5.73, 95% CI 2.01-16.33; Z = 3.33, P = 0.0009) without heterogeneity (chi(2) = 2.12, P = 0.5473).Conclusions: The FDA AERS provided strong HBV-R safety signals; however, literature-based cases provided a significantly more complete description. Furthermore, meta-analysis of HBcAb(+) series identified a more than fivefold increased rate of rituximab-associated HBV-R.