Rituximab-associated hepatitis B virus (HBV) reactivation in lymphoproliferative diseases: Metaanalysis and examination of FDA safety reports

A. M. Evens*, B. D. Jovanovic, Y. C. Su, D. W. Raisch, D. Ganger, S. M. Belknap, M. S. Dai, B. C.C. Chiu, B. Finte, Y. Cheng, S. S. Chuang, M. Y. Lee, T. Y. Chen, S. F. Lin, C. Y. Kuo

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

232 Scopus citations

Abstract

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 rituximabassociated 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 (χ2 = 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.

Original languageEnglish (US)
Pages (from-to)1170-1180
Number of pages11
JournalAnnals of Oncology
Volume22
Issue number5
DOIs
StatePublished - 2011

Keywords

  • FDA
  • HBV reactivation
  • Hepatitis B virus
  • Non-Hodgkin's lymphoma
  • Rituximab

ASJC Scopus subject areas

  • Hematology
  • Oncology

Fingerprint Dive into the research topics of 'Rituximab-associated hepatitis B virus (HBV) reactivation in lymphoproliferative diseases: Metaanalysis and examination of FDA safety reports'. Together they form a unique fingerprint.

Cite this