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, Tsai-Yun Chen, S. F. Lin, C. Y. Kuo

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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
Pages (from-to)1170-1180
Number of pages11
JournalAnnals of Oncology
Volume22
Issue number5
DOIs
Publication statusPublished - 2011 May 5

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Satellite Viruses
United States Food and Drug Administration
Hepatitis B virus
Safety
Confidence Intervals
Meta-Analysis
Hepatitis B Antibodies
Rituximab
Odds Ratio
Databases

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology

Cite this

Evens, A. M., Jovanovic, B. D., Su, Y. C., Raisch, D. W., Ganger, D., Belknap, S. M., ... Kuo, C. Y. (2011). Rituximab-associated hepatitis B virus (HBV) reactivation in lymphoproliferative diseases: Metaanalysis and examination of FDA safety reports. Annals of Oncology, 22(5), 1170-1180. https://doi.org/10.1093/annonc/mdq583
Evens, A. M. ; Jovanovic, B. D. ; Su, Y. C. ; Raisch, D. W. ; Ganger, D. ; Belknap, S. M. ; Dai, M. S. ; Chiu, B. C.C. ; Finte, B. ; Cheng, Y. ; Chuang, S. S. ; Lee, M. Y. ; Chen, Tsai-Yun ; Lin, S. F. ; Kuo, C. Y. / Rituximab-associated hepatitis B virus (HBV) reactivation in lymphoproliferative diseases : Metaanalysis and examination of FDA safety reports. In: Annals of Oncology. 2011 ; Vol. 22, No. 5. pp. 1170-1180.
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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.",
author = "Evens, {A. M.} and Jovanovic, {B. D.} and Su, {Y. C.} and Raisch, {D. W.} and D. Ganger and Belknap, {S. M.} and Dai, {M. S.} and Chiu, {B. C.C.} and B. Finte and Y. Cheng and Chuang, {S. S.} and Lee, {M. Y.} and Tsai-Yun Chen and Lin, {S. F.} and Kuo, {C. Y.}",
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Evens, AM, Jovanovic, BD, Su, YC, Raisch, DW, Ganger, D, Belknap, SM, Dai, MS, Chiu, BCC, Finte, B, Cheng, Y, Chuang, SS, Lee, MY, Chen, T-Y, Lin, SF & Kuo, CY 2011, 'Rituximab-associated hepatitis B virus (HBV) reactivation in lymphoproliferative diseases: Metaanalysis and examination of FDA safety reports', Annals of Oncology, vol. 22, no. 5, pp. 1170-1180. https://doi.org/10.1093/annonc/mdq583

Rituximab-associated hepatitis B virus (HBV) reactivation in lymphoproliferative diseases : Metaanalysis and examination of FDA safety reports. / Evens, A. M.; Jovanovic, B. D.; Su, Y. C.; Raisch, D. W.; Ganger, D.; Belknap, S. M.; Dai, M. S.; Chiu, B. C.C.; Finte, B.; Cheng, Y.; Chuang, S. S.; Lee, M. Y.; Chen, Tsai-Yun; Lin, S. F.; Kuo, C. Y.

In: Annals of Oncology, Vol. 22, No. 5, 05.05.2011, p. 1170-1180.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Rituximab-associated hepatitis B virus (HBV) reactivation in lymphoproliferative diseases

T2 - Metaanalysis and examination of FDA safety reports

AU - Evens, A. M.

AU - Jovanovic, B. D.

AU - Su, Y. C.

AU - Raisch, D. W.

AU - Ganger, D.

AU - Belknap, S. M.

AU - Dai, M. S.

AU - Chiu, B. C.C.

AU - Finte, B.

AU - Cheng, Y.

AU - Chuang, S. S.

AU - Lee, M. Y.

AU - Chen, Tsai-Yun

AU - Lin, S. F.

AU - Kuo, C. Y.

PY - 2011/5/5

Y1 - 2011/5/5

N2 - 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.

AB - 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.

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U2 - 10.1093/annonc/mdq583

DO - 10.1093/annonc/mdq583

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