Low risk of hepatitis B virus reactivation in HBsAg-negative/anti-HBc-positive carriers receiving rituximab for rheumatoid arthritis: A retrospective multicenter Italian study

V. Varisco, Mauro Viganò, Alberto Batticciotto, Pietro Lampertico, Antonio Marchesoni, Patrizia Gibertini, Raffaele Pellerito, Guido Rovera, Roberto Caporali, Monica Todoerti, M. Covelli, Antonella Notarnicola, Fabiola Atzeni, Piercarlo Sarzi-Puttini

Research output: Contribution to journalArticle

Abstract

Objective. Patients with resolved hepatitis B virus (HBV) infection, i.e., hepatitis B surface antigen (HBsAg)-negative/antihepatitis B core antigen (anti-HBc)-positive, undergoing rituximab (RTX)-based chemotherapy for hematological malignancies without anti-HBV prophylaxis are at risk of HBV reactivation, but the risk in such patients receiving RTX for rheumatological disorders is not clear. We evaluated this risk in HBsAg-negative/anti-HBc-positive patients with rheumatoid arthritis (RA) undergoing RTX without prophylaxis. Methods. Thirty-three HBsAg-negative/anti-HBc-positive outpatients with RA with undetectable HBV DNA by sensitive PCR assay [73% women, median age 60 years, 85% with HBsAg antibodies (anti-HBs), 37% with antihepatitis B envelope antigen] received a median of 3 cycles of RTX (range 1-8) over 34 months (range 0-80) combined with disease-modifying antirheumatic drugs (DMARD) without prophylaxis. All underwent clinical and laboratory monitoring during and after RTX administration, including serum HBsAg and HBV DNA measurements every 6 months or whenever clinically indicated. Results. None of the patients seroreverted to HBsAg during RTX treatment, but 6/28 (21%) showed a > 50% decrease in protective anti-HBs levels, including 2 who became anti-HBs-negative. One patient (3%) who became HBV DNA-positive (44 IU/ml) after 6 months of RTX treatment was effectively rescued with lamivudine before any hepatitis flare occurred. Among the 14 patients monitored for 18 months (range 0-70) after RTX discontinuation, no HBV reactivation was observed. Conclusion. The administration of RTX + DMARD in patients with RA with resolved HBV infection leads to a negligible risk of HBV reactivation, thus suggesting that serum HBsAg and/or HBV DNA monitoring but not universal anti-HBV prophylaxis is justified.

Original languageEnglish
Pages (from-to)869-874
Number of pages6
JournalJournal of Rheumatology
Volume43
Issue number5
DOIs
Publication statusPublished - May 1 2016

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Hepatitis B Surface Antigens
Hepatitis B virus
Multicenter Studies
Rheumatoid Arthritis
Antigens
Antirheumatic Agents
DNA
Virus Diseases
Rituximab
Lamivudine
Hematologic Neoplasms
Serum
Hepatitis
Anti-Idiotypic Antibodies
Outpatients
Drug Therapy
Polymerase Chain Reaction

Keywords

  • HBsAg
  • HBV DNA
  • Hepatitis B virus reactivation
  • Rheumatoid arthritis
  • Rituximab

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Immunology and Allergy

Cite this

Low risk of hepatitis B virus reactivation in HBsAg-negative/anti-HBc-positive carriers receiving rituximab for rheumatoid arthritis : A retrospective multicenter Italian study. / Varisco, V.; Viganò, Mauro; Batticciotto, Alberto; Lampertico, Pietro; Marchesoni, Antonio; Gibertini, Patrizia; Pellerito, Raffaele; Rovera, Guido; Caporali, Roberto; Todoerti, Monica; Covelli, M.; Notarnicola, Antonella; Atzeni, Fabiola; Sarzi-Puttini, Piercarlo.

In: Journal of Rheumatology, Vol. 43, No. 5, 01.05.2016, p. 869-874.

Research output: Contribution to journalArticle

Varisco, V, Viganò, M, Batticciotto, A, Lampertico, P, Marchesoni, A, Gibertini, P, Pellerito, R, Rovera, G, Caporali, R, Todoerti, M, Covelli, M, Notarnicola, A, Atzeni, F & Sarzi-Puttini, P 2016, 'Low risk of hepatitis B virus reactivation in HBsAg-negative/anti-HBc-positive carriers receiving rituximab for rheumatoid arthritis: A retrospective multicenter Italian study', Journal of Rheumatology, vol. 43, no. 5, pp. 869-874. https://doi.org/10.3899/jrheum.151105
Varisco, V. ; Viganò, Mauro ; Batticciotto, Alberto ; Lampertico, Pietro ; Marchesoni, Antonio ; Gibertini, Patrizia ; Pellerito, Raffaele ; Rovera, Guido ; Caporali, Roberto ; Todoerti, Monica ; Covelli, M. ; Notarnicola, Antonella ; Atzeni, Fabiola ; Sarzi-Puttini, Piercarlo. / Low risk of hepatitis B virus reactivation in HBsAg-negative/anti-HBc-positive carriers receiving rituximab for rheumatoid arthritis : A retrospective multicenter Italian study. In: Journal of Rheumatology. 2016 ; Vol. 43, No. 5. pp. 869-874.
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abstract = "Objective. Patients with resolved hepatitis B virus (HBV) infection, i.e., hepatitis B surface antigen (HBsAg)-negative/antihepatitis B core antigen (anti-HBc)-positive, undergoing rituximab (RTX)-based chemotherapy for hematological malignancies without anti-HBV prophylaxis are at risk of HBV reactivation, but the risk in such patients receiving RTX for rheumatological disorders is not clear. We evaluated this risk in HBsAg-negative/anti-HBc-positive patients with rheumatoid arthritis (RA) undergoing RTX without prophylaxis. Methods. Thirty-three HBsAg-negative/anti-HBc-positive outpatients with RA with undetectable HBV DNA by sensitive PCR assay [73{\%} women, median age 60 years, 85{\%} with HBsAg antibodies (anti-HBs), 37{\%} with antihepatitis B envelope antigen] received a median of 3 cycles of RTX (range 1-8) over 34 months (range 0-80) combined with disease-modifying antirheumatic drugs (DMARD) without prophylaxis. All underwent clinical and laboratory monitoring during and after RTX administration, including serum HBsAg and HBV DNA measurements every 6 months or whenever clinically indicated. Results. None of the patients seroreverted to HBsAg during RTX treatment, but 6/28 (21{\%}) showed a > 50{\%} decrease in protective anti-HBs levels, including 2 who became anti-HBs-negative. One patient (3{\%}) who became HBV DNA-positive (44 IU/ml) after 6 months of RTX treatment was effectively rescued with lamivudine before any hepatitis flare occurred. Among the 14 patients monitored for 18 months (range 0-70) after RTX discontinuation, no HBV reactivation was observed. Conclusion. The administration of RTX + DMARD in patients with RA with resolved HBV infection leads to a negligible risk of HBV reactivation, thus suggesting that serum HBsAg and/or HBV DNA monitoring but not universal anti-HBV prophylaxis is justified.",
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T1 - Low risk of hepatitis B virus reactivation in HBsAg-negative/anti-HBc-positive carriers receiving rituximab for rheumatoid arthritis

T2 - A retrospective multicenter Italian study

AU - Varisco, V.

AU - Viganò, Mauro

AU - Batticciotto, Alberto

AU - Lampertico, Pietro

AU - Marchesoni, Antonio

AU - Gibertini, Patrizia

AU - Pellerito, Raffaele

AU - Rovera, Guido

AU - Caporali, Roberto

AU - Todoerti, Monica

AU - Covelli, M.

AU - Notarnicola, Antonella

AU - Atzeni, Fabiola

AU - Sarzi-Puttini, Piercarlo

PY - 2016/5/1

Y1 - 2016/5/1

N2 - Objective. Patients with resolved hepatitis B virus (HBV) infection, i.e., hepatitis B surface antigen (HBsAg)-negative/antihepatitis B core antigen (anti-HBc)-positive, undergoing rituximab (RTX)-based chemotherapy for hematological malignancies without anti-HBV prophylaxis are at risk of HBV reactivation, but the risk in such patients receiving RTX for rheumatological disorders is not clear. We evaluated this risk in HBsAg-negative/anti-HBc-positive patients with rheumatoid arthritis (RA) undergoing RTX without prophylaxis. Methods. Thirty-three HBsAg-negative/anti-HBc-positive outpatients with RA with undetectable HBV DNA by sensitive PCR assay [73% women, median age 60 years, 85% with HBsAg antibodies (anti-HBs), 37% with antihepatitis B envelope antigen] received a median of 3 cycles of RTX (range 1-8) over 34 months (range 0-80) combined with disease-modifying antirheumatic drugs (DMARD) without prophylaxis. All underwent clinical and laboratory monitoring during and after RTX administration, including serum HBsAg and HBV DNA measurements every 6 months or whenever clinically indicated. Results. None of the patients seroreverted to HBsAg during RTX treatment, but 6/28 (21%) showed a > 50% decrease in protective anti-HBs levels, including 2 who became anti-HBs-negative. One patient (3%) who became HBV DNA-positive (44 IU/ml) after 6 months of RTX treatment was effectively rescued with lamivudine before any hepatitis flare occurred. Among the 14 patients monitored for 18 months (range 0-70) after RTX discontinuation, no HBV reactivation was observed. Conclusion. The administration of RTX + DMARD in patients with RA with resolved HBV infection leads to a negligible risk of HBV reactivation, thus suggesting that serum HBsAg and/or HBV DNA monitoring but not universal anti-HBV prophylaxis is justified.

AB - Objective. Patients with resolved hepatitis B virus (HBV) infection, i.e., hepatitis B surface antigen (HBsAg)-negative/antihepatitis B core antigen (anti-HBc)-positive, undergoing rituximab (RTX)-based chemotherapy for hematological malignancies without anti-HBV prophylaxis are at risk of HBV reactivation, but the risk in such patients receiving RTX for rheumatological disorders is not clear. We evaluated this risk in HBsAg-negative/anti-HBc-positive patients with rheumatoid arthritis (RA) undergoing RTX without prophylaxis. Methods. Thirty-three HBsAg-negative/anti-HBc-positive outpatients with RA with undetectable HBV DNA by sensitive PCR assay [73% women, median age 60 years, 85% with HBsAg antibodies (anti-HBs), 37% with antihepatitis B envelope antigen] received a median of 3 cycles of RTX (range 1-8) over 34 months (range 0-80) combined with disease-modifying antirheumatic drugs (DMARD) without prophylaxis. All underwent clinical and laboratory monitoring during and after RTX administration, including serum HBsAg and HBV DNA measurements every 6 months or whenever clinically indicated. Results. None of the patients seroreverted to HBsAg during RTX treatment, but 6/28 (21%) showed a > 50% decrease in protective anti-HBs levels, including 2 who became anti-HBs-negative. One patient (3%) who became HBV DNA-positive (44 IU/ml) after 6 months of RTX treatment was effectively rescued with lamivudine before any hepatitis flare occurred. Among the 14 patients monitored for 18 months (range 0-70) after RTX discontinuation, no HBV reactivation was observed. Conclusion. The administration of RTX + DMARD in patients with RA with resolved HBV infection leads to a negligible risk of HBV reactivation, thus suggesting that serum HBsAg and/or HBV DNA monitoring but not universal anti-HBV prophylaxis is justified.

KW - HBsAg

KW - HBV DNA

KW - Hepatitis B virus reactivation

KW - Rheumatoid arthritis

KW - Rituximab

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