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Research article
Hepatitis B virus Reactivation in Patients Receiving Tocilizumab for Rheumatoid Arthritis: A Long‐term, Retrospective Observational Study
Chih-Wei Tseng
Corresponding Author
ORCiD: https://orcid.org/0000-0002-6951-4646
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Aim To investigate the risk of hepatitis B virus (HBV) reactivation in patients undergoing long-term tocilizumab (TCZ) therapy for rheumatoid arthritis (RA).
Method From January 2011 through August 2019, a total of 134 RA patients who received TCZ at Dalin Tzu Chi Hospital were screened. Patients were excluded if they were < 20 years, without complete data, or received TCZ for less than 3 months. A total of 97 patients were enrolled in this retrospective study. Clinical data, co-medications, and the occurrence of HBV reactivation were recorded.
Results Of the 97 enrolled patients, 7 were HBsAg+ (7.2%), 64 were HBsAg−/HBcAb+ (61%) and 26 were HBsAg−/HBcAb+ (26.8%). The median disease follow-up time was 9 years (range, 1–18 years). TCZ was administered for a median of 29 months (range, 3–91 months). Four patients (4.1%) experienced HBV reactivation after TCZ therapy. Of the 7 HBsAg+ patients, 4 received antiviral prophylaxis and had no HBV reactivation; the remaining 3 patients had no antiviral prophylaxis, and all 3 (100%) experienced early HBV reactivation and hepatitis flare (median time to event, 6 months; range, 5–8 months). Hyper-bilirubinemia occurred in 2 of these 3 patients, with mild prothrombin time prolongation in one. After salvage entecavir treatment, all patients had a favorable outcome. Of the 64 HBsAg−/HBcAb+ patients, only one became positive for serum HBV DNA (2.5 × 10 7 IU/mL) after 18 months of TCZ treatment (1.6%; 1/64). This patient was immediately treated with entecavir, which prevented hepatitis flare.
Conclusions HBsAg+ RA patients undergoing TCZ treatment are at high risk of HBV reactivation, which is prevented by antiviral prophylaxis. HBsAg−/HBcAb+ patients also are at risk of HBV reactivation. Although their risk of reactivation is lower than that of HBsAg+ patients, strict monitoring of their HBV status is still necessary.
Keywords
HBV reactivation, Hepatitis flare, Rheumatoid Arthritis, Tocilizumab
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Kuo meng hsuan
commented on 12 May, 2020
HBV reactivation rate of tocilizumab in RA patients is diverse in present literatures.We reviewed our local data and find the rate was very different in HBsAg (+) and HBsAg-/antiHBc+ patients.
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This is a preprint. It has not completed peer review.
Research article
Hepatitis B virus Reactivation in Patients Receiving Tocilizumab for Rheumatoid Arthritis: A Long‐term, Retrospective Observational Study
Chih-Wei Tseng
Corresponding Author
ORCiD: https://orcid.org/0000-0002-6951-4646
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 12 May, 2020
Community comments: 1
Metrics
Comments: 1
PDF Downloads: ...
HTML Views: ...
Subject Areas
Rheumatology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Aim To investigate the risk of hepatitis B virus (HBV) reactivation in patients undergoing long-term tocilizumab (TCZ) therapy for rheumatoid arthritis (RA).
Method From January 2011 through August 2019, a total of 134 RA patients who received TCZ at Dalin Tzu Chi Hospital were screened. Patients were excluded if they were < 20 years, without complete data, or received TCZ for less than 3 months. A total of 97 patients were enrolled in this retrospective study. Clinical data, co-medications, and the occurrence of HBV reactivation were recorded.
Results Of the 97 enrolled patients, 7 were HBsAg+ (7.2%), 64 were HBsAg−/HBcAb+ (61%) and 26 were HBsAg−/HBcAb+ (26.8%). The median disease follow-up time was 9 years (range, 1–18 years). TCZ was administered for a median of 29 months (range, 3–91 months). Four patients (4.1%) experienced HBV reactivation after TCZ therapy. Of the 7 HBsAg+ patients, 4 received antiviral prophylaxis and had no HBV reactivation; the remaining 3 patients had no antiviral prophylaxis, and all 3 (100%) experienced early HBV reactivation and hepatitis flare (median time to event, 6 months; range, 5–8 months). Hyper-bilirubinemia occurred in 2 of these 3 patients, with mild prothrombin time prolongation in one. After salvage entecavir treatment, all patients had a favorable outcome. Of the 64 HBsAg−/HBcAb+ patients, only one became positive for serum HBV DNA (2.5 × 10 7 IU/mL) after 18 months of TCZ treatment (1.6%; 1/64). This patient was immediately treated with entecavir, which prevented hepatitis flare.
Conclusions HBsAg+ RA patients undergoing TCZ treatment are at high risk of HBV reactivation, which is prevented by antiviral prophylaxis. HBsAg−/HBcAb+ patients also are at risk of HBV reactivation. Although their risk of reactivation is lower than that of HBsAg+ patients, strict monitoring of their HBV status is still necessary.
Figure 1
Figure 2
Kuo meng hsuan
commented on 12 May, 2020
HBV reactivation rate of tocilizumab in RA patients is diverse in present literatures.We reviewed our local data and find the rate was very different in HBsAg (+) and HBsAg-/antiHBc+ patients.