J Korean Med Sci. 2023;38(28):e216.

Efficacy of Antiviral Prophylaxis up to 6 or 12 Months From Completion of Rituximab in Resolved Hepatitis B Patients: A Multicenter, Randomized Study.

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제1저자 장희준, 유수종 · 교신저자 김윤준

PMID 37463687 PMC10353911 DOI 10.3346/jkms.2023.38.e216 IF 3.2 소화기내과

소속 (5)

Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Korea.
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Division of Hematology-Oncology, Department of Internal Medicine, Konkuk University Medical Center, Seoul, Korea.
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea. yoonjun@snu.ac.kr.

Abstract

BACKGROUND Rituximab occasionally induces reactivation of hepatitis B virus (HBV) in patients with resolved HBV, at times with fatal consequences. The optimal duration of prophylactic antiviral therapy in this situation is unclear. We aimed to investigate the difference in HBV reactivation according to the duration of prophylactic tenofovir disoproxil fumarate (TDF) in patients with resolved HBV and receiving rituximab.

METHODS A multicenter, randomized, open-label, prospective study was conducted in hepatitis B surface antigen-negative and anti-HBc-positive non-Hodgkin's lymphoma patients treated with rituximab-based chemotherapy. A total of 90 patients were randomized and received prophylactic TDF from the initiation of rituximab until 6 months (the 6-month group) or 12 months (the 12-month group) after the completion of rituximab. The primary outcome was the difference in HBV reactivation and the secondary outcomes were the difference in hepatitis flare and adverse events between the two groups.

RESULTS In an intention to treat (ITT) analysis, HBV reactivation occurred in 1 of 43 patients (2.3%; 95% confidence interval [CI], 0.41-12%) at a median of 13.3 months in the 6-month group and 2 of 41 patients (4.9%; 95% CI, 1.4-16%) at a median of 13.7 months in the 12-month group. In a per protocol (PP) analysis, HBV reactivation occurred in 1 of 18 patients (5.6%; 95% CI, 0.99-26%) at 13.3 months in the 6-month group and 1 of 13 patients (7.7%; 95% CI, 1.4-33%) at 9.7 months in the 12-month group. The cumulative incidence of HBV reactivation was not significantly different between the two groups in ITT and PP analyses (P = 0.502 and 0.795, respectively). The occurrence of adverse events was not significantly different between the two groups in ITT (9.3% in the 6-month group, 22.0% in the 12-month group, P = 0.193) and PP analyses (5.6% in the 6-month group, 7.7% in the 12-month group, P > 0.999).

CONCLUSION Prophylactic TDF up to 6 months after completion of rituximab-based chemotherapy is sufficient in terms of the efficacy and safety of reducing HBV reactivation in patients with resolved HBV.

TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02585947.

Keywords

Hepatitis BProphylaxisReactivationResolvedTenofovir

Figures

**Fig. 1** Consolidated Standards of Reporting Trials diagram. ITT = intention to treat, PP = per protocol.

**Fig. 2** Cumulative incidence of hepatitis B virus reactivation according to the duration of prophylactic tenofovir administration after rituximab-based chemotherapy in (A) intention to treat analysis and (B) per protocol analysis.

그림 출처: PubMed Central 공개 논문 (PMC10353911)

Conflict of interest statement

Su Jong Yu received compensation for lectures from Bayer HealthCare Pharmaceuticals. Jeong-Hoon Lee received compensation for lectures from GreenCross Cell, Daewoong Pharmaceuticals and Gilead Korea; Jung-Hwan Yoon received a research grant from Bayer HealthCare Pharmaceuticals, Bukwang Pharmaceuticals and Daewoong Pharmaceuticals; and Yoon Jun Kim received research grants from BTG, AstraZeneca, Gilead Sciences, Daewoong, Bayer, Samjin, and Yuhan Pharmaceuticals.

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