Randomized prospective study evaluating tenofovir disoproxil fumarate prophylaxis against hepatitis B virus reactivation in anti-HBc-positive patients with rituximab-based regimens to treat hematologic malignancies: The Preblin study

PLoS One. 2017 Sep 12;12(9):e0184550. doi: 10.1371/journal.pone.0184550. eCollection 2017.

Abstract

Background: Hepatitis B virus (HBV) reactivation in patients with resolved HBV infection (HBsAg negative, antiHBc positive) is uncommon, but potentially fatal. The role of HBV prophylaxis in this setting is uncertain. The aim of this study was to compare the efficacy of tenofovir disoproxil fumarate (TDF) prophylaxis versus close monitoring in antiHBc-positive, HBsAg-negative patients under treatment with rituximab (RTX)-based regimens for hematologic malignancy.

Methods: PREBLIN is a phase IV, randomized, prospective, open-label, multicenter, parallel-group trial conducted in 17 hospitals throughout Spain. Anti-HBc-positive, HBsAg-negative patients with undetectable HBV DNA were randomized to receive TDF 300 mg once daily (Group I) or observation (Group II). The primary endpoint was the percentage of patients showing HBV reactivation during 18 months following initiation of RTX treatment. Patients with detectable HBV DNA (Group III) received the same dose of TDF and were analyzed together with Group I to investigate TDF safety.

Results: Sixty-one patients were enrolled in the study, 33 in the TDF treatment group and 28 in the observation group. By ITT analysis, HBV reactivation was 0% (0/33) in the study group and 10.7% (3/28) in the observation group (p = 0.091). None of the patients in either group showed significant differences in liver function parameters between baseline and the last follow-up sample. TDF was generally well tolerated and there were no severe treatment-related adverse events.

Conclusion: In patients with hematological malignancy and resolved hepatitis B infection receiving RTX-based regimens, HBV reactivation did not occur in patients given TDF prophylaxis.

Publication types

  • Clinical Trial, Phase IV
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects*
  • Antiviral Agents / therapeutic use
  • Female
  • Hepatitis B / blood
  • Hepatitis B / complications
  • Hepatitis B / drug therapy*
  • Hepatitis B / prevention & control
  • Hepatitis B virus / immunology
  • Humans
  • Leukemia / complications
  • Leukemia / drug therapy
  • Leukemia / virology*
  • Male
  • Middle Aged
  • Post-Exposure Prophylaxis / methods
  • Rituximab / administration & dosage
  • Rituximab / therapeutic use
  • Serologic Tests
  • Tenofovir / administration & dosage
  • Tenofovir / adverse effects*
  • Tenofovir / therapeutic use

Substances

  • Antineoplastic Agents
  • Antiviral Agents
  • Rituximab
  • Tenofovir

Grants and funding

Medical Department of Gilead Sciences supplied the medications used in this study and its funding regardless of the study results. Medical Department of Gilead Sciences had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.