Abstract

To investigate the incidence and risk factors of hepatitis B virus (HBV) reactivation in HBV surface antigen (HBsAg)−/ HBV core antibody (HBcAb)+ patients who underwent rituximab (RTX) therapy for rheumatoid arthritis (RA). From January 2000 through December 2017, a total of 134 RA patients with various HBV serostatuses who received RTX at Dalin Tzu Chi Hospital were screened. Finally, 50 HBsAg−/HBcAb+ patients were enrolled in this retrospective study. Baseline characteristics, comedications, and the occurrence of HBV reactivation were recorded. Four HBsAg−/HBcAb+ RA patients (8%; 4/50) experienced HBV reactivation after treatment with RTX. Hepatitis flare-up occurred in 2 of these 4 patients, with a fatal outcome in one. HBV reactivation occurred approximately 1–4 years after the first dose of RTX and 0.5–1.5 years after the last one. In HBsAg−/HBcAb+ patients, HBV reactivation was significantly more common in those who were HBV surface antibody (HBsAb)− at baseline than in those who were HBsAb+ (30% vs 4%; p = 0.02). A history of adalimumab use was associated with HBV reactivation (100% vs 39%; p = 0.02). A moderate risk of HBV reactivation was observed in HBsAg−/HBcAb+ RA patients receiving RTX therapy. The reactivation may induce acute hepatitis and even death. To reduce the risk of HBV reactivation, regular monitoring of liver function is insufficient; monitoring of viral load and HBsAg or prophylaxis with antiviral therapy should be considered.

Highlights

  • Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease characterized by proliferative synovitis

  • Rituximab administration is associated with an increased risk of hepatitis B virus (HBV) reactivation in patients with chronic infection with hepatitis B surface antigen (HBsAg)-positive HBV or hepatitis B core antibody (HBcAb)-positive HBV6

  • A total of 50 HBsAg−/HBcAb+ rheumatoid arthritis (RA) patients who received RTX therapy were enrolled in this study

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Summary

Introduction

Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease characterized by proliferative synovitis. HBV reactivation is an emerging problem and a potentially life-threatening complication in patients receiving chemotherapy or immunosuppressive therapy, especially in epidemic regions. Among those bDMARDs currently used, rituximab (RTX) has received particular attention. The guidelines recommended anti-HBV prophylaxis for HBsAg−/HBcAb+ patients receiving anti-CD20 antibody therapy (e.g., rituximab in the oncohematological setting)[11,12] Those suggestions were based on the evidence from rituximab studies in the oncohematological setting (risk > 10%)[12]. We aimed to determine the incidence of HBV reactivation and hepatitis flare-ups in HBsAg−/ HBcAb+ patients after receiving RTX therapy for RA at our hospital

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