Risk of hepatitis B reactivation in HBsAg-/HBcAb+ patients after biologic or JAK inhibitor therapy for rheumatoid arthritis: A meta-analysis

Immun Inflamm Dis. 2023 Feb;11(2):e780. doi: 10.1002/iid3.780.

Abstract

Background: The risk of hepatitis B virus (HBV) reactivation after biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) therapy in patients with rheumatoid arthritis (RA) combined with HBsAg-/HBcAb+ is still inconsistent.

Methods: We conducted a systematic review of existing databases from 1977 to August 22, 2021. Studies of RA patients combined with HBsAg-/HBcAb +, treated with b/tsDMARDs and the reported number of HBV reactivation were included.

Results: We included 26 studies of 2252 HBsAg-/HBcAb+ RA patients treated with b/tsDMARDs. The pooled HBV reactivation rate was 2.0% (95% confidence interval [CI]: 0.01-0.04; I2 = 66%, p < .01). In the subgroup analysis, the HBV reactivation rate of rituximab (RTX), abatacept, and inhibitors of Janus kinase (JAK), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were 9.0% (95% CI: 0.04-0.15; I2 = 61%, p = .03), 6.0% (95% CI: 0.01-0.13; I2 = 40%, p = .19), 1.0% (95% CI: 0.00-0.03; I2 = 41%, p = .19), 0.0% (95% CI: 0.00-0.02; I2 = 0%, p = .43), 0.0% (95% CI: 0.00-0.01; I2 = 0%, p = .87), respectively. While HBsAb- patients have a significant risk of reactivation (odds ratio [OR] = 4.56, 95% CI = 2.45-8.48; I2 = 7%, p = .37), low HBsAb+ group also display a significant risk of reactivation (OR = 5.45, 95% CI: 1.35-21.94; I2 = 0%, p = .46).

Conclusions: This meta-analysis demonstrates the highest potential risk of HBV reactivation in HBsAg-/HBcAb+ RA patients receiving RTX treatment, especially HBsAb- patients. Our study furthers the understanding of the prophylactic use of anti-HBV drugs in such patients. However, it is relative safety to use the inhibitors of IL-6, TNF-α, and JAK in these patients.

Keywords: biologic therapy; hepatitis B virus; reactivation; rheumatoid arthritis.

Publication types

  • Systematic Review
  • Meta-Analysis
  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid* / drug therapy
  • Biological Products* / adverse effects
  • Biological Products* / therapeutic use
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Hepatitis B virus / physiology
  • Hepatitis B* / chemically induced
  • Hepatitis B* / drug therapy
  • Humans
  • Interleukin-6
  • Janus Kinase Inhibitors* / adverse effects
  • Janus Kinase Inhibitors* / therapeutic use
  • Rituximab / adverse effects
  • Rituximab / therapeutic use
  • Tumor Necrosis Factor-alpha

Substances

  • Biological Products
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Interleukin-6
  • Janus Kinase Inhibitors
  • Rituximab
  • Tumor Necrosis Factor-alpha