Reactivation of hepatitis B virus infection in patients with rheumatoid arthritis receiving tofacitinib

Int J Rheum Dis. 2021 Nov;24(11):1362-1369. doi: 10.1111/1756-185X.14217. Epub 2021 Sep 10.


Objectives: The aim of this study was to investigate hepatitis B virus (HBV) reactivation in patients with rheumatoid arthritis (RA) receiving tofacitinib.

Method: This was a retrospective study performed in a regional teaching hospital in southern Taiwan. During January 2017 and December 2020, patients with a clinician-confirmed diagnosis of RA using tofacitinib for at least 3 months were enrolled. Serum HBV DNA levels and serum alanine aminotransferase were followed up around every 3 to 6 months to assess HBV reactivation.

Results: A total of 98 patients with RA were enrolled, and eight were hepatitis B surface antigen positive (HBsAg+) (8.1%), 64 were HBsAg-negative (HBsAg-)/hepatitis B core antibody positive (HBcAb+) (65.3%). In the HBsAg+ patients, two patients received antiviral prophylaxis, and none of them had HBV reactivation or hepatitis flare-up. The HBV reactivation rate was 33.3% (2/6) in the HBsAg+ RA patient without antiviral prophylaxis. Among the HBsAg-/HBcAb+ patients, the HBV reactivation rate was 3.1% (2/64). The incidence rate of HBV reactivation was 153.8 per 1000 person-years for overall HBsAg+ patients and 250 per 1000 person-years after excluding patients receiving antiviral prophylaxis. The incidence rate was 11.2 per 1000 person-years for HBsAg-/HBcAb+ patients with RA receiving tofacitinib.

Conclusion: Tofacitinib could induce HBV reactivation in both HBsAg+ and HBsAg-/HBcAb+ RA patients. HBsAg+ patients receiving tofacitinib have a high incidence rate of HBV reactivation, which could be prevented by antiviral prophylaxis. Although the risk of reactivation is low in HBsAg-/HBcAb+ patients, closely monitoring HBV DNA and alanine aminotransferase should be suggested.

Keywords: hepatitis B virus; reactivation; rheumatoid arthritis; tofacitinib.

MeSH terms

  • Aged
  • Antirheumatic Agents / adverse effects*
  • Antiviral Agents / therapeutic use
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Female
  • Hepatitis B virus / drug effects*
  • Hepatitis B virus / genetics
  • Hepatitis B virus / growth & development
  • Humans
  • Janus Kinase Inhibitors / adverse effects*
  • Male
  • Middle Aged
  • Piperidines / adverse effects*
  • Pyrimidines / adverse effects*
  • Retrospective Studies
  • Taiwan
  • Time Factors
  • Treatment Outcome
  • Viral Load
  • Virus Activation / drug effects*


  • Antirheumatic Agents
  • Antiviral Agents
  • Janus Kinase Inhibitors
  • Piperidines
  • Pyrimidines
  • tofacitinib