Association of hepatitis B with antirheumatic drugs: a case-control study

Mod Rheumatol. 2013 Jul;23(4):694-704. doi: 10.1007/s10165-012-0709-7. Epub 2012 Jul 18.


Background: Though concern of hepatitis B virus (HBV) reactivation by antirheumatic agents has limited therapeutic opportunities in HBV-infected rheumatoid arthritis (RA) patients, the relative risks (RR) among such agents have not been clarified.

Objective: We compared the reporting of antirheumatic-agent-associated hepatitis B.

Patients: We assessed 92 hepatitis B cases and 98,069 controls from a population of 98,161 RA patients registered into the US Food and Drug Administration's (FDA's) adverse event database between 2004 and 2010.

Measurements: A reporting odds ratio (ROR), a signal suggesting a risk for hepatitis B among antirheumatic agents, was measured.

Results: Treatment with corticosteroids [ROR 2.3 (95% confidence interval 1.3-4.0)], methotrexate [4.9 (3.9-6.0)], rituximab [7.2 (5.3-9.9)], tacrolimus [4.2 (1.5-11.9)], or reporting from Japan [2.2 (1.1-4.2)] were associated with higher signal, whereas adalimumab had a lower ROR [0.2 (0.1-0.4)].

Limitations: There are known limitations of spontaneous reporting, such as underreporting, the Weber effect, reporting bias, indication bias, and limited clinical information such as HBV status.

Conclusions: Adalimumab's low reporting rate is most likely be due to notoriety. However, the possibility that adalimumab might suppress reactivation of HBV cannot be denied. Until the possibility is clarified in well-designed clinical studies, physicians should use adalimumab cautiously in patients with HBV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antirheumatic Agents / adverse effects*
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / virology
  • Case-Control Studies
  • Female
  • Hepatitis B / immunology*
  • Hepatitis B / virology
  • Hepatitis B virus / immunology*
  • Humans
  • Male
  • Middle Aged
  • United States
  • Virus Activation / drug effects*
  • Virus Activation / immunology


  • Antirheumatic Agents