- In Asia, tocilizumab and tofacitinib have been reported to reactivate hepatitis B virus infection (HBV)
- This study examined data on 20 patients in the Boston area who were prescribed tocilizumab or tofacitinib up to 2018 and had resolved HBV
- At baseline, all patients were positive for the hepatitis B core antibody and negative for the hepatitis B surface antigen, and most were positive for the hepatitis B surface antibody
- Over the median follow-up of three to four years, no patient had an episode of HBV reactivation
- This small case series suggests that tocilizumab or tofacitinib may be prescribed safely for patients with resolved HBV infection, but pretreatment HBV screening is still important because a theoretical risk of HBV reactivation remains
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The use of tumor necrosis factor inhibitors, rituximab and other immunosuppressive biologic agents can reactivate hepatitis B virus infection (HBV), and this can lead to liver failure and death. In Asia, HBV reactivation has been reported with both tocilizumab and tofacitinib, which interfere with the interleukin-6 signaling that moderates immune control of chronic HBV.
In a retrospective study, research fellow Naomi Serling-Boyd, MD, and physician Zachary S. Wallace, MD, MSc, of the Division of Rheumatology, Allergy and Immunology at Massachusetts General Hospital, and colleagues observed no episodes of HBV reactivation in patients treated with tocilizumab or tofacitinib at Mass General and affiliated hospitals. Their report appears in the Annals of the Rheumatic Diseases.
The study examined data on 20 people who were prescribed tocilizumab or tofacitinib between 1995 and 2018, most often for rheumatoid arthritis, and had resolved or chronic HBV. Reactivation of HBV was defined as:
- >10-fold increase in HBV DNA level from baseline or absolute increase >105 copies/mL; or
- A positive test for hepatitis B surface antigen (HBsAg) when previously negative
Medication Exposures and Baseline Serology
Twelve patients received only tocilizumab, four received only tofacitinib and four received both drugs (sequentially). At baseline, all 20 patients were positive for the hepatitis B core antibody (HBcAb) and negative for HBsAg. All 16 patients treated with tocilizumab and seven of the eight treated with tofacitinib were positive for the hepatitis B surface antibody (HBsAb) at baseline.
Median follow-up after treatment initiation was 4 years for tocilizumab-treated patients and 3.1 years for tofacitinib-treated patients. Six patients experienced mild, transient aminotransferase elevations and one had severe elevation (>10 times normal) attributed to ischemic injury. No episode was attributed to HBV reactivation.
88% of the tocilizumab group and 75% of the tofacitinib group had HBV DNA or HBsAg assessed at least once after treatment initiation. No test was positive.
Recommendations for Clinicians
These findings suggest that tocilizumab or tofacitinib may be prescribed safely for patients with resolved HBV infection, particularly those who are HBsAb-positive. However, although HBsAb positivity reduces the likelihood of HBV reactivation, it does not eliminate the risk and this study was not powered to fully measure that risk. Pretreatment HBV screening remains important.
Refer a patient to the Rheumatology Unit