Background/Purpose

HBV infection represents a major issue in patients with rheumatoid arthritis (RA) undergoing biological disease-modifying anti-rheumatic drugs (bDMARDs) (1). While the risk of hepatitis reactivation under anti-TNF agents has been well described, experience with drugs as tocilizumab (TCZ) and abatacept (ABA) is still limited (2). Aim of this study is to retrospectively assess the risk of HBV reactivation in real-life RA patients treated with ABA and TCZ.

Methods

RA patients with a past HBV infection history (‘chronic inactive carriers’ with HBsAg+ and undetectable or <2,000 IU/mL viral load + normal liver function tests (LFT) and ‘occult carriers' with only HBcAb+) and treated with ABA or TCZ, have been retrospectively analyzed for the risk of ‘viral re-activation' (rise in viral load≥1 log10 IU/mL compared with baseline values, or detection of previously undetected serum HBV-DNA) and/or ‘viral hepatitis B' (increase in LFT and serum HBV-DNA, necroinflammation and/or fibrosis in liver biopsy)  by regularly detecting HBsAg, HBV-DNA, LFT throughout follow-up.

Results

Out of a total of 125 RA patients, 17 (13,6%) were HbcAb+: 16 occult carriers (8 treated with ABA+8 treated with TCZ), and 1 chronic inactive carrier treated with ABA. Patients have been followed for a median time (IQR) of 1.2 (0.7-1.5) years. They were previously treated with a median (IQR) number of 2 (1-3) synthetic DMARDs (sDMARDs) and 0 (0-1) bDMARDs. The mean age (sd) was 54.7 (13.8) years, the median disease duration was 5.8 (1.8-7.6) years. Most patients were treated with concomitant methotrexate (8/9 in the ABA group, 5/8 in the TCZ group) and corticosteroids. In the ABA group, 1 patient with chronic HCV co-infection (HCV-RNA+) started lamivudine, due to LFT elevation (<2-fold ULN) occurring 2 months after ABA initiation; amelioration of LFT along with undetectable viral load occurred throughout 12 months of follow-up. 2 patients (1 occult carrier and 1 chronic inactive carrier) underwent lamivudine before ABA with no HBV-related adverse events; among the other 6 ABA patients not receiving lamivudine only 1 experienced a temporary positivization of viral load (85 UI/mL) without LFT elevation at 12 months of follow-up: spontaneous negativization of viral load was registered at 18 months. In the TCZ group, no patient received lamivudine with no HBV reactivation.

Conclusion

Despite limited to few patients and short follow-up, the use of ABA and TCZ in RA patients with past history of HBV infection seems relatively safe. However, periodic monitoring of liver function tests and viral load is mandatory. According to scientific literature, viral prophylaxis might be considered mainly in patients undergoing ABA. Further data are needed to clarify long-term safety issues.

References

(1) Vassillopoulos D, et al. Nat Rev Rheumatol 2012.

(2) Kim PS, et al. Arthritis Care Res 2012.

Table 1. Characteristics of patients with RA and past HBV infection treated with ABA and TCZ.