Background Our previous study showed approximately 11% of Chinese RA patients combined with chronic Hepatitis B virus (HBV) infection and 32% with resolved HBV infection. HBV reactivation may occur as an adverse event of biologic DMARDs and TNFIs or abatacept have been categoried as moderate risk of HBV reactivation, rituximab as high risk . However, tocilizumab (TCZ) is still unclassified due to few data. TCZ has been approved for RA patients in combination with csDMARDs by CFDA in November 2013 and most of Chinese RA patients can only afford short course of TCZ for self-paid and expensive price.
Objectives To investigate the impact of short course of TCZ on HBV reactivation in RA patients.
Methods RA patients with moderate or high disease activity were recruited. Three consecutive doses of intravenous TCZ were given combined with csDMARDs. RA disease activity, liver function and HBV infection status were evaluated at baseline, week 4, week 8 and week 12 during TCZ based therapy.
Results Fifty-seven RA patients were recruited and 51 were qualified for statistics (Figure 1). They were divided into chronic HBV infection group (n=7, 13.7%), resolved HBV infection group (n=33, 64.7%) and non-HBV infection group (n=11, 21.6%). Three patients (6%) developed HBV reactivation after 1–3 doses of TCZ and all of them had chronic HBV infection without antiviral prophylaxis. All reactivation patients were asymptomatic along with normal aminotransferases and resolution of virological response after therapeutic antiviral therapy. None of patients with resolved HBV infection suffered from HBV reactivation. Aminotransferases elevated in 24% (12/51) of RA patients with 4% (2/51) exceeding 2-fold of ULN and returned to normal 4 weeks after adding hepatinica. Anti-HBs titer was positive (≥10 IU/L) in 82% (27/33) of patients with resolved HBV infection and reduced significantly after first dose of TCZ compared to baseline [426 (59–978) IU/L vs. 446 (78–000) IU/L, P<0.05], which was below protective level (<10 IU/L) in 19% (5/27) of patients and unable to recover in 7% (2/27) up to week 28–36. All patients were kept follow-up after 12 weeks. No additional HBV reactivation occurred during 4–80 weeks on extended period.
Conclusions This real-world, prospective cohort study suggests that short course of TCZ has moderate risk of HBV reactivation in RA patients and high risk in RA patients with chronic HBV infection especially without antiviral prophylaxis, which indicate the importance of HBV screening and antiviral prophylaxis for patients with chronic HBV infection before starting TCZ therapy.
Reddy KR, Beavers KL, Hammond SP, et al. American Gastroenterological Association Institute guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology, 2015,148:215–219.
Acknowledgement This work was supported by National Natural Science Foundation of China (No. 81471597), Specialized Research Fund for the Doctoral Program of Higher Education (No.20130171110075) and Guangdong Natural Science Foundation (No.2014A030313074).
Disclosure of Interest None declared