Background Our previous study showed 11.2% of Chinese patients with rheumatoid Arthritis (RA) suffered chronic Hepatitis B virus (HBV) infection (HBsAg+) and 32.3% suffered past HBV infection (anti-HBc+/HBsAg-). Tocilizumab (TCZ) was the first non-TNFα bDMARD for refractory RA launched in China since October 2013. Little is known about its influence on HBV infection and liver outcome.
Objectives To explore the risk of HBV reactivation and the influence of host immunity to HBV infection in RA patients receiving TCZ Therapy.
Methods Refractory patients with active RA were enrolled from December 2013 to August 2014. HBV infection was screened at baseline and patients with HBsAg+, anti-HBc+/HBsAg- or anti-HBs were identified. All patients were treated with TCZ (4–8mg/kg, every 4 weeks, at least 12 weeks) plus MTX and/or other csDMARD(s). Antiviral prophylaxis was recommended for HBsAg+ patients. HBsAg or anti-HBs titer, HBV-DNA load and liver function were evaluated at 4th, 12th, 24th week. HBV reactivation was defined as a 10-fold rise of HBV-DNA compared to baseline or switch from undetectable to detectable or HBsAg seroconversion from negative to positive.
Results (1) Twenty-nine patients were enrolled and 5 of them received only one TCZ infusion for economic reason. Among the 24 patients, 79% were female, age (median and IQR, similarly hereinafter) was 53 (37–64) years, disease duration was 28 (6–120) months and DAS28-CRP was 5.3 (4.6–6.3). There were 3 RA patients with HBsAg+, 11 patients with anti-HBc+/HBsAg- and 10 patients did not suffer from HBV infection.
(2) One HBsAg+ RA patient who refused antiviral prophylaxis developed HBV reactivation (HBV-DNA elevated from 3990 IU/mL to 81700 IU/mL) with normal aminotransferases after 12-week TCZ+MTX+SSZ+HCQ therapy (Fig.1). The other 2 HBsAg+ RA patients whose baseline HBV-DNA was 7.97×107 and 1.30×106 IU/mL respectively received antiviral prophylaxis and none of them developed HBV reactivation. One HBsAg+ RA patient developed transient 5-times elevation of aminotransferases after first TCZ infusion and aminotransferases returned to normal at 12th week. None of patients with anti-HBc+/HBsAg- developed HBV reactivation. All 10 patients without HBV infection at baseline didn't develop de novo HBV infection during 24-week follow-up.
(3) Among 16 patients with anti-HBs, there was no significant change of HBsAb titer among baseline, 4th, 12th and 24th week according to repeated measures analysis of variance (F=1.468, P=0.266) and Wilcoxon Matched-Pairs Signed-Ranks Test (all P>0.05).
Conclusions Although TCZ seems to be safe for RA patients with past HBV infection and doesn't interfere with host immunity to HBV infection, our preliminary results suggest the risk of HBV reactivation in HBsAg+ RA patients treated with TCZ combination therapy without antiviral prophylaxis. Further multi-center study with more patients is needed.
Acknowledgements This work was supported by National Natural Science Foundation of China (81471597), Specialized Research Fund for the Doctoral Program of Higher Education (20130171110075) and Guangdong Natural Science Foundation (S2013010014396).
Disclosure of Interest None declared