Safety of long‐term biologic therapy in rheumatologic patients with a previously resolved hepatitis B viral infection

Abstract

European and Asian studies report conflicting data on the risk of hepatitis B virus (HBV) reactivation in rheumatologic patients with a previously resolved HBV (prHBV) infection undergoing long-term biologic therapies. In this patient category, the safety of different immunosuppressive biologic therapies, including rituximab, was assessed. A total of 1218 Caucasian rheumatologic patients, admitted consecutively as outpatients between 2001 and 2012 and taking biologic therapies, underwent evaluation of anti-HCV and HBV markers as well as liver amino transferases every 3 months. Starting from January 2009, HBV DNA monitoring was performed in patients with a prHBV infection who had started immunosuppressive biologic therapy both before and after 2009. Patients were considered to have elevated aminotransferase levels if values were >1× upper normal limit at least once during follow-up. We found 179 patients with a prHBV infection (14 treated with rituximab, 146 with anti-tumor necrosis factor-alpha, and 19 with other biologic therapies) and 959 patients without a prHBV infection or other liver disease (controls). The mean age in the former group was significantly higher than the controls. Patients with a prHBV infection never showed detectable HBV DNA serum levels or antibody to hepatitis B surface antigen/hepatitis B surface antigen seroreversion. However, when the prevalence of elevated amino transferases in patients with prHBV infection was compared to controls, it was significantly higher in the former group only for aminotransferase levels >1× upper normal limit but not when aminotransferase levels >2× upper normal limit were considered. Conclusion: Among patients with a prHBV infection and rheumatologic indications for long-term biologic therapies, HBV reactivation was not seen; this suggests that universal prophylaxis is not justified and is not cost-effective in this clinical setting. (Hepatology 2015)

Harmful Effects and Potential Benefits of Anti-Tumor Necrosis Factor (TNF)-α on the Liver

“…Interestingly, despite the fact that HBV reactivation during therapeutic immunosuppression can be effectively prevented with the use of antivirals [46,47,48,49], among HBsAg positive patients the antiviral prophylaxis was administered in less than half of the cases (lamivudine in 35, entecavir in 3, and telbivudine in 1 case) [45]. In recent years, other studies were carried out for assessing the effect of anti-TNF-α therapy in patients with both HbsAg and anti-HBc positivity confirming the aforementioned findings [26,28,50,51]. Therefore, in the next paragraph we provide practical recommendations for the proper management of patients with positive markers of hepatitis B or C receiving anti-TNF-α agents as a treatment.…”

Admissions for hepatitis B reactivation in patients receiving immunosuppressive therapy remain unchanged from 1999 to 2014

“…[16][17][18][19]. While the most compelling studies demonstrating the cost-effectiveness of universal screening have been performed among high-risk patients receiving chemotherapies and anti-CD20 agents, there is also evidence to support screening among patients who are at lower risk for reactivation [16,18,20]. Nevertheless, controversy remains concerning whether it is more cost-effective to conduct universal versus targeted screening in patients who will be receiving IST with low or moderate risk of HBV reactivation, particularly in countries with low prevalence of HBV infection.…”

Reactivation of Hepatitis B Virus and Its Prevention in Patients with Rheumatic Diseases Receiving Immunosuppressive Therapy

“…It is assumed that the risk of reactivation may be high in HBsAg-positive rheumatic patients. However, the incidence of HBV reactivation is less than 1% with resolved HBV infection in rheumatic patients who received rituximab [52,56,57]. T cell inhibitor (abatacept), IL-6 inhibitor (Tocilizumab), or kinase inhibitor (imatinib, nilotinib) are also related to moderate risk (1% to 10%) of HBV reactivation [10,53], while disease modifying anti-rheumatic drugs, traditional immunosuppressive agents such as azathioprine, short-course of corticosteroids ＜1 week, or intra-articular steroid injection showed low risk (＜1%) of HBV reactivation [10].…”