Risk of hepatitis B virus reactivation in rheumatoid arthritis patients undergoing biologic treatment: Extending perspective from old to newer drugs

Abstract

Hepatitis B virus (HBV) reactivation in rheumatoid arthritis (RA) patients undergoing biological therapy is not infrequent. This condition can occur in patients with chronic hepatitis B as well as in patients with resolved HBV infection. Current recommendations are mainly focused on prevention and management strategies of viral reactivation under tumor necrosis factor-α inhibitors or chimeric monoclonal antibody rituximab. In recent years, growing data concerning HBV reactivation in RA patients treated with newer biological drugs like tocilizumab and abatacept have cumulated. In this review, epidemiology, pathogenesis and natural history of HBV infection have been revised first, mainly focusing on the role that specific therapeutic targets of current biotechnological drugs play in HBV pathobiology; finally we have summarized current evidences from scientific literature, including either observational studies and case reports as well, concerning HBV reactivation under different classes of biological drugs in RA patients. Taking all these evidences into account, some practical guidelines for screening, vaccination, prophylaxis and treatment of HBV reactivation have been proposed.

Risk of Serious Infection in Juvenile Idiopathic Arthritis Patients Associated With Tumor Necrosis Factor Inhibitors and Disease Activity in the German Biologics in Pediatric Rheumatology Registry

“…Within the ETN cohort, patients using monotherapy had an incidence rate of 43 per 1,000 patient-years (95% CI 32-57) compared to 72 per 1,000 patient-years (95% CI 54-93) in combination therapy with MTX. In addition, 64 first serious infections were reported, with 46 occurring with ETN (22 monotherapy, 24 combination therapy, with a rate of 22 per 1,000 patient-years [95% CI [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]). The adjusted HR of serious infections for the ETN-treated patients versus those taking MTX was only 1.36 (95% CI 0.6-3.07) and not significantly different.…”

“…Compared with those patients, JIA patients treated with neither MTX nor TNF blockers had a 2-fold increased infection rate (HR 2.0 [95% CI 1.5-2.5]), adjusted for baseline characteristics. The rate of bacterial infections in patients treated with TNFi (35 per 1,000 patient-years [95% CI 26-45]) or MTX (33 per 1,000 patient-years [95% CI [27][28][29][30][31][32][33][34][35][36][37][38][39][40]) was similar to that in patients not taking MTX or TNFi (25 per 1,000 patientyears [95% CI [22][23][24][25][26][27][28][29]). All rates were considerably higher than the total bacterial infection rate in our study of 2.4 per 1,000 patient-years.…”

Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016

“…An immunosuppressed state enables the proliferation of hbv dna, and clinical reactivation of hbv occurs as a result of immune reconstitution after myelosuppressive antineoplastic therapy is discontinued 77 . One retrospective study of 156 patients positive for the hbv surface antigen (including 16 with hematologic malignancies and 140 with solid tumours) and receiving chemotherapy showed a 4% risk of severe acute exacerbations of chronic hbv infection 78 .…”

Biological Therapy and Infection in Rheumatoid Arthritis Patients: Modern Aspects

“…В настоящее время большинство авторов, включая экспертов EULAR, полагают, что у неактивных HBV-носителей ГИБП-терапия может быть проведена при обязательном профилактическом применении современ-ных противовирусных препаратов [81][82][83][84]. Выбор проти-вовирусного препарата и длительность его применения зависят от планируемой продолжительности ГИБП-терапии и HBV-статуса, поэтому окончательное решение принимается только после консультации гепатолога.…”