Risk of Reactivation of Hepatitis B Virus (HBV) and Tuberculosis (TB) and Complications of Hepatitis C Virus (HCV) Following Tocilizumab Therapy: A Systematic Review to Inform Risk Assessment in the COVID-19 Era

Abstract

Objectives: Tocilizumab (TCZ), an IL-6 receptor antagonist, is used in the treatment of severe COVID-19 caused by infection with SARS-CoV-2. However, unintended consequences of TCZ therapy include reactivation of tuberculosis (TB) or hepatitis B virus (HBV), and worsening of hepatitis C virus (HCV). We set out to assimilate existing data for these complications, in order to help inform evidence-based risk assessments for the use of TCZ, and thus to reduce the risk of serious but preventable complications.Methods: We searched the global WHO database of Individual Case Safety Reports (ICSRs) and adverse drug reactions (ADRs) (“VigiBase”) and undertook a systematic literature review, in accordance with PRISMA guidelines. We generated mean cumulative incidence estimates for infection complications.Results: Mean cumulative incidence of HBV and TB were 3.3 and 4.3%, respectively, in patients receiving TCZ. Insufficient data were available to generate estimates for HCV. These estimates derive from heterogeneous studies pre-dating SARS-CoV-2, with differing epidemiology and varied approaches to screening and prophylaxis, so formal meta-analysis was not possible.Conclusions: We underline the need for careful individual risk assessment prior to TCZ prescription, and present an algorithm to guide clinical stratification. There is an urgent need for ongoing collation of safety data as TCZ therapy is used in COVID.

Predictors of poor outcome in tocilizumab treated patients with Sars-CoV-2 related severe respiratory failure: A multicentre real world study

“…Tocilizumab is the most studied IL-6 antagonists in the context of COVID-19. Overall, evidence deriving from RCTs and cohort studies is favourable, demonstrating that Tocilizumab added on standard treatment significantly reduces 30-day mortality and needing for OTI, without serious adverse events such as sepsis and/or hepatitis or tubercolosis recurrence [9] , [10] , [21] . Despite this efficacy, a not negligible percentage of patients with severe SARS-CoV-2 respiratory failure treated by Tocilizumab dies or undergoes OTI due to respiratory deterioration.…”

Prevalence of Viral Hepatitis in Unselected, Consecutively Enrolled Patients Hospitalised for SARS-CoV-2

“…People with HBcAb positivity are at risk of reactivation of HBV infection when exposed to immunosuppressive therapies [ 19 , 20 ]. As some immunosuppressive drugs used for COVID-19, like tocilizumab and baricitinib can lead to HBV reactivation [ 21 ], HBV screening should be offered with significant attention paid to patients eligible for these therapies, even though the risk appears to be low in patients with previous and resolved HBV infections [ 22 ]. Most data stems from studies about autoimmune diseases in which these medications were administered together with some other agents, such as high dose and prolonged corticosteroids therapy or other disease-modifying antirheumatic drugs (DMARDs) [ 23 , 24 ].…”

COVID-19 as Another Trigger for HBV Reactivation: Clinical Case and Review of Literature

“…The use of TCZ seems less dangerous, given the low frequency of HBV reactivation observed in a previous study (3.3%), the data of which should be taken with caution because it was obtained in a different context [ 54 ].…”