Preserved C-reactive protein responses to blood stream infections following tocilizumab treatment for COVID-19

Wey, Emmanuel; Bristow, Clare; Nandani, Aarti; O'Farrell, Bryan; Pang, Jay; Lanzman, Marisa; Yang, Shuang; Ho, Soo; Mack, Damien; Spiro, Michael; Balakrishnan, Indran; Pollara, Gabriele

doi:10.1101/2021.07.03.21259949

Cited by 2 publications

(1 citation statement)

References 13 publications

(16 reference statements)

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“…Nevertheless, expanding awareness of the potential risk of complications remains important, such that vigilance can be applied, as recommendations are relevant not just at the point of TCZ prescription but during follow-up, with clinical awareness of potential complications in the weeks and months after treatment. As TCZ may blunt markers of infection such as C-reactive protein (CRP), reactivation events may be more difficult to diagnose in this group (1), although increases in CRP are still recognised in response to bloodstream infections (55). In individuals with potential risk of HBV reactivation, monitoring of liver enzymes and HBV markers (HBsAg and viral load), should be considered.…”

Section: Specific Clinical Recommendationsmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Specific Clinical Recommendationsmentioning

confidence: 99%

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

et al. 2021

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Altered IL-6 signalling and risk of tuberculosis disease: a meta-analysis and Mendelian randomisation study

Hamilton

Schurz

Yates

et al. 2023

Preprint

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IL-6 responses are ubiquitous in Mycobacterium tuberculosis (Mtb) infections, but their role in determining human tuberculosis (TB) disease risk is unknown. We used single nucleotide polymorphisms (SNPs) in and near the IL-6 receptor (IL6R) gene, focusing on the non-synonymous variant, rs2228145 associated with reduced classical IL-6 signalling, to assess the effect of altered IL-6 activity on TB disease risk. We identified 16 genome wide association studies (GWAS) of TB disease collating 17,982 cases of TB disease and 972,389 controls across 4 continents. Meta-analyses and Mendelian randomisation analyses revealed that reduced classical IL-6 signalling was associated with lower odds of TB disease, a finding replicated using multiple, independent SNP instruments and 2 separate exposure variables. Our findings establish a causal relationship between IL-6 signalling and the outcome of Mtb infection, suggesting IL-6 antagonists do not increase the risk of TB disease and should be investigated as adjuncts in treatment.

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Preserved C-reactive protein responses to blood stream infections following tocilizumab treatment for COVID-19

Cited by 2 publications

References 13 publications

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

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

Altered IL-6 signalling and risk of tuberculosis disease: a meta-analysis and Mendelian randomisation study

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