Interleukin (IL)-6 blocking agents for the treatment of COVID-19 A living systematic review

Interleukin (IL)-6 is a pleiotropic, pro-inflammatory cytokine produced by a variety of cell types, including lymphocytes, monocytes, and fibroblasts. IL-6 blocking agents are a class of therapeutics whose compounds are directed against either the IL-6 peptide or the IL-6 receptor. All currently available IL-6 blocking agents are monoclonal antibodies classified as anti-IL-6 receptor monoclonal antibodies (e.g., sarilumab, tocilizumab) and anti-IL-6 monoclonal antibodies (siltuximab). These include Tocilizumab, Sarilumab, Siltuximab, Levilimab, Olokizumab, and Clazakizumab. Other compounds might become available in the future.

In this review we aim to assess the effectiveness of IL-6 blocking agents compared to placebo, standard of care or no treatment on outcomes in patients with COVID-19.

This review is part of a larger project: the COVID-NMA project (Boutron 2020a). The COVID-NMA project aims to provide decision-makers with a complete, high-quality and up-to-date synthesis of evidence on interventions for the prevention and treatment of COVID 19. For this purpose, we perform a living mapping of all registered randomized controlled trials and a living evidence synthesis of data from RCTs. We developed a master protocol on the effect of all interventions for the prevention and treatment of COVID-19 (first published on April 8, 2020; an update on May 11, 2020, June 17, 2020, and September 8, 2020) (Boutron 2020b). We set-up a platform (https://covid-nma.com) where all our results are made available and updated weekly.