Treatment of severe covid-19 with interleukin 6 receptor inhibition

Rajasundaram, Skanda; Burgess, Stephen

doi:10.1136/bmjmed-2022-000144

Cited by 2 publications

(2 citation statements)

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Section: Identifying Repurposing Opportunities For An Established Drugsupporting

confidence: 64%

“…A protective effect of inhibition of IL-6 signaling was identified for this disease outcome, a finding which has been corroborated by clinical trial evidence for a beneficial effect of tocilizumab on disease activity in PMR (Devauchelle-Pensec et al, 2022 ). This approach was also used to identify a protective effect of genetically proxied IL-6 signaling on risk of COVID-19 incidence and severity, a finding consistent with results from clinical trials of IL-6 receptor inhibitors (Bovijn et al, 2020 ; Larsson et al, 2021 ; Rajasundaram et al, 2022 ). As an example of a hypothesis-free approach, an MR-PheWAS analysis using genetic data from the Million Veterans Program identified a potential repurposing opportunity for IL-6 receptor antagonists for prevention of aortic aneurysm (Cai et al, 2018 ), a finding replicated in the UK Biobank dataset (Georgakis et al, 2021 ).…”

Section: Post-phase 3: Using Mr To Identify Repurposing Opportunities...mentioning

confidence: 60%

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Mendelian randomization as a tool to inform drug development using human genetics

Daghlas¹

2023

Camb. prisms Precis. med.

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Drug development is essential to the advancement of human health, however the process is slow, costly, and at high risk of failure at all stages. A promising strategy for expediting and improving the probability of success in the drug development process is the use of naturally randomized human genetic variation for drug target identification and validation. These data can be harnessed using the Mendelian randomization (MR) analytic paradigm to proxy the lifelong consequences of genetic perturbations of drug targets. In this review we discuss the myriad applications of the Mendelian randomization (MR) paradigm for human drug target identification and validation. We review the methodology and applications of MR, key limitations of MR, and potential future opportunities for research. Throughout the Review, we refer to illustrative examples of MR analyses investigating consequences of genetic inhibition of interleukin 6 signaling which, in some cases, have anticipated results from randomized controlled trials. As human genetic data become more widely available, we predict that MR will serve as a key pillar of support for drug development efforts.

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