Risk of severe COVID-19 outcomes associated with immune-mediated inflammatory diseases and immune modifying therapies

Risk of severe COVID-19 outcomes associated with immune-mediated inflammatory diseases and immune modifying therapies: a nationwide cohort study in the OpenSAFELY platform

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How to cite: Brian MacKenna, Nicholas A. Kennedy, Amir Mehkar, Anna Rowan, James Galloway, Kathryn E. Mansfield, Katie Bechman, Julian Matthewman, Mark Yates, Jeremy Brown, Anna Schultze, Sam Norton, Alex J. Walker, Caroline E Morton, David Harrison, Krishnan Bhaskaran, Christopher T. Rentsch, Elizabeth Williamson, Richard Croker, Seb Bacon, George Hickman, Tom Ward, Simon Davy, Amelia Green, Louis Fisher, William Hulme, Chris Bates, Helen J. Curtis, John Tazare, Rosalind M. Eggo, David Evans, Peter Inglesby, Jonathan Cockburn, Helen I. McDonald, Laurie A. Tomlinson, Rohini Mathur, Angel YS Wong, Harriet Forbes, John Parry, Frank Hester, Sam Harper, Ian J. Douglas, Liam Smeeth, Charlie W Lees, Stephen JW Evans, Ben Goldacre, Catherine Smith, Sinéad M. Langan medRxiv 2021.09.03.21262888; https://doi.org/10.1101/2021.09.03.21262888


Background: It is unclear if people with immune-mediated inflammatory diseases (IMIDs) (joint, bowel and skin) and on immune modifying therapy have increased risk of serious COVID-19 outcomes.

Methods: With the approval of NHS England we conducted a cohort study, using OpenSAFELY, analysingroutinely-collected primary care data linked to hospital admission, death and previously unavailable hospital prescription data. We used Cox regression (adjusting for confounders) to estimate hazard ratios (HR) comparing risk of COVID-19-death, death/critical care admission, and hospitalisation (March to September 2020) in: 1) people with IMIDs compared to the general population; and 2) people with IMIDs on targeted immune modifying drugs (e.g., biologics) compared to standard systemic treatment (e.g., methotrexate).

Results: We identified 17,672,065 adults; of 1,163,438 (7%) with IMIDs, 19,119 people received targeted immune modifying drugs, and 200,813 received standard systemics. We saw evidence of increased COVID-19-death (HR 1.23, 95%CI 1.20, 1.27), and COVID-19 hospitalisation (HR 1.32, 95%CI 1.29, 1.35) in individuals with IMIDs overall compared to individuals without IMIDs of the same age, sex, deprivation and smoking status. We saw no evidence of increased COVID-19 deaths with targeted compared to standard systemic treatments (HR 1.03, 95%CI 0.80, 1.33). There was no evidence of increased COVID-19-related death in those prescribed TNF inhibitors, IL-12/23, IL7, IL-6 or JAK inhibitors compared to standard systemics. Rituximab was associated with increased COVID-19 death (HR 1.68, 95%CI 1.11, 2.56); however, this finding may relate to confounding.

Conclusions: COVID-19 death and hospitalisation was higher in people with IMIDs. We saw no increased risk of adverse COVID-19 outcomes in those on most targeted immune modifying drugs for IMIDs compared to standard systemics.