Risk of severe COVID-19 in patients with inflammatory rheumatic diseases treated with immunosuppressive therapy in Scotland

Abstract

Objective

To investigate the association of severe coronavirus disease 2019 (COVID-19) in patients with inflammatory rheumatic diseases (IRDs) treated with immunosuppressive drugs.

Method

A list of 4633 patients on targeted – biological or targeted synthetic – DMARDs in March 2020 was linked to a case–control study that includes all cases of COVID-19 in Scotland.

Results

By 22 November 2021, 433 of the 4633 patients treated with targeted DMARDS had been diagnosed with COVID-19, of whom 58 had been hospitalized. With all those in the population not on DMARDs as the reference category, the rate ratio for hospitalized COVID-19 associated with DMARD treatment was 2.14 [95% confidence interval (CI) 2.02–2.26] in those on conventional synthetic (cs) DMARDs, 2.01 (95% CI 1.38–2.91) in those on tumour necrosis factor (TNF) inhibitors as the only targeted agent, and 3.83 (95% CI 2.65–5.56) in those on other targeted DMARDs. Among those on csDMARDs, rate ratios for hospitalized COVID-19 were lowest at 1.66 (95% CI 1.51–1.82) in those on methotrexate and highest at 5.4 (95% CI 4.4–6.7) in those on glucocorticoids at an average dose > 10 mg/day prednisolone equivalent.

Conclusion

The risk of hospitalized COVID-19 is elevated in IRD patients treated with immunosuppressive drugs compared with the general population. Of these drugs, methotrexate, hydroxychloroquine, and TNF inhibitors carry the lowest risk. The highest risk is associated with prednisolone. A larger study is needed to estimate reliably the risks associated with each class of targeted DMARD.

Acknowledgements

We thank Jen Bishop, Ciara Gribben, and David Caldwell for undertaking the linkage analysis in Public Health Scotland, and staff from the rheumatology service in the contributing centres for preparing the list of patients receiving these treatments.

Disclosure statement

All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. No potential conflict of interest was reported by the authors.

Authors’ contributions and transparency declaration

All authors provided substantial contributions to the conception of the study and the drafting of the manuscript. PM undertook the statistical analysis. All authors contributed to revising the manuscript critically for important intellectual content and approved the final manuscript. PM, as the manuscript’s guarantor, affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as originally planned and registered have been explained. This manuscript has been generated directly from the source data by a reproducible research pipeline.

Data availability statement

The component data sets used here are available via the Public Benefits and Privacy Panel for Health and Social Care at https://www.informationgovernance.scot.nhs.uk/pbpphsc/ for researchers who meet the criteria for access to confidential data. All source code used for derivation of variables, statistical analysis, and generation of this manuscript is available at https://github.com/pmckeigue/covid-scotland_public.

Additional information

Funding

No specific funding was received for this study.