Identification of Risk Factors for COVID‐19 Hospitalization in Patients With Anti‐Rheumatic Drugs: Results From a Multicenter Nested Case Control Study
Merel A A Opdam, Sophie Benoy, Lise M Verhoef, Sandra Van Bijnen, Femke Lamers‐karnebeek, René A M Traksel, Petra Vos, Alfons A Den Broeder, Jasper Broen
Clinical Pharmacology & Therapeutics, doi:10.1002/cpt.2551
Patients with inflammatory rheumatic diseases (IRDs) do not have an increased risk for coronavirus disease 2019 (COVID-19) compared with the general population. However, it remains uncertain whether subgroups of patients with IRD using different immunosuppressive antirheumatic drugs carry a higher risk for severe COVID-19 compared with other patients with IRD. The aim of this study is to identify risk factors for severe COVID-19, requiring hospitalization in patients with IRD. This is a multicenter nested case control study conducted in the Netherlands. Cases are hospital known patients with IRD requiring hospitalization for COVID-19 between March 1, 2020, and May 31, 2020. Controls are hospital known patients with IRD not requiring hospitalization for COVID-19 in this period, included at a 4:1 ratio. Patient, disease, and treatment characteristics were extracted from electronic medical records and a questionnaire. Potential risk factors were analyzed using unconditional logistic regression, corrected for confounders and multiple testing. Eighty-one cases and 396 controls were included. General risk factors of older age and obesity apply to patients with IRD as well (odds ratio (OR) for age ≥75 3.5, 95% confidence interval (CI) 1.9-6.3, OR for body mass index ≥40 4.5, 95% CI 1.5-14). No significantly increased ORs for COVID-19 hospitalization were found for any antirheumatic agent or IRD. A protective effect was found for use of methotrexate (OR 0.53, 95% CI 0.31-0.92). In conclusion, similar to the general population, elderly and obese patients with IRD have a higher risk for hospitalization for COVID-19. We did not identify a specific antirheumatic agent or IRD to increase the risk of COVID-19 hospitalization in patients with IRD, except for a possible protective effect of methotrexate.
SUPPORTING INFORMATION Supplementary information accompanies this paper on the Clinical Pharmacology & Therapeutics website (www.cpt-journal.com).
ACKNOWLEDGMENTS The authors would like to thank the research assistants who contributed to data collection. Preliminary results of this study were presented as a poster at the EULAR conference 2021. 20
FUNDING This work was supported by a research grant from Gilead Sciences.
CONFLICTS OF INTEREST M.O. reports received grants (to the institution) from Gilead Sciences. A.d.B. has received consultancy honoraria, congress invitations, and research grants (to the institution) from Abbvie, Amgen, Cellgene, Roche, Biogen, Lilly, Novartis, Celltrion Sanofi, and Gilead. Is coinventor on a rituximab related patent (pending). J.B. has received consultancy fees from Novartis, UCB, Gilead, and Galapagos. All other authors declared no competing interests for this work.
AUTHOR CONTRIBUTIONS All authors wrote the manuscript. M.O., S.B., L.V., R.T., A.dB., and J.B. designed the research. M.O., S.B., J.B., S.vB., F.L., and P.V. performed the research. M.O., A.dB., and J.B. analyzed the data.
References
Anbarasu, Ramaiah, Livingstone, Vaccine repurposing approach for preventing COVID 19: can MMR vaccines reduce morbidity and mortality?, Hum. Vaccine Immunother
Charpiat, Bleyzac, Tod, Proton pump inhibitors are risk factors for viral infections: even for COVID-19?, Clin. Drug Investig
Fa12r/Sfr, Severity of COVID-19 and survival in patients with rheumatic and inflammatory diseases: data from the French RMD COVID-19 cohort of 694 patients, Ann. Rheum. Dis
Gianfrancesco, Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physicianreported registry, Ann. Rheum. Dis
Gold, Analysis of Measles-Mumps-Rubella (MMR) titers of recovered COVID-19 patients, MBio
Ho, Modifiable and non-modifiable risk factors for COVID-19, and comparison to risk factors for influenza and pneumonia: results from a UK Biobank prospective cohort study, BMJ Open
Isaia, Medico, Associations between hypovitaminosis D and COVID-19: a narrative review, Aging Clin. Exp. Res
Listing, Gerhold, Zink, The risk of infections associated with rheumatoid arthritis, with its comorbidity and treatment, Rheumatology
Lo, Angiotensin converting enzyme inhibitors and angiotensin II receptor blockers and outcomes in patients with COVID-19: a systematic review and meta-analysis, Expert Rev. Cardiovasc. Ther
Mehta, Mcauley, Brown, Sanchez, Tattersall et al., COVID-19: consider cytokine storm syndromes and immunosuppression, Lancet
Opdam, Pos1197 in depth identification of risk factors for severe COVID-19, requiring hospitalization, in patients with inflammatory rheumatic diseases: results of a Dutch nested case control study (preliminary results), Ann. Rheum. Dis
Pijls, Demographic risk factors for COVID-19 infection, severity, ICU admission and death: a meta-analysis of 59 studies, BMJ Open
Safavi, Nath, Silencing of immune activation with methotrexate in patients with COVID-19, J. Neurol. Sci
Sepriano, Safety of synthetic and biological DMARDs: a systematic literature review informing the 2019 update of the EULAR recommendations for the management of rheumatoid arthritis, Ann. Rheum. Dis
Singh, Risk of serious infection in biological treatment of patients with rheumatoid arthritis: a systematic review and meta-analysis, Lancet
Smolen, EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological diseasemodifying antirheumatic drugs: 2013 update, Ann. Rheum. Dis
Ssentongo, Renin-angiotensin-aldosterone system inhibitors and the risk of mortality in patients with hypertension hospitalised for COVID-19: systematic review and meta-analysis, Open Heart
Strangfeld, Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry, Ann. Rheum. Dis
Williamson, Factors associated with COVID-19-related death using OpenSAFELY, Nature
Ziade, Prevalence and pattern of comorbidities in chronic rheumatic and musculoskeletal diseases: the COMORD study, Sci. Rep
