Rituximab is associated with worse COVID-19 outcomes in patients with rheumatoid arthritis: A retrospective, nationally sampled cohort study from the U.S. National COVID Cohort Collaborative (N3C)

Namrata Singh; Vithal Madhira; Chen Hu; Amy L. Olex; Timothy Bergquist; Kathryn C. Fitzgerald; Jared D. Huling; Rena C. Patel; Jasvinder A. Singh

doi:10.1016/j.semarthrit.2022.152149

Rituximab is associated with worse COVID-19 outcomes in patients with rheumatoid arthritis: A retrospective, nationally sampled cohort study from the U.S. National COVID Cohort Collaborative (N3C)

Namrata Singh
, Vithal Madhira
, Chen Hu
, Amy L. Olex
, Timothy Bergquist
, Kathryn C. Fitzgerald
, Jared D. Huling
, Rena C. Patel
, Jasvinder A. Singh

Biostatistics

Research output: Contribution to journal › Article › peer-review

47 Scopus citations

Abstract

Objective: To assess whether rituximab (RTX) is associated with worse COVID-19 outcomes among patients with rheumatoid arthritis (RA). Methods: We used the National COVID Cohort Collaborative (N3C), the largest US cohort of COVID-19 cases and controls, to identify patients with RA (International Classification of Diseases (ICD)-10 code, M05.X or M06.X). Key outcomes were COVID-19-related hospitalization, intensive care unit (ICU) admission, 30-day mortality, and World Health Organization (WHO) classification for COVID-19 severity. We used multivariable logistic regression models to assess the association between RTX use and the odds of COVID-19 outcomes compared with the use of conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs), adjusting for demographics, medical comorbidities, smoking status, body mass index, US region and COVID-19 treatments. Results: A total of 69,549 patients met our eligibility criteria of which 22,956 received a COVID-19 positive diagnosis between 1/1/2020 and 9/16/2021. Median (IQR) age of the cohort was 63 (52–72) years, 76% of the cohort was female, 68% was non-Hispanic/Latinx White, and 73% was non-smokers. Prior to their first COVID-19 diagnosis, 364 patients were exposed to RTX. Compared to the use of csDMARDs, RTX use was associated with an increased odds of COVID-19-related hospitalization (adjusted odds ratio [aOR] 2.1, 95% confidence interval 1.5–3.0), ICU admission (aOR 5.2, 1.8–15.4) and invasive ventilation (aOR 2.7, 1.4–5.5). Results were confirmed in multiple sensitivity analyses. Conclusion: Our findings can guide patients, providers, and policymakers regarding the increased risks associated with RTX use during the COVID-19 pandemic. These results can help risk stratification and prognosis-assessment.

Original language	English (US)
Article number	152149
Journal	Seminars in Arthritis and Rheumatism
Volume	58
DOIs	https://doi.org/10.1016/j.semarthrit.2022.152149
State	Published - Feb 2023

Bibliographical note

Funding Information:
The analyses described in this publication were conducted with data or tools accessed through the NCATS N3C Data Enclave covid.cd2h.org/enclave and supported by NCATS U24 TR002306. This research was possible because of the patients whose information is included within the data from participating organizations (covid.cd2h.org/dtas) and the organizations and scientists (covid.cd2h.org/duas) who have contributed to the on-going development of this community resource (cite this https://doi.org/10.1093/jamia/ocaa196).RCP was supported by NIAID of the NIH (K23AI120855). JAS was supported by the resources and use of facilities at the Birmingham VA Medical Center, Birmingham, Alabama, USA. The funding body did not play any role in design, in the collection, analysis, and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication. NS was supported by the Rheumatology Research Foundation and the American Heart Association. TB was supported by the Bill and Melinda Gates Foundation (INV018455). ALO was supported by CTSA award No. UL1TR002649 from the National Center for Advancing Translational Sciences. Its contents are solely the responsibility of the authors and do not necessarily represent official views of the National Center for Advancing Translational Sciences or the National Institutes of Health.

Funding Information:
RCP was supported by NIAID of the NIH ( K23AI120855 ). JAS was supported by the resources and use of facilities at the Birmingham VA Medical Center, Birmingham, Alabama, USA. The funding body did not play any role in design, in the collection, analysis, and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication. NS was supported by the Rheumatology Research Foundation and the American Heart Association. TB was supported by the Bill and Melinda Gates Foundation ( INV018455 ). ALO was supported by CTSA award No. UL1TR002649 from the National Center for Advancing Translational Sciences. Its contents are solely the responsibility of the authors and do not necessarily represent official views of the National Center for Advancing Translational Sciences or the National Institutes of Health.

Publisher Copyright:
© 2022 Elsevier Inc.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

COVID-19
COVID-19 outcomes
Rheumatoid arthritis
Rituximab

Publisher link

10.1016/j.semarthrit.2022.152149

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Singh, N., Madhira, V., Hu, C., Olex, A. L., Bergquist, T., Fitzgerald, K. C., Huling, J. D., Patel, R. C., & Singh, J. A. (2023). Rituximab is associated with worse COVID-19 outcomes in patients with rheumatoid arthritis: A retrospective, nationally sampled cohort study from the U.S. National COVID Cohort Collaborative (N3C). Seminars in Arthritis and Rheumatism, 58, Article 152149. https://doi.org/10.1016/j.semarthrit.2022.152149

Rituximab is associated with worse COVID-19 outcomes in patients with rheumatoid arthritis: A retrospective, nationally sampled cohort study from the U.S. National COVID Cohort Collaborative (N3C). / Singh, Namrata; Madhira, Vithal; Hu, Chen et al.
In: Seminars in Arthritis and Rheumatism, Vol. 58, 152149, 02.2023.

Research output: Contribution to journal › Article › peer-review

Singh, N, Madhira, V, Hu, C, Olex, AL, Bergquist, T, Fitzgerald, KC, Huling, JD, Patel, RC & Singh, JA 2023, 'Rituximab is associated with worse COVID-19 outcomes in patients with rheumatoid arthritis: A retrospective, nationally sampled cohort study from the U.S. National COVID Cohort Collaborative (N3C)', Seminars in Arthritis and Rheumatism, vol. 58, 152149. https://doi.org/10.1016/j.semarthrit.2022.152149

@article{d2617e010778412797d21744eca5efe4,

title = "Rituximab is associated with worse COVID-19 outcomes in patients with rheumatoid arthritis: A retrospective, nationally sampled cohort study from the U.S. National COVID Cohort Collaborative (N3C)",

abstract = "Objective: To assess whether rituximab (RTX) is associated with worse COVID-19 outcomes among patients with rheumatoid arthritis (RA). Methods: We used the National COVID Cohort Collaborative (N3C), the largest US cohort of COVID-19 cases and controls, to identify patients with RA (International Classification of Diseases (ICD)-10 code, M05.X or M06.X). Key outcomes were COVID-19-related hospitalization, intensive care unit (ICU) admission, 30-day mortality, and World Health Organization (WHO) classification for COVID-19 severity. We used multivariable logistic regression models to assess the association between RTX use and the odds of COVID-19 outcomes compared with the use of conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs), adjusting for demographics, medical comorbidities, smoking status, body mass index, US region and COVID-19 treatments. Results: A total of 69,549 patients met our eligibility criteria of which 22,956 received a COVID-19 positive diagnosis between 1/1/2020 and 9/16/2021. Median (IQR) age of the cohort was 63 (52{\textendash}72) years, 76\% of the cohort was female, 68\% was non-Hispanic/Latinx White, and 73\% was non-smokers. Prior to their first COVID-19 diagnosis, 364 patients were exposed to RTX. Compared to the use of csDMARDs, RTX use was associated with an increased odds of COVID-19-related hospitalization (adjusted odds ratio [aOR] 2.1, 95\% confidence interval 1.5{\textendash}3.0), ICU admission (aOR 5.2, 1.8{\textendash}15.4) and invasive ventilation (aOR 2.7, 1.4{\textendash}5.5). Results were confirmed in multiple sensitivity analyses. Conclusion: Our findings can guide patients, providers, and policymakers regarding the increased risks associated with RTX use during the COVID-19 pandemic. These results can help risk stratification and prognosis-assessment.",

keywords = "COVID-19, COVID-19 outcomes, Rheumatoid arthritis, Rituximab",

author = "Namrata Singh and Vithal Madhira and Chen Hu and Olex, \{Amy L.\} and Timothy Bergquist and Fitzgerald, \{Kathryn C.\} and Huling, \{Jared D.\} and Patel, \{Rena C.\} and Singh, \{Jasvinder A.\}",

note = "Funding Information: The analyses described in this publication were conducted with data or tools accessed through the NCATS N3C Data Enclave covid.cd2h.org/enclave and supported by NCATS U24 TR002306. This research was possible because of the patients whose information is included within the data from participating organizations (covid.cd2h.org/dtas) and the organizations and scientists (covid.cd2h.org/duas) who have contributed to the on-going development of this community resource (cite this https://doi.org/10.1093/jamia/ocaa196).RCP was supported by NIAID of the NIH (K23AI120855). JAS was supported by the resources and use of facilities at the Birmingham VA Medical Center, Birmingham, Alabama, USA. The funding body did not play any role in design, in the collection, analysis, and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication. NS was supported by the Rheumatology Research Foundation and the American Heart Association. TB was supported by the Bill and Melinda Gates Foundation (INV018455). ALO was supported by CTSA award No. UL1TR002649 from the National Center for Advancing Translational Sciences. Its contents are solely the responsibility of the authors and do not necessarily represent official views of the National Center for Advancing Translational Sciences or the National Institutes of Health. Funding Information: RCP was supported by NIAID of the NIH ( K23AI120855 ). JAS was supported by the resources and use of facilities at the Birmingham VA Medical Center, Birmingham, Alabama, USA. The funding body did not play any role in design, in the collection, analysis, and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication. NS was supported by the Rheumatology Research Foundation and the American Heart Association. TB was supported by the Bill and Melinda Gates Foundation ( INV018455 ). ALO was supported by CTSA award No. UL1TR002649 from the National Center for Advancing Translational Sciences. Its contents are solely the responsibility of the authors and do not necessarily represent official views of the National Center for Advancing Translational Sciences or the National Institutes of Health. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",

year = "2023",

month = feb,

doi = "10.1016/j.semarthrit.2022.152149",

language = "English (US)",

volume = "58",

journal = "Seminars in Arthritis and Rheumatism",

issn = "0049-0172",

publisher = "W.B. Saunders",

}

TY - JOUR

T1 - Rituximab is associated with worse COVID-19 outcomes in patients with rheumatoid arthritis

T2 - A retrospective, nationally sampled cohort study from the U.S. National COVID Cohort Collaborative (N3C)

AU - Singh, Namrata

AU - Madhira, Vithal

AU - Hu, Chen

AU - Olex, Amy L.

AU - Bergquist, Timothy

AU - Fitzgerald, Kathryn C.

AU - Huling, Jared D.

AU - Patel, Rena C.

AU - Singh, Jasvinder A.

N1 - Funding Information: The analyses described in this publication were conducted with data or tools accessed through the NCATS N3C Data Enclave covid.cd2h.org/enclave and supported by NCATS U24 TR002306. This research was possible because of the patients whose information is included within the data from participating organizations (covid.cd2h.org/dtas) and the organizations and scientists (covid.cd2h.org/duas) who have contributed to the on-going development of this community resource (cite this https://doi.org/10.1093/jamia/ocaa196).RCP was supported by NIAID of the NIH (K23AI120855). JAS was supported by the resources and use of facilities at the Birmingham VA Medical Center, Birmingham, Alabama, USA. The funding body did not play any role in design, in the collection, analysis, and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication. NS was supported by the Rheumatology Research Foundation and the American Heart Association. TB was supported by the Bill and Melinda Gates Foundation (INV018455). ALO was supported by CTSA award No. UL1TR002649 from the National Center for Advancing Translational Sciences. Its contents are solely the responsibility of the authors and do not necessarily represent official views of the National Center for Advancing Translational Sciences or the National Institutes of Health. Funding Information: RCP was supported by NIAID of the NIH ( K23AI120855 ). JAS was supported by the resources and use of facilities at the Birmingham VA Medical Center, Birmingham, Alabama, USA. The funding body did not play any role in design, in the collection, analysis, and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication. NS was supported by the Rheumatology Research Foundation and the American Heart Association. TB was supported by the Bill and Melinda Gates Foundation ( INV018455 ). ALO was supported by CTSA award No. UL1TR002649 from the National Center for Advancing Translational Sciences. Its contents are solely the responsibility of the authors and do not necessarily represent official views of the National Center for Advancing Translational Sciences or the National Institutes of Health. Publisher Copyright: © 2022 Elsevier Inc.

PY - 2023/2

Y1 - 2023/2

N2 - Objective: To assess whether rituximab (RTX) is associated with worse COVID-19 outcomes among patients with rheumatoid arthritis (RA). Methods: We used the National COVID Cohort Collaborative (N3C), the largest US cohort of COVID-19 cases and controls, to identify patients with RA (International Classification of Diseases (ICD)-10 code, M05.X or M06.X). Key outcomes were COVID-19-related hospitalization, intensive care unit (ICU) admission, 30-day mortality, and World Health Organization (WHO) classification for COVID-19 severity. We used multivariable logistic regression models to assess the association between RTX use and the odds of COVID-19 outcomes compared with the use of conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs), adjusting for demographics, medical comorbidities, smoking status, body mass index, US region and COVID-19 treatments. Results: A total of 69,549 patients met our eligibility criteria of which 22,956 received a COVID-19 positive diagnosis between 1/1/2020 and 9/16/2021. Median (IQR) age of the cohort was 63 (52–72) years, 76% of the cohort was female, 68% was non-Hispanic/Latinx White, and 73% was non-smokers. Prior to their first COVID-19 diagnosis, 364 patients were exposed to RTX. Compared to the use of csDMARDs, RTX use was associated with an increased odds of COVID-19-related hospitalization (adjusted odds ratio [aOR] 2.1, 95% confidence interval 1.5–3.0), ICU admission (aOR 5.2, 1.8–15.4) and invasive ventilation (aOR 2.7, 1.4–5.5). Results were confirmed in multiple sensitivity analyses. Conclusion: Our findings can guide patients, providers, and policymakers regarding the increased risks associated with RTX use during the COVID-19 pandemic. These results can help risk stratification and prognosis-assessment.

AB - Objective: To assess whether rituximab (RTX) is associated with worse COVID-19 outcomes among patients with rheumatoid arthritis (RA). Methods: We used the National COVID Cohort Collaborative (N3C), the largest US cohort of COVID-19 cases and controls, to identify patients with RA (International Classification of Diseases (ICD)-10 code, M05.X or M06.X). Key outcomes were COVID-19-related hospitalization, intensive care unit (ICU) admission, 30-day mortality, and World Health Organization (WHO) classification for COVID-19 severity. We used multivariable logistic regression models to assess the association between RTX use and the odds of COVID-19 outcomes compared with the use of conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs), adjusting for demographics, medical comorbidities, smoking status, body mass index, US region and COVID-19 treatments. Results: A total of 69,549 patients met our eligibility criteria of which 22,956 received a COVID-19 positive diagnosis between 1/1/2020 and 9/16/2021. Median (IQR) age of the cohort was 63 (52–72) years, 76% of the cohort was female, 68% was non-Hispanic/Latinx White, and 73% was non-smokers. Prior to their first COVID-19 diagnosis, 364 patients were exposed to RTX. Compared to the use of csDMARDs, RTX use was associated with an increased odds of COVID-19-related hospitalization (adjusted odds ratio [aOR] 2.1, 95% confidence interval 1.5–3.0), ICU admission (aOR 5.2, 1.8–15.4) and invasive ventilation (aOR 2.7, 1.4–5.5). Results were confirmed in multiple sensitivity analyses. Conclusion: Our findings can guide patients, providers, and policymakers regarding the increased risks associated with RTX use during the COVID-19 pandemic. These results can help risk stratification and prognosis-assessment.

KW - COVID-19

KW - COVID-19 outcomes

KW - Rheumatoid arthritis

KW - Rituximab

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Rituximab is associated with worse COVID-19 outcomes in patients with rheumatoid arthritis: A retrospective, nationally sampled cohort study from the U.S. National COVID Cohort Collaborative (N3C)

Abstract

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