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The US Centers for Disease Control and Prevention (CDC) recommends three SARS-CoV-2 messenger ribonucleic acid (mRNA) vaccine doses, rather than two, to complete the initial vaccine series for immunosuppressed patients. However, they may remain at risk for breakthrough COVID-19 due to immunomodulators that blunt vaccine responses.1 Identifying patients at highest risk for breakthrough COVID-19 can prioritise resources for prevention. Therefore, we investigated the risk of breakthrough COVID-19 among fully vaccinated patients with rheumatoid arthritis (RA) using disease-modifying antirheumatic drugs (DMARDs) and/or glucocorticoids, hypothesising that CD20 inhibitor (CD20i) users would have higher breakthrough COVID-19 risk than tumour necrosis factor inhibitor (TNFi) users.
We performed a retrospective cohort study investigating immunomodulators and breakthrough COVID-19 risk among patients with RA who received three mRNA vaccines at Mass General Brigham, a multicentre healthcare system in Boston, Massachusetts, USA. A previously validated algorithm was used to identify patients with RA (postive predictive value 90%).2 COVID-19 was identified from positive PCR tests or patient reports to the hospital/clinic of home rapid antigen tests.2 Patients were followed from the date of the third vaccine (index date) until breakthrough COVID-19 (occurring ≥14 days after index date), non-COVID-19 death or end of follow-up (18 January 2023). A previously defined hierarchy categorised immunomodulator medications at index date into mutually exclusive groups.2 Covariates included demographics, lifestyle, calendar time and clinical factors. We used multivariable Cox regression models to estimate HRs for breakthrough COVID-19 by immunomodulator class. We then used propensity score (PS) overlap-weighting to further account for confounding and compare users of CD20i versus TNFi for breakthrough COVID-19.
We analysed 5781 patients with RA …
Footnotes
ZSW and JAS are joint senior authors.
Handling editor Josef S Smolen
X @zach_wallace_md, @jeffsparks
ZSW and JAS contributed equally.
Contributors AS, ZSW and JAS designed the study, were responsible for acquisition, analysis and interpretation of data, and drafted and revised the article. XW was involved in the analysis and interpretation of the data. NJP, YK, JLH, EK, CC, KV, GQ, KB, AS, SS, ZKW and RV were involved in the data acquisition, interpretation and revision of the manuscript. JAS and ZSW are joint senior authors. All authors approved the final version of the article. JAS accepts full responsibility for the work and the conduct of the study, had access to the data and controlled the decision to publish.
Funding NJP is supported by the Rheumatology Research Foundation. ZSW is funded by NIH/NIAMS (R01 AR080659, K23 AR073334 and R03 AR078938). JAS is funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant numbers R01 AR080659, R01 AR077607, P30 AR070253 and P30 AR072577), the R. Bruce and Joan M. Mickey Research Scholar Fund, and the Llura Gund Award funded by the Gordon and Llura Gund Foundation. represent the official views of Harvard University, its affiliated academic healthcare centers, or the National Institutes of Health.
Disclaimer The funders had no role in the decision to publish or preparation of this manuscript. The content is solely the responsibility of the authors and does not necessarily
Competing interests NJP reports consulting fees from FVC Health unrelated to this work. ZSW reports research support from Bristol-Myers Squibb and Principia/Sanofi and consulting fees from Viela Bio, Zenas BioPharma and MedPace unrelated to this work. JAS has received research support from Bristol Myers Squibb and performed consultancy for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, Pfizer and ReCor unrelated to this work. All other authors report no competing interests.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
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