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We thank Santos-Moreno et al for their response to our commentary.1 2 The authors provide data on cardiovascular adverse events associated with maintenance antimalarial use for patients with rheumatoid arthritis (RA). In addition to our previous correspondence response3 from Erre et al,4 these additional data are reassuring to patients with rheumatic diseases on chronic doses of antimalarials regarding the continued safety of these medications.
However, as we have also addressed in a previous response, the safety profile of antimalarials in patients with COVID-19 infection compared with patients with rheumatic disease may differ widely. Observational data regarding cardiovascular events in hospitalised patients with COVID-19 treated with hydroxychloroquine (HCQ) with or without azithromycin have found variable rates of QTc prolongation and arrhythmias.5–7 Lane et al recently used combined electronic health record and administrative data from five countries and a new user, active comparator cohort design to address two scientific questions among adults with RA8: (1) the risk of serious adverse events, particularly cardiovascular events, among individuals with RA initiating therapy with HCQ versus sulfasalazine; (2) the risk of these outcomes when azithromycin is started (compared with starting amoxicillin) among prevalent HCQ users with RA. The cardiovascular outcomes assessed in that study included cardiovascular mortality, cardiac arrhythmia, and heart failure, and were identified using ICD codes.8 However, there was no statistically significant association between HCQ use and cardiac arrhythmia, compared with sulfasalazine use (calibrated HR 0.89, 95% CI 0.77 to 1.04) among individuals with RA.8 Although a similarly designed study using population-level data could be conceived to assess the study question presented by Santos-Moreno et al, the surrogate outcome of QTc prolongation would be more difficult to ascertain using administrative/claims data.
In summary, we agree that these data offer additional support that the possible cardiotoxicity of antimalarials for treatment of COVID-19 should not be extrapolated to patients with rheumatic disease where its safety and efficacy is well established.
JWL and ERG are joint first authors.
JAS and AHK are joint senior authors.
Handling editor Josef S Smolen
Twitter @jeffsparks, @alhkim
JWL and ERG contributed equally.
JAS and AHK contributed equally.
Correction notice This article has been corrected since it published Online First. The title has been corrected.
Contributors JWL, ERG, JAS and AHK contributed to the conception and drafting of the article. All listed authors provided critical revision for important intellectual content and final approval.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests JAS reports grants from NIH/NIAMS/NIAID/Autoimmune Centers of Excellence, the Rheumatology Research Foundation, the Brigham Research Institute, and the R. Bruce and Joan M. Mickey Research Scholar Fund as well as personal fees from Bristol-Myers Squibb, Gilead, Inova, Janssen and Optum. AHK reports grants from NIH/NIAMS and Rheumatology Research Foundation and personal fees from Exagen Diagnostics, Inc. and GlaxoSmithKline.
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.
Patient consent for publication Not required.
Provenance and peer review Commissioned; internally peer reviewed.
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