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We thank Carbillon et al for their correspondence.1 The use of hydroxychloroquine (HCQ) in pregnant women with systemic lupus erythematosus (SLE) is not controversial.2 3 Similar to its primary role in the prophylaxis and treatment of SLE, discontinuation of HCQ in pregnancy has been linked to increased disease activity and glucocorticoid use in women with lupus.4–6 Given its benefit and preferable safety profile, the continuation of baseline HCQ therapy in pregnant women with lupus is recommended to maintain disease remission,2 3 regardless of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) status. In contrast, there is currently no evidence to suggest that baseline use of HCQ in pregnant women with lupus is protective of SARS-CoV-2 infection or severe COVID-19.
The authors adequately summarise our findings that patients with lupus—even if they are using an antimalarial such as HCQ as baseline therapy—can develop SARS-CoV-2 infection and severe COVID-19 at similar frequency as patients not on antimalarials.7 We agree that unequal distribution of comorbidities and disease-modifying antirheumatic drug therapy have to be considered as sources of confounding, and statistical correction for such variables may be informative as sample size increases. In a recent publication by the COVID-19 Global Rheumatology Alliance examining 600 patients with rheumatic disease with COVID-19, 22% were taking antimalarials prior to hospitalisation.8 No significant association between baseline antimalarial use and hospitalisation was observed after adjusting for sex, age over 65 years, smoking status, underlying rheumatic disease, comorbidities, conventional synthetic disease-modifying antirheumatic drug (csDMARD) monotherapy, biological disease-modifying antirheumatic drug (bDMARD)/targeted synthetic disease-modifying antirheumatic drug (tsDMARD) monotherapy, csDMARD–bDMARD/tsDMARD combination therapy (excluding antimalarials), use of non-steroidal anti-inflammatory drugs and glucocorticoid dose (OR=0.94, 95% CI 0.57 to 1.57; p=0.82).8 The null effect remained in additional models controlling for disease activity. In light of these findings, but also acknowledging the innate limitations of observational and physician-reported data, patients with lupus on HCQ do not appear to be protected from severe COVID-19. We await the results of ongoing randomised controlled trials to clarify whether HCQ has any role in the prophylaxis or treatment of COVID-19.
Adding to these clinical data, we provide a pharmacokinetic rationale why antiviral properties of HCQ at doses commonly prescribed in lupus (400 mg daily or less) are not expected to be protective of SARS-CoV-2 infection.7 Importantly, this does not preclude potential benefits of HCQ for the hypercoagulable state observed in some patients with COVID-19. While HCQ has been shown to be protective against arterial and venous thrombosis in SLE,9 10 extrapolating these benefits to the coagulopathy of COVID-19 is premature. Ongoing controlled trials of HCQ in patients without lupus will likely be informative to explore potential antithrombotic benefits for COVID-19 coagulopathy.
The views expressed here are those of the authors and participating members of the COVID-19 Global Rheumatology Alliance (full list of collaborators at https://rheum-covid.org/about/) and do not necessarily represent the views of the American College of Rheumatology, the European League Against Rheumatism or any other organisation.
Handling editor Josef S Smolen
Twitter @MaxKonigMD, @philipcrobinson
Collaborators COVID-19 Global Rheumatology Alliance (full list of collaborators at https://rheum-covid.org/about/)
Contributors All authors contributed to data interpretation, writing and final approval of the manuscript.
Funding This study was funded by National Institute of Arthritis and Musculoskeletal and Skin Diseases (T32AR048522).
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.
Patient consent for publication Not required.
Provenance and peer review Commissioned; internally peer reviewed.