RT Journal Article
SR Electronic
T1 Hydroxychloroquine in Patients with Rheumatic Disease Complicated by COVID-19: Clarifying Target Exposures and the Need for Clinical Trials
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 1424
OP 1430
DO 10.3899/jrheum.200493
VO 47
IS 9
A1 Stephen J. Balevic
A1 Christoph P. Hornik
A1 Thomas P. Green
A1 Megan E.B. Clowse
A1 Daniel Gonzalez
A1 Anil R. Maharaj
A1 Laura E. Schanberg
A1 Amanda M. Eudy
A1 Geeta K. Swamy
A1 Brenna L. Hughes
A1 Michael Cohen-Wolkowiez
YR 2020
UL http://www.jrheum.org/content/47/9/1424.abstract
AB Objective. To characterize hydroxychloroquine (HCQ) exposure in patients with rheumatic disease receiving longterm HCQ compared to target concentrations with reported antiviral activity against the coronavirus disease 2019 caused by SARS-CoV-2 (COVID-19).Method. We evaluated total HCQ concentrations in serum and plasma from published literature values, frozen serum samples from a pediatric systemic lupus erythematosus trial, and simulated concentrations using a published pharmacokinetic model during pregnancy. For each source, we compared observed or predicted HCQ concentrations to target concentrations with reported antiviral activity against SARS-CoV-2.Results. The average total serum/plasma HCQ concentrations were below the lowest SARS-CoV-2 target of 0.48 mg/l in all studies. Assuming the highest antiviral target exposure (total plasma concentration of 4.1 mg/l), all studies had about one-tenth the necessary concentration for in vitro viral inhibition. Pharmacokinetic model simulations confirmed that pregnant adults receiving common dosing for rheumatic diseases did not achieve target exposures; however, the models predict that a dosage of 600 mg once a day during pregnancy would obtain the lowest median target exposure for most patients after the first dose.Conclusion. We found that the average patient receiving treatment with HCQ for rheumatic diseases, including children and non-pregnant/pregnant adults, are unlikely to achieve total serum or plasma concentrations shown to inhibit SARS-CoV-2 in vitro. Nevertheless, patients receiving HCQ long term may have tissue concentrations far exceeding that of serum/plasma. Because the therapeutic window for HCQ in the setting of SARS-CoV-2 is unknown, well-designed clinical trials that include patients with rheumatic disease are urgently needed to characterize the efficacy, safety, and target exposures for HCQ.