TY - JOUR 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 DO - 10.3899/jrheum.200493 SP - jrheum.200493 AU - Stephen J. Balevic AU - Christoph P. Hornik AU - Thomas P. Green AU - Megan E.B. Clowse AU - Daniel Gonzalez AU - Anil R. Maharaj AU - Laura E. Schanberg AU - Amanda M. Eudy AU - Geeta K. Swamy AU - Brenna L. Hughes AU - Michael Cohen-Wolkowiez Y1 - 2020/05/11 UR - http://www.jrheum.org/content/early/2020/05/08/jrheum.200493.abstract N2 - Objective To characterize hydroxychloroquine exposure in patients with rheumatic disease receiving long-term hydroxychloroquine compared to target concentrations with reported antiviral activity against the 2019 coronavirus SARS-CoV-2. Methods We evaluated total hydroxychloroquine concentrations in serum and plasma from published literature values, frozen serum samples from a pediatric lupus trial, and simulated concentrations using a published pharmacokinetic model during pregnancy. For each source, we compared observed or predicted hydroxychloroquine concentrations to target concentrations with reported antiviral activity against SARS-CoV-2. Results The average total serum/plasma hydroxychloroquine 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 approximately 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 hydroxychloroquine 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 hydroxychloroquine long-term may have tissue concentrations far exceeding that of serum/plasma. Because the therapeutic window for hydroxychloroquine 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 hydroxychloroquine. ER -