Hydroxychloroquine in Patients with Rheumatic Disease Complicated by COVID-19: Clarifying Target Exposures and the Need for Clinical Trials.

Journal Article (Journal Article)

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). METHODS: 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.

Full Text

Duke Authors

Cited Authors

  • Balevic, SJ; Hornik, CP; Green, TP; Clowse, MEB; Gonzalez, D; Maharaj, AR; Schanberg, LE; Eudy, AM; Swamy, GK; Hughes, BL; Cohen-Wolkowiez, M

Published Date

  • May 11, 2020

Published In

PubMed ID

  • 32393664

Pubmed Central ID

  • PMC7655510

International Standard Serial Number (ISSN)

  • 0315-162X

Digital Object Identifier (DOI)

  • 10.3899/jrheum.200493

Language

  • eng

Conference Location

  • Canada