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0 0.5 1 1.5 2+ Mortality -48% Improvement Relative Risk HCQ for COVID-19  Lyashchenko et al.  LATE TREATMENT Is late treatment with HCQ beneficial for COVID-19? Retrospective 3,256 patients in the USA (March - June 2020) Higher mortality with HCQ (p<0.000001) Lyashchenko et al., British J. Clinica.., Aug 2022 Favors HCQ Favors control

Systemic Exposure to Hydroxychloroquine and its relationship with outcome in severely ill COVID-19 patients in New York City

Lyashchenko et al., British Journal of Clinical Pharmacology, doi:10.1111/bcp.15489
Aug 2022  
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Retrospective very late stage hospitalized patients in New York during the first wave, showing no significant relationship between HCQ levels and outcomes. Authors note that the patients with data were the sickest patients. This study is excluded in the after exclusion results of meta analysis: substantial unadjusted confounding by indication likely.
risk of death, 47.7% higher, RR 1.48, p < 0.001, treatment 389 of 1,419 (27.4%), control 341 of 1,837 (18.6%).
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Lyashchenko et al., 12 Aug 2022, retrospective, USA, peer-reviewed, 6 authors, study period March 2020 - June 2020, average treatment delay 9.5 days.
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Systemic exposure to hydroxychloroquine and its relationship with outcome in severely ill COVID‐19 patients in New York City
Alex K Lyashchenko, Yifan Yu, Donald J Mcmahon, Robert Bies, MD Michael T Yin, Orcid ID Serge Cremers
British Journal of Clinical Pharmacology, doi:10.1111/bcp.15489
Aim: To investigate the relationship between systemic exposure to Hydroxychloroquine (HCQ) and its metabolite Desethylhydroxychloroquine (DHCQ) and clinical outcome in severely ill patients treated with a standard oral dose regimen of HCQ during the first wave of COVID-19 in New York City. Methods: We correlated retrospective clinical data with drug exposure prospectively assessed from convenience samples using population pharmacokinetics and Bayesian estimation. Systemic exposure was assessed in 215 patients admitted to ICU or COVID-ward for whom an interleukin-6 level was requested and who were still alive 24h after the last dose of HCQ. Patients received oral HCQ 600 mg bid on day 1 followed by 4 days of 400 mg qd. Results: Fifty-three% of the patients were intubated at 5.4 ± 6.4 days after admission. 26.5% died at an average of 32.2 ± 19.1 days. QTc at admission was 448 ± 34 msec. Systemic exposure to HCQ and DHCQ demonstrated substantial variability. Cumulative HCQ AUC0-inf =71.4 ± 19.3 h*mg/L and DHCQ AUC0-inf= 56.5 ± 28.3 h*mg/L. Variability in systemic exposure was not clearly explained by renal function, liver function or inflammatory state. In turn, systemic exposure did not correlate with intubation status, survival or QTc prolongation. Conclusion: This study in severely ill patients was not able to find any relationship between systemic exposure to HCQ and DHCQ and clinical outcome at a routine dose regimen and adds to the growing body of evidence that oral HCQ does not alter the course of disease in COVID-19 patients.
Conflicts of interest None of the authors has a conflict of interest for this work.
Al-Kofahi, Finding the Dose for Hydroxychloroquine Prophylaxis for COVID-19: The Desperate Search for Effectiveness, Clin Pharmacol Ther, doi:10.1002/cpt.1874
Alvarez, Population Pharmacokinetics of Hydroxychloroquine and 3 Metabolites in COVID-19 Patients and Pharmacokinetic/Pharmacodynamic Application, Pharmaceuticals, doi:10.3390/ph15020256
Balevic, Pharmacokinetics of Hydroxychloroquine in Pregnancies with Rheumatic Diseases, Clin Pharmacokinet, doi:10.1007/s40262-018-0712-z
Barrett, Labbe, Pfister, Application and impact of population pharmacokinetics in the assessment of antiretroviral pharmacotherapy, Clin Pharmacokinet, doi:10.2165/00003088-200544060-00003
Carmichael, Charles, Tett, Population pharmacokinetics of hydroxychloroquine in patients with rheumatoid arthritis, Ther Drug Monit, doi:10.1097/00007691-200312000-00005
Cl/F, Vc, Vp, Ka, Fm et al., 341 Nearest 1 st HCQ MDRD, abnl) n=84
Corral Alaejos, External evaluation of population pharmacokinetic models of imatinib in adults diagnosed with chronic myeloid leukaemia, Br J Clin Pharmacol, doi:10.1111/bcp.15122
Denney, Duvvuri, Buckeridge, Simple, Automatic Noncompartmental Analysis: The PKNCA R Package, J Pharmacokinet Phar
Eveleens Maarse, Effect of hydroxychloroquine on the cardiac ventricular repolarization: A randomized clinical trial, Br J Clin Pharmacol, doi:10.1111/bcp.15013
Funk, Factors associated with reduced infliximab exposure in the treatment of pediatric autoimmune disorders: a cross-sectional prospective convenience sampling study, Pediatr Rheumatol Online J, doi:10.1186/s12969-021-00548-8
Garcia-Cremades, Optimizing Hydroxychloroquine Dosing for Patients With COVID-19: An Integrative Modeling Approach for Effective Drug Repurposing, Clin Pharmacol Ther, doi:10.1002/cpt.1856
Geleris, Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19, N Engl J Med, doi:10.1056/NEJMoa2012410
Goldman, Cardiovascular adverse events associated with hydroxychloroquine and chloroquine: A comprehensive pharmacovigilance analysis of pre-COVID-19 reports, Br J Clin Pharmacol, doi:10.1111/bcp.14546
Gulick, Sobieszczyk, Landry, Hollenberg, Prioritizing clinical research studies during the COVID-19 pandemic: lessons from New York City, J Clin Invest, doi:10.1172/JCI142151
Junqueira, Rowe, Efficacy and safety outcomes of proposed randomized controlled trials investigating hydroxychloroquine and chloroquine during the early stages of the COVID-19 pandemic, Br J Clin Pharmacol, doi:10.1111/bcp.14598
Le, Rationale of a loading dose initiation for hydroxychloroquine treatment in COVID-19 infection in the DisCoVeRy trial, J Antimicrob Chemother, doi:10.1093/jac/dkaa191
Lim, Pharmacokinetics of hydroxychloroquine and its clinical implications in chemoprophylaxis against malaria caused by Plasmodium vivax, Antimicrob Agents Chemother, doi:10.1128/AAC.00339-08
Liu, Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19, J Clin Virol, doi:10.1016/j.jcv.2020.104370
Marzolini, Effect of Systemic Inflammatory Response to SARS-CoV-2 on Lopinavir and Hydroxychloroquine Plasma Concentrations, Antimicrob Agents Chemother, doi:10.1128/AAC.01177-20
Neely, Rakhmanina, Pharmacokinetic optimization of antiretroviral therapy in children and adolescents, Clin Pharmacokinet, doi:10.2165/11539260-000000000-00000
Nomura, Comprehensive assessment of exposure to clozapine in association with side effects among patients with treatment-resistant schizophrenia: a population pharmacokinetic study, Ther Adv Psychopharmacol, doi:10.1177/20451253211016189
Raj, Population Pharmacokinetics of Hydroxychloroquine Sulfate in Healthcare Workers, Given for Prophylaxis Against Coronavirus Disease 2019 (COVID-19) in India, J Clin Pharmacol, doi:10.1002/jcph.2092
Rubin, Cardiac Corrected QT Interval Changes Among Patients Treated for COVID-19 Infection During the Early Phase of the Pandemic, JAMA Netw Open, doi:10.1001/jamanetworkopen.2021.6842
Tang, Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial, BMJ, doi:10.1136/bmj.m1849
Tett, Cutler, Day, Brown, A dose-ranging study of the pharmacokinetics of hydroxy-chloroquine following intravenous administration to healthy volunteers, Br J Clin Pharmacol, doi:10.1111/j.1365-2125.1988.tb05281.x
Themans, Model informed dosing of hydroxycholoroquine in COVID-19 patients: Learnings from the recent experience, remaining uncertainties and gaps, Br J Clin Pharmacol, doi:10.1111/bcp.14436
Vc, Fm, Cl, Apparent volume of distribution of the central compartment for the parent drug; CL/F, Vc/F, Vp/F
Vc, None
Vmetc, None
Vmetp, None
Vp, None
Yao, Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Clin Infect Dis, doi:10.1093/cid/ciaa237
Yeo, Impact of Disease on Plasma and Lung Exposure of Chloroquine, Hydroxychloroquine and Azithromycin: Application of PBPK Modeling, Clin Pharmacol Ther, doi:10.1002/cpt.1955
Zahr, Pharmacokinetics and pharmacodynamics of hydroxychloroquine in hospitalized patients with COVID-19, Therapie, doi:10.1016/j.therap.2021.01.056
Zeitlinger, Pharmacokinetics/Pharmacodynamics of Antiviral Agents Used to Treat SARS-CoV-2 and Their Potential Interaction with Drugs and Other Supportive Measures: A Comprehensive Review by the PK/PD of Anti-Infectives Study Group of the European Society of Antimicrobial Agents, Clin Pharmacokinet, doi:10.1007/s40262-020-00924-9
Late treatment
is less effective
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