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      Expanding horizons for clinical applications of chloroquine, hydroxychloroquine, and related structural analogues

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          Abstract

          Several experimental and clinical studies have transformed the traditional antimalarial role of chloroquine (CHQ) and related structural analogues to potent therapeutic agents for a host of nonmalarial indications. The expanding clinical applicability for these drugs includes rheumatological and cardiovascular disorders (CVD), chronic kidney disease (CKD), oncology, and a variety of nonmalarial infections. These clinical advancements are primarily related to pleiotropic pharmacological actions of these drugs, including immunomodulation, anti-inflammatory properties, and capabilities of inducing autophagy and apoptosis at a cellular level. Historically, many clinical benefits in nonmalarial indications were first recognized through serendipitous observations; however, with numerous ongoing systematic clinical studies, the clinical horizons of these drugs have a promising future.

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          Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review.

          G Ruiz-Irastorza, M. Ramos-Casals, P. Brito-Zeron … (2010)
          Antimalarial drugs (AMs), chloroquine (CQ) and hydroxychloroquine (HCQ), are frequently withdrawn in patients with lupus with either severe or remitting disease. However, additional effects beyond immunomodulation have been recently described. The aim of the present work was to analyse all the published evidence of the beneficial and adverse effects of AM therapy in systemic lupus erythematosus (SLE). A systematic review of the English literature between 1982 and 2007 was conducted using the MEDLINE and EMBASE databases. Randomised controlled trials (RCTs) and observational studies were selected. Case reports were excluded except for toxicity reports. The GRADE system was used to analyse the quality of the evidence. A total of 95 articles were included in the systematic review. High levels of evidence were found that AMs prevent lupus flares and increase long-term survival of patients with SLE; moderate evidence of protection against irreversible organ damage, thrombosis and bone mass loss. Toxicity related to AMs is infrequent, mild and usually reversible, with HCQ having a safer profile. In pregnant women, high levels of evidence were found that AMs, particularly HCQ, decrease lupus activity without harming the baby. By contrast, evidence supporting an effect on severe lupus activity, lipid levels and subclinical atherosclerosis was weak. Individual papers suggest effects in preventing the evolution from SLE-like to full-blown SLE, influencing vitamin D levels and protecting patients with lupus against cancer. Given the broad spectrum of beneficial effects and the safety profile, HCQ should be given to most patients with SLE during the whole course of the disease, irrespective of its severity, and be continued during pregnancy.
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            The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy.

            Ronald B Melles, Michael F Marmor (2014)
            Hydroxychloroquine sulfate is widely used for the long-term treatment of autoimmune conditions but can cause irreversible toxic retinopathy. Prior estimations of risk were low but were based largely on short-term users or severe retinal toxicity (bull's eye maculopathy). The risk may be much higher because retinopathy can be detected earlier when using more sensitive screening techniques.
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              Global extent of chloroquine-resistant Plasmodium vivax: a systematic review and meta-analysis

              Ric Price, Lorenz von Seidlein, Neena Valecha … (2014)
              Summary Background Chloroquine is the first-line treatment for Plasmodium vivax malaria in most endemic countries, but resistance is increasing. Monitoring of antimalarial efficacy is essential, but in P vivax infections the assessment of treatment efficacy is confounded by relapse from the dormant liver stages. We systematically reviewed P vivax malaria treatment efficacy studies to establish the global extent of chloroquine resistance. Methods We searched Medline, Web of Science, Embase, and the Cochrane Database of Systematic Reviews to identify studies published in English between Jan 1, 1960, and April 30, 2014, which investigated antimalarial treatment efficacy in P vivax malaria. We excluded studies that did not include supervised schizonticidal treatment without primaquine. We determined rates of chloroquine resistance according to P vivax malaria recurrence rates by day 28 whole-blood chloroquine concentrations at the time of recurrence and study enrolment criteria. Findings We identified 129 eligible clinical trials involving 21 694 patients at 179 study sites and 26 case reports describing 54 patients. Chloroquine resistance was present in 58 (53%) of 113 assessable study sites, spread across most countries that are endemic for P vivax. Clearance of parasitaemia assessed by microscopy in 95% of patients by day 2, or all patients by day 3, was 100% predictive of chloroquine sensitivity. Interpretation Heterogeneity of study design and analysis has confounded global surveillance of chloroquine-resistant P vivax, which is now present across most countries endemic for P vivax. Improved methods for monitoring of drug resistance are needed to inform antimalarial policy in these regions. Funding Wellcome Trust (UK).
              Article 0 comments Cited 191 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Drugs Context
                Journal ID (iso-abbrev): Drugs Context
                Journal ID (publisher-id): DIC
                Title: Drugs in Context
                Publisher: BioExcel Publishing Ltd
                ISSN (Print): 1745-1981
                ISSN (Electronic): 1740-4398
                Publication date Collection: 2019
                Publication date (Electronic): 25 November 2019
                Volume: 8
                Electronic Location Identifier: 2019-9-1
                Affiliations
                [1 ]North Florida/South Georgia, Veteran Healthcare System, Gainesville, FL, USA
                [2 ]Department of Medicine, Division of Nephrology, College of Medicine, University of Florida, Gainesville, FL, USA
                [3 ]Department of Neurology, College of Medicine, University of Florida, Gainesville, FL, USA
                Author notes
                Correspondence: Aparna Wagle Shukla MD, Norman Fixel Institute for Neurological Diseases, 3009 Williston Road, Gainesville, FL 32608, USA. aparna.shukla@ 123456neurology.ufl.edu
                Article
                Publisher ID: dic-2019-9-1
                DOI: 10.7573/dic.2019-9-1
                PMC ID: 6905642
                SO-VID: a7cb50d8-bf81-4fdb-be4e-855c857ff1d9
                Copyright © Copyright © 2019 Shukla AM, Wagle Shukla A.
                License:

                Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.

                History
                Date received : 01 September 2019
                Date revision received : 08 October 2019
                Date accepted : 09 October 2019
                Categories
                Subject: Review

                Keywords: antimalarials,cardiovascular disease,chloroquine,chronic kidney disease,hydroxychloroquine,rheumatology
                Data availability:
                Keywords: antimalarials, cardiovascular disease, chloroquine, chronic kidney disease, hydroxychloroquine, rheumatology

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