Benefits and adverse effects of hydroxychloroquine, methotrexate and colchicine: searching for repurposable drug candida
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Rheumatology International https://doi.org/10.1007/s00296-020-04694-2
INTERNATIONAL
REVIEW
Benefits and adverse effects of hydroxychloroquine, methotrexate and colchicine: searching for repurposable drug candidates Durga Prasanna Misra1 · Armen Yuri Gasparyan2 · Olena Zimba3 Received: 10 August 2020 / Accepted: 21 August 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Repurposing of antirheumatic drugs has garnered global attention. The aim of this article is to overview available evidence on the use of widely used antirheumatic drugs hydroxychloroquine, methotrexate and colchicine for additional indications. Hydroxychloroquine has endothelial stabilizing and anti-thrombotic effects. Its use has been explored as an adjunctive therapy in refractory thrombosis in antiphospholipid syndrome. It may also prevent recurrent pregnancy losses in the absence of antiphospholipid antibodies. Hydroxychloroquine favourably modulates atherogenic lipid and glycaemic profiles. Methotrexate has been tried for modulation of cardiovascular events in non-rheumatic clinical conditions, although a large clinical trial failed to demonstrate a benefit. Colchicine has been shown to successfully reduce the risk of recurrent cardiovascular events in a large multicentric trial. Potential antifibrotic effects of colchicine require further exploration. Hydroxychloroquine, methotrexate and colchicine are also being tried at different stages of the ongoing Coronavirus Disease 19 (COVID-19) pandemic for prophylaxis and treatment. While the use of these agents is being diversified, their adverse effects should be timely diagnosed and prevented. Hydroxychloroquine can cause retinopathy and rarely cardiac and auditory toxicity, retinopathy being dose and time dependent. Methotrexate can cause transaminitis, cytopenias and renal failure, particularly in acute overdoses. Colchicine can rarely cause myopathies, cardiomyopathy, cytopenias and transaminitis. Strong evidence is warranted to keep balance between benefits of repurposing these old antirheumatic drugs and risk of their adverse effects. Keywords Hydroxychloroquine · Methotrexate · Colchicine · Thrombosis · Cardiovascular risk · Fibrosis Abbreviations 18-FDG 18-Fluorodeoxyglucose ACS Acute coronary syndromes AICAR Enzyme 5-aminoimidazole-4-carboxamide ribonucleoside * Durga Prasanna Misra [email protected] Armen Yuri Gasparyan [email protected] Olena Zimba [email protected] 1
Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Rae Bareli Road, Lucknow 226014, India
2
Departments of Rheumatology and Research and Development, Dudley Group NHS Foundation Trust (Teaching Trust of the University of Birmingham, UK), Russells Hall Hospital, Dudley, West Midlands, UK
3
Department of Internal Medicine #2, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
aPL Antiphospholipid antibodies ATIC AICAR transformylase APS Antiphospholipid antibody syndrome CAD C
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