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You are here: Home / Articles / The History of Treating Lupus with Hydroxychloroquine

The History of Treating Lupus with Hydroxychloroquine

June 15, 2020 • By Ruth Jessen Hickman, MD

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Given how unexpectedly front and center hydroxychloroquine has been in discussions about the treatment of COVID-19 this year, it makes sense to look at how it became so central to the treatment of a rheumatologic condition.

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In 1991, an article appeared in The New England Journal of Medicine that would alter the way rheumatologists approached treatment for systemic lupus erythematosus: “A Randomized Study of the Effects of Withdrawing Hydroxychloroquine Sulfate in Systemic Lupus Erythematosus.”1 Although questions remained about optimal dosing, the study opened the way for much follow-up research that would confirm the drug’s critical importance for lupus patients.

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Antimalarials: Background

Scientists synthesized the first antimalarial drugs shortly before the start of World War II. Malaria was a leading cause of death among soldiers, particularly in the South Pacific. The first antimalarial, quinacrine, produced numerous side effects, prompting researchers to develop derivate compounds. The U.S. Army introduced chloroquine, one of these compounds, in 1943.2

In 1951, Francis Page, MD, reported that quinacrine had beneficial effects on lupus symptoms.3 A similar report appeared two years later, when James Charles Shee, MD, published findings demonstrating that soldiers with rheumatoid arthritis (RA) or lupus taking chloroquine showed clinical improvement.4

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Michelle Petri, MD, MPH, co-director of the Johns Hopkins Lupus Center and a professor of medicine at Johns Hopkins School of Medicine, Baltimore, elaborates on the discovery of the drug’s use in inflammatory conditions. “The military personnel who had rheumatoid arthritis and lupus felt much better when they were taking the malaria medicine and then wanted to continue it when they left the military,” she explains. “It’s almost a discovery made accidentally, as so many medical discoveries are. It’s a nice story of physicians listening to their patients.”

Modifications to chloroquine eventually led to the introduction of an anti­malarial purported to have fewer side effects, hydroxychloroquine, which the U.S. Food & Drug Administration (FDA) approved in 1955.2 The most commonly reported adverse effects of antimalarials are mild, such as gastrointestinal discomfort or headache. However, other concerns about the safety of antimalarials emerged over time, partly because doses for rheumatological conditions were much higher than those used for malaria prophylaxis.

A population-based, case-controlled study from 2019 demonstrated that the mortality risk increased almost fourfold in people who had to stop taking their hydroxychloroquine. It is the only drug that has been demonstrated to improve the survival of lupus patients.

In the late 1950s, reports began to appear documenting retinopathy resulting from chloroquine treatment.5 This important potential adverse effect continues to influence prescribing practices to this day.

Both chloroquine and hydroxychloroquine can potentially bind in the retinal pigment epithelium and cause degeneration of photoreceptors, leading to retinopathy.6 Eventually, research demonstrated that hydroxychloroquine posed less of a risk of retinopathy than chloroquine.

In the U.S. and Canada, hydroxychloroquine has largely replaced chloroquine as a treatment for lupus in the antimalarial drug class.

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Pages: 1 2 3 4 5 | Single Page

Filed Under: Conditions, SLE (Lupus) Tagged With: Lost & Found, retinopathy, SLE Resource CenterIssue: June 2020

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  • Reflections on Living with Lupus, and on Treating It

About Ruth Jessen Hickman, MD

Ruth Jessen Hickman, MD, was born and raised in eastern Kentucky, where she first cultivated her love of literature, writing and personal narratives. She attended Kenyon college, where she received a Bachelor of Arts in philosophy, summa cum laude. She worked with individuals with psychiatric conditions and later in a neuroscience lab at the University of Illinois, Chicago, before graduating from Indiana University Medical School in 2011. Instead of pursuing clinical medicine, Ruth opted to build on her strength of clearly explaining medical topics though a career as a freelance medical writer, writing both for lay people and for health professionals. She writes across the biomedical sciences, but holds strong interests in rheumatology, neurology, autoimmune diseases, genetics, and the intersection of broader social, cultural and emotional contexts with biomedical topics. Ruth now lives in Bloomington, Ind., with her husband, son and cat. She can be contacted via her website at ruthjessenhickman.com.

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