Hydroxychloroquine – An Answer or False Hope for COVID-19?

Hydroxychloroquine – An Answer or False Hope for COVID-19?

Scientists and physicians are working tirelessly to find ways to treat COVID-19. Currently under study are two related drugs – hydroxychloroquine and chloroquine. In a variety of studies, these drugs have exhibited antiviral activity, an ability to moderate the activity of the immune system, and has a recognized safety profile at suitable doses, leading to the hypothesis that it may also be useful in the treatment of COVID-19. It is important to note that neither of these drugs have been approved by the Food and Drug Administration (FDA) for the treatment of COVID-19, as such they should only be used when recommended by your physician. However, on 28 March 2020, the FDA issued an Emergency Use Authorization (EUA) to allow hydroxychloroquine sulfate and chloroquine phosphate products donated to the Strategic National Stockpile (SNS) to be distributed and used for certain people who are hospitalized with COVID-19. In anticipation of product shortages, the FDA issued product-specific guidance for chloroquine phosphate and for hydroxychloroquine sulfate for generic drug manufacturers.

Current Uses and Potential Side Effects

Hydroxychloroquine is an oral tablet sold under the brand name Plaquenil. Existing uses for the drug include the prevention and treatment of malaria as well the treatment of Rheumatoid Arthritis, Lupus and Porphyria Cutanea Tarda. It is also widely used in the treatment of post-Lyme arthritis. It may have both an anti-spirochaete activity and an anti-inflammatory activity, similar to the treatment of rheumatoid arthritis. Hydroxychloroquine was approved for medical use in 1955 in the United States. The most frequent adverse side effects of hydroxychloroquine use include mild nausea and occasional stomach cramps with mild diarrhea. The most severe adverse effects involve the eye, with dose-related retinopathy as a concern even after hydroxychloroquine use is discontinued. Prolonged treatment of lupus or rheumatoid arthritis can lead to the same acute symptoms above and include a multitude of possible additional effects including altered eye pigmentation, acne, anemia, bleaching of hair, blisters in mouth and eyes, blood disorders, convulsions, vision difficulties, diminished reflexes, emotional changes, excessive coloring of the skin, hearing loss, hives, itching, liver problems or liver failureloss of hair, muscle paralysis, weakness or atrophy, nightmares, psoriasis, reading difficulties, tinnitus, skin inflammation and scaling, skin rash, vertigoweight loss, and urinary incontinence. Hydroxychloroquine can worsen existing cases of psoriasis. Children appear to be at greater risk of developing the negative side effects associated with use of this drug.

The World Health Organization (WHO) maintains a list of essential medicine which includes the safest and most effective medications required in a health system. Despite the listed potential negative side effects, hydroxychloroquine is on this list. In 2017, it was the 128th most commonly prescribed medication in the United States, with more than five million prescriptions being issued. This is indicative of the large number of patients that use this medication for treatment unrelated to COVID-19 and who may be affected if shortages occur. This further calls into question whether this drug should be given freely as a COVID-19 treatment without scientific evidence of its effectiveness.

A Need for Numbers

A small randomized trial in China, consisting of 30 patients, found no demonstrable effect of using hydroxychloroquine to treat COVID-19. The sole publication, in International Journal of Antimicrobial Agents (IJAA), claiming hydroxychloroquine benefits patients with COVID-19 is vague. Although it appears the publication was subjected to peer review the International Society of Antimicrobial Chemotherapy (ISAC) along with Elsevier, the publishers of the journal released a joint statement regarding the paper. “At present, additional independent peer review is ongoing to ascertain whether concerns about the research content of the paper have merit. Given this process of post-publication assessment is on-going, it would be premature to comment at this time. The study authors have been contacted and asked to address the concerns.” The ISAC has stated in no uncertain terms that they share the concerns raised regarding this paper.

A preliminary study out of Brazil on the use of chloroquine diphosophate to treat patients with Covid-19 symptoms ended early after several patients died and researchers found that a high dose of the drug was associated with a severe type of arrhythmia, or irregular heartbeat. The study has not yet been published in a peer-reviewed medical journal but was published to the online medical server medRxiv. In the study, which was halted based on these numbers, 16 patients out of 41 on a high dose of the drug died, compared to 6 out of 41 patients who were given a low dose of the drug. The difference in survival rates was found to be significant. Patients with COVID-19 are often also on other drugs including antibiotics like azithromycin which are considered cardiotoxic. Although no control groups (not using the drug, or not used in conjunction with other drugs) were observed during the study, this does support the idea that much greater research is required before off label use of these drugs occur.  

NIH Seeks Clarity

In order to get clarity on these issues, the National institutes of Health (NIH) has started a clinical trial on the potential of hydroxychloroquine as a treatment for COVID-19 which will evaluate the effectiveness and safety of the drug. The study is being conducted by the Prevention and Early Treatment of Acute Lung Injury (PETAL) Clinical Trials Network of the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health.

The first participants have enrolled in the trial at Vanderbilt University Medical Center, Nashville, one of dozens of centers in the PETAL Network. The study is a blind, placebo-controlled randomized trial. The aim is to enroll 500 adult patients currently hospitalized for COVID-19 or those who are considered likely to require hospitalization. All participants will continue to receive clinical care with those randomized to the experimental intervention also receiving hydroxychloroquine.

Fools Rush In

There is no doubt that a great need exists to find effective treatments for COVID-19. This need has led to a number of hospitals using hydroxychloroquine as a first-line therapy for patients hospitalized due to COVID-19 despite the fact that clinical data supporting this use is extremely limited. Therefore, sound clinical data is desperately needed to inform clinical practice. Given that patients that utilize this drug effectively for a number of conditions (for which it has received FDA approval) may face severe shortages, it is essential that this data is available as soon as possible. The urgency with which treatments are needed for COVID-19 should not weaken the scientific rigor with which we approach sound scientific testing. More harm than good may be done if trials are rushed and treatments are given that have not been subjected to appropriate testing.

Those who use these drugs to treat existing conditions, such as RA and Lupus, should contact their rheumatologist or treating physician to discuss potential alternative treatment protocols should they not be able to get hydroxychloroquine.


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Article Author
Arthritis National Research Foundation

The Arthritis National Research Foundation's mission is to provide initial research funding to brilliant, investigative scientists with new ideas to cure arthritis and related autoimmune diseases. There are several ways to support research through the ANRF. Find out more and donate today.

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