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Hydroxychloroquine as a COVID Preventive Still in the News

January 27, 2021
UK researchers looked at data from those with rheumatoid arthritis and lupus who were taking the drug prior to the pandemic in search of more clues to its efficacy.


A big fuss ensued in March 2020 when the former US President Trump began to promote the use of hydroxychloroquine (HCQ) as a treatment – or possibly a preventive – for COVID-19 infection. Some studies had indicated intriguing possibilities about the drug’s potential. Others not so much. The controversy over the former president’s vigorous promotion of the drug, typically used to treat malaria and rheumatological disorders, including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), served to somewhat obscure the evidence – or lack of evidence – on the issue. The US Government ordered supplies of the drug, and some physicians began prescribing it for COVID-19 patients (in some cases, leading to fears of a drug shortage). But still, at the time, little was known about HCQ’s actual benefits or risks in this population.1-3

Noting that some studies had shown HCQ could prevent SARS-CoV-2 from entering epithelial cells in vitro but did not reduce mortality in infected patients, a team of researchers at the London School of Hygiene and Tropical Medicine in the UK designed a study to assess HCQ’s potential benefits. Their approach, published in The Lancet Rheumatology this month (January 2021), was unique in that it looked at the effect of ongoing pre-exposure use of HCQ on COVID-19 infection or severe outcomes.4


HCQ Pre-Exposure Study Design

The population-based observational cohort study used primary care data and death registrations in England to analyze whether routine treatment with HCQ – prior to the outbreak of the pandemic – was effective in reducing mortality after being infected with COVID-19. The team utilized OpenSAFELY, a secure data analytics platform managed by England’s National Health Service to provide researchers with secure and quick access to EHR data during the pandemic. The data set covers roughly 40% of the population in England.

The team analyzed data from 194,637 patients with diagnoses of either RA or SLE. Of these, 30,569 had received two or more prescriptions of HCQ in the six months prior to March 1, 2020. The patients who received HCQ were younger (median age 63 years) than non-users (median age 66 years) and primarily women (76.3%).

The researchers adjusted for variables such as sex, age, ethnicity, and use of other immunosuppressive drugs. Other variables included BMI, hypertension, diabetes, heart, liver, and respiratory disease (excluding asthma), kidney disease, and cancer. The primary outcome measure was mortality due to COVID-19, as recorded on the death certificate.

Findings: HCQ and COVID Prevention in Patients with Rheumatic Disease

Between March 1, 2020 and July 13, 2020, 547 people in the cohort with RA or SLE died of COVID-19, 70 of whom were regular users of HCQ. The difference between deaths of users and non-users was 0.008%. The results showed no evidence that previous treatment with HCQ had a beneficial effect on COVID-19 mortality.

“Taken together, our findings do not provide any strong support for a major protective effect from ongoing routine hydroxychloroquine use,” the authors wrote in their paper.4 They also pointed out that their research demonstrates the safe and effective use of the OpenSAFELY platform for studying the effects of medicines in order to inform regulatory bodies engaged in decision-making in circumstances where there is a lack high-quality randomized trial data. However, they also noted that, because of the observational nature of their study, there is a still uncertainty that can only be addressed in large scale RCTs.

Are More HCQ COVID Studies Needed or Is It Time to Move On?

Jean Mulcahy Levy, associate professor of pharmacology at the University of ColoradoAnschutz Medical Campus, agrees that further studies would be best.

“Hydroxychloroquine has been in use since the 1960s and 70s, and millions of people around the world have taken it for various reasons, including people with rheumatological disorders who take it for prolonged periods of time,” she told PPM. “Dosed appropriately, it is a very safe drug. I think it would be good if we could answer the question [about potential benefits for COVID-19] definitively and move on.”

It’s unlikely that we will get a definitive answer any time soon, however. “It’s hard in the setting of a pandemic to do well-crafted studies,” says Dr. Mulcahy Levy. “Those normally take years.”

Meanwhile, providers will have to wait until there are better studies before they can make an informed decision about the use of HCQ use as a way to reduce mortality from COVID-19. More important, perhaps, the Rentsch study does offer some evidence that patients already prescribed HCQ regularly need not fear that the medication could make COVID-19 worse if they do contract the virus.

See our past coverage of HCQ and COVID and HCQ use in immune diseases.



Last updated on: January 27, 2021
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