Hydroxychloroquine (HCQ) has had a rollercoaster ride of a year. Touted as a miracle cure for COVID-19 at the beginning of the pandemic, it finished the year plagued with concerns about adverse cardiac events.
Yet, HCQ is a remarkable medication with a fascinating history. The active ingredient is quinine, derived from the bark of cinchona trees native to South America. Initially used to prevent and treat malaria and classified as an anti-malarial drug, the medication is better understood today, has multiple medical uses and is on the World Health Organization’s List of Essential Medicines.
Although HCQ has not been proven as an effective treatment for COVID-19, it remains the cornerstone of therapy for autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Research presented at the American College of Rheumatology (ACR) annual meeting in November reiterated HCQ’s safety and restored its good reputation.
U.S. President Donald Trump made hydroxychloroquine a household word when he tweeted at the beginning of the pandemic that it had “a real chance to be one of the biggest game changers in the history of medicine.” He then added: “What do you have to lose? I’ll say it again: What do you have to lose? Take it.”
Shortly after Trump’s false claims, the U.S. Food and Drug Administration (FDA) issued emergency-use authorization for HCQ in the treatment of COVID-19.
More recently, Detroit’s Henry Ford Health System quietly ended a study on the prophylactic benefits of HCQ as protection from COVID-19 for front-line workers. The study began in April and aimed to recruit 3,000 front-line workers but was able to recruit only 624 participants after waning evidence and enthusiasm for the drug became public.
Janet Pope, a professor of medicine in the Division of Rheumatology at Western University in London who commonly prescribes HCQ, saw her patients’ attitudes toward the drug evolve during the pandemic. Pope, who has published more than 455 peer-reviewed articles, 15 chapters, 500 abstracts and several Cochrane meta-analysis reviews, says that at first, patients who hadn’t been on HCQ clamored for prescriptions and those who had been on it in the past wanted it restarted. Because of the rampant COVID-19 speculation, this led to fears of shortages among patients who needed HCQ to keep their rheumatic disease in remission.
But in June, after the FDA determined the drug and its counterpart, chloroquine, were unlikely to be effective in treating COVID-19 and that there were serious concerns about adverse cardiac events, Pope’s office began receiving “panicked phone calls from patients who thought it was unsafe to take HCQ and that it would give them a fatal arrhythmia,” she says.
Pope says some pharmacists misinformed patients about drug interactions that were not relevant to the doses they were taking for rheumatic disease and some were even telling patients that HCQ could result in a fatal heart arrhythmia. Even patients who had been taking HCQ for years were given incorrect information, Pope says.
“Some (lupus) patients stopped their (HCQ), did not inform me and then flared,” she notes. A flare represents active disease and active lupus can be life-threatening.
Jack Cush, director of clinical rheumatology at the Baylor Research Institute and a professor of medicine and rheumatology at Baylor University Medical Centre in Dallas, says he noticed similar patterns in his rheumatology practice.
Cush, who is also the executive editor of RheumNow.com, a news, information and commentary site dedicated to the field of rheumatology, says that “all the misinformation about HCQ” scared up to half of his patients taking it, causing about 20 per cent to “stop HCQ without guidance.”
“Moreover, up to one third of patients noted a shortage or limitation of HCQ dispensing between April and September,” he adds.
A press release on the study presented at the ACR meeting in November stated that “hydroxychloroquine remains the foundation of disease-modifying antirheumatic drug therapy in rheumatic disease patients.”
“Given recent concerns surrounding HCQ’s use in COVID patients and subsequent arrhythmic events, we wanted to examine the associations between its use and the QTc length on electrocardiograms in a large, asymptomatic cohort of RA and SLE patients,” Elizabeth Park, a Rheumatology Fellow at Columbia University Irving Medical Center in New York and co-author of the study, wrote.
The QTc length is a measurement made on a heart tracing used to assess some of the electrical properties of the heart. An abnormally long or short interval is associated with an increased risk of developing abnormal heart rhythms and even of sudden cardiac death.
Park and her colleagues analyzed data on 681 RA and SLE patients without heart disease. The researchers explored the association between QTc length and HCQ use among these patients. Their results showed that HCQ use did not prolong the QTc interval in RA and SLE patients.
“Our findings reinforce the fact that HCQ remains a safe, effective, long-term, disease-modifying drug for our rheumatic disease patients,” Park concluded.
The confusion over HCQ is understandable because, as Pope acknowledges, “we wanted hope for COVID treatment.” The media shares some of the blame, Pope says, because “there was not always due diligence with respect to peer-review and also was truly often quoting articles that in a normal year would have been either not published or disregarded due to the nature of the studies.”
“In fairness,” adds Pope, “the public, too, received so much information and they, too, did not filter the study results. I think it was information overload that led to misinformation.”
Pope says health reporters should develop a framework when reporting on medications and studies. “For instance, any new drug that comes out is often overblown with a promise of hope, then reality sets in and later articles are almost at the other extreme, for example, when reporting side effects.
“A framework could be something like: reporting on the current treatments available prior to a new drug; what the new drug has to offer; potential risks and benefits and scope of the problem or disease; and who it might apply to.”
Pope stresses that “we have to continue to believe in the scientific method and COVID certainly showed us that when we jump the gun, we can have significant misinformation.”
For better or worse, hydroxychloroquine had its year in the spotlight. While it is not an effective treatment for COVID-19, it is an old drug that has come a long way from the bark of the cinchona tree and is still the cornerstone therapy of RA and SLE.