The GREAT Hydroxychloroquine Debate – When Theory & Science Diverge

August 3, 2020
Ene Ojile M.D.
Posted in Around The World Home and Wellbeing

Image credit: Cleo

Recently there has been a lot of information in the media about the treatment of Coronavirus disease (COVID) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 ). Without question we are in unprecedented times. Who would have thought that people would be walking around with masks on. Masks have become the norm. I have stopped to look around and let all this sink in and at times it feels like a movie. There is an eerie feeling around us.

The big question that remains unanswered is: When will the pandemic end? Even more questions: Will it end when there is a cure, when there is a vaccine or when we all develop some sort of herd immunity?

I am a physician and I attended medical school and trained in the United States. However, I also had the opportunity of attending medical school for two years in my home country of Nigeria before I relocated to America to pursue my medical education. Consequently, I have experienced healthcare in both settings.

Growing up in Nigeria, I took Hydroxychloroquine probably twice a year either to treat or prevent malaria. Maybe even more often than most as my father was a pharmacist and made sure we were always covered prophylactically. The most common side effect of Hydroxychloroquine was excessive itching. I don’t remember a case of death from Hydroxychloroquine but again in developing nations the right tools might not be available to determine the risks associated with the use of medications. That being said, Hydroxychloroquine has been used for decades and millions have used it especially in malaria ridden parts of the world. It is generally a safe drug. However, is it safe for use in COVID patients?

It is worth stating here that in the United States a medication has to be approved by the United States Food and drug administration (FDA) for a particular use to be in the market. The FDA ensures that high standards are met before a drug is approved. Nonetheless, it is not uncommon practice amongst physicians that medications are used off label. To elaborate, there are several medications used outside of their FDA approval. An example is a drug called Gabapentin. Initially this drug was made to treat seizures and has the FDA approval for the seizures or post-herpetic neuralgia. However, physicians noticed that Gabapentin had an unintended “side effect” of alleviating a type of pain related to the nerves called neuropathic pain. Currently it is common practice that Gabapentin is prescribed for neuropathic pain. This is its most common use now amongst physicians rather than for its FDA approved use.

Hydroxychloroquine is FDA approved for malaria parasites, lupus and rheumatoid arthritis. It was approved in the 1950s for treatment of lupus and rheumatoid arthritis and did not undergo the conventional drug development needed for FDA approval, but its use has become a part of current treatment guidelines. It is also used serendipitously and empirically for the treatment of various rheumatic diseases outside of lupus and rheumatoid arthritis.

On March 29th, 2020 the FDA issued Emergency Use Authorization (EUA) of Hydroxychloroquine amid the Coronavirus pandemic to allow Hydroxychloroquine and Chloroquine for coronavirus (COVID-19) treatment. In another turn of events, in June 2020, the U.S. Food and Drug Administration (FDA) revoked the emergency use authorization allowed for Chloroquine Phosphate and Hydroxychloroquine Sulfate donated to national agencies.

The FDA determined that the legal criteria for issuing an EUA were no longer met. Based on its ongoing analysis of the EUA and emerging scientific data, the FDA determined that Chloroquine and Hydroxychloroquine are unlikely to be effective in treating COVID-19 for the authorized uses in the EUA. Additionally, in light of ongoing serious cardiac adverse events and other potential serious side effects on patients, the known and potential benefits of Chloroquine and Hydroxychloroquine no longer outweigh the known and potential risks for the authorized use. Thus at this time any use of Hydroxychloroquine for COVID is an off label use.

Read | A Group Of Physicians Claim a COVID-19 Cure Exists and America Erupts

A little science here, Hydroxychloroquine works for various conditions because it is a weak base that penetrates the cell and reduces the acidic activity of the cells. This is how it works to kill the malaria parasite. Some researchers believe that the reduction of this acidity in the cells might affect the propagation of SARS CoV-2 virus. The malaria parasite is a type of organism called a Protozoa which is very different from a virus. It may be farfetched to assume that the virus would be killed by Hydroxychloroquine because viruses are “smart and elusive”. However, it has also been theorized that Hydroxychloroquine could block or interfere with the acidification process not only in treatment, but as prevention for COVID. This is one of theories behind its use in COVID.

Theory and Science

Theory is not enough in science but is the start of it. Theories should not be thrown away. They should be entertained and explored and then discarded if proven wrong. The highest level of science to verify or deny a theory in clinical research is a randomized double-blinded clinical trial. This proves the efficacy of a drug and eliminates bias. We currently do not have that type of trial to be certain that Hydroxychloroquine is effective or not effective in treating COVID.

One major concern in the medical community is the potentially lethal side effects of the Hydroxychloroquine. It can cause arrhythmias in patients who are really sick or in critical condition. This can also complicate recovery.

Physicians who have empiric claims that Hydroxychloroquine is effective tend to be physicians who treat in an outpatient setting. Their demographic of patients tend to be less sickly and have less risk factors such as heart disease and diabetes. They are generally healthy people who contract the COVID who don’t require hospitalization. It is possible that they would have recovered anyway but also plausible that Hydroxychloroquine use in these patients may help or at the very least not cause the severe side effects seen in hospitalized patients. The outcomes for outpatient treatment will thus be better because these physicians tend to have healthier subjects to begin with or patients with non-life-threatening symptoms. The recent claim by some physicians that they have not seen any deaths after Hydroxychloroquine use is one that needs further scientific evaluation to validate or deny the claim.

In the medical community objective data is paramount. It would be a good thing to start tracking these patients to know if this is a valid claim.

It is worth noting here that the National institute of health (NIH) halted a clinical trial to evaluate the safety and effectiveness of Hydroxychloroquine for the treatment of adults hospitalized with coronavirus disease (COVID-19). The NIH Data and Safety Monitoring Board (DSMB) determined that while there was no harm, the study drug was very unlikely to be beneficial to hospitalized patients.

This study would have used the highest level of research (randomized, double blinded and placebo controlled). They aimed to enroll more than 500 adults who were currently hospitalized with COVID-19 or in an emergency department with anticipated hospitalization. More than 470 were enrolled at the time of study’s closure. This would have provided maybe the most reliable information we need.

As it stands, there are physicians who swear by Hydroxychloroquine efficacy anecdotally. Anecdotal use of medications is not new amongst physicians. As long as risks are minimized and no intended harm is done, generally the state medical boards and/or FDA do not have a heavy hand in reprimanding against this practice.

I think most doctors tend not to be political, at least not in their intent for the use of a medication. They practice based on science and at times anecdotal experience. There are doctors who will not use Hydroxychloroquine for COVID and those who will just like many other drugs used off label.

The media has made this political. If I treat my patient’s headaches with Acetaminophen and a certain politician does the same, does that mean I’m doing it for political reasons? I doubt that most physicians are and I am yet to meet a colleague personally who practices along those lines. The intellectual task of becoming and practicing as a physician tends to weed out eccentric people that practice along those lines. Do they exist? Of course there are bad eggs out there as in any profession but I assure you most physicians don’t think that way.

The jury is still out on a “cure” for COVID. An antiviral Remdesivir appears to be promising. In the meantime, patients are treated by managing their symptoms and providing supportive care.

Let us not make this political. Let’s push for better trials to determine what works to treat or prevent COVID-19. In the meantime, wear your masks, social distance, keep your hands clean and away from your face.

Ene Ojile M.D.
Board Certified Physical Medicine and Rehabilitation
Ene is also a singer/songwriter/inspirational writer. You can follow her on IG or Facebook @enemusicweb

References:
https://www.nature.com/articles/s41584-020-0372-x
https://www.medpagetoday.com/infectiousdisease/covid19/85934
https://www.fda.gov/drugs/drug-safety-and-availability/fda-cautions-against-use-hydroxychloroquine-or-chloroquine-covid-19-outside-hospital-setting-or

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