Explainer: Global controversy over hydroxychloroquine [update]

Efficacy not proven, potentially harmful side effects

Hydroxychloroquine is a medicine commonly used to prevent malaria or treat arthritis, according to the U.S. Centers for Disease Control and Prevention. It is usually available by prescription for adults and children of all ages, including pregnant women.

Amid the global COVID-19 pandemic, however, this relatively well-tolerated drug with minor side effects has become highly controversial around the world.

In countries like Brazil, El Salvador, India, France, and the United States, some medical experts and politicians have promoted hydroxychloroquine as an effective treatment for COVID-19, despite early warnings by the European Medicines Agency and scientists from other countries that there is no data supporting the therapeutic effects and that the medication appears to cause serious side effects such as heart arrhythmia in some COVID-19 patients.

U.S. President Donald Trump repeatedly recommended the use of hydroxychloroquine during White House briefings and said he took the drug himself as a preventive treatment.

On May 21, he tweeted that the drug has “a real chance to be one of the biggest game changers in the history of medicine” and said he hopes the treatment will be “put in use IMMEDIATELY.”

On May 25, the World Health Organization (WHO) suspended testing hydroxychloroquine in COVID-19 patients due to safety concerns.

The health organization, which had already recommended against the use of the malaria medication in prevention or treatment of the disease, stated that the drug has “not been found to be effective” and warned of dangerous side effects.

[Update on June 5] WHO resumed its trial after reviewing the data concerning potential heart risks and decided the trial should go on without any modification.

Despite the WHO’s warning, it is still used as a potential treatment in several countries. On May 26, Salvadoran President Nayib Bukele said he uses hydroxychloroquine as a preventive measure, as do “most of the world’s leaders.”

More recently, he said the drug was no longer part of El Salvador’s coronavirus treatment protocol but it would remain available for patients who wish to use it for prevention.

Brazilian President Jair Bolsonaro also touted the drug as effective in a video posted on Facebook. The social platform later removed the video as it breached its misinformation guidelines, but Brazil’s health ministry declared that it would not change its recommendation to treat COVID-19 with hydroxychloroquine.

Questionable research in France

In March, Didier Raoult, a French microbiologist specialized in infectious diseases, started promoting a treatment combining hydroxychloroquine and azithromycin, a common antibiotic, as a cure for COVID-19.

On March 16, the microbiologist released the results of a clinical trial which showed a 100% cure rate. Raoult’s treatment regimen was soon authorized for testing or use in several countries, including France, China, Italy and India.

Raoult’s study has been widely debated by scientists, health authorities and political figures.

In France, Raoult’s call for the wider use of hydroxychloroquine has gained a lot of support from political opposition groups on social media. They have accused the French government of “helping big pharma to make profit over the COVID-19 pandemic” by banning the prescription of the inexpensive drug.

Numerous Facebook groups, including some anti-Macron groups, started sharing posts and articles promoting the use of hydroxychloroquine. Some of them have attracted close to half a million members.

By late March, Raoult became one of France’s most popular public figures according to an opinion poll.

In early April, French President Emmanuel Macron even paid a visit to Raoult as part of a large group of consultations after nearly 580,000 people signed a petition asking the government to allow the wider use of hydroxychloroquine as a treatment for COVID-19 while the International Journal of Antimicrobial Agents, which published Raoult’s study, withdrew its support in the same month, stating that the study did not meet the journal’s “expected standard.”

Controversy continues

On May 22, the peer-reviewed medical journal The Lancet published a study on the use of hydroxychloroquine to treat COVID-19 patients, reviewing the results of close to 100,000 patients in 671 hospitals across the world.

The observational study ran between Dec. 20, 2019, and April 14, 2020, and concluded there is no evidence supporting the efficiency of hydroxychloroquine as a treatment for COVID-19.

The study also revealed that the risk of developing serious heart arrhythmia was more than five times greater in patients who were given the drug, increasing the death rate from 9% to 13%.

[Update on June 5] The Lancet retracted the paper on June 3. The statement said the authors of the study were “unable to complete an independent audit of the data underpinning their analysis” and could no long vouch for the veracity of their findings.

After The Lancet study came out, the French government reversed its decision to allow the prescription of hydroxychloroquine for coronavirus patients, and the country’s medical watchdog recommended “not to use hydroxychloroquine for the treatment of COVID-19” outside of clinical trials.

Raoult commented on the results of the study by downplaying the health risks caused by the treatment and called the publication “a bogus study made with big data.”

Raoult’s controversial paper included the results of 36 patients treated with two different regimens which both included hydroxychloroquine; there was also a control group of 16 patients.

Results showed that the six patients treated with a combination of hydroxychloroquine and azithromycin all recovered after six days, after which Raoult decided to stop the trial because of the successful results.

However, the results of six other patients who received the same treatment were not included in the results because of “early cessation of treatment.”

According to the reasons given, three of the patients had to stop treatment as they were transferred to intensive care, while one developed nausea, one decided to leave the hospital before the end of the treatment cycle, and one died.

In addition, the study offered no data on clinical outcomes. Overall, the trial’s small size, the non-randomized assignment of the treatment to patients and the various errors and flaws in the methodology attracted considerable criticism from international medical experts.

Questions have also been raised about the origins of the data used by The Lancet study, as reported by the Guardian. However, an Australian researcher quoted in the Guardian article indicated that even if the study proved to be problematic, the potentially severe and even deadly side effects of hydroxychloroquine if used inappropriately remained.

He emphasized that no “strong” study has demonstrated the effectiveness of the drug to treat COVID-19.