Study Critical of Hydroxychloroquine Withdrawn by Medical Journal

By Pat Anson, PNN Editor

One of the world’s most respected medical journals has issued a rare retraction, essentially disowning a controversial study published last month that claimed the use of hydroxychloroquine and chloroquine for treating COVID-19 had no benefit for hospitalized coronavirus patients.

The Lancet issued the retraction after receiving a letter from the study’s authors saying they were unable to complete an independent audit of the data underpinning their analysis. As a result, the authors concluded they “can no longer vouch for the veracity of the primary data sources.”

The study looked at data from nearly 15,000 patients with COVID-19 who received the antimalarial drugs hydroxychloroquine or chloroquine. They were compared to a control group of over 81,000 patients who did not take the drugs. The study included patients being treated at 671 hospitals in North America, Europe, Asia, Africa, South America and Australia.

The study concluded that chloroquine and hydroxychloroquine significantly increased the risk of death for COVID-19 patients, particularly when taken with an antibiotic.

However, soon after publication, critics began questioning the legitimacy of data used in the study, pointing to inconsistencies such as five Australian hospitals reporting more coronavirus deaths than had been found on the entire continent.

In a letter to The Lancet, study authors Mandeep Mehra, Frank Ruschitzka, and Amit Patel said they could not get full access to the data and could not conduct an independent peer-review of their own research:

“After publication of our Lancet Article, several concerns were raised with respect to the veracity of the data and analyses conducted by Surgisphere Corporation and its founder and our co-author, Sapan Desai, in our publication. We launched an independent third-party peer review of Surgisphere with the consent of Sapan Desai to evaluate the origination of the database elements, to confirm the completeness of the database, and to replicate the analyses presented in the paper.

Our independent peer reviewers informed us that Surgisphere would not transfer the full dataset, client contracts, and the full ISO audit report to their servers for analysis as such transfer would violate client agreements and confidentiality requirements. As such, our reviewers were not able to conduct an independent and private peer review and therefore notified us of their withdrawal from the peer-review process.

We always aspire to perform our research in accordance with the highest ethical and professional guidelines. We can never forget the responsibility we have as researchers to scrupulously ensure that we rely on data sources that adhere to our high standards. Based on this development, we can no longer vouch for the veracity of the primary data sources. Due to this unfortunate development, the authors request that the paper be retracted.

We all entered this collaboration to contribute in good faith and at a time of great need during the COVID-19 pandemic. We deeply apologise to you, the editors, and the journal readership for any embarrassment or inconvenience that this may have caused.”

The Lancet’s retraction is likely to lead to more claims and conspiracy theories that the coronavirus has been “politicized” by mainstream medicine and left-leaning media to embarrass President Trump.

In recent months, the president and conservative media have touted hydroxychloquine as a possible "game changer" in the treatment of COVID-19. Trump took the drug as a preventative treatment last month after two White House staff members tested positive for coronavirus. A statement from the president’s doctor yesterday indicated he suffered no ill effects.

“I’m not going to get hurt by it. It’s been around for 40 years,” Trump said last month. “For malaria, for lupus, for other things. I take it. Front-line workers take it. A lot of doctors take it."

Hydroxychloroquine is only approved for the treatment of autoimmune diseases such as lupus and rheumatoid arthritis. The FDA has warned against using hydroxychloroquine as a treatment for COVID-19 outside of a hospital or clinical study because of “serious and potentially life-threatening heart rhythm problems.”

The FDA's Adverse Events Reporting System lists over 10,000 reported cases involving hydroxychloroquine in the past decade, many of them serious or resulting in hospitalizations. Nearly 600 people have died since 2010, including 48 deaths so far this year.

A study published yesterday in The New England Journal of Medicine, found that hydroxychloroquine was no better than a placebo in preventing COVID-19 infections.

Prescriptions for Hydroxychloroquine Surge, But Drop for Hydrocodone

By Pat Anson, PNN Editor

Prescriptions for the antimalarial drugs hydroxychloroquine and chloroquine surged dramatically over the last few months, likely due to their off-label use for treating COVID-19, according to a new analysis published in JAMA. The study also found a significant decline in prescriptions for the opioid painkiller Vicodin and other hydrocodone/acetaminophen combinations.  

Researchers at Brigham and Women's Hospital studied prescription drug data from over 58,000 chain, independent and mail-order pharmacies in the U.S. from February 16 to April 25, and compared them to prescriptions over the same period in 2019.

Prescriptions for hydroxychloroquine and chloroquine spiked in mid-March – rising over 2,000 percent in one week -- soon after President Trump began touting the drugs as a possible treatment for the coronavirus. Brigham researchers estimate there were close to half a million additional prescriptions filled for hydroxychloroquine/chloroquine in 2020 compared to the year before.

SOURCE: JAMA

Hydroxychloroquine is only approved by the Food and Drug Administration to treat autoimmune diseases such as lupus and rheumatoid arthritis. Increased demand for the drug and government stockpiling soon led to spot shortages of hydroxychloroquine.

"There have been indications that hydroxychloroquine (HCQ) prescribing had increased and shortages had been reported, but this study puts a spotlight on the extent to which excess hydroxychloroquine/chloroquine prescriptions were filled nationally," said corresponding author Haider Warraich, MD, an associate physician in the Division of Cardiovascular Medicine at the Brigham.

"This analysis doesn't include patients who were prescribed HCQ in a hospital setting -- this means that patients could have been taking the drugs at home, without supervision or monitoring for side effects."

Last month President Trump took hydroxychloroquine for about two weeks with a doctor’s permission, even though the FDA warned that hydroxychloroquine should not be used as a treatment for COVID-19 outside of a hospital or clinical study because it could aggravate heart problems. The drug has been linked to at least 48 deaths in the U.S. so far this year, according to an FDA database.

On Sunday, the White House announced the U.S. supplied Brazil with 2 million doses of hydroxychloroquine. Brazil reported a record 33,274 new cases of the coronavirus over the weekend. Its death toll now ranks only below the United States, Britain and Italy.

Other Drugs Impacted by Pandemic

Brigham researchers say prescriptions for hydrocodone/acetaminophen fell by nearly 22 percent over the study period. There were also notable declines in prescriptions for the antibiotics amoxicillin and azithromycin, the blood pressure drug lisinopril, and the nerve drug gabapentin. Researchers said there are a variety of reasons why the drugs are being prescribed less often.

“The modest decline for most common long-term therapies after peak could represent reduced contact with prescribing clinicians, restricted access to pharmacies, pharmacist rationing, loss of insurance from unemployment, or replete supplies from early stockpiling,” researchers said. “Steep declines for amoxicillin and azithromycin appeared out of proportion to expected seasonal declines and could represent fewer outpatient prescriptions for upper respiratory tract infection symptoms.”

The pandemic appears to be taking a toll on the nation’s mental health. In the early stages of the outbreak, pharmacy benefit manager Express Scripts reported a surge in prescriptions for anti-anxiety medications such as Xanax and Valium, as well as antidepressants and anti-insomnia drugs.

A recent survey by the Kaiser Family Foundation found that nearly half of Americans said that they or a family member had cancelled or postponed medical care because of the pandemic. About one in every ten said the person’s medical condition worsened as a result of the delayed care.

Study Debunks Use of Hydroxychloroquine for COVID-19

By Pat Anson, PNN Editor

A large international study on the use of hydroxychloroquine and chloroquine for treating COVID-19 has found the antimalarial drugs offer no benefit for hospitalized coronavirus patients and appear to significantly raise the risk of death, particularly when taken with antibiotics.

The study, published in the peer-reviewed journal The Lancet, looked at data from nearly 15,000 patients with COVID-19 who received hydroxychloroquine or chloroquine, with or without the use of antibiotics. They were compared to a control group of over 81,000 patients who did not take the drugs. The study included patients being treated at 671 hospitals in North America, Europe, Asia, Africa, South America and Australia.

(Update: On June 4, The Lancet retracted this study after the authors said were unable to complete an independent audit of their research and concluded they “can no longer vouch for the veracity of the primary data sources.”)

“We found no evidence of benefit of hydroxychloroquine or chloroquine when used either alone or with a macrolide (antibiotic),” researchers said. “Our study included a large number of patients across multiple geographic regions and provides the most robust real-world evidence to date on the usefulness of these treatment regimens. Although observational studies cannot fully account for unmeasured confounding factors, our findings suggest not only an absence of therapeutic benefit but also potential harm.”

The study found that 9.3% of patients in the control group died in the hospital. Of those treated with chloroquine or hydroxychloroquine alone, 16.4% died. The outcomes were even worse for patients who used chloroquine with an antibiotic (22.2%) or hydroxychloroquine with an antibiotic (23.8%).

Researchers also found that serious cardiac arrhythmias, which cause the lower chamber of the heart to beat rapidly and irregularly, were more common in the groups that took hydroxychloroquine or chloroquine.

“This is the first large scale study to find statistically robust evidence that treatment with chloroquine or hydroxychloroquine does not benefit patients with COVID-19. Instead, our findings suggest it may be associated with an increased risk of serious heart problems and increased risk of death,” said lead author Mandeep Mehra, MD, Executive Director of the Brigham and Women’s Hospital Center for Advanced Heart Disease.

“Randomised clinical trials are essential to confirm any harms or benefits associated with these agents. In the meantime, we suggest these drugs should not be used as treatments for COVID-19 outside of clinical trials.”

President Trump disclosed this week that he has been taking hydroxychloroquine as a preventative treatment for COVID-19, even though there is only anecdotal evidence the drug may work against the virus. The president said he was prescribed the drug by his physician after two White House staff members were diagnosed with the virus. Trump said he would only take hydroxychloroquine for about two weeks.

The Food and Drug Administration has said hydroxychloroquine or chloroquine should not be used as frontline treatments for COVID-19 outside of hospitals and clinical trials.

The FDA has only approved chloroquine to treat malaria and hydroxychloquine as a treatment for lupus and rheumatoid arthritis. Both drugs have good safety profiles for those conditions.

Chloroquine and hydroxychloquine have been shown to have antiviral effects in laboratory tests, which has sparked interest in their use as potential treatments for COVID-19. Some countries have been stockpiling the drugs. In March, the FDA added hydroxychloquine and chloroquine to its list of drug shortages. Chloroquine was recently taken off the list.

“Several countries have advocated use of chloroquine and hydroxychloroquine, either alone or in combination, as potential treatments for COVID-19,” said co-author Frank Ruschitzka, MD, Director of the Heart Center at University Hospital Zurich.

“Justification for repurposing these medicines in this way is based on a small number of anecdotal experiences that suggest they may have beneficial effects for people infected with the SARS-CoV-2 virus. However, previous small-scale studies have failed to identify robust evidence of a benefit and larger, randomised controlled trials are not yet completed. However, we now know from our study that the chance that these medications improve outcomes in COVID-19 is quite low.”

In addition to their findings on chloroquine and hydroxychloroquine, researchers also noted that obesity, heart disease, diabetes and smoking raise the risk of death for hospitalized COVID-19 patients. Interestingly, patients being treated with statins or ACE inhibitors for high blood pressure had a lower risk of mortality, suggesting that medications that stabilize the cardiovascular system may be beneficial.

Controversy Grows Over Trump's Use of Hydroxychloroquine

By Pat Anson, PNN Editor

President Trump on Tuesday defended his use of hydroxychloroquine (Plaquenil) as a preventative treatment for COVID-19, even though there is only anecdotal evidence the drug may work against the virus and it may be harmful to some patients. Hydroxychloroquine has been linked to at least 48 deaths in the U.S. so far this year, according to an FDA database.

The president first disclosed his use of hydroxychloquine on Monday, claiming that White House physician Sean Conley said it was okay for him to take the drug.

“I asked him, ‘What do you think?’ He said, ‘Well, if you’d like it.’ I said, ‘Yeah, I’d like it. I’d like to take it,’” Trump said.

Dr. Conley confirmed that account in a statement.

“After numerous discussions (Trump) and I had regarding the evidence for and against the use of hydroxychloroquine, we concluded the potential benefit from treatment outweighed the relative risk," Conley said.

The Food and Drug Administration has only approved hydroxychloquine for the treatment of malaria, lupus and rheumatoid arthritis. However, nothing prevents a doctor from prescribing a drug "off-label" to treat another condition.

In recent months, Trump has touted hydroxychloquine as a possible "game changer" in the treatment of COVID-19. He said he started taking the drug as a preventative measure a week and a half ago, at about the same time two White House staff members tested positive for coronavirus.

“I’m not going to get hurt by it. It’s been around for 40 years,” Trump said. “For malaria, for lupus, for other things. I take it. Front-line workers take it. A lot of doctors take it."

Last month, the FDA warned against using hydroxychloroquine as a treatment for COVID-19 outside of a hospital or clinical study because of “serious and potentially life-threatening heart rhythm problems.” Patients with heart and kidney disease are especially at risk, the agency said.

The FDA's Adverse Events Reporting System lists over 10,000 reported cases involving hydroxychloroquine in the past decade, most of them serious, life threatening or resulting in hospitalizations. Nearly 600 people have died since 2010, including 48 deaths so far this year.

The number of adverse events involving hydroxychloroquine has soared in recent years, from less than a hundred cases in 2010 to over 4,500 in 2019

SOURCE: FDA ADVERSE EVENTS REPORTING SYSTEM

'Reckless Action'

"President Trump’s use of hydroxychloroquine to prevent Covid-19 infection without any clinical evidence of its utility is dangerous and will cause untoward toxicities, likely including death, in some people following his lead," Dr. Michael Polis, a fellow at the Infectious Diseases Society of America, told The New York Times.

"He needs to be strongly criticized by the medical community for this reckless action."

A recent study funded by the National Institutes of Health looked at patients at VA hospitals who were given hydroxychloroquine to treat COVID-19. They concluded the drug was ineffective and raised the risk of patients dying.

“In this study, we found no evidence that use of hydroxychloroquine, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with Covid-19. An association of increased overall mortality was identified in patients treated with hydroxychloroquine alone. These findings highlight the importance of awaiting the results of ongoing prospective, randomized, controlled studies before widespread adoption of these drugs,” researchers found.

Trump dismissed the research as a "phony study" by his political enemies.

“There was a false study done where they gave it to very sick people, extremely sick people, people that were ready to die,” he said Tuesday. “It was given by obviously not friends of the administration.” 

Several patients who are prescribed hydroxychloroquine for rheumatoid arthritis or lupus have told PNN they are worried about possible shortages due to Trump's touting of the drug.

“I have been on hydroxychloroquine for five years for my autoimmune disease and had never had an issue getting the medication until the virus. In March, I had to check 3 different pharmacies before I found one that had any in stock,” one patient said. “My usual pharmacy said that not a single one of their local chains had it in stock and that they were back-ordered. The pharmacy that did have it, was only able to do a partial refill.” 

“I am currently on Plaquenil for lupus and having Trump declare it is the cure for COVID-19 has limited my access to my medication. I am worried there won’t be enough,” another patient said.  

“I am in a horrible RA flare at this moment. I have no doubt that the stress of being concerned about getting my needed medication has helped to bring this flare on," said another. "I am really concerned about being able to get my much-needed hydroxychloroquine. There is no reasonable explanation for drug shortages in this country other than ignorance.” 

Former Vice-President Joe Biden said Trump was “absolutely irresponsible” for taking hydroxychloroquine, which could encourage others to take it to prevent COVID-19 infections.

"It's like saying maybe if you injected Clorox into your blood, maybe it'll cure you. What is he doing? What in God's name is he doing?" said the presumptive Democratic 2020 nominee. “Look, this is absolutely irresponsible. There's no serious medical personnel out there saying to use that drug. It's counterproductive. It's not going to help."

Prescriptions for Anti-Anxiety Meds Surge Due to Coronavirus

By Pat Anson, PNN Editor

After weeks of isolation and the uncertainty of dealing with the coronavirus outbreak, it’s no surprise that many Americans are feeling depressed, anxious and not sleeping well.

“The trauma of a loved one being in the ICU, alone and not knowing if you'll ever see them again is horrific. It also adds to personal health anxiety,” one patient told us in our recent survey on the coronavirus.

“This is an extremely scary time. My anxiety is through the roof for many reasons,” another patient said. “I’m extremely worried I won’t pull through this or my husband and daughter won’t pull through this if they contract the virus! We’ve already lost my aunt and best friend both to coronavirus. One was 34, the other 62.”

“I feel more depressed and find my anxiety level is up. I worry most about getting my medications,” said another. 

New research from pharmacy benefit manager Express Scripts shows the stress is having a significant impact on the nation’s mental health. 

From February 16 to March 15, the number of prescriptions filled in the U.S. for anti-anxiety medications rose by a third (34.1%), along with antidepressants (18.6%) and anti-insomnia drugs (14.8%).

More than three quarters (78%) of the prescriptions were new – meaning they weren’t refills.

“As COVID-19 began to significantly impact the U.S., we observed an increase in the use of prescription drugs that treat mental health conditions, particularly commonly used anti-anxiety medications known as benzodiazepines,” Express Script said in a new report called “America’s State of Mind.”

SOURCE: EXPRESS SCRIPTS

The increased use of benzodiazepines such as Xanax and Valium is striking, because the drugs had fallen out of favor in recent years in large part due to fears that they raise the risk of respiratory depression and overdose when used with opioids.

Prescriptions for anti-anxiety medication rose more for women (39.6%) than men (22.7%) between February 16 and March 15, according to Express Scripts.

Hydroxychloroquine Shortages

Some patients with rheumatoid arthritis, lupus and other autoimmune diseases say their stress levels are up because they worry about losing access hydroxychloroquine (Plaquenil), a drug repeatedly touted by President Trump as a possible treatment for COVID-19.

“I am currently on Plaquenil for lupus and having Trump declare it is the cure for COVID-19 has limited my access to my medication. I am worried there won’t be enough,” a patient said.  

“No chronic pain patient should have to sit and have the anxiety from concerns on being able to have access to medication needed to treat their illness,” a rheumatoid arthritis sufferer said. “I am in a horrible RA flare at this moment. I have no doubt that the stress of being concerned about getting my needed medication has helped to bring this flare on. I am really concerned about being able to get my much-needed hydroxychloroquine. There is no reasonable explanation for drug shortages in this country other than ignorance.” 

“I have been on hydroxychloroquine for five years for my autoimmune disease and had never had an issue getting the medication until the virus. In March, I had to check 3 different pharmacies before I found one that had any in stock,” another patient said. “My usual pharmacy said that not a single one of their local chains had it in stock and that they were back-ordered. The pharmacy that did have it, was only able to do a partial refill.” 

When she told her doctor what happened, he agreed to write a 3-month prescription for hydroxychloroquine to make sure she’d have an adequate supply. Her insurance company, however, refused to pay for more than a month’s supply. 

“Not only do I worry about running out of medication, but each time I have to go to the pharmacy for various medications, I am exposing myself to others which could cause me to get the virus. As someone who has a compromised immune system, I want to leave the house as little as possible to avoid exposure,” the patient said.

On Friday, the Food and Drug Administration warned against using hydroxychloroquine or chloroquine as a treatment for COVID-19 outside a hospital or clinical study because of “serious and potentially life-threatening heart rhythm problems.” Patients with heart and kidney disease are especially at risk.

The FDA said patients taking the drugs for approved reasons, including malaria and autoimmune conditions like lupus, should continue taking them as prescribed.

Osteoarthritis Drug Works No Better Than Placebo

By Pat Anson, Editor

Hydroxychloroquine (Plaquenil) is a medication commonly used to treat rheumatoid arthritis, lupus and other autoimmune diseases. It’s also being prescribed off-label to treat inflammation and pain caused by hand osteoarthritis, a joint condition that affects nearly a third of patients over the age of 70.

But in a new study published in the Annals of Internal Medicine, British researchers reported that hydroxychloroquine is no more effective than a placebo in relieving moderate to severe pain caused by hand osteoarthritis.

Researchers at the Leeds Institute of Rheumatic and Musculoskeletal Medicine and the Leeds Biomedical Research Centre randomly assigned 248 patients with radiographic hand osteoarthritis to either hydroxychloroquine (200 to 400 mg) or placebo for a year.

Most of the patients had symptoms of hand osteoarthritis for about 5 years, and their average pain level was 7 out of 10.

After 3, 6 and 12 months, there were no significant differences in treatment outcomes between the hydroxychloroquine and placebo groups.

“We found that HCQ (hydroxychloroquine) was not a more effective analgesic than placebo when added to usual care in persons with moderate to severe hand osteoarthritis,” researchers reported. “Background analgesic use did not differ between groups, and baseline inflammation and structural damage did not affect response to HCQ. The study therefore presents no evidence that HCQ should be considered within the management plan of patients with hand osteoarthritis.”

Two doctors who reviewed the study say more research is needed to find drugs that can treat the inflammation caused by hand osteoarthritis, a condition for which there are no effective therapies.

“The negative findings in this carefully done trial beg the question of what went awry. Did HCQ fail to reduce inflammation, or did reduced inflammation not translate to pain relief?” wrote Elena Losina, PhD, and Jefferey Katz, MD in an editorial.

“Although HCQ is safe, it is also a weak anti-inflammatory agent seldom used in contemporary practice as a solo disease-modifying therapy for rheumatoid arthritis and other inflammatory conditions. Further therapeutic studies of the effects of anti-inflammatory therapy on nodal hand osteoarthritis will need to use more potent agents or compounds developed to more specifically target the inflammatory pathways documented in this condition.”