Infectious Disease

Medicine repurposed to deal with COVID-19 various primarily based on “must do one thing”.

February 06, 2021

3 min read

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Kadri does not report any relevant financial information. In the study you will find all relevant financial information from all other authors.

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A study evaluating the inpatient use of drugs to treat patients with COVID-19, including hydroxychloroquine, corticosteroids, and tocilizumab, showed rapid prescription changes in response to emerging reports.

“At the start of the pandemic, doctors were eager to help their sick COVID-19 patients but had almost no evidence to guide their actions.” Sameer S. Kadri, MD, MS, FIDSA, Healio said, director of clinical epidemiology in the intensive care unit at the NIH.

COVID data

After evaluating the inpatient use of medication to treat COVID-19, researchers identified rapid prescription changes in response to emerging reports of safety concerns.
Photo credit: Adobe Stock

As a result, drugs used for other conditions – for example, hydroxychloroquine for rheumatological conditions, azithromycin for bacterial infections, and corticosteroids and tocilizumab for their anti-inflammatory and immunomodulatory effects – have been used for COVID-19 based on questionable signals from in in vitro studies , Extrapolations from analogous clinical scenarios such as flu, media exposure, emergency approval and peer pressure, ”said Kadri.

“The need to do something to make patients worse led to a great deal of empiricism in treatment. Instead of waiting for the results of large randomized clinical trials (RCTs), out of sheer desperation, doctors decided to use these drugs anyway, ”he said.

To understand how and when these reused drugs were being used in hospitals for COVID-19 – and how, when, and why the application was changed – Kadri and colleagues examined the patterns of off-label drug use in patients with COVID -19 were hospitalized from 318 US hospitals between March and May 2020.

A total of 35,259 inpatients with COVID-19 coding were admitted to these hospitals, of whom 5,950 (16.9%) received mechanical ventilation. According to the study, drug use varied between hospitals, although a total of 16,164 (45.8%) patients received hydroxychloroquine in 302 hospitals, 18,164 (51.5%) received azithromycin in 311 hospitals, and 7,570 (21.5%) corticosteroids in 299 hospitals and 2,005 (5.7%) received tocilizumab in 188 hospitals.

They found that use of hydroxychloroquine and azithromycin was higher in mechanically ventilated patients than in non-ventilated patients, although the relative difference between corticosteroids and tocilizumab was much greater. Compared to non-ventilated patients with COVID-19, mechanically ventilated patients with COVID-19 were three times more likely to receive corticosteroids (22% versus 61.8%) and six times more likely to receive tocilizumab (3% versus 18.9%). The study also showed that corticosteroid use in ventilated patients with COVID-19 (62%) was similar to use in mechanically ventilated influenza patients prior to COVID-19 (68%).

Another evaluation of the reused drugs found that inpatient use of hydroxychloroquine decreased by 80% when reports of possible cardiac arrhythmias related to the occurrence were published, while corticosteroids and tocilizumab were initiated two days earlier in May compared to March 2020. In addition, two-thirds of ventilated patients with COVID-19 were already receiving corticosteroids from March to May, similar to patients on mechanical ventilation before COVID.

According to Kadri, corticosteroids “save lives” in COVID-19, especially in patients who require oxygen and mechanical ventilation. He said hydroxychloroquine is not helpful for patients with COVID-19 – a fact that has been “pounded” by several RCTs.

Kadri added that tocilizumab’s effectiveness remains unclear, with mixed signals of potential benefit and lack of benefit across RCTs and persistent concerns about the risk of secondary infections due to its immunosuppressive effects, while secondary infection risk has been a problem with long corticosteroids for years.

According to Kadri, the “sweet spot” with regard to the duration of corticosteroid therapy, which offers an optimal and lasting effect in COVID-19 respiratory failure and at the same time minimizes the risk of secondary infections, is still being worked out.

“While our results are historic, they offer a cautionary story and important lessons for the future,” said Kadri. “In scenarios like deadly viral pandemics, routine care can easily be influenced by sub-optimal evidence, mass media, anecdotal experience, and the need to do something. Fortunately, inpatient doctors seem to be rapidly changing prescribing behavior in response to signals of harm. “

Going forward, multiple stakeholders, including clinicians, trialists, regulators, and guideline reviewers, will need to weigh earlier adoption of treatment candidates against the potential for direct harm, which is often unknown at the time of adoption, Kadri said. Furthermore, he said the urge to get therapies out quickly before reviewing them in RCTs can cause fatal delays in the systematic generation of definitive evidence, as is the case with convalescent plasma.

“Ongoing assessment of the real world use of candidate therapies for COVID-19 can tell us whether the guidelines for the real world are being followed,” Kadri said. “You can also spot changes in common patterns of care that are important to incorporate into future RCTs that will be used to compare novel COVID-19 therapies to a real standard of care.”

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