Safety and Efficacy of Remdesivir in the Treatment of Covid-19: A Rapid Review of Available Evidence

• Main Authors: Zahra Gharibnaseri, Alireza Olyaeemanesh
• Format: Article
• Language: English
• Published: Tehran University of Medical Sciences 2020-10-01
• Series: Health Technology Assessment in Action
• Online Access: https://htainaction.tums.ac.ir/index.php/hta/article/view/32

Abstract Introduction: Remdesivir is an antiviral drug manufactured by Gilead Sciences, Inc., which in-vitro studies have shown positive results in controlling coronavirus infection. Therefore, this drug has been proposed as a possible effective option in the treatment of Covid-19, and although it has not yet received any approval from the countries’ pharmaceutical authorities and has not passed the first and second phases of clinical trials, it is prescribed on a trial basis for patients with Covid-19. Researchers in more than 20 countries are monitoring the results of using the drug in a clinical setting to prescribe Remdesivir to larger populations if patients respond positively. Materials and methods: This article is a rapid review of health technology assessment studies that collects related articles by searching medical databases and tries to create a policy guide for Remdesivir through their analysis. The search was conducted on the MEDLINE and Cochrane Library database using keywords including drug name and disease name. The titles and abstracts of the articles were reviewed, and the studies were selected based on the inclusion and exclusion criteria. In addition, the list of related study references were reviewed and added to the study list in cases where a new related article was found. Inclusion criteria included: studies that examined the safety and efficacy of Remdesivir in the population of patients with Covid-19, studies in Persian or English, and all types of studies. The search of the mentioned databases was carried out on April 21, 2020. In order to identify ongoing clinical trials in Iran and some countries, clinical trial registration systems were also searched.   Results: After matching the inclusion and exclusion criteria on the search results, a cohort study was found that declared positive response of Remdesivir efficacy in compassionate use. The study has emphasized that due to design limitations, the results obtained on the efficacy of Remdesivir were not reliable, and only through randomized clinical trials sufficient confidence can be achieved. Among other search results, there were two studies on patients receiving this drug. There is also a letter to the editor that introduces Remdesivir as a good possible treatment for Covid-19. Most of the studies were review studies (25 studies), most of which reported on the course of treatment for Covid-19 disease and devoted part to Remdesivir position in the treatment of this disease. None of these studies were systematic reviews. Also, in search of clinical trial registration systems, 15 phases two and three clinical trials were found, as well as a retrospective observation study that assessed Remdesivir safety and efficacy. Of the 15 trials, 13 were in the patient recruitment phase, one was terminated early, and the other was suspended. The results of the terminated trial have been published in the Lancet journal . This study, which was the first clinical trial to be randomized and controlled with placebo, 237 patients were divided into two groups: placebo and Remdesivir groups. The results obtained on the 28th day of the trial show that; although the rate of recovery in the Remdesivir group was numerically better than the placebo group, this difference was not statistically significant and studies on a higher number of patients were needed to prove the significance of this difference. On the other hand, this drug has not been shown to reduce viral load in samples taken from the upper respiratory tract. This study also showed that the incidence of side effects in the group receiving the drug was higher than the control group. Twelve percent of patients in the Remdesivir group had to discontinue the drug due to serious side effects, while in the control group, it occurred in only 5 percent of patients. Despite the publication of the results of the trial and the ambiguity in the results of other clinical trials, the US Food and Drug Administration (FDA) issued a letter on May 1, 2020, in which it authorized Gilead to distribute its drug under an emergency use authorization (EUA). Under this license, Remdesivir is prescribed only for hospitalized patients with severe Covid-19, including those with SpO2≤94% and requiring supplemental oxygen or mechanical respiratory support, under the supervision of health care professionals and under strict EUA conditions. Conclusion: Based on the results of this study, it was found that the evidence for certain decision about the safety and efficacy of Remdesivir in the treatment of Covid-19 is very limited, and only if clinical trials that have begun extensively in multiple countries are completed, a decision can be made to approve or reject the prescription. Due to the ambiguity in the efficacy of Remdesivir, its prescription in patients with Covid-19 has so far been limited to clinical trials, compassionate use, or emergency use.