Desperate pleas for Remdesivir have filled up social media but we need to ask: when do we really need the anti-viral drug? And more importantly, is it effective against COVID?
The World Health Organization’s Chief Scientist Dr Soumya Swaminathan said,
"“Based on available evidence, there were about five trials...which essentially showed that Remdesivir given to hospitalised patients, didn’t reduce mortality, it didn’t reduce the duration of hospitalisation and it didn’t affect the progression of the disease.”" -
In conversation with India Today TV on Monday, 13 April, Dr Swaminathan and WHO Technical Lead on COVID, Dr Maria Van Kerkhove, said that Remdesivir did not stop mortality or reduce the need for mechanical ventilation among hospitalised COVID-19 patients.
As far back as 15 October 2020, the WHO released the results from their Solidarity Therapeutics Trial and found that Gilead Sciences Inc’s Remdesivir had either no or very little effect on COVID-19 patient’s chances of survival or length of hospital stay.
Who Does Remdesivir Work For?
First, we need to ask “what is the evidence for its effectiveness?” says Dr Sumit Ray HOD, Critical Care Medicine, Holy Family, Delhi.
Is Remdesivir the miracle drug it is touted to be? Does it work?
“The evidence for this is mixed. Some positive studies say it shortens the length of stay in hospital, but doesn’t reduce mortality and patients going on ventilators. Even in the WHO Solidarity Trial, it did not show a positive result, only in some subgroup analysis was it shown to be effective in some patients who were on low dosage of oxygen in terms of shortening hospital stay.”
"“If the patient is not on oxygen or requiring higher oxygen support, they do not benefit even in the length of the stay. It only works in a small subset of patients.”" - Dr Sumit Ray, HOD, Critical Care Medicine, Holy Family, Delhi.
As per a The Times of India article, Pune doctors told their state COVID-19 task force that is very capable of saving patients without Remdesivir. They added that it “only reduces hospital stay by two days at the most.”
Who is the ideal Remdesivir patient?
“As per the clinical trials on those with mild to moderate illness, it was found that hospitalised patients who are requiring minimal amounts of oxygen – those in the ward – would benefit in terms of reduced hospital stay. Of course, this is a statistical number, so not everyone who fits this profile would benefit. If they start worsening, if lung damage worsens, then it is not effective.”
"“It’s not a miracle drug and its real benefit is questionable. Unfortunately, for most viral illnesses, there is no one drug – you do symptomatic treatment.” " - Dr Sumit Ray, HOD, Critical Care Medicine, Holy Family, Delhi
Infectious disease expert, Dr Parikshit Prayag, told TOI that, "Remdesivir only shortens duration of illness in carefully selected patients – like those with early hypoxia (low blood oxygen saturation) or high-grade fever with lower respiratory involvement. This impression, that it is life-saving, makes a patient desperate and anxious when she or he does not get it. Unfortunately, many people are being unnecessarily put on the drug."
What should we consider before administering Remdesivir?
“The timing is important, meaning the drug has to be given early when the virus is in the body. After day 9, it is rare that the live virus is in the body (instead, we treat the symptoms). In severe cases, it stays till maximum 12 days. And the severity of the disease is important to consider too,” says Dr Ray.
Is it a PR haze we are in?
“In part. It has been publicised and when there is mass panic, it is seen as a miracle drug. We need to look at the evidence. Similar for treatments like plasma therapy – which is also being requested despite ICMR’s study explaining that it is ineffective. But I know that people in this time want to try for everything they can – even if the evidence for effectiveness is not as strong,” says Dr Ray.
There is no one treatment but various interventions, based on the symptoms, that are being used. So often, a mix of oxygen therapy, blood thinners, steroids and Remdesivir is effective.
But during the panic of the second wave, relatives of patients are understandably worried. “It’s complex – on one hand, relatives insist on the drug and blame us if we don’t administer it. On the other, doctors often make the families run to procure it, thereby putting the onus on the family,” adds Dr Ray.
"“There was an article that said Remdesivir is a drug in search of a disease. It failed in Ebola, it failed in SARS and MERS. So, we were skeptical.”" - Dr Sumit Ray HOD, Critical Care Medicine, Holy Family Hospital, Delhi.
He adds that we need to focus on our public health messaging to calm the panic over drugs and “control the numbers urgently. Our hospitals can deal with the cases if the numbers are controlled.”
What Is India Doing?
Still, Maharashtra Health Minister Rajesh Tope has asked the Centre to allow the exporters of Remdesivir to supply to the state.
In a press conference on Friday, 16 April, Union Health Minister Harsh Vardhan said,
"“Companies manufacturing COVID-19 drug Remdesivir have been asked to ramp up production. I assure you that strict action will be taken against those who are involved in black marketing of the drug and other malpractices.”" - Union Health Minister Harsh VardhanUnderstanding the Basics
Let’s go back to the basics. What is Remdesivir and how was it supposed to help?
Remdesivir is an antiviral drug developed by American pharmaceutical giant Gilead Sciences. It was made to treat Hepatitis C and respiratory syncytial viruses over a decade ago, but it never got marketing approval.
Antivirals are drugs used for treating viral infections.
COVID-19 brought the drug back into the picture – and US President Trump offered Remdesivir to UK Prime Minister Boris Johnson, despite no clinical evidence that it worked for COVID-19.
Gilead, too, did not claim it worked, but it got thrust into the limelight as a potentially promising drug. Soon in April, the New England Journal of Medicine published a study where out of 61 patients who were hospitalised with COVID-19, 53 were given the drug and 68 percent improved while 13 percent died. However, they were not able to say this was due to the drug as there was no control group. It is important to note that Gilead employees co-authored the paper. “This presents a huge conflict of interest,” says Dr Ray.
Remdesivir and COVID-19
COVID-19 has 2 phases:
Viremia phase: where the virus is in the body
Acute phase where the immune response creates an issue
In an earlier FIT article, Dr Ray explained, “The role of steroids is usually when our immune response is causing a problem, and here those on oxygen and ventilators benefit the most,” says Dr Ray.
“Because steroids are so successful, everyone is prescribing steroids the day COVID-19 is detected and that is actually causing a big problem. It is prolonging the viremia and suppressing the immune response when at that phase, it is necessary. The immune response is a necessary evil, and we need a balanced one for COVID-19 – one that attacks the virus well but not our body. ”
Now, if steroids are needed, doctors were administering Remdesivir. “But given the studies, the role of Remdesivir becomes questionable.”
"“COVID-19 is a fast-replicating, respiratory virus – unlike HIV, Hepatitis B or C which are much slower viruses. Antivirals work in slower replicating viruses because the build-up takes time so you can block that by antivirals. But in faster replicating viruses, the ideal time to give the antiviral is before the symptoms even start and before the virus starts rapidly replicating – if you can tell the patient has the infection by then.”" - Dr Sumit Ray HOD, Critical Care Medicine, Holy Family Hospital, Delhi.
He adds that you will not need this for “90 percent of patients". Hypothetically, if you could detect that someone has the viral infection without symptoms, that is the best time for the antiviral to be given for it to work. “Once the virus starts replicating there is not much the antiviral can do,” adds Dr Ray.
This is no mean feat – how can we determine who has the virus before symptoms persist? “This has always been the chicken and egg question with antivirals for respiratory illnesses.”
This happens in general with all antivirals, but focusing on Remdesivir and COVID-19, Dr Ray said that we need to examine the results from Solidarity Trial and the Adaptive COVID-19 Treatment Trial (ACCT1), which was a large trial in the UK and Europe. Now the ACCT1 trial showed a reduction in the length of hospital stay but it is important to analyse the subgroups of patients from the large trial.
"“The positive result that came in the ACCT1 trial was predominately because it seems to have worked in patients who got Remdesivir early and needed low oxygen. So those who did not get oxygen also did not benefit, those who got very high oxygen (ie, they needed more oxygen support) or ventilators, which means they had a severe disease, also did not benefit.”" - Dr Sumit Ray
So like it was said before, the timing of administering the drug and the severity of the infection are crucial determinants.
"“On the other hand, if the patient had a mild disease that did not require oxygen, they were not benefited because anyway the person would improve on their own – and therefore, Remdesivir would not show any difference in the outcomes.”" - Dr Sumit Ray
Therefore, from the subgroup analysis from the ACCT1 trial, it’s clear that if at all anyone benefited, it was those patients on low oxygen. Dr Ray added that among the subgroup, racially and geographically, it was only beneficial to white people from North America – not in Europeans, Asians or Black people. “So its role is questionable,” adds Dr Ray.
However, in the Solidarity Trial, no one benefited from any subgroup.
“Like in most respiratory diseases, most antivirals do not seem to have any benefit. Usually, the focus on those patients who have a severe disease is ICU care, oxygen etc,” says Dr Ray.
(This story was first published in FIT and has been republished with permission.)
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