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Drugs That Work on Corona
Recent information from China (from here) suggested that drugs for rheumatoid arthritis worked a treat on the virus. People on death’s door got up and walked away a few days later. China’s willing to experiment on people. The theory was that the primary danger isn’t the virus, but the response. [Supporting data here, here, and here.]
(I’ll bet you haven’t heard that anywhere.)
By suppressing the immune response, the threat was lifted.
This might be why children are safe. Their immune response is relatively weaker than their organs. In the elderly, their immune response is relatively stronger than their organs. Same goes for smokers.
Okay. This is a data point.
So, a US company that makes a leading drug for rheumatoid arthritis, which is fundamentally an auto-immune problem. They’ve decided to start testing it. They laid out their emergency timeline. Two weeks to start the test. And then a few months to gather data. And then they can use the drug.
Why not accept the Chinese data?
Well, it wasn’t controlled and it wasn’t double-blind so it isn’t statistically valid. In addition, the Chinese data overall has proven to be highly suspect.
All of this is true.
But this drug company plans to take a few months to do their testing. In a few months, the whole situation will probably be over. If the virus is bad it will have run over people and economies alike.
Clinicians on the front lines already have a good idea of what a normal process looks like. They can assess those at a very high likelihood of dying. And they can see abnormal recoveries. They don’t need a double-blind study to assess whether a drug is working in an emergent situation.
This drug is already on the market. It is already reasonably safe for generally healthy older people. So, forget the traditional study. Provide the drug, no double-blind, to the sickest patients. Compare their recovery to data prior to the drug – even anecdotally. Assess how it looks in the space of a week or two.
Forget the stupid regulations.
Published in General
Makes sense to me! They also ought to track this kind of testing to see the pluses and minuses; maybe it will shine a light on the ridiculous limitations we’ve set on the drug industry and how they’ve put people at risk.
And the liability if the drug has other effects that are not salutary? Who will that fall on?
Do the test. You will have to test it on actual COVID19 cases any way so even the testing will have a benefit on fighting the disease. Plus the virus wont go away. We may get past the initial hump in a few months but we will have cases for years to come.
Do things right.
Perhaps this might fall under right-to-try guidlines.
I saw somewhere that an AIDS drug being developed in Norway has had a 100% cure rate for those with the COVID -19. It apparently is only weeks away from launch. Sorry I don’t know where I saw the article or have more details.
That’s very interesting. However…
The drugs to which you refer are immuno-suppressants. Suppressing someone’s immune system while they are fighting an infection is not necessarily wrong (we give such people other immuno-suppressants, like steroids, all the time), but it should be done cautiously.
It is true that our immune response to an infection can be worse than the infection itself. But are you going to bet someone’s life on that speculation in a particular case? Man, I don’t know. Remember that a major risk of these drugs is tuberculosis and other respiratory infections – the labeling warns doctors that respiratory infections could be much more severe in presence of these drugs.
The mechanism you propose is plausible, but we really do need research.
If someone with Coronavirus wants to try this, I suppose that should be the choice of the patient. But there are a lot of things in medicine that seem like they ought to work, that simply don’t. So careful, here…
I’m not scientific, but this makes sense to me. But is that because I am desperate to make sense of this, and this theory fits my point of view?
I guess that is what a theory is. And there is risk in going with a theory.
iWe,
This is what the “right to try” is all about. You’ve got somebody already in ICU with a more than 50% likelihood that they are only getting out to go to the morgue then it’s time to try.
Go for it!
Regards,
Jim
Whether this is true medically will be discovered in due course. However, it is clearly true of the economic damage that is being done by the current panic in the stock markets.
If there’s one thing I’ve learned in business it’s this:
When you have a procedure in place, do not change it on a whim just to try to provide better service for a customer. This almost always results in providing worse service.
The customer might not know why you have the procedure, and you have probably forgotten yourself, but it is there in order to avoid a number of problems that no longer exist precisely because the procedure was put into place.
Procedures exist because of the bigger picture. The bigger picture tends to be forgotten when dealing with an individual need.
Also, apart from the ethical implications of “do no harm,” there are practical considerations for the drug companies. In a world where lawsuit-happy families view drug companies as a source of extra cash, there is no reason for a company to rush its products onto the scene. (Someone might say, “Well people shouldn’t be able to use the courts this way,” but they may as well say that we should live in a world where drinking from a bottle can shrink you to the size of a white rabbit.)
So should we just “accept the Chinese data” about this drug?
Sure. Accept it. And then verify it.
But don’t trust it. I don’t trust China’s stats on the virus or what their motives might be regarding its containment or spread.
If I had an older relative with this illness, I would certainly militate to try this off-label use.
Link.
Could an arthritis medication show promise as a treatment for the symptoms related to the coronavirus? That’s what Regeneron and Sanofi intend to find out.
The longtime developmental partners are aiming to see if Kevzara, a treatment for rheumatoid arthritis, could be effective against symptoms related to COVID-19. Regeneron Chief Scientific Officer George Yancopoulos told The Wall Street Journal if Kevzara could ease damage to the lungs and respiratory system caused by the body’s overreaction to COVID-19. Kevzara would not treat the underlying virus, just the immune system responses. Yancopoulos said the companies hope to have a trial “up and running” over the next several weeks or months in order to have data.
Researchers are turning to multiple drugs on the market as there are yet no approved treatments or vaccines for the novel coronavirus. In China, researchers have been using Roche’s Actemra, a drug similar to Kevzara, to help a small group of patients with severe or critical Covid-19 disease recover, the Journal reported. Pointing to the reports of that treatment option, Yancopoulos said several patients who received the Roche treatment “got out of death’s bed and walked out of the hospital.” Still, in his interview with the Journal, Yancopoulos was cautious because the work done in China was with a small group of patients and did not have controls, nor did it have defined parameters for success.
Both rheumatoid arthritis drugs are inhibitors of interleukin-6 (IL-6). The IL-6 protein triggers the body’s immune and inflammatory response to fight infections. However, if the immune system overreacts, healthy tissue and organs can be attacked, which seems to be the case with some coronavirus patients. Naimish Patel, Sanofi’s head of global development for immunology and inflammation, told the Journal that in some cases, the coronavirus is causing an acceleration of immune responses, which have attacked and damaged the lungs. By inhibiting IL-6, Patel said it could keep the body from attacking itself.
“Even though the virus is diminishing, it’s sending signals to the immune system to keep attacking,” Patel told the Journal. “If there’s too much inflammation, you end up killing cells that aren’t infected and leading to more damage than you really need.”
“I’m from the government and I’m here to help you.”“I’m from the government and I’m here to
helpinject you.”The reason methods like controlled trials were developed is to eliminate bias and control our tendency to fool ourselves into thinking things that don’t work are effective, which is pronounced and severe at times like this.
We have to be sure the claims are true.
To what end?
Do the math. What level (percentage) of certainty traded against the costs of a given drug yields a net positive result?
Assume a given drug, like Kevzara, costs $3k a treatment. Balance that cost for at-risk patients with coronavirus against crippling the business of MOST businesses.
What percentage chance of success does it need to have to “succeed” justifies going ahead without certainty?
If there’s a significant number of arthritis patients out there who are taking Kevzara already, you could have a “no-trial trial” by just counting the number of old people who come down with the Wuhan virus while taking that drug. If a lot of them recover or never have severe symptoms, that’s a huge data point.
I agree.
Remdesivir has already proven to work in one case and is undergoing a study for efficacy and side effects. I the NEJM case described, it resolved all symptoms and clinical findings in 24 hours. Chloroquine is also reported to be effective, It is an old malaria drug in use since WWII.
https://www.nejm.org/doi/full/10.1056/NEJMoa2001191
Given the radiographic findings, the decision to administer oxygen supplementation, the patient’s ongoing fevers, the persistent positive 2019-nCoV RNA at multiple sites, and published reports of the development of severe pneumonia3,4 at a period consistent with the development of radiographic pneumonia in this patient, clinicians pursued compassionate use of an investigational antiviral therapy. Treatment with intravenous remdesivir (a novel nucleotide analogue prodrug in development10,11) was initiated on the evening of day 7, and no adverse events were observed in association with the infusion. Vancomycin was discontinued on the evening of day 7, and cefepime was discontinued on the following day, after serial negative procalcitonin levels and negative nasal PCR testing for methicillin-resistant Staphylococcus aureus.
On hospital day 8 (illness day 12), the patient’s clinical condition improved. Supplemental oxygen was discontinued, and his oxygen saturation values improved to 94 to 96% while he was breathing ambient air. The previous bilateral lower-lobe rales were no longer present.
There are 4500 doses for the clinical trial and 90,000 doses have been ordered.
I presume there is a sterile, technical definition for that term.
iWe,
I think the last argument you should make is a broad general economic analysis. Nobody who has other options should be rolling the dice with unproven drugs. However unproven the drug might be, if the illness is extremely well documented and the patient has run out of options and faces a high probability of death then there is no reason to withhold the option of trying an unproven drug. This is usually done in a controlled setting where a phase 1 test has already been done usually on less than 100 patients. The phase 2 test that is normally about 500-1000 patients is opened up to those that wish to be included in the study because their other options are so poor and their prognosis so bleak.
I emphasize that what I just described is not “open season” to wildly try anything on anyone. The phase 1 test is usually conducted by a highly experienced physician in the treatment of the disease with a stellar reputation. Being included in the phase 2 test is strictly optional with the patient being fully informed of both the upside and downside possibilities of the untested drug. They should also be fully informed of the possibilities resulting from doing nothing.
Regards,
Jim
IIUC there are also some protease inhibitors showing promise and they’re relatively safe drugs.
It was not yet approved by the FDA.
If I recall, most of the anti-RA immunosuppressants work against TNF-beta, or is my recollection flawed? I’m not sure how that affects viruses. General note (not directed at Dr Bastiat)- the anti-AIDS drugs make sense because many of them prevent virus replication (in the case of AIDS, a retrovirus), so you would not be surprised tosee some other collateral antivirus effect.
iWe, you’re a very smart man, but not a pharmacologist. (My neighbor tells me it’s the pharmacologists that really know how drugs work, not the doctors.)
I think this is far more complex than you appear to think it is. If it were so easy to cure someone, I think doctors would be falling all over themselves to test and implement. Do you really trust rumors of cures from Chinese medicine? Remember they were allegedly jailing or otherwise gagging doctors who wanted to report the disease. I’m not ready to abandon our system on that basis.
Appeals to authority are not arguments either.
I can read the papers the same as anyone else. But most of medicine is not pharmacological theory – it is founded in trial and error. That is why we HAVE tests and protocols!
Many drugs are still not understood (Aspirin being a famous example). We use them anyway.
Time will tell. Given that the immune system is what kills a person, it is not crazy that suppressing that system can help someone heal. We have lots of precedent for this approach.
Doctors are well trained that if they expose themselves to a lawsuit, their lives are over. This is why most drugs are used off-label today! Doctors will only use something that is “approved” (or they lose their licenses). And at times like these, lawyers are circling. Doctors who innovate are risking everything.
I think reports by doctors of proposed solutions (successes and failures) should be reported and shared. It beats the heck out of running around and screaming that the sky is falling.
Our system kills people. The FDA approves half a dozen new drugs a year. Each drug, counting all the investment, is a multi-billion-dollar cost . Again, this is why so many applications of drugs are “off-label” – our system is TERRIBLE at getting new drugs approved.
But once approved, doctors can improvise and apply the “approved” drugs for untested uses. Is that really such a great system?
But you’re suggesting that we abandon tests and protocols. I’m confused by your argument. Of course the idea is sound enough, but your evidence that this works is based on reports from a country that just finished spraying streets with bleach.
I read just recently a theory that the 1918 Spanish Flu was so deadly because they gave everyone aspirin and somehow that made patients die in much greater numbers. I don’t pretend to understand why that would be. The point is that medicine is not well understood much of the time and protocols exist for very good reasons. I’m not panicked enough to ignore them yet.
I am suggesting that we loosen the control lines in cases where patients can accept the risks and sign away legally recourse.
Standard protocols are not centered around fixing the illness. There is a balance between different needs: legal liability limitations, new drugs (as opposed to off-patent options), etc.
We are trying to build knowledge. We cannot build certainty. But in the move toward more knowledge, even poor knowledge is better than none. As knowledge grows, decisions can be honed.
Not so. Look at Kennedy’s quote above. Google Corona and Chloroquine. There is more data.
My point is that we ALREADY ignore them – when we do off-label use (which for many drugs is MOST of their application!) So why are we trying to be holier than the pope in this case?
Interesting. I’ve been on immune system suppressants for Rheumatoid Arthritis for 30 years: Prednisone and in the last few years a drug called Xeljanz. I don’t recall having a severe virus during that time, except for a really nasty bout of stomach flu four years ago. I have no evidence that the drugs have prevented illness, but I think research is appropriate re corona-virus. I don’t get out much, so that undoubtedly helps. I will miss mass on Sunday, but I do need to go to the grocery store tonight (we will not hoard, just buy enough for 10 days or so). I do think that panic is the real danger. Gun buying has increased in massive amounts. This is unwise, I think. This is not the zombie apocalypse.
From the video comments:
Andrew W Saul : Many of my followers have been wanting to know how the vitamin C treatment is progressing at the front lines. This just in (and I mean minutes ago) from Dr. Hyoungjoo Shin reporting from Korea:
“I live in Daegu, South Korea, a city of 2.5 million, where 1,579 people have confirmed infected by the COVID-19 virus. here was in increase of 447 confirmed cases during one day alone. The city was immediately locked down.
“At my hospital in Daegu (Onvit Hospital), all inpatients and all staff members have been using vitamin C orally since last week, and also, to increase their immunity, all patients and staff received vitamin D 200,000 IU intramuscular injections. Some people this week had a mild fever, headaches and coughs, and those who had symptoms got the blood test, and then, 30,000 mg intravenous vitamin C. Some people got better after about two days, and most had symptoms go away after one injection. The patients and staff of my hospital look very bright and healthy. I will keep telling people. I will send information to the Korean Medical Association and also to the local governments. I will send the data to them again and again.” Hospital website (in Korean): http://onvith.cafe24.com/