How strong is the evidence for hydroxychloroquine?
post by Chris_Leong · 2020-04-05T09:32:00.058Z · LW · GW · 7 commentsThis is a question post.
Contents
Answers 8 johnlawrenceaspden 3 Gunnar_Zarncke 3 leggi 3 Kevin None 7 comments
There has been a lot of discussion of hydroxychloroquine (see the megathread on Effective Altruism Coronavirus Discussion, note you need to answer two questions to gain access). Doctors treating COVID-19 have rated hydroxychloroquine the most effective drug based on their experience. But on the other hand, results have been mixed with a recent RCT showing no effect.
At this stage how strong is the evidence for hydroxychloroquine and if it works, how effective does it appear to be as a treatment?
Disclaimer: Please seek medical advice before taking any substance, particularly those like hydroxychloroquine that have known side effects.
Answers
It occurs to me that chloroquine is still taken widely in malarial regions as a prophylaxis, even though malaria has developed resistance to it.
So if it worked to deter COVID19, we should be seeing very few cases in, say, Nigeria, where it's a popular over-the-counter treatment even though it's no longer recommended as first-line treatment, and in, say, the Dominican Republic, where malaria isn't yet resistant and it's still the best treatment.
↑ comment by johnlawrenceaspden · 2020-04-12T10:31:07.060Z · LW(p) · GW(p)
Having had a look, it does seem to me that the malarial areas of the world are much less affected than malaria-free Europe and America, not sure what to read into that, how accurate their figures are, when the first cases were, how slowly we expect coronaviruses to spread in hot places, etc
A shame, since either not-spreading-there or going-like-wildfire would have given a pretty clear answer to the chloroquine question.
At the moment I'm guessing it's weak evidence in favour of effectiveness.
Seems like Algeria and Morocco improved after starting to use HCQ;
https://twitter.com/Covid19Crusher/status/1254176105730359300
A study, not peer-reviewed:
Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19
HC= hydroxychloroquine,
HC+AZ = hydroxychloroquine and azithromycin
no HC = no hydroxychloroquine
RESULTS: A total of 368 patients were evaluated
(HC, n=97; . HC+AZ, n=113; . no HC, n=158).
Rates of death in the HC, HC+AZ, and no HC groups were 27.8%, 22.1%, 11.4%, respectively.
Rates of ventilation in the HC, HC+AZ, and no HC groups were 13.3%, 6.9%, 14.1%, respectively.
Compared to the no HC group, the risk of death from any cause was higher in the HC group (adjusted hazard ratio, 2.61; 95% CI, 1.10 to 6.17; P=0.03) but not in the HC+AZ group (adjusted hazard ratio, 1.14; 95% CI, 0.56 to 2.32; P=0.72).
The risk of ventilation was similar in the HC group (adjusted hazard ratio, 1.43; 95% CI, 0.53 to 3.79; P=0.48) and in the HC+AZ group (adjusted hazard ratio, 0.43; 95% CI, 0.16 to 1.12; P=0.09), compared to the no HC group.
CONCLUSIONS:
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.
.....
However, given its increasingly widespread use, not only as therapy but also as prophylaxis for Covid-19, there is a great and immediate need to obtain insights into the clinical outcomes among patients currently treated with hydroxychloroquine, particularly because of the non-negligible toxicities associated with its use.
↑ comment by zby · 2020-05-24T20:23:33.767Z · LW(p) · GW(p)
The same result bigger n: https://blogs.sciencemag.org/pipeline/archives/2020/05/22/hydroxychloroquine-enough-already
Replies from: Vanilla_cabs↑ comment by Vanilla_cabs · 2020-09-04T01:23:29.802Z · LW(p) · GW(p)
The paper was retracted.
Dose matters enormously. Hydroxychloroquine is acutely toxic to humans, so using hydroxychloroquine requires you to balance its toxicity versus its antiviral effects. My read of the evidence is that it is ineffective to harmful at the late stages of COVID19 in the dosages high enough to "do something", but taken in the very early stage of the disease (asymptomatic) it might keep the virus contained to its area of initial infection and prevent the disease from migrating to the lungs.
7 comments
Comments sorted by top scores.
comment by Chris_Leong · 2020-04-07T12:51:26.870Z · LW(p) · GW(p)
This document summarises a lot of the evidence.
Replies from: TheMajor↑ comment by TheMajor · 2020-04-08T17:34:03.568Z · LW(p) · GW(p)
Thanks for sharing! I'm not a doctor, so I found this a tough read. This document is clearly a proposal (attempting to convince the reader) instead of a summary, but it still contains a lot of useful information. Nevertheless, there were some parts I found especially confusing.
On page 2 they mention there are currently 22 studies, of which one has completed, on the effect of hydroxychloroquine (HCQ) treatment on COVID-19 patients. Further down in the piece (in particular in the section "What about the studies that show no benefit from HCQ?" on page 11) they dismiss some studies showing little or no effect. Is there a place to find more discussion on which studies are being discounted, and for what reason? They link one study only, citing that "only 400mg daily for 5 days was used", although the suggested treatment in this document is "HCQ: 6.5-15mg/kg PO in divided loading dose followed by 400-800mg/day in divided doses for 4-9 days" (which encompasses 400mg daily for 5 days).
The recommended treatment is a combination treatment with four different components - an initial oral hydroxychloroquine administration and a daily treatment of hydroxychloroquine and two other medicines (zinc and Azithromycin). Furthermore the document states that this treatment is expected to work a lot better in early stages of the disease (this part is also unclear to me - again on page 11 they state that "[some studies] waited to initiate treatment until the disease was too far progressed to be effective" as grounds for dismissal). Does this mean this treatment is expected to have next to no effect in late stages? I'm worried about Bonferfoni-esque situations here; are 21 incomplete and 1 complete study strong enough to motivate this complicated treatment, especially if we allow ourselves to discount some papers with conflicting conclusions as well as restrict the time period over which the treatment is supposed to be effective?
comment by ioannes (ioannes_shade) · 2020-04-05T15:18:55.828Z · LW(p) · GW(p)
Gautret et al. 2020 [LW(p) · GW(p)] and Chen et al. 2020 are studies of hydroxychloroquine efficacy.
I stumbled onto these during the course of my internet reading, would be great to see a proper lit review.
Replies from: filipe-marchesini↑ comment by Filipe Marchesini (filipe-marchesini) · 2020-04-05T18:35:35.562Z · LW(p) · GW(p)
Gautret et al. 2020° shouldn't be considered a study of hydroxychloroquine efficacy. It should be considered a failed attempt at studying hydroxychloroquine efficacy. Here is why [LW · GW] I believe that.
Replies from: ioannes_shade↑ comment by ioannes (ioannes_shade) · 2020-04-05T20:13:46.322Z · LW(p) · GW(p)
Yes, I pointed out some of the limitations in the original link. Should still be included in a lit review though.
comment by Jonathan_Graehl · 2020-04-05T21:49:03.274Z · LW(p) · GW(p)
[I know you didn't advocate this, just saying:] If we had the option to wait and obtain rigorous proof, we would prefer that. We don't have that option. Concurrent with obtaining more certain information, it should be used (and is being used) off-label at safe doses in combination with azithromycin to ward off secondary infections.