Hard Data on Remdesivir, and on Hydroxychlorquine

Let’s catch up with some things that (by this point) feel a bit like old news. But it’s important to do it, because (A) the big reason they feel that way is because of the bizarre world we’ve been living in the last few months, and (B) the pace of medical discovery is not set to human preferences, anyway. I’m talking about remdesivir and hydroxychloroquine. And yes, I know that I said I wasn’t going to mention the latter one again, but I figured the points being made today are important enough to justify it. I might regret that.

The New England Journal of Medicine today has the final report from the team studying remdesivir in a >1000 patient randomized controlled trial. This group was randomized and divided roughly half-and-half to standard of care plus remdesivir versus standard of care plus placebo, blinded. So this is the most solid look we have at the drug’s efficacy in coronavirus patients. The good news is that the patients receiving the drug had a shorter time to recovery (9 to 11 days, in the 95% confidence interval, versus 13 to 18 days with non-remdesivir standard of care. That’s real, but it’s not real dramatic, either, which is what you would realistically expect from a single broad-spectrum antiviral drug. This ain’t sofosbuvir clearing out hepatitis C, and even that one doesn’t do the job by itself.

As for the hardest endpoint of all, mortality by Day 29 for these patients was 11.4% with remdesivir therapy as compared to 15.2% with the controls. So again, that’s a real improvement and very much worth having, but it’s not a Miracle Drug, either. Adverse events were actually lower in the treatment group, which is of course good news. You can see that these were indeed at-risk patients – the overall mortality rate in the general population for coronavirus infections is nowhere near those rates, and it’s a damn good thing it isn’t. The mean age of the patients was 59 years, 64% male, with 50% of them having hypertension, 45% of them obese, and 30% with Type 2 diabetes. So even though they were characterized as mild-to-moderate on enrollment, this was just the sort of group that you’d worry about as a physician.

So remdesivir is indeed a worthwhile drug, especially when given to people in higher-risk patient groups. This confirms the preliminary reports, and (to be honest) is somewhat better than some of the early reads. Not everything gets worse when you look at it closely! But you have to look at it closely and rigorously – there is no substitute and there are no shortcuts.

That point is illustrated by a second paper in the same issue of NEJM, the report from the RECOVERY study on hydroxychloroquine. In this one, 1561 patients got HCQ plus standard of care, versus 3155 who had standard of care without it. There would have been even more treatment patients, but enrollment was closed in early June after an interim analysis showed a strong likelihood of no benefit. Both cohorts were followed thereafter, with 28-day mortality as the primary endpoint.

The HCQ-treated patients did not survive better than those not getting the drug: 27% of them died within 28 days, versus 25% in the standard of care group. The data are shown below:

Overall, 59.6% of the HCQ patients were discharged during that 28-day period versus 62.9% of the control group. Meanwhile, 30.7% of the HCQ group ended up on ventilators during that period (none were, at entry into the trial) versus 26.9% of the control patients. Every single one of these trends is in the wrong direction and every single one of them was seen in all the pre-specified patient subgroups. As for adverse effects, there were numerically more cardiac events in the HCQ group, but it was not statistically significant. Note that patients with existing QT prolongation were excluded from the study.

I’m not in a mood to be subtle. Hydroxychloroquine treatment for coronavirus does not work. It is not beneficial, and in fact appears to be actively harmful. As far as I’m concerned, administering it to infected patients now constitutes medical malpractice. I have no interest in goalpost-moving efforts to say that they didn’t administer zinc or azithromycin, or they picked the wrong patients or the wrong loading dose or whatever. No. This is special pleading, and it is not backed up by any hard data. None of the countries or regions where HCQ was enthusiastically adopted, with or without the addition of zinc, azithromycin or what have you have seen discernable benefits. It. Does. Not. Work. Give it up.

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