Hydroxychloroquine Still Doesn’t Do Anything, New Data Shows

It doesn’t work.

The stalwart drug hydroxychloroquine, a decades-old antimalarial that people have more recently used to treat lupus and rheumatoid arthritis, started getting attention as a possible treatment and preventative against Covid-19 as early as February. Hydroxychloroquine and the related drug chloroquine killed the virus that causes the disease in vitro—that is to say, in petri dishes. Health care workers gave hospitalized people the drug in the early days of the pandemic (because they didn’t have much else to give), and influential voices like carmaker Elon Musk and President Donald Trump advocated for it as a possible cure.All that happened before scientists could determine whether that was true. And with the release of two new sets of data this week, one from a massive drug trial in the United Kingdom on Wednesday and the other from researchers at the University of Minnesota today, the answer appears to be: no. Hydroxychloroquine does not appear to keep people from getting the disease after they’ve been exposed to someone who has it. It does not change how many people hospitalized with Covid-19 die of the disease. It does not reduce symptoms for people with milder cases who aren’t in the hospital.

Scientists have lots of different kinds of studies they can run. Some are observational, meaning the researchers take a group that meets some set of criteria, like “people who have Covid-19,” and follow their progress as they get different kinds of treatment. Others are retrospective; researchers go over people’s records later to see if they’ve recovered or died. It’s possible to learn from these sorts of studies, but they’re vulnerable to all sorts of errors. Sicker people tend to be more likely to improve more slowly, or die, even if they get the same drug as someone who isn’t as ill. That makes it hard to tell whether the drug actually helps—or harms.

So the so-called gold standard of drug trials is called an RCT, short for Randomized Controlled Trial. That means people sick with the thing you’re trying to study get put into one of two groups, or cohorts, from the very start. They either get the drug or they don’t, and no one—not the researchers, not the health care workers, not the participants in the study—knows who got what. (That’s called “double-blinding.”) And the researchers try to make those groups as similar as possible in every other way. They’re trying to eliminate all the possible external factors that could mess up the study.
The two sets of results that came out this week were both RCTs. The first was part of a massive trial in the UK called Randomised Evaluation of Covid-19 Therapy, or “Recovery.” The researchers running it have been sending thousands of people hospitalized with Covid-19 into one of a half-dozen groups testing different drugs against a control group, and then checking to see if they’re still alive 28 days later. Recovery is an “adaptive” trial, which means it’s designed for researchers to look at the data as it rolls in and adjust on the fly, cutting off or adding new study arms to accommodate new information. So far, the trial showed the corticosteroid drug dexamethasone reduced mortality rates and, in June, cancelled the arm of the study looking at hydroxychloroquine.

The new paper from the researchers, an un-peer-reviewed preprint, details what actually happened in the hydroxychloroquine arm—1,561 people got hydroxychloroquine, and 418 of them, 26.8 percent, were dead within 28 days. And 3,155 people got standard care without the drug; 788 of them died. That’s 25 percent. So: Hydroxychloroquine didn’t reduce mortality. Its use also correlated with longer time spent in the hospital and a higher likelihood of having to go on a mechanical ventilator. As the paper puts it: “not an effective treatment.”