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Doctors Are Skeptical of Pricey Drug Given Emergency Approval for Covid
Baricitinib, an arthritis drug made by Eli Lilly, may reduce recovery time by a day, but costs about $1,500 and comes with side effects.
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In mid-November, an arthritis drug with a tricky name hit a pandemic milestone — then slipped back into relative obscurity.
The drug, baricitinib, was granted an emergency authorization by the Food and Drug Administration to treat a subset of hospitalized Covid-19 patients in combination with another medication, the antiviral remdesivir. It is one of only a handful of treatments to have earned the agency’s green light.
But baricitinib’s reception by the medical community has been lukewarm. It doesn’t work all that well, for one thing, and comes with side effects, such as blood clots. And at a cost of roughly $1,500 per patient, many doctors don’t know when it would make sense to use the drug, which might have overlapping roles with cheap and widely available steroids like dexamethasone.
In a clinical trial sponsored by the National Institutes of Health, hospitalized Covid-19 patients treated with baricitinib and remdesivir recovered one day faster than patients who had received remdesivir alone.
“I think it’s really a nothing burger,” said Dr. Ilan Schwartz, an infectious disease physician at the University of Alberta. “We’re talking about adding a drug that reduces the time to clinical improvement by one day, in a disease that takes weeks to recover.”
These results, which were announced through a series of news releases by drugmaker Eli Lilly, have yet to be published in a peer-reviewed scientific journal. Kristen Porter Basu, a spokeswoman for the company, wrote in an email that a “more detailed analysis” would be published “very soon.”
When an emergency authorization has been released but the data have not, doctors are caught “in a difficult place,” said Dr. Manuela Cernadas, a critical care physician at Brigham and Women’s Hospital in Boston. “It’s not entirely clear where this drug fits in our armamentarium of drugs we’re comfortable using.”
Baricitinib is a repurposed arthritis treatment that, like a steroid, dampens inflammation, which, in severe cases of Covid-19, can spiral out of control and destroy healthy tissues. The drug acts like a molecular muffler, preventing the cells from responding to alarm signals that could make the body’s immune response spiral out of control.
The N.I.H. trial was designed to test whether baricitinib could boost the benefits of remdesivir, now the standard of care for Covid-19 patients. Remdesivir by itself speeds recovery by several days. The researchers found that the addition of baricitinib clipped an additional day off a patient’s recovery time and kept a few extra people off ventilators. But these and other results largely failed to impress experts, many of whom said the drug would need to have far bigger benefits to outweigh its price tag and potential harms.
“It seems more incremental than blockbuster,” said Dr. Taison Bell, a critical care physician at the University of Virginia, who was involved in the clinical trial. Although Dr. Bell described baricitinib as a reasonable addition to the Covid treatment toolbox, and even deserving of an emergency approval, “I don’t think it’s a game changer,” he said.
Still, the findings were enough to convince the F.D.A., which issued an emergency authorization on Nov. 19. The drug is now allowed to be paired with remdesivir, but only to hospitalized patients who need supplemental oxygen, mechanical ventilation or other breathing support.
The agency’s limited clearance aligns with the subset of patients in the N.I.H. trial who benefited the most from the dual drug combo, said Dr. Andre Kalil, an infectious disease physician at the University of Nebraska Medical Center and one of the lead researchers on the trial.
But this same population of patients — people sick enough to need some form of breathing support — would also be great candidates for steroids like dexamethasone, said Dr. Phyllis Tien, an infectious disease physician at the University of California, San Francisco.
Dexamethasone, unlike baricitinib, has been shown in studies to curb mortality in severely sick Covid-19 patients. A generic drug, it’s also cheap, costing cents or dollars per day of treatment, and has for months been a part of the coronavirus treatment playbook.
“I’m asking myself, ‘Who would I think about using baricitinib in, over dexamethasone?’” Dr. Tien said.
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But Dr. Boghuma Kabisen Titanji, an infectious disease physician at Emory University who pioneered early studies of baricitinib against the coronavirus, offered a more sobering perspective on dexamethasone. Steroids are “blunt knives,” she said, quashing inflammation on a broader scale than drugs like baricitinib do. That’s why steroids come with a host of unwanted side effects, including exacerbating conditions like diabetes or osteoporosis, she said.
The family of drugs that includes baricitinib, on the other hand, may offer more therapeutic precision, Dr. Titanji said. There’s also been some evidence that baricitinib might be able to block the coronavirus from entering cells.
Still, baricitinib comes with its own problems, such as raising the risk of blood clots — already an issue in many cases of Covid-19. “That does give you pause,” Dr. Cernadas said.
Both baricitinib and dexamethasone also blunt immune function, increasing the likelihood that other viruses or bacteria might infiltrate the bodies of the people they’re used in. But of the two, dexamethasone is “the devil you know,” said Dr. Lauren Henderson, a pediatric rheumatologist at Boston Children’s Hospital. “I would probably not turn to baricitinib as a first line.”
Dr. Tien and other experts echoed this sentiment, saying they would be likely to choose dexamethasone over baricitinib when treating someone with a serious case of Covid-19, unless there was an obvious reason their patient might respond poorly to steroids.
A head-to-head comparison between baricitinib and dexamethasone might clarify which patients would be better off taking one drug over another. At the end of November, the N.I.H. announced a trial that will compare outcomes between hospitalized Covid-19 patients who receive either a combination of remdesivir and dexamethasone, or a combination of remdesivir and baricitinib. But Dr. Schwartz and others raised ethical concerns about this trial, which he said would by definition deprive some patients of a lifesaving steroid therapy.
Eli Lilly is also running a trial to study the effects of baricitinib on its own in hospitalized patients. In this study, which isn’t likely to finish until next summer, all participants will receive dexamethasone.
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