Adding an arthritis drug called baricitinib to Covid treatment regimens that contains the antiviral drug remdesivir can cut recovery times by a day or more, especially for those who are seriously ill, according to a study published Friday.
The results of a government-sponsored clinical trial were released more than three weeks after the Food and Drug Administration received an emergency approval for double treatment. Earlier this month, some experts said they were uncomfortable using medication without a chance to review the underlying data backing their performance. Last month, the World Health Organization also recommended rejecting remdesivir for treating Covid patients as there was no evidence of its use.
In previous press releases, limited results were disclosed showing that hospitalized Covid patients treated with baricitinib and remdesivir recovered one day faster than those who received remdesivir alone.
Some questioned the adoption of the combination treatment because baricitinib came at a high price – which could be around $ 1,500 per patient – and also cited side effects like blood clots. Several doctors also wondered if adding baricitinib would be worth it, since steroids like dexamethasone were cheap and widely available. Both baricitinib and dexamethasone are believed to suppress the excessive inflammation that causes many severe cases of Covid.
The new paper, published in the New England Journal of Medicine, adds some granularity to the results and shows that certain subsets of patients benefited far more from the addition of baricitinib than others. The study included more than 1,000 hospital patients with Covid, all of whom received remdesivir. People who were sick enough to need high doses of supplemental oxygen or non-invasive ventilation recovered eight days faster when baricitinib was included in their medication.
In these groups, “I think the data clearly support a role for baricitinib,” said Dr. Boghuma Kabisen Titanji, an infectious disease doctor at Emory University who pioneered early studies of baricitinib against the coronavirus.
Dr. Titanji also noted that the data suggested that certain patients may be less likely to die or need a ventilator when taking baricitinib in addition to remdesivir. However, like those showing faster recovery times, these results were inconsistent among study participants.
Dr. Lauren Henderson, a pediatric rheumatologist at Boston Children’s Hospital, said she was encouraged by the results and the prospect of another option in the coronavirus treatment arsenal.
She and several other experts added that they may still have a tendency to use dexamethasone as a treatment for seriously ill Covid-19 patients who needed respiratory support.
In contrast to baricitinib, studies have shown that dexamethasone inhibits mortality in seriously ill Covid patients. It’s also inexpensive and easy to get hold of, while baricitinib is more of a specialty drug and may pose barriers to the supply chain, said Dr. Erin McCreary, Infectious Disease Pharmacist at the University of Pittsburgh.
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Confused By The Terms To Treat Covid-19? Let us help:
- ACE-2: A protein that sits on the surface of certain types of human cells. The coronavirus has to bind to ACE-2 in order to enter cells.
- Adverse event: A health problem that occurs in volunteers in a clinical trial with a vaccine or drug. An adverse event is not always caused by the treatment tested in the study.
- Antibody: A protein produced by the immune system that can attach to a pathogen such as the coronavirus and prevent it from infecting cells.
- Antiviral drug: A drug that affects the ability of a virus to replicate in cells. The first drug approved in the United States for Covid-19, Remdesivir, is antiviral.
- Approval, Licensing, and Approval for Emergency Use: Medicines, vaccines and medical devices cannot be sold in the US for no profit approval by the Food and Drug Administration, also known as Licensing. After a company submits the results of clinical studies to the FDA for review, the agency decides whether the product is safe and effective. This process usually takes many months. If the country faces an emergency – like a pandemic – a company can file an application instead Emergency approvalthat can be granted much faster.
- Compassionate Use: A term used to describe treatments given to seriously ill people even though they have not yet been approved for that use by the Food and Drug Administration.
- Cytokine storm: An overactive immune system reaction that can lead to massive inflammation and tissue damage. Cytokine storms can be responsible for many of the severe cases of Covid-19, and a number of researchers are testing drugs that may calm them down.
- Interferon: A molecule of the immune system. Certain types of interferons can cause inflammation in the body while others can contain it. Still other types can stimulate cells to strengthen their defenses against viruses. Researchers are investigating whether treating synthetic interferons can help people fight off the coronavirus.
- Monoclonal Antibodies: Monoclonal antibodies made in a laboratory mimic the natural antibodies made by the immune system. A number of companies have developed these treatments for Covid-19. President Trump received Regeneron’s antibody treatment soon after the disease was diagnosed.
- Phases 1, 2 and 3 studies: Clinical trials typically take place in three phases. Phase 1 studies typically involve a few dozen people to determine whether a vaccine or drug is safe. In Phase 2 trials that involve hundreds of people, researchers can try different doses and take more measurements of the vaccine’s effects on the immune system. Phase 3 trials, involving thousands or tens of thousands of volunteers, determine the safety and effectiveness of the vaccine or medicine by waiting to see how many people are protected from the disease it is intended to be used against.
- Placebo: A substance with no therapeutic effect that is widely used in clinical trials. For example, to see if a vaccine can prevent Covid-19, researchers can inject the vaccine into half of their volunteers while the other half are given a placebo with salt water. You can then compare how many people are infected in each group.
- Post-market surveillance: The surveillance that occurs after a vaccine or drug has been approved and regularly prescribed by doctors. This typically confirms that the treatment is safe. Rarely, side effects are noted in certain groups of people that were overlooked during clinical trials.
- Preclinical Research: Studies that take place prior to the start of a clinical trial typically include experiments that test a treatment on cells or animals.
- Test protocol: A series of procedures that must be performed during a clinical trial.
- Retrospective study: A study that analyzes data collected in the past to determine how effective a treatment is. Retrospective studies can provide useful information, but they are not as definitive as randomized clinical studies.
- Spike protein: A protein that sits on the surface of coronaviruses. The spike protein binds to the ACE-2 receptor on human cells using a region called the receptor binding domain (RBD). As soon as the protein accumulates, the virus can enter the cell. Many vaccines and monoclonal antibody treatments are designed to stick to the tip.
- Standard of care: A treatment that is accepted by medical experts as an appropriate method to treat a specific type of disease. Once a standard for treating a disease is established, new experimental treatments are usually tested against it rather than a placebo.
Several experts pointed to another study by the National Institutes of Health that seeks to directly compare two combination treatment regimens: one in which hospital patients receive remdesivir and baricitinib, and one in which remdesivir is paired with dexamethasone. Dr. McCreary also noted the importance of studying patients receiving both baricitinib and dexamethasone “to see if there is any incremental benefit.”
Dr. Andre Kalil, an infectious disease doctor at the University of Nebraska Medical Center and lead researcher on the new paper, noted that while dexamethasone had already become a widely accepted treatment for Covid-19, the steroid still needed further study. He cited “a variety of serious safety issues” with the drug that warranted thorough investigation.
Like other steroids, dexamethasone, which largely reduces inflammation, can be associated with a variety of undesirable side effects, including worsening conditions like diabetes or osteoporosis.