Adding an arthritis drug called baricitinib to Covid treatment regimens including remdesivir, an antiviral drug, could reduce recovery times by a day or more, especially for people with severe severity, according to a study published Friday. sick.
The results of a government-sponsored clinical trial were made public more than three weeks after the Food and Drug Administration issued an emergency use authorization for the dual treatment. Earlier this month, some experts said they were uncomfortable rolling out drugs without the ability to verify the underlying data supporting their performance. Last month, the World Health Organization also recommended against using remdesivir as a treatment for patients with Covid, as evidence to support its use was lacking.
Limited results were announced earlier in press releases, showing that hospitalized Covid patients treated with baricitinib and remdesivir recovered a day faster than those who received remdesivir alone.
Some questioned the adoption of the combination treatment given the high price of baricitinib – which could be around $ 1,500 per patient – and also cited side effects such as blood clots. Several doctors have also questioned whether adding baricitinib was worth it because steroids like dexamethasone were cheap and widely available. Baricitinib and dexamethasone are thought to work by reducing excessive inflammation, which leads to many severe cases of Covid.
The new article, published in the New England Journal of Medicine, adds some granularity to the results, showing that some patient subgroups benefited from the addition of baricitinib much more than others. The trial recruited more than 1,000 hospitalized patients with Covid, all of whom received remdesivir. People who were sick enough to require a high dose of supplemental oxygen or a non-invasive form of ventilation recovered eight days faster when baricitinib was included in their drug regimen.
In these groups, “I think the data clearly support the role of baricitinib,” said Dr Boghuma Kabisen Titanji, an infectious disease physician at Emory University who pioneered the first studies of baricitinib against coronavirus.
Dr Titanji also noted that the data suggested that some patients may be less likely to die or need a ventilator if they take baricitinib in addition to remdesivir. But these results, like the results that showed faster recovery times, were not consistent among trial participants.
Dr Lauren Henderson, a pediatric rheumatologist at Boston Children’s Hospital, said she was encouraged by the results and the prospect of having another option in the coronavirus treatment arsenal.
But she and several other experts added that they may still be inclined to abandon dexamethasone as a treatment for critically ill Covid-19 patients who need respiratory assistance.
Dexamethasone, unlike baricitinib, has been shown in studies to reduce mortality in critically ill Covid patients. It is also inexpensive and easy to obtain, while baricitinib is seen more as a specialty drug, which could pose supply chain barriers, said Dr Erin McCreary, infectious disease pharmacist at the ‘University of Pittsburgh.
Don’t know how to treat Covid-19? Let us help you:
- ACE-2: A protein that is found on the surface of certain types of human cells. The coronavirus must bind to ACE-2 to enter cells.
- Adverse event: A health problem that arises in volunteers during a clinical trial of a vaccine or drug. An adverse event is not always caused by the treatment tested in the trial.
- Antibody: A protein produced by the immune system that can attach to a pathogen such as coronavirus and prevent it from infecting cells.
- Antiviral drug: A drug that interferes with the ability of a virus to replicate inside cells. The first drug approved for Covid-19 in the United States, remdesivir, is an antiviral.
- Emergency use approval, license and authorization: Medicines, vaccines and medical devices cannot be sold in the United States without winning approval of the Food and Drug Administration, also known as license to practice. After a company submits clinical trial results to the FDA for review, the agency decides whether the product is safe and effective, a process that typically takes several months. If the country is faced with an emergency – such as a pandemic – a company can request a emergency use authorization, which can be granted much faster.
- Compassionate Use: Term used to describe treatments given to seriously ill people although they have not yet been approved by the Food and Drug Administration for this use.
- Cytokine storm: An overactive immune system response that can lead to massive inflammation and tissue damage. Cytokine storms may be responsible for many severe cases of Covid-19, and a number of researchers are testing drugs that may be able to calm them down.
- Interferon: A molecule made by the immune system. Some types of interferons can trigger inflammation in the body, while others reduce it. However, other types can cause cells to strengthen their defenses against viruses. Researchers are studying whether synthetic interferon treatments can help people fight the coronavirus.
- Monoclonal antibodies: Monoclonal antibodies, created in the laboratory, mimic natural antibodies produced by the immune system. A number of companies have developed these treatments for Covid-19. President Trump received Regeneron’s antibody treatment shortly after being diagnosed with the disease.
- Phase 1, 2 and 3 trials: Clinical trials generally take place in three stages. Phase 1 trials typically involve a few dozen people and are designed to observe whether a vaccine or drug is safe. Phase 2 trials, involving hundreds of people, allow researchers to try different doses and gather 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 drug while waiting to see how many people are protected against the disease they are supposed to be fighting for.
- Placebo: A substance with no therapeutic effect, often used in a clinical trial. To see if a vaccine can prevent Covid-19, for example, researchers can inject half of their volunteers with the vaccine, while the other half are given a saltwater placebo. They can then compare the number of people in each group infected.
- Post-market surveillance: The follow-up that takes place after the approval of a vaccine or drug and is regularly prescribed by doctors. This usually confirms that the treatment is safe. On rare occasions, it detects side effects in certain groups of people that were missed in clinical trials.
- Preclinical research: Studies that take place before a clinical trial begins, usually involving experiments where a treatment is tested in cells or in animals.
- Test protocol: A series of procedures to be performed during a clinical trial.
- Retrospective study: A study that analyzes data collected in the past to assess the effectiveness of a treatment. Retrospective studies can offer useful information, but are not as definitive as randomized clinical trials.
- Peak protein: A protein that is found 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). Once the protein is attached, the virus can enter the cell. Many vaccines and monoclonal antibody treatments are designed to attach to the peak.
- Standard of care: A treatment accepted by medical experts as an appropriate way to treat a certain type of disease. Once a standard of care emerges for a disease, any new experimental treatment is usually tested against it, rather than a placebo.
Several experts pointed to another National Institutes of Health trial that will conduct a direct comparison of two combined treatment regimens: one that puts hospital patients on remdesivir and baricitinib, and another that combines remdesivir with dexamethasone. Dr. McCreary also stressed the importance of studying patients who receive both baricitinib and dexamethasone “to determine if there is an additional benefit”.
Dr Andre Kalil, an infectious disease physician at the University of Nebraska Medical Center and principal investigator of the new document, noted that while dexamethasone had already become a widely accepted treatment for Covid-19, the steroid still needed study. further. He cited “a host of serious safety concerns” with the drug that deserved careful consideration.
Like other steroids, dexamethasone, which largely eases inflammation, can cause a host of unwanted side effects, including aggravating conditions like diabetes or osteoporosis.