Drug used for arthritis could also be effective for critically ill patients with COVID-19

Drugs tofacitinib It is used alone or with other medicines to treat rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis, among other conditions. It belongs to a class of medicines called Janus kinase inhibitors (JAKs) and works by reducing the activity of the immune system. There is now more evidence that tofacitinib could become an option for treating critically ill patients with COVID-19 and pneumonia who are admitted to hospitals.

Clinical researchers from Israelita Albert Einstein Hospital in São Paulo, Brazil, with a team from other medical institutions and with funding from the Pfizer company, which produces the drug, conducted a randomized, controlled trial to assess whether it may be indicated in critically ill patients with coronavirus, who have developed pneumonia. They published the results in the magazine The New England Journal of Medicine.

“Study results with tofacitinib in critically ill patients with COVID-19 and pneumonia are interesting. We already have experience with this drug as we indicate it in patients with rheumatoid arthritis and lung damage. It has good patient tolerance and a good safety profile. The new work is methodologically well done, ”he said. Infobae the pulmonologist José Manuel Viudes, from the Italian hospital in Buenos Aires and home care coordinator for the prepaid Swiss Medical Group. The expert was not involved in the conduct of the tofacitinib trial.

“If administered in Argentina, it could be administered on the first day of patients’ hospitalization to prevent the progression of pneumonia and lead to the use of a ventilator. With the impact of the variants, we observe that young patients without risk factors require a ventilator on average 7 days after infection. If there was more evidence, the drug tofacitinib could be added early, ”the doctor added.

Despite the rapid development of vaccines, a large portion of the world’s population remains at risk of contracting COVID-19. Therefore, Effective, safe and easy-to-administer therapies are needed for COVID-19 hospital patients, the researchers said. The severe manifestations of coronavirus infection are associated with an exaggerated immune response elicited by interleukin 6 and other cytokines, a process called a “cytokine storm”.

The medicine tofacitinib is administered as tablets and acts on different molecular mechanisms. As a result, no cellular response is triggered and cytokine production is indirectly suppressed. The researchers took into account that the action of tofacitinib on several pathways of the inflammatory cascade may improve progressive lung damage induced by inflammation in hospitalized COVID-19 patients.

To have evidence of the drug’s benefits, a multicenter, randomized, double-blind, placebo-controlled trial was conducted to investigate the efficacy and safety of tofacitinib in hospitalized patients with COVID-19 pneumonia who were not receiving non-invasive or invasive ventilation.

In the clinical trial, 289 patients participated who were randomized in 15 centers in Brazil. Deaths from all causes up to Day 28 occurred in 2.8% of patients in the tofacitinib group and 5.5% of those in the placebo group. Serious adverse events occurred in 20 patients (14.1%) in the tofacitinib group and in 17 (12.0%) in the placebo group.

In conclusion of the study, researchers argue in reported work that “among hospitalized patients with COVID-19 pneumonia, tofacitinib resulted in a lower risk of death or respiratory failure through day 28 than placebo.”

Half of the participants received the drug in a 10 milligram tablet twice a day and standard care such as glucocorticoids that suppress an overactive immune response, while the other half received a placebo and standard care. After 28 days, 18.1 percent of the tofacitinib group progressed to respiratory failure or death, compared with 29 percent of the placebo group. Means that administration of tofacitinib represented a statistically significant relative risk reduction of 63%.

“We are encouraged by the first results of our randomized trial of tofacitinib in hospitalized patients with COVID-19 pneumonia. These results provide new information indicating that the use of tofacitinib when added to standard therapy, which includes glucocorticoids, may further reduce the risk of death or respiratory failure in this patient population ”, Dr Otavio Berwanger, director of the University Research Organization at Israelita Albert Einstein Hospital, said in a press release. “The study is based on the hypothesis that inhibition of Janus kinase (JAK) could attenuate systemic and alveolar inflammation in patients with COVID-19-related pneumonia.”

Since the start of the pandemic, pharmaceutical companies and public and private scientific institutions around the world have started to research existing drugs and develop new ones. Recently, the Pan American Health Organization warned that “the need to develop high-quality randomized clinical trials that include patients with COVID-19 in order to develop reliable management strategies remains urgent. The importance of properly designed randomized controlled clinical trials is essential for making evidence-based decisions ”.

This health agency made this claim because it considered that “so far, most research in the field of COVID-19 has very low methodological quality, which makes its use and application difficult.” Treatment suggestions are circulating on social media that have not been evaluated by controlled trials. These studies are essential because they involve the comparison between patients who receive the drug and other patients to whom it is not administered. This way you can tell if the benefits of a drug outweigh the risks.

According to the Pan American Health Organization’s live evidence review guide, steroid drugs have been evaluated in fifteen randomized controlled clinical trials. They show that administration of low and moderate doses (the dose used in the RECOVERY study was dexamethasone 6 mg per day orally or intravenously for 10 days) likely reduces mortality in patients with severe COVID infection. -19.

This guide also considered that the drug tocilizumab, based on the results of thirteen trials, likely reduces mortality and ventilator requirements without a significant increase in serious side effects in patients with severe or critical illness. Meanwhile, it has been noted that the results of three clinical trials show that sarilumab may reduce mortality and the need for invasive ventilation without significantly increasing serious side effects in patients with severe or critical illness. However, the certainty of the evidence was low and more information is needed to confirm these results.

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