Explained: How two newly WHO-recommended drugs work against Covid

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The World Health Organization (WHO) recommended two drugs, baricitinib and sotrovimab, for the treatment of Covid-19.

Drugs

Baricitinib, which is also used to treat rheumatoid arthritis, was “strongly recommended” for patients with severe or critical Covid-19 in combination with corticosteroids. It is part of a class of drugs called Janus kinase (JAK) inhibitors that suppress overstimulation of the immune system. It is an oral medication that offers an alternative to other arthritis medications called interleukin-6 receptor blockers recommended by the WHO in July 2021.

Sotrovimab, developed by GlaxoSmithKline with its American partner Vir Biotechnology Inc, is an experimental monoclonal antibody intended for use in the treatment of conditions caused by the coronavirus. The WHO has conditionally recommended its use to treat mild or moderate Covid-19 in patients at high risk of hospitalization. These include patients who are older, immunocompromised and with underlying conditions such as diabetes, hypertension and obesity, and who are unvaccinated. The United States Food and Drug Administration (FDA) has also approved an Emergency Use Authorization (EUA) for the therapy for the treatment of mild to moderate Covid-19 in patients over 12 years of age.

how they work

Baricitinib, an immunomodulator, is an alternative to tocilizumab: either of these drugs is given to patients who have severe Covid-19, are progressing clinically on steroids and have elevated inflammatory markers.

“Basically, during the severe phase of Covid-19, there is inflammation that triggers severe disease. This is mediated by certain inflammatory markers which are then inhibited by baricitinib,” said Dr Sanjay Pujari, member of the ICMR National Covid-19 Task Force.

Infectious disease experts have said they have been using baricitinib since the COV BARRIER study on the drug was published. During the wave of Delta infections, there was a shortage of tocilizumab and baricitinib was an alternative drug. “The two have different mechanisms of action, but studies have shown a mortality benefit if used with steroids in patients with severe Covid-19 disease,” Dr Pujari said.

Rheumatologist Dr. Arvind Chopra said Olumiant (baricitinib) is a prescription drug used to treat adults with moderate to severe active rheumatoid arthritis. “Its ability to inhibit inflammation is also clearly demonstrated as an antiviral drug. However, doctors are advised not to prescribe in mild to moderate cases,” he said.

The casirivimab-imdevimab antibody cocktail is not active against the Omicron variant whereas sotrovimab can be used in mild disease with both Delta and Omicron patients at high risk of progression, said Dr. Amit Dravid, infectious disease consultant.

Availability in India

Baricitinib is inexpensive and widely available. It is given to control hyperinflammation, which usually starts between days 7 and 14. “The patient starts to become short of breath and that’s when we use steroids and add tocilizumab. If there is a spike hospital admissions, there is an alternative, baricitinib, which is widely available,” Dr. Dravid said.

Sotrovimab is not available in India. However, experts said that since Omicron now makes up the bulk of infections, currently available monoclonal antibodies should only be used if there is clear evidence that the person has been infected with the Delta variant.

What the recommendation means

The latest WHO recommendations are the eighth update to WHO’s living guidelines on therapeutics and Covid-19. They are based on evidence from seven trials involving more than 4,000 patients with non-severe, severe and critical Covid-19.

According to Professor K Srinath Reddy, Chairman of the Public Health Foundation of India, the approval will be granted by the national regulator who may take into consideration the recommendation of credible national agencies like the WHO.

Baricitinib has long been recommended in the United States and Europe in their guidelines.

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