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Covid Update
Baricitinib Plus Remdesivir for Hospitalized Adults with COVID-19 : The New England journal of Medicine
India
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New Delhi, December 13, 2020 :
Salient Features
- Severe coronavirus disease 2019 (Covid-19) is associated with Dysregulated inflammation which leads to severe disease •
- In A double-blind, Randomized, placebo-controlled trial received Baricitinib with and without Remdesivir with a primary out come of time to recovery
- The trial was conducted on 1033 patients in eight countries. Patients receiving Baricitinib had a median time to recovery of 7 days (95% confidence interval [CI], 6 to 8), as compared with 8 days (95% CI, 7 to 9) with control( P=0.03). There was 30% higher odds of improvement in clinical status at day 15 with combination therapy.
- In patients requiring high flow oxygen the recovery time was 8 days in Baricitinib as compared to 18 days in control group
- The 28-day mortality was 5.1% in the combination group as compared to 7.8% ( statistically insignificant)
- Serious adverse events were less frequent in the combination group than in the control group (16.0% vs. 21%).
According to Dr G C Khilani, With better understanding of Covid, the mortality is consistently coming down, however, there is very little contribution of pharmacotherapy except corticosteroids and Remdesivir. All the drugs including Hydroxychloroquine, Azithromycin, Doxycycline and ivermectin have not shown clinical benefit in properly conducted Randomized trials.
Among antivirals Remdesivir has shown convincing clinical benefit (ACTT-1 trial). We have all observed in clinical practice that Dysregulated hyperimmune response causes enhanced severity leading to respiratory failure and death. It that case mitigating the immune response and preventing a Hyperinflammatory state is likely to improve outcome. In a recent study (NEJM, 10th Dec ; N Engl J Med 2020; 383:2387-2388) Tociluzimab was found to be ineffective in improving outcome.
Baricitinib is a selective inhibitor of Janus kinase (JAK) 1 and 2, is administered orally. It inhibits the intracellular signalling pathway of cytokines known to be elevated in severe Covid-19, including interleukin-2, interleukin-6, interleukin10, interferon-γ, and granulocyte–macrophage colony-stimulating factor; acts against SARS-CoV-2 through the impairment of AP2-associated protein kinase 1 and the prevention of SARS-CoV-2 cellular entry and infectivity; and improves lymphocyte counts in patients with Covid
This large (1033 patients) Randomized trial conducted in 8 countries have shown that the combination of Remdesivir and Baricitinib significantly reduced recovery time . Also patients(with a baseline ordinal score of 6) who received combination treatment were more likely to have clinical improvement at day 15 (odds ratio, 2.2; 95% CI, 1.4 to 3.6). The survival rate and the time-to death analyses favoured combination treatment. The mortality was lower in combination therapy (5.1% v/s 7.8%) which was statistically insignificant.There were no adverse effects. A faster recovery would presumably lead to lower chances of secondary infections and improved outcome.
This study is a novel hope in enhancing the armamentarium in the management of Covid which has shattered our lives. I think, this may not have as promising effect as steroids, however, it would certainly add to management of serious disease for control of Dysregulated hyperimmune syndrome . Another study with the same molecule is `ongoing’ and we hope to have results soon.
Author : G C Khilnani Chairman, PSRI Institute of Pulmonary, Critical care and Sleep Medicine, PSRI Hospital, New Delhi. Formerly, Professor and Head Dept of Pulmonary Critical care and Sleep Medicine, AIIMS, New Delhi-110029
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