Infectious Diseases I
| (A) | At enrollment, 32% of patients had severe disease, with 10.7% of patients requiring |
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MV or ECMO. Patients receiving corticosteroids for COVID-19 were excluded.
| (B) | Overall, patients receiving baricitinib plus remdesivir had a shorter time to |
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recovery (7 days; 95% CI 6β8 vs. 8 days; 95% CI 7β9; rate ratio 1.16; 95% CI,
1.01β1.32), which was most pronounced in patients receiving high-flow oxygen
or noninvasive ventilation at enrollment (10 days vs. 18 days; rate ratio 1.51; 95%
CI, 1.10β2.08).
| (C) | No difference was noted in 28-day mortality (5.1% vs. 7.8%; hazard ratio 0.65; |
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95% CI 0.39β1.09).
| (2) | The COV-BARRIER trial (Lancet Respir Med 2021; www.thelancet.com/journals/ |
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lanres/article/PIIS2213-2600(21)00331-3/fulltext) was a multinational, placebo-
controlled, randomized trial in 1525 hospitalized patients with COVID-19 pneumonia
and elevated inflammatory markers. Patients receiving MV were excluded.
| (A) | Patients were randomized 1:1 to receive baricitinib 4 mg/day (renally-adjusted as |
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necessary) orally or placebo in addition to usual care; 92% of patients received
concomitant dexamethasone.
| (B) | No between-group difference were noted in disease progression. |
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| (C) | Patients receiving baricitinib overall had lower 28-day all-cause mortality (8% vs. |
13%; hazard ratio 0.57; 95% CI 0.41β0.78).
| (D) | The treatment effect for mortality was most notable among the subgroup of 370 |
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pa-tients receiving high-flow oxygen or noninvasive ventilation at baseline (17.5%
vs. 29.4%; hazard ratio 0.52; 95% CI, 0.33β0.80).
| (3) | The COV-BARRIER Addendum was an exploratory randomized, placebo-controlled |
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trial evaluating baricitinib in 101 patients with confirmed COVID-19 and 1 or more
elevated inflammatory markers (CRP, D-dimer, LDH, or ferritin) and MV or ECMO
| (A) | Patients were randomized 1:1 to receive baricitinib 4 mg/day (renally-adjusted as |
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necessary) orally or placebo in addition to usual care; 86% of patients received
concomitant dexamethasone.
| (B) | 28-day mortality: baricitinib 39% versus placebo 58% (hazard ratio 0.54; 95% CI, |
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0.31β0.96; p=0.030). Baricitinib relative reduction in mortality similar as seen in
less severely ill population from COV-BARRIER parent trial.
| (C) | Number of ventilator-free days and duration of hospitalization: no significant |
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difference between arms
| (4) | Baricitinib use is supported by an FDA EUA for treatment of COVID-19 in hospitalized |
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patients from 2 to less than 18 years of age requiring supplemental oxygen, non-
invasive or invasive MV, or ECMO. Baricitinib was approved on May 10, 2022, for the
treatment of COVID-19 in hospitalized adults requiring supplemental oxygen, non-
invasive or invasive mechanical ventilation, or ECMO.
| (5) | Baricitinib can be administered orally or via oral dispersion or gastrostomy or nasogas- |
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tric tube.
| (6) | Possible adverse effects include elevations of transaminases, fungal pneumonia, |
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thrombosis, and cytopenias.
| (c) | Although preclinical models and early clinical reports have been enthusiastic, data are |
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insufficient to support routine use of other immunomodulators in patients with COVID-19.
Ongoing clinical trials are anticipated. Additional drug classes/agents reported include:
| (1) | IL-1 inhibitors (e.g., anakinra) |
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| (2) | Interferon alfa or beta |