Infectious Diseases I
| (1) | The COVACTA trial (N Engl J Med 2021;384:1503-16) was a randomized, placebo- |
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controlled trial in 438 hospitalized adults with severe COVID-19 pneumonia.
| (A) | Patients were randomized 2:1 to either a single intravenous infusion of tocilizumab |
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(8 mg/kg actual body weight) or placebo; 25% of patients received a second dose
of tocilizumab.
| (B) | At enrollment, 37% of patients required MV and 22.4% received concomitant |
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corticosteroids.
| (C) | No between-group differences were observed in clinical progression or 28-day |
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mortality (tocilizumab, 19.7% vs. placebo, 19.4%; weighted difference 0.3%; 95%
CI, –7.6 to 8.2).
| (2) | The REMAP-CAP trial (N Engl J Med 2021;384:1491-502) randomized 803 patients |
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within 24 hours of ICU admission (median 1.2 days from hospitalization) to open-label
tocilizumab 8 mg/kg actual body weight (max of 800 mg) (353 patients), sarilumab
400 mg (48 patients), or standard of care (402 patients).
| (A) | Most patients (552 [68.7%]) were free of MV and/or ECMO at enrollment; 76% of |
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patients received concomitant corticosteroids.
| (B) | Tocilizumab was associated with reduced in-hospital mortality (28% vs. 36%; |
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OR 1.64; 95% CI, 1.25–2.14) and higher median days free of respiratory and
cardio-vascular organ failure (10 days vs. 0 days; OR 1.64; 95% CI, 1.25–2.14).
| (C) | Tocilizumab was also associated with decreased progression to MV, ECMO, or |
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death (OR 0.59; 95% CI, 0.41–0.86).
| (3) | The RECOVERY trial (Lancet 2021;397:1637-45) was a randomized, controlled, |
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open-label study in 4116 hospitalized patients with COVID-19 demonstrating acute
hypoxia and evidence of systemic inflammation (i.e., C-reactive protein ≥75 mg/L).
| (A) | Patients were randomized 1:1 ratio to usual care vs. usual care plus tocilizumab |
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400 mg–800 mg intravenously once; 29% of tocilizumab patients received a
second dose at provider discretion.
| (B) | At enrollment, 82% of patients received concomitant corticosteroids and 13.8% |
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required MV.
| (C) | Tocilizumab was associated with a decreased 28-day mortality overall |
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(tocilizumab, 31% vs. usual care, 35%; rate ratio 0.85; 95% CI 0.76–0.94) and
across prespeci-fied subgroups based on illness severity.
| (D) | Patients not requiring MV at enrollment who received tocilizumab were less |
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likely to progress to MV or death (35% vs 42%; risk ratio 0.84; 95% CI 0.77–0.92).
| (4) | Tocilizumab is authorized for use under an FDA Emergency Use Authorization (EUA) |
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for treatment of COVID-19 in hospitalized patients from 2 to less than 18 years of age
who are receiving systemic corticosteroids and require supplemental oxygen, non-
invasive or invasive mechanical ventilation, or ECMO. On December 21, 2022, the
FDA approved tocilizumba for the treatment of COVID-19 in hospitalized adults who
are receiving systemic corticosteroids and require supplemental oxygen, non-invasive
or invasive mechanical ventilation, or ECMO.
| (5) | Possible adverse effects include serious infections, fungal pneumonia, gastrointestinal |
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perforation, hepatotoxicity, and cytopenias.
| (b) | Baricitinib: Janus kinase inhibitor (alternative class agent: tofacitinib) |
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| (1) | The ACTT-2 study (N Engl J Med 2021;384:795-807) was a double-blind, randomized, |
placebo-controlled trial evaluating baricitinib 4 mg/day orally or via nasogastric tube
plus remdesivir (200 mg on day one, then 100 mg daily for 5-10 days) versus placebo
in 1033 hospitalized patients with COVID-19.