JAMA. Published online January 21
Digest Author(s): Stylianos Loukides, e-Learning Director / 31 January, 2021
As the SARS-CoV-2 virus continues to spread rapidly worldwide, monoclonal antibodies are being studied more extensively as a possible treatment strategy for COVID-19. A recent study published in the prestigious journal JAMA evaluated the effect of bamlanivimab monoclonal antibody monotherapy as well as the combination therapy of bamlanivimab and etesevimab on SARS-CoV-2 viral load levels in mild to moderate COVID-19 disease.
This is the BLAZE-1 study, a randomized, phase II / III study conducted in 49 US centers between June 17, 2020 and September 3, 2020, and included 613 ambulatory patients who were positive for COVID-19 and had at least one mild or moderate symptom. The above patients were randomized to receive either a single infusion of bamlanivimab at a dose of 700mg (n = 101), 2800mg (n = 107) or 7.000mg (n = 101), or a combination therapy of bamlanivimab and etesevimab monoclonal antibodies at a dose of 2800mg each (n = 112) or placebo (n = 156).
The primary outcome of the study was the change in SARS-CoV-2 viral load levels on day 11. Secondary outcomes included other measurements of assessing viral load, symptoms, and finally prognostic aspects like COVID-19 disease-related hospitalizations, emergency department visits, or mortality on day 29.
A total of 577 patients aged 44.7 years were randomized in the study. The logarithmic reduction in viral load from onset to day 11 was 3.72 for 700 mg, 4.08 for 2800 mg and 3.49 for 7000 mg bamlanivimab, 4.37 for combination therapy with bamlanivimab and etesevimab, and 3.80 for placebo. Compared with placebo, the differences in the logarithmic change of viral load on day 11 were 0.09 increase for 700 mg, decrease 0.27 for 2800 mg, increase 0.31 for 7000 mg, and decrease 0, 57 for combination therapy. In terms of secondary endpoints, the symptom assessment did not allow authors to draw strong conclusions since any significant differences were not in favor of combined monoclonal antibodies. The percentage of patients with hospitalization associated with COVID-19 infection or visits to emergency departments was 5.8% (9 events) for the placebo group, 1.0% (1 event) for the 700 mg group, 1.9% (2 events) for the 2800 mg and 2.0% (2 events) group for the 7000 mg bamlanivimab group while the corresponding rate for combination therapy was 0.9% (1 event). The above differences reached statistical significance only for the combination group.
Immediate hypersensitivity reactions occurred in 9 patients (6 in the bamlanivimab group, 2 in the combination therapy group, and 1 in placebo patients). There were no deaths during the study.
The authors finally concluded that among non-hospitalized patients with mild to moderate COVID-19 disease, combination treatment with bamlanivimab and etesevimab was associated with a statistically significant reduction in SARS-CoV-2 viral load on day 11 compared with placebo. No significant difference was observed in the reduction of viral load for patients receiving bamlanivimab monotherapy. There was a weak difference in terms of hospitalizations but not in terms of symptoms.
Comment:
The main arising question from the above study is whether the reduction of viral load corresponds to clinical improvement aspects. The latest is crucial since it clearly implicates in the prognosis of the disease. A further step is to design a study where the primary outcome will be the hospitalization rate.