Background

Steroids, remdesivir, and baricitinib were determined by clinical trials to be effective. These are all treatments for at least moderate-to-severe diseases that require supplemental oxygen. Casilibimab/imdebimab, an antibody cocktail therapy, was approved in Japan on July 19, 2021, as a drug considered to have an effect in patients with mild COVID-19. However, its effectiveness has not been established, and it was determined that it has a great clinical significance in planning CQ.

Recommendation rationale ▪ Balance of benefit and harm

In 5,135 cases of patients with mild COVID-19 in three RCTs,43-45 all-cause mortality was expected to decrease by 7 per 1,000; clinical improvement was expected to increase by 29 per 1,000; and serious adverse events were expected to decrease by 26 per 1,000. In all outcomes, the intervention group was shown to have benefits. By contrast, in 9,144 cases of moderate/severe patients in one RCT, all-cause mortality was expected to decrease by 8 per 1,000 and clinical improvement was expected to increase by 7 per 1,000, but there were no available data to assess serious adverse events (Fig. 7).

Recommendations of casirivimab/imdevimab (CQ9). We recommend casirivimab/imdevimab administration to patients with mild COVID-19 and have not made a clear recommendation on casirivimab/imdevimab administration to patients with moderate and severe COVID-19. Net effect estimates of casirivimab/imdevimab in all patients with COVID-19 were calculated with the effects of each outcome, in which the importance of mortality was considered as three times higher than those of other outcomes. Overall imprecisions across outcomes were assessed as “net benefit” in mild COVID-19 and “likely net benefit” in moderate and severe COVID-19, based on the magnitude of point estimate and 95% confidence intervals of the calculated net effect estimates. CoE, certainty of evidence; COVID-19, coronavirus disease 2019; CQ, clinical question; GRADE, Grades of Recommendation, Assessment, Development, and Evaluation; SAE, severe adverse event.

Based on these conclusions, the benefits outweighed harm in patients with mild COVID-19, whereas it was indeterminate in patients with moderate/severe COVID-19. ▪ Certainty of evidence

The certainty of evidence in all-cause mortality, clinical improvement, and serious adverse events was “low,” “moderate,” “low” in patients with mild COVID-19, respectively, and “moderate,” “moderate,” and no data in patients with moderate/severe COVID-19, respectively. Taking that direction of effectiveness into account, the overall certainty of evidence was determined to be “moderate” for patients with mild COVID-19 and “low” for patients with moderate/severe COVID-19.