Pittsburgh—EUAs by the FDA of five mAbs have all been suspended or revoked based on in vitro evidence of evolving loss of efficacy against new SARS-CoV-2 variants.

That most recently occurred on November 30, 2022, with the revocation of the EUA for bebtelovimab to treat high-risk outpatients with mild-to-moderate COVID-19, according to an article in Annals of Internal Medicine.

“Such decisions about changes to EUAs are often based on in vitro potency alone, as randomized trials and real-world data predate evolving variants,” wrote University of Pittsburgh Medical Center–led researchers. “There are limited, large-scale observational clinical data for use of mAb products in infected patients, including during the current Omicron variant era. Taken together, these realities underscore the need for near-real-time evaluation of individual mAb products as new variants emerge, with the goal of identifying patient populations most likely to benefit from treatment.”

The study team sought to evaluate whether early outpatient treatment with mAbs was associated with reduced risk for hospitalization or death at 28 days. The research took into account overall mAb use and by mAb product, presumed SARS-CoV-2 variant, and immunocompromised status.

The hypothetical pragmatic, randomized trial from observational data comparing mAb-treated patients with a propensity score–matched, nontreated control group was conducted at a large U.S. healthcare system. Included as participants were outpatients eligible for mAb treatment under any EUA with a positive SARS-CoV-2 test result from December 8, 2020, to August 31, 2022.

The focus was on single-dose IV mAb treatment with bamlanivimab, bamlanivimab-etesevimab, sotrovimab, bebtelovimab, or IV or subcutaneous casirivimab-imdevimab administered within 2 days of a positive SARS-CoV-2 test result.

The researchers tracked the primary outcome of hospitalization or death at 28 days among treated patients versus a nontreated control group, who either had no treatment or treatment more than 3 days after a SARS-CoV-2 test date.

The results indicated that the risk for hospitalization or death at 28 days was 4.6% in 2,571 treated patients and 7.6% in 5,135 nontreated control patients (risk ratio [RR] 0.61; 95% CI, 0.50-0.74). The researchers pointed out that in sensitivity analyses, the corresponding RRs for 1- and 3-day treatment grace periods were 0.59 and 0.49, respectively.

Subgroup analyses found that those receiving mAbs when the Alpha and Delta variants were presumed to be predominant had estimated RRs of 0.55 and 0.53, respectively, compared with 0.71 for the Omicron variant period. “Relative risk estimates for individual mAb products all suggested lower risk for hospitalization or death. Among immunocompromised patients, the RR was 0.45 (CI, 0.28 to 0.71),” the authors advised.

The study concluded that early mAb treatment among outpatients with COVID-19 is associated with a lower risk for hospitalization or death for various mAb products and SARS-CoV-2 variants.

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