Monoclonal Antibodies Most Effective in Patients With Greatest COVID-19 Risks

Pharmacists and other healthcare professionals might have wondered why neutralizing monoclonal antibodies appear to have worked so much better for some patients than others. A new study has some answers, finding that the therapy, which is effective overall, seems to work especially well in unvaccinated patients and those who are immunocompromised. It also advises that the SARS-C0V-2 variant circulating can make a significant difference in outcomes. Here are more details.

BEDFORD, MA -- Risk-targeting strategies are important for optimizing outcomes in patients receiving neutralizing monoclonal antibody (nMAb) therapies for the treatment of COVID-19, according to a new study.

The report in JAMA Network Open questioned whether nMAb therapy is associated with a reduced risk of adverse outcomes of COVID-19 in subpopulations at high risk of poor outcomes and across multiple SARS-CoV-2 variants.

The retrospective cohort study led by the Mitre Corporation and involving major universities around the United States involved 167, 183 nonhospitalized patients with COVID-19 who were eligible for nMAb treatment. It found that the association between nMAbs and reduced risk of poor outcomes was strongest among immunocompromised and unvaccinated patients.

“Combining multiple factors into a risk estimation model to stratify patients further highlighted differences in outcomes; by variant,” the authors add, “nMAb treatment was associated most strongly with reduced risk of poor outcomes in patients infected with the Delta variant, whereas the associations were weaker in patients infected with the Omicron BA.1 variant.”

Patients reviewed in the study were from a consortium of 4 health care systems based in California, Minnesota, Texas, and Utah. They were all outpatients 12 years and older with a positive COVID-19 laboratory test collected between Nov. 9, 2020, and Jan. 31, 2022, who met at least 1 emergency use authorization criterion for risk of a poor outcome. Participants had a mean age of 47 and 57.2% were female. Most, 83.4%, were white and 83.1% were non-Hispanic. Of the patients, 25 241 patients received treatment with nMAbs.

The study examined the use of four nMAb products -- bamlanivimab, bamlanivimab-etesevimab, casirivimab-imdevimab, and sotrovimab-- administered in the outpatient setting. Researchers used clinical and SARS-CoV-2 genomic sequence data and propensity-adjusted marginal structural models to assess the association between treatment with nMAbs and 4 outcomes:

  • all-cause emergency department (ED) visits,
  • hospitalization,
  • death, and
  • a composite of hospitalization or death within 14 days and 30 days of the index date (defined as the date of the first positive COVID-19 test or the date of referral).

Patient index dates were categorized into 4 variant epochs: pre-Delta (Nov. 9, 2020, to June 30, 2021), Delta (July 1 to Nov. 30, 2021), Delta and Omicron BA.1 (Dec. 1 to 31, 2021), and Omicron BA.1 (Jan. 1 to 31, 2022).

Results indicate that treatment with nMAbs was associated with lower odds of ED visits within 14 days (odds ratio [OR], 0.76; 95% CI, 0.68-0.85), hospitalization within 14 days (OR, 0.52; 95% CI, 0.45-0.59), and death within 30 days (OR, 0.14; 95% CI, 0.10-0.20).

“The association between nMAbs and reduced risk of hospitalization was stronger in unvaccinated patients (14-day hospitalization: OR, 0.51; 95% CI, 0.44-0.59), and the associations with hospitalization and death were stronger in immunocompromised patients (hospitalization within 14 days: OR, 0.31 [95% CI, 0.24-0.41]; death within 30 days: OR, 0.13 [95% CI, 0.06-0.27]),” the researchers report. “The strength of associations of nMAbs increased incrementally among patients with a greater probability of poor outcomes; for example, the ORs for hospitalization within 14 days were 0.58 (95% CI, 0.48-0.72) among those in the third (moderate) risk stratum and 0.41 (95% CI, 0.32-0.53) among those in the fifth (highest) risk stratum.”

The study also advises that the association of nMAb treatment with reduced risk of hospitalizations within 14 days was strongest during the Delta variant epoch (OR, 0.37; 95% CI, 0.31-0.43) but not during the Omicron BA.1 epoch (OR, 1.29; 95% CI, 0.68-2.47). “These findings were corroborated in the subset of patients with viral genomic data.”

Still, the authors point out, “Treatment with nMAbs was associated with a significant mortality benefit in all variant epochs (pre-Delta: OR, 0.16 [95% CI, 0.08-0.33]; Delta: OR, 0.14 [95% CI, 0.09-0.22]; Delta and Omicron BA.1: OR, 0.10 [95% CI, 0.03-0.35]; and Omicron BA.1: OR, 0.13 [95% CI, 0.02-0.93]). Potential adverse drug events were identified in 38 treated patients (0.2%).”

Overall, the research found nMAb treatment for COVID-19 to be safe and associated with reductions in ED visits, hospitalization, and death, although it was not linked with reduced risk of hospitalization during the Omicron BA.1 epoch.