Background:
Treatment guidelines and emergency use authorizations (EUAs) of monoclonal antibodies (mAbs) from the US Food and Drug Administration for the treatment of high-risk outpatients with mild to moderate COVID-19 changed frequently as different SARS-CoV-2 variants emerged.
Aim:
To evaluate whether early outpatient treatment with monoclonal antibodies (mAb), overall and by mAb product, suspected SARS-CoV-2 variant, and immunocompromised status, is associated with a reduced risk of hospitalization or death at 28 days.
Design:
Hypothetical pragmatic randomized trial from observational data comparing monoclonal antibody (mAb)-treated patients with a propensity score-matched untreated control group.
Participants:
High-risk outpatients eligible for monoclonal antibody (mAb) treatment under any EUA with a positive SARS-CoV-2 test result from December 8, 2020 to August 31, 2022.
Intervention:
Single-dose intravenous monoclonal antibody (mAb) treatment with intravenous or subcutaneous bamlanivimab, bamlanivimab-etesevimab, sotrovimab, bebtelovimab, or casirivimab-imdevimab administered within 2 days of a positive SARS-CoV-2 test result.
Measurements:
The primary outcome was hospitalization or death at 28 days among treated patients versus an untreated control group (no treatment or treatment ≥3 days after the date of SARS-CoV-2 testing).
Results:
The risk of hospitalization or death at 28 days was 4.6% in 2,571 treated patients and 7.6% in 5,135 untreated control patients (relative risk [RR], 0.61 [95% CI, 0 .50 to 0.74]). In sensitivity analyses, the corresponding RRs for the 1- and 3-day treatment grace periods were 0.59 and 0.49, respectively.
In subgroup analyses, those who received mAbs when the alpha and delta variants were assumed 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 suggested a lower risk of hospitalization or death. Among immunocompromised patients, the RR was 0.45 (CI, 0.28 to 0.71).
Limitations:
Observational study design , SARS-CoV-2 variant assumed by date rather than genotyping, no data on symptom severity and partial data on vaccination status.
| Conclusion: In conclusion, in this large study of outpatients with COVID-19, early treatment with 5 different mAb products used in accordance with current authorizations and guidelines for specific SARS-CoV-2 variants was consistently associated with lower risk of hospitalization or death for almost 2 years. The rapid evolution of new SARS-CoV-2 variants warrants continued and timely evaluation of both mAb and non-mAb treatment approaches. |
Comments
The COVID-19 pandemic created a real-life experiment that required healthcare providers across the country to quickly set up clinics to administer an evolving supply of monoclonal antibody treatments that, although initially shown to be safe and effective in clinical trials and were approved under federal emergency use authorization, they had never been tested on such a scale.
The task was enormous and the real-world benefit uncertain, particularly for monoclonals approved later in the pandemic based on laboratory data alone. An analysis published today in the Annals of Internal Medicine by doctors and scientists at UPMC and the University of Pittsburgh School of Medicine shows it was worth it.
“The virus was a moving target, and for two years, monoclonal antibodies were approved, revoked, sometimes reauthorized, and sometimes in short supply,” said lead author Kevin Kip, Ph.D., vice president of clinical trials at UPMC. . “Using UPMC’s database of patients treated with monoclonal antibodies, one of the largest in the U.S., we can ultimately conclude that overcoming all of these challenges unequivocally saved lives and prevented hospitalizations.”
Monoclonal antibodies are human-made antibodies specifically designed to prevent a pathogen, in this case the virus that causes COVID-19, from entering human cells, replicating, and causing severe disease. The U.S. Food and Drug Administration granted emergency use authorization to five different monoclonal antibody treatments for COVID-19 at various times between 2020 and 2022. All were restricted to people 12 years or older with medical conditions. risk that made them more susceptible to the poor outcomes of COVID-19. 19 Treatments had to be administered intravenously or by injection by a healthcare professional. As the virus evolved, new monoclonal antibodies were introduced and older ones, which were no longer effective, were removed.
Beginning with first authorization in late 2020, UPMC has opened dozens of clinics, set up emergency department infrastructure, and organized home visits to maximize its ability to provide monoclonal antibodies to patients in Pennsylvania, New York, and Maryland. After the emergency use authorization for the last monoclonal antibody was revoked on November 30, 2022 and no new monoclonal antibodies were introduced, UPMC extracted anonymized clinical data from 2,571 patients treated with monoclonal antibodies and compared it with data from 5,135 patients with COVID-19. 19 who were eligible for monoclonal antibodies but did not receive them.
On average, people who received monoclonal antibodies within two days of a positive COVID-19 test reduced their risk of hospitalization or death by 39% compared to their peers who did not receive the treatment. Patients with immunocompromising conditions, regardless of age, had an even greater reduced risk.
Patients treated when the alpha and delta variants of the virus were circulating experienced greater benefit than their untreated peers compared to those treated when the omicron variant was circulating, likely because the earlier variants were more deadly and people had less prior immunity from infection or prior vaccination. By the time omicron was in circulation, the risk of death and hospitalization had decreased overall, so treatment with monoclonal antibodies had less overall benefit, but still a clinically significant benefit, particularly in vulnerable patients, the co-author explained. Erin McCreary, Pharm.D., director of infectious disease improvement and clinical research innovation at UPMC.
“At this time, COVID-19 has a relatively low risk of death for the general population, but we have seen how quickly this virus can mutate and spread. “No one can say with certainty that a future variant will not be more lethal,” McCreary said. “Should that happen, our real-world data provides peace of mind that investing in the infrastructure and knowledge of health care workers to rapidly administer antibody treatments keeps people in the communities we serve alive and out of harm’s way.” hospital".
Final message : Early treatment with monoclonal antibodies (mAb) among outpatients with COVID-19 is associated with a lower risk of hospitalization or death for several mAb products and SARS-CoV-2 variants.
