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Role of mAb in COVID-19: Q&A
The Role of Monoclonal Antibodies in COVID-19 Prophylaxis and Treatment: Questions and Answers

Released: December 08, 2021

Expiration: December 07, 2022

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In this commentary, Arun Mattappallil, PharmD, and Jessica K. Ortwine, PharmD, BCIDP, answer questions about monoclonal antibody (mAb) therapies for the treatment of COVID-19 from a ProCE webinar titled “Emerging Insights on the Role of Monoclonal Antibodies in Patients With COVID-19.” Slides from the webinar are also available for self-study or to use in your noncommercial presentations.

Are there any clinical trials using mAb infusions in the inpatient setting?

Jessica K. Ortwine, PharmD, BCIDP:
The most promising inpatient trial results to date come from the RECOVERY trial, assessing the combination of casirivimab and imdevimab vs standard of care alone in adult and pediatric patients 12 years of age or older admitted to the hospital with suspected or confirmed COVID-19. The primary outcome was 28-day, all-cause mortality assessed first among patients who were seronegative at baseline, and Hornby and colleagues found a mortality benefit favoring casirivimab and imdevimab. However, when all patients (both seronegative and seropositive) were included in the analysis, no mortality benefit was observed.

Another recently published trial looked at adults with confirmed COVID-19 experiencing ≤10 days of symptoms either on low-flow or no supplemental oxygen at baseline. A primary clinical efficacy outcome was progression to mechanical ventilation or death among patients with high baseline viral loads, and the results were not statistically significant. However, Somersan-Karakaya and colleagues found a 56% relative risk reduction in 28-day, all-cause mortality and in progression to mechanical ventilation or death among patients who were seronegative at baseline. I believe the study results have been submitted to the FDA and will expand the current indications for use of this mAb combination.

Can mAb infusions be used to treat breakthrough infections?

Jessica K. Ortwine, PharmD, BCIDP:
Based on what we know at this time, the vaccination status of the patient should not affect the decision to use mAb therapy if the patient meets Emergency Use Authorization (EUA) criteria. The National Institutes of Health (NIH) COVID-19 Treatment Guidelines state that, assuming no logistical or supply constraints, prior vaccination against SARS-CoV-2 should not affect decisions regarding the use of monoclonal antibody treatment. A recent study out of the Mayo Clinic looked at fully vaccinated patients with breakthrough COVID-19 infections, of which 38% received treatment with mAb. The authors found that there was a significantly lower rate of hospitalization among the ambulatory patients with breakthrough infections who received mAb therapy.

Are screening tests suggested before the administration of mAb?

Arun Mattappallil, PharmD:
Currently, rapid serology (antibody) testing that can identify seronegative individuals in real time is not widely available. The NIH COVID-19 Treatment Guidelines and FDA EUAs for all currently available COVID-19 mAb do not emphasize the need for serology testing (within authorized use) to determine patient eligibility for therapy. Recently, Bierle and colleagues found that mAb therapy also prevented disease progression in high-risk, seropositive individuals (this population was vaccinated). However, the utility of preadministration serology testing remains unclear. 

What is the route of administration and optimal temperature for casirivimab and imdevimab in limited-resource settings?

Arun Mattappallil, PharmD:
Subcutaneous administration of casirivimab and imdevimab is a reasonable alternative administration method for COVID-19 treatment or for postexposure prophylaxis. As specified in the EUA, casirivimab and imdevimab should equilibrate to room temperature before administration and be administered as 4 consecutive injections at different injection sites. The preadministration procedures are similar whether being used for COVID-19 treatment or postexposure prophylaxis. Use of the subcutaneous route of administration still requires significant logistical coordination and training to ensure success.

How do hospitals monitor patients during the postinfusion, 1-hour observation period? Should vitals signs be monitored, or is observation adequate?

Arun Mattappallil, PharmD:
All EUAs for anti–SARS-CoV-2 mAb have the following requirement: “Clinically monitor patients after injections and observe patients for at least 1 hour.” No details about the methods of clinical monitoring are included in the EUA, although these infusions must be administered in settings with immediate access to medications to treat severe infusion or hypersensitivity reactions and the ability to activate emergency medical systems. So healthcare facilities should develop and follow a clear protocol regarding patient monitoring to ensure uniform practice within their facility.

Anecdotally, I have heard of facilities implementing a post-mAb observation protocol similar to their post–COVID-19 vaccine monitoring protocol. The Department of Health and Human Services Monoclonal Antibody Clinical Implementation Guide recommends taking vital signs at patient intake, which provides a baseline indicator of clinical status should adverse events occur post infusion.

Have pharmacoeconomic analyses shown that mAb infusions for postexposure prophylaxis are cost-effective?

Jessica K. Ortwine, PharmD, BCIDP:
There have not been any pharmacoeconomic analyses performed to date and the products are currently provided by the drug companies themselves and allocated free of charge by the federal government. I think that cost-effectiveness will be determined once the allocation process is discontinued and healthcare facilities are required to start purchasing the agents on their own. We don’t yet know what the costs of these agents will be.

Arun Mattappallil, PharmD:
The only overt pharmacoeconomic benefit that we are familiar with is the reduction in hospitalization costs. In terms of the product itself, the cost remains unclear until it becomes available for commercial purchase. There will also be added costs for preparation, administration, and monitoring that will need to be factored into the equation, and these will be more institution specific.

Can patients have worsening symptoms after receiving mAb?

Jessica K. Ortwine, PharmD, BCIDP:
While mAb significantly decreases the risk for hospitalization or death, it does not remove all possibility of these outcomes occurring. I think the vast majority of clinical worsening seen in some patients who received mAb is related to worsening COVID-19 symptoms and not new issues caused by the infusion itself.

As an example, in the phase III trial for outpatient treatment of mild to moderate infection with combination casirivimab and imdevimab, 46 of the events leading to medical attention among patients who received antibody therapy were related to COVID-19 disease, and 7 were not.

In the COMET-ICE study, which assessed the efficacy and safety of sotrovimab in preventing mild to moderate COVID-19 progression to severe disease, no serious adverse events (fatal or otherwise) were deemed to be related to study treatment. In all 3 key phase III ambulatory treatment trials, infusion-related reactions and adverse events severe enough to necessitate infusion interruption or study withdrawal were low (≤1%).

The EUA Provider Fact Sheets do include a disclaimer that monoclonal antibodies may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high-flow oxygen or mechanical ventilation.

Your Thoughts?
How have your patients with COVID-19 responded to mAb therapy? Join the conversation by posting in the comments section.

For more information on mAb therapies for COVID-19, see our program here.

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