EXECUTIVE SUMMARY

Clinicians can use new monoclonal antibody (mAb) therapies to treat high-risk patients presenting with mild-to-moderate COVID-19 symptoms. However, despite the promise to depress viral loads, logistical and other challenges continue to stand in the way of larger-scale use. Still, some EDs are trying the therapeutics, with promising results.

  • Any eligible patient with mild-to-moderate COVID-19 symptoms can receive mAb at RWJBarnabas Health in New Jersey.
  • In a group of more than 2,100 patients who received mAb treatment in an RWJBarnabas Health ED, fewer than 5% required a return trip to the hospital for worsening COVID-19 symptoms.
  • In Michigan, every hospital in the state has received mAb doses, but fewer than half of those facilities reported they were using the treatment. Of treatment administered, more than one-third of infusions are occurring in emergency settings.
  • Michigan investigators reported that out of 772 cases followed for two weeks after the mAb infusions took place, only 39 patients were hospitalized later.

When the FDA issued an emergency use authorization (EUA) for the investigational monoclonal antibody (mAb) therapy bamlanivimab on Nov. 9, it provided a new weapon for frontline providers to use for high-risk patients presenting with mild-to-moderate COVID-19.

The agency issued an EUA on Nov. 21 for a second mAb therapy involving a cocktail of casirivimab and imdevimab. Finally, the agency issued an EUA for a third mAb therapy comprised of bamlanivimab and etesevimab received on Feb. 9.

However, much of the supply that has been distributed to hospitals has gone unused, and it is not entirely clear why. For emergency providers, there are logistical challenges, considering the therapies are delivered through IV infusions, which might be perceived as a drain on already-thin staffing. Experts explain there are communications challenges and, perhaps, some reticence to embrace a new treatment backed by limited data.

Still, some EDs have jumped on the opportunity to provide their patients with access to this option. Although it is early, results thus far are encouraging, both in terms of patient outcomes and in enabling hospitals to conserve inpatient resources.

Identify Eligible Patients

Soon after the FDA issued its EUA for bamlanivimab, RWJBarnabas Health, a multihospital system in New Jersey, acted quickly. “It sounded like the treatment was promising. In the BLAZE trial,1 looking at a placebo group vs. a monoclonal antibody group, there was definitely a benefit to that high-risk patient,” notes Christopher Freer, DO, FAAEM, FACEP, the senior vice president in charge of the health system’s 11 EDs. “We sort of took the ball and ran with it right then. Within nine days we started rolling [the treatment] out across our EDs.”

Freer stresses the EDs worked closely with pharmacy to put a system in place to facilitate the mAb treatments. “I am sure many EDs know how vital pharmacists have become over the last five to 10 years to our practice. We thought these would be the best two groups to discuss how we would roll [these new treatments] out,” he explains.

It is not difficult to identify potential candidates for mAb. In its initial EUA, the FDA established clear eligibility criteria.2 The Department of Health and Human Services (HHS) has made available clear guidance on this, too.3

Any non-hospitalized patient with mild-to-moderate COVID-19 who is age 65 years or older can receive the treatment. Patients age 55 years or older with heart disease, high blood pressure, COPD, or another chronic respiratory disease are eligible as well. Further, patients of any age who are obese, diabetic, present with chronic kidney disease, or live with a weakened immune system can receive mAb.

Even some children (age 12 to 17 years) with COVID-19 can receive mAb treatment if they are obese, use medical technology such as a ventilator or feeding tube, or they live with a developmental condition such as cerebral palsy, sickle cell disease, heart disease, or a chronic respiratory problem that requires medicine for control.

“This treatment is different from remdesivir and some of the other treatments [for COVID-19] that are more restrictive and ... require more infectious disease involvement [in ascertaining whether a candidate is eligible],” Freer observes.

Consider Logistics

Delivering mAb treatment requires time and space, factors that always are an issue for busy EDs. “This involves a one-hour infusion and then another hour or two of observation,” Freer says. “Our volumes are at historically low numbers, and we felt like we could ... coordinate this in our own EDs rather than send patients to an infusion center for treatment.”

The approach has worked well. Typically, patients undergoing mAb treatment are placed in a hospital bed in a negative pressure room either in the ED or observation, although the logistics may differ depending on the size and characteristics of the ED.

“Some of the smaller EDs have had to work with their hospital administrations to find areas where they can expand a little bit for these patients,” Freer reports.

Freer and other leaders were concerned about whether access to mAb treatment would be constrained. However, that problem has not materialized. “Fortunately for us, not a lot of health systems are using this, and [New Jersey officials] told us the more you use, the more you will get,” Freer explains. “We probably have more doses [of mAb] than we have ever had right now because [the state] sees that we are doing this well.”

Freer adds coordination between the state, health system, and pharmacies at each site have ensured participating EDs never run out of the medicine. At this point, Freer estimates emergency providers are delivering between 50 and 100 doses of mAb treatment to patients every day.

Now that the word is out, RWJBarnabas EDs are hearing from primary care physicians and other health systems interested in accessing mAb treatment for their patients.

“We are making sure that we have a doctor-to-doctor communication before [these patients] come in,” Freer observes. “We don’t want them to send someone who is 40 years old and healthy to come in and then get upset that he can’t get it, so we talk to the doctors over the phone.”

Leverage the EMR

Why are more health systems not similarly enthused about taking advantage of mAb treatment? Freer acknowledges the answer is unclear, but he suspects some administrators view the process of offering mAb treatments through their EDs as more complex than it needs to be.

“I just saw this, as did the other ED providers and nurses [at RWJBarnabas Health], as a way for us to be more proactive,” Freer says.

Some health systems are creating infusion centers where mAb treatments can be delivered off site. Still, the ample surplus suggests more patients could benefit from the infusions. Freer contends more EDs could bridge this gap. “You have to be vocal, say that you can do this, and then coordinate it,” he suggests. “I don’t think there is really any other magic to it.”

Freer gives his pharmacy colleagues and IT personnel a lot of credit for making the rollout process go smoothly. All the eligibility criteria for mAb treatments are embedded in the health system’s EMR, along with the educational information providers can use when discussing the treatment with patients. There also is easy access to patient consent forms as well as a link in the EMR for easy ordering.

Also in place is a way to keep tabs on patients who have received mAb infusions after discharge. “We have case managers come to the bedside, give [patients] a pulse oximeter, and explain how [the device] works,” Freer says. “Then, [patients] call our access center ... and get telehealth visits on days one and three [after ED discharge].”

Balance Risks, Benefits

The way Freer and colleagues look at it, mAb treatment is a new weapon to leverage against COVID-19 after living through months with few options for high-risk patients.

“I saw what happened [to that type of patient] in March and April [2020]. I now have something I can give,” Freer shares. “That conversation starts between the emergency physician and the patient.”

In Freer’s experience so far, patients have been eager to receive the treatment. “There is a less than 1% chance of developing an allergic reaction,” Freer explains. “This is an easy conversation.”

However, one other factor to consider is how long a patient has been ill. The EUA for mAb treatment indicates the therapeutic is most effective when given within 10 days of a patient developing COVID-19 symptoms. Freer believes that is a little long. He prefers administering mAb treatment within seven days. “I would say the sooner we can get this in you, the better to stop the viral load,” he adds.

Investigators at RWJBarnabas Health are closely monitoring results from the mAb infusions. The results so far are promising. At press time, more than 2,100 patients had received the infusions, with fewer than 5% requiring a return trip to the hospital for worsening COVID-19 symptoms.

“Obviously, the No. 1 thing [to consider] is better outcomes for our patients,” says Freer, adding that fully leveraging this treatment offers other benefits, too. “Preserving resources for future admissions is a huge part of this.”

Monitor Usage

Michigan initially supplied the medicine exclusively to hospital providers there, but early data suggest only a fraction of this supply has been used.

William Fales, MD, FACEP, FAEMS, medical director of the Michigan Department of Health and Human Services, division of EMS and trauma, said in January that, at that time, little of the state’s mAb treatment supply had been used.

“We view that as a problem. While we allocated mAb to every hospital, less than half of our hospitals report using it,” Fales said during an HHS Technical Resources, Assistance Center, and Information Exchange (TRACIE) session.4

Fales observed some regions have been more inclined to use the new treatment than others. “We’ve been rather surprised to see more patients treated in our very rural Upper Peninsula than in the city of Detroit. We see more, smaller hospitals than larger hospitals using mAb.”

Only 3% of Michigan’s population resides in the Upper Peninsula, but Fales reported that, at the time, that region accounted for a significant portion of mAb treatments administered.

Fales also reported strong mAb treatment use in Flint and Saginaw. Among the top 10 hospitals that have reported using mAb, five are level I or level II trauma centers while the other five are community hospitals, according to Fales. “A little over one-third of the infusions are currently occurring in EDs, and this percentage has steadily decreased as more infusion centers have come online,” Fales said. “Infusion centers are now the primary site of mAb therapy initiation. Outpatient clinics and long-term care settings each represent about 6%.”

Michigan officials have been tracking metrics associated with mAb treatment closely, finding most patients receiving the treatment tend to skew older, noted Fales. For instance, out of a total of 1,506 patients, 936 were eligible to receive the treatment because they were age 65 years or older, with another 251 patients between ages 55 to 64 with risk factors.

A total of 423 patients receiving mAb were obese, 255 had diabetes, and 86 had chronic kidney disease. Fales indicated 70 patients receiving mAb had immunosuppressive disease, and 64 were on immunosuppressive therapies.

Following mAb infusions, most patients returned home, but 2.6% ended up admitted to the hospital. This was almost always because of disease progression that occurred during the infusion, according to Fales.

However, state investigators have found the treatment to be quite safe, with no problems associated with 95% of infusions.

“We have not identified any severe adverse events attributed to the medicine, nor any cases of anaphylaxis or life-threatening allergic reactions,” Fales said. “In the 5% of cases that did report [adverse reactions], most were relatively mild and self-limited, and aligned with symptoms that are also consistent with COVID-19.”

For instance, there were two cases of altered mental status following the infusions that resulted in hospital admission, but these reactions could not be attributed to the medicine. Clinicians believed they were potentially the result of COVID-19.

Looking at outcomes, state investigators report that out of 772 of cases that were followed for two weeks after the mAb infusions took place, 39 patients were hospitalized later. Among those hospitalized, 22 were older than age 64. “We don’t have a Michigan control group for comparison. That makes it a little more challenging to measure the impact. However, the reported hospitalization rates in untreated, placebo patients who are high risk from clinical trials range from 9% to 15%,” Fales said.

Further, in phone interviews conducted with 152 patients who received mAb infusions, two-thirds reported clinical improved within two days of the infusion, and 96% reported improvement at the time of the phone interview, which usually was at least 14 days following the mAb treatment.

Spread the Word

“The ability of mAb [treatment] to reduce hospitalization remains to be determined, but our preliminary experience in Michigan is certainly encouraging, and it supports continuation and expansion,” Fales said.

However, he noted spreading the word about mAb treatment has proven challenging. “The targeted ... clinicians are not just sitting around and waiting to read the newest articles; they are taking care of patients right now.”

To solve the communication challenges, Michigan health officials have developed a multipronged approach.

“We started out by doing some webinars and conference calls with different professional associations, our Federally Qualified Health Centers, and nursing home medical directors,” Fales shared. “That still has not been enough to get the word out, so we just initiated a mass mailing to almost 300,000 licensed clinicians throughout the state through our licensing agency. It explains what mAb therapy is all about, provides information on qualifying patients, and how [clinicians] might be able to access the treatment for their patients.”

Now, Michigan officials are considering how they might begin making patients aware of mAb treatment.

“There is nothing wrong with a patient asking their primary care provider or the clinician who ordered the [COVID-19] test how they might seek monoclonal antibody therapy if it is appropriate for them,” Fales stressed.

The fact mAb  treatment is delivered through an IV infusion may well have prompted some hospitals not to become involved, but Fales noted the logistics are not as burdensome as some administrators suspect. “It does not require one-on-one nursing and it does not require an intravenous infusion pump,” he explained.

Flint and Saginaw, areas with strong mAb treatment adoption, also include facilities that have been hit hardest during the pandemic. “One nurse and one paramedic can easily take care of four or five patients at a time, so it isn’t a huge burden, I don’t believe, in terms of staffing,” Fales said.

Hearing from colleagues who are using mAb treatment can be particularly effective in convincing clinicians to consider mAb for their patients.

“We were able to bring in representatives from two of our hospitals, one large tertiary care hospital and one community hospital. They both just talked for about five minutes on their experience in more of a peer-to-peer [exchange],” Fales said. “After that, we definitely saw an uptake in hospital use [of the medicine].”

REFERENCES

  1. Chen P, Nirula A, Heller B, et al. SARS-CoV-2 neutralizing antibody LY-CoV555 in outpatients with COVID-19. N Engl J Med 2021;384:229-237.
  2. U.S. Food & Drug Administration. Coronavirus (COVID-19) update: FDA authorizes monoclonal antibody for treatment of COVID-19. Nov. 9, 2020.
  3. CombatCOVID.HHS.gov. Monoclonal antibodies for high-risk COVID-19-positive patients.
  4. TRACIE Healthcare Emergency Preparedness Information Gateway. Healthcare operations during the COVID-19 pandemic - speaker series. January 2021.