While the FDA granted emergency use authorization to Regeneron and Eli Lilly's antibody treatments in November 2020, many healthcare organizations have been slow to adopt these treatments due to a web of logistical challenges.
The treatment entails a one-hour infusion followed by a one-hour monitoring period that must be performed in healthcare settings capable of managing an anaphylactic reaction in the rare instance it occurs.
"That's a long time to have someone in a devoted space where they need to have nursing resources and supervision," said Brandon Webb, MD, an infectious disease physician at Salt Lake City-based Intermountain Healthcare.
What's more, infusion centers typically treat patients with cancer or autoimmune diseases who have suppressed immune systems, so bringing actively contagious COVID-19 patients to these settings for antibody treatment also poses infection control hurdles.
Dr. Webb spoke with Becker's about how Intermountain overcame these obstacles to roll out a successful antibody treatment program that's reached at least 1,000 patients, alongside a research effort to better understand real-world efficacy.
Editor's note: Responses have been edited for length and clarity.
Question: How did Intermountain ensure antibody treatments were going to the patients who would benefit from them the most?
Dr. Brandon Webb: Once it became clear that the two antibody products were going to be authorized by the FDA, we realized we were going to be in a situation again — just like with remdesivir — where our supply was far less than our demand. At that point, we were headed into the peak of our community transmission. The number of cases was the highest ever in the pandemic. At the state level, we participated with other health systems, including [Nashville, Tenn.-based] HCA Healthcare, [Dallas-based] Steward Health Care and others, and collectively decided that we wanted to focus the limited capacity we did have on patients who were at the highest risk of hospitalization and most likely to benefit. Rather than doing some type of first-come, first-serve model or lottery system, we used a clinical prediction score that was adapted from a previously published risk score. We validated that score in a population of more than 22,000 Utah patients to make sure it accurately stratified patients for their hospitalization risk.
Once we determined that the risk score was indeed accurate, we then voted to adopt that as our eligibility criteria at a state level. The reason we did not use the FDA's emergency use authorization criteria was this: We recognized very early on that the FDA's eligibility criteria would capture more than 25 percent of all positive patients. In November and December, that meant there would be hundreds and hundreds of eligible patients every single day. It was pretty obvious we didn't have enough drug nor infusion center capacity to treat all those patients. By using a more refined risk score, we were able to match the supply or the capacity to infuse to a patient population who were at the highest risk and stood to benefit the most. That risk-adapted strategy has actually been a very good investment at the state level.
Q: How did you inform patients they were eligible for antibody treatments?
BW: We set up a dedicated referral hotline and email inbox so that primary care physicians and other physicians across the referral area could very easily assess eligibility and then send in a referral. Many people with COVID-19 are not connected to healthcare. Their only connection is their test, and in many cases, those tests are just done at a drive-thru site. So the majority of patients with COVID-19 haven't checked into primary care. Relying only on referrals was not likely to identify the patients who were at most risk. Right now, Intermountain Laboratories are doing about 50 percent of all testing in Utah. And because of the research platform we built, every day we have a list generated of everyone with a positive test. So we built the risk calculator that was adopted at the state level into that daily list.
We also recruited about a dozen redeployed physicians and advanced practice providers who were furloughed or had slow practices to form what we call the "Mab squad," short for monoclonal antibodies. Their role is to field referrals through the hotline and email. And then maybe more importantly, they would go through the list of positive patients and proactively reach out to them, verify their eligibility, let them know there is a therapy they are eligible for, talk to them about the risks and benefits. For patients who were interested, these clinicians would then make an appointment at the nearest infusion site, write the orders and coordinate with those infusion sites on any reactions that might occur. That prospective identification of patients has been really effective and gratifying to watch because it captures a lot of patients who wouldn't know about the treatment or would potentially have had long delays in accessing the treatment. We're averaging about 48 hours from the time of testing until the time of treatment — so less than a two-day span is the time for patients to get tested, find out they're positive and then get in to receive the antibody treatment.
Q: How did you ensure infusion sites could safely treat both COVID-19 patients and cancer patients?
BW: First we looked at our integrated health network's geographic footprint, where our population density was and where COVID-19 case density was to pinpoint where it made most sense to open infusion sites. We worked with these centers to develop creative ways to open infusion times starting at 1 or 2 in the afternoon and going late into the evening so they could serve the oncology patients in the morning and then have no overlap and pivot to serve COVID-19 patients in the afternoon and evening. That really helped with overcoming that barrier of infection control. With the number of cancer patients in the state, it became clear that even with those creative scheduling efforts, our capacity would still be far inadequate. So then we went to our urgent care leadership and asked if we could train the urgent care nurses to prepare the treatment and manage these infusions. And they said absolutely. That engagement was awesome. We then filled in the gaps around the infusion centers with urgent care sites in geographically strategic locations that would serve high COVID-19 density places. By doing that, we were able to open 17 infusion sites, which essentially covered the majority of a population corridor representing about 2.5 million people. This meant no one would have to drive more than 60 minutes to get to an infusion site. In most cases it was much shorter than that.
Q: What do you think has been key to Intermountain's successful rollout?
BW: We've been participating in the clinical trial that led to the authorization of these treatments, so we were able to get some familiarity of how the infusions work even before they were authorized by the FDA. The other thing that was helpful was the fact that we were already doing clinical trials in outpatient COVID-19 populations. Because of our research participation, we had already developed a platform for identifying patients who were at higher risk and would stand to benefit from treatments designed to prevent hospitalization.
I think two factors gave us confidence. One, that we could appropriately match the drug supply and infusion capacity that we did have to the patients who were most likely to benefit. And two, that we already had the framework to do that because of our participation in clinical research.
Q: Do you have any insights on how well the treatment appears to be working in your patient population?
BW: When we started this program, we paired it with a planned approach to do research analysis to understand how well they work. We recognized that while FDA-authorized, these antibody treatments are still technically investigational, and we have an incomplete understanding of their safety and effectiveness.
As of March 11, Intermountain alone has delivered 1,000 treatments. We have now treated enough patients that we have a large enough sample to do a meaningful analysis. So we are just now starting to do that analysis. I can speak to some very preliminary numbers right now. Of the patients who receive infusions, about 4.5 percent of them end up being hospitalized. By our estimation, we are targeting a population that normally would be hospitalized at a rate of at least 10 percent to 15 percent. So very preliminarily, we expect that this treatment is indeed preventing hospitalization, and we are anxious to have a more robust analysis with adjustment for other factors that will help us and others know even better in a real-world setting how well this actually works.
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