Respiratory Syncytial Virus (RSV) Update – PediaCast CME 101
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Show Notes
Description
- Dr Pablo Sanchez, Lindsey Glaze, and members of our clinical pharmacy program visit the studio as we consider respiratory syncytial virus (RSV) and share updates on its management and prevention. We hope you can join us!
Instructions to obtain CME/CE Credit
- Read this information page.
- Listen to the podcast.
- Complete the post-test at Nationwide Children’s CloudCME.
- You can view your transcript and print a certificate of completion at Cloud CME.
- Need help creating a Cloud CME account? Click Here.
- Still have questions? Contact CMEOffice@nationwidechildrens.org
Topics
- Respiratory Syncytial Virus (RSV)
- Bronchiolitis
- Synagis (palivizumab)
- Beyfortis (nirsevimab)
Presenters
-
Lindsey Glaze
Inpatient Pharmacy Educator
Nationwide Children’s Hospital
-
Colleen Djordjevich
Clinical Pharmacist
Neonatal Intensive Care
Nationwide Children’s Hospital
-
Megan Lewis
Clinical Pharmacist
Cardiothoracic Transplant and Heart Center
Nationwide Children’s Hospital
-
Dr Pablo Sanchez
Pediatric Infectious Disease
Neonatal Intensive Care
Nationwide Children’s Hospital
Learning Objectives
At the end of this activity, participants should be able to:
- Describe the epidemiology and clinical manifestations of RSV in infants and young children.
- Compare the prophylaxis options that limit severe RSV disease in infants and high-risk children
- Understand the administration of nirsevimab for RSV prophylaxis at Nationwide Children’s Hospital and clinics.
- ​Evaluate the safety and efficacy of maternal RSV vaccination and passive immunization with nirsevimab in infants and high-risk children.
References
- Pierangeli A, Scagnolari C, Antonelli G. Respiratory syncytial virus. Minerva Pediatr. 2018;70(6):553-565.
- Piedimonte G, Perez MK. Respiratory syncytial virus infection and bronchiolitis [published correction appears in Pediatr Rev. 2015 Feb;36(2):85]. Pediatr Rev. 2014;35(12):519-530.
- Kyler KE, McCulloh RJ. Current Concepts in the Evaluation and Management of Bronchiolitis. Infect Dis Clin North Am. 2018;32(1):35-45.
- Hannah Bahakel, Alpana Waghmare, Rebecca Pellet Madan, Impact of Respiratory Viral Infections in Transplant Recipients, Journal of the Pediatric Infectious Diseases Society, Volume 13, Issue Supplement_1, February 2024, Pages S39–S48.
- Liu M, Worley S, Arrigain S, et al. . Respiratory viral infections within one year after pediatric lung transplant. Transplant Inf Dis 2009; 11:304–12.
- American Academy of Pediatrics. "Respiratory Syncytial Virus". Red Book 2021-2024. Report of the Committee on Infectious Diseases, 32nd edition.
- American Academy of Pediatrics (AAP). Committee on Infectious Diseases and Bronchiolitis Guidelines Committee. Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics. 2014;134(2):415-420. doi:10.1542/peds.2014-1665.
- Caserta MT, O'Leary ST, Munoz FM, Ralston SL; Committee on Infectious Diseases. Palivizumab prophylaxis in infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics. 2023;152(1):e2023061803. doi:10.1542/peds.2023-061803.
- Griffin, et al, Single-Dose Nirsevimab for Prevention of RSV in Preterm Infants. N Engl J Med. 2020;383(7):698.
- Hammitt LL, Dagan R, Yuan Y, Baca Cots M, Bosheva M, Madhi SA, Muller WJ, Zar HJ, Brooks D, Grenham A, Wählby Hamrén U, Mankad VS, Ren P, Takas T, Abram ME, Leach A, Griffin MP, Villafana T; MELODY Study Group. Nirsevimab for Prevention of RSV in Healthy Late-Preterm and Term Infants. N Engl J Med. 2022 Mar 3;386(9):837-846.
- Jones JM, Fleming-Dutra KE, Prill MM, et al. Use of Nirsevimab for the Prevention of Respiratory Syncytial Virus Disease Among Infants and Young Children: Recommendations of the Advisory Committee on Immunization Practices — United States, 2023. MMWR Morb Mortal Wkly Rep 2023; 72(34):920–5.
- DCD HAN00499: Limited Availability of Nirsevimab in the United States—Interim CDC Recommendations to Protect Infants from Respiratory Syncytial Virus (RSV) during the 2023–2024 Respiratory Virus Season. October 23, 2023.
- Sanofi launches Beyfortus® (nirsevimab-alip) Reservation Program for 2024-2025 RSV season in U.S. Sanofi. News release. February 1, 2024. Accessed February 2, 2024.
- American Academy of Pediatrics (AAP). Committee on Infectious Diseases. Modified Recommendations for Use of Palivizumab for Prevention of Respiratory Syncytial Virus Infections. Pediatrics. 2009; 124:1694-1701.
Disclosure Statement
- No one in a position to control content has any relationships with commercial interests.
Commercial Support
- Nationwide Children’s has not received any commercial support for this activity.
CME/CE Information
- In support of improving patient care, Nationwide Children’s Hospital is jointly accredited by the American Nurses Credentialing Center (ANCC), the Accreditation Council for Pharmacy Education (ACPE), and the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for the healthcare team. (1.0 ANCC contact hours; 1.0 ACPE hours; 1.0 CME hours)
- Nationwide Children's Hospital has been authorized by the American Academy of PAs (AAPA) to award AAPA Category 1 CME credit for activities planned in accordance with AAPA CME Criteria. This activity is designated for 1.0 AAPA Category 1 CME credits. Approval is valid for 2 years from the date of the activity. PAs should only claim credit commensurate with the extent of their participation.
- As a Jointly Accredited Organization, Nationwide Children's Hospital is approved to offer social work continuing education by the Association of Social Work Boards (ASWB) Approved Continuing Education (ACE) program. Organizations, not individual courses, are approved under this program. State and provincial regulatory boards have the final authority to determine whether an individual course may be accepted for continuing education credit. Nationwide Children's Hospital maintains responsibility for this course. Social workers completing this course receive 1.0 continuing education credits.
- Continuing Education (CE) credits for psychologists are provided through the co-sponsorship of the American Psychological Association (APA) Office of Continuing Education in Psychology (CEP). The APA CEP Office maintains responsibility for the content of the programs.
Contact Us
- CMEOffice@nationwidechildrens.org
Episode Transcript
[Dr Mike Patrick]
This episode of PediaCast CME is brought to you by Neonatology and Pharmacy Services at Nationwide Children's Hospital. Hello everybody, and welcome once again to PediaCast CME. It's a continuing medical education podcast for healthcare providers.
This is Dr. Mike coming to you from the campus of Nationwide Children's Hospital. We're in Columbus, Ohio. It's episode 101.
We're calling this one respiratory syncytial virus, or RSV, an update. We want to welcome all of you to the program. So, this is our annual really important topic for you because we do cover RSV and the illness that it causes, bronchiolitis, in one way or another, just about every year in the fall on this podcast.
And whether it's the parent version of PediaCast over at pediacast.org, or it is this version where we offer CME credit for medical providers, in one way or another, pretty much every year we cover respiratory syncytial virus. And that is because this virus is the most significant cause of bronchiolitis, and it is the leading cause of hospitalizations and deaths for babies around the world. So, we cover RSV and bronchiolitis again in one manner or another, just about every year.
And this year we're going to explore RSV, including its management and especially its prevention through the lens of a clinical pharmacy and neonatology. And as you know, we maintain joint accreditation for continuing medical education here on PediaCast CME, and that includes continuing education for pharmacists. Additionally, there are some major updates to report on RSV prevention this year.
So, when our clinical pharmacists pitched the idea for this episode, it was a no brainer. Yes, of course we should cover this. It's really important stuff.
So, we have a terrific episode planned for you today and not just for pharmacists, but really all providers who take care of kids, including physicians, nurse practitioners, PAs, nurses, social workers, you get the idea. And of course, in our usual PediaCast fashion, we have several terrific guests joining us this week, Colleen Djordjevich and Megan Lewis and Jackie Magers. They are all clinical pharmacists at Nationwide Children's Hospital.
We also have Dr. Pablo Sanchez. He is a neonatologist and a pediatric infectious disease expert at Nationwide Children's. And we also have a guest host who's going to guide the conversation this week, Lindsey Glaze.
She is an inpatient pharmacy educator at Nationwide Children's Hospital. Right out of the gate, I want to mention something that's going to be important as you listen to this podcast, because it can get kind of confusing. And so, I want to mention this again, right up front, you know, in general on educational podcasts and things associated with the academic world.
In general, we like to use the generic name of medications. And this is particularly important when there are multiple options of the same drug. So it may be, you know, made by a particular company, but there also may be generic versions of it out there.
And so, we don't necessarily want to promote one business over another because they are still companies that are making the generic version. They don't just appear on trees. You know, someone makes them and sells them.
And so, it is important that we sort of, you know, maintain neutrality. On the flip side of that, oftentimes the trade name is the one that we are most familiar with and the one that we often use when we talk to patients, because that is the name that our patients are most familiar with. And in this situation, and we're going to be talking about a couple of drugs that there is no generic version.
There's only the brand name version. And so, you're going to notice that we use the generic name and the brand name kind of interchangeable at times during the podcast. But I want to let everyone know that we do not, none of us involved in this podcast, the guests, the guest hosts, myself have any financial incentive, you know, to talk about these things.
So, we are definitely neutral when it comes to the finances. And so, I just wanted to mention the names because I think the audience out there, you're going to know the trade names a little better than the generics and, but you're going to hear the generics a lot during this. So, I just wanted to give you a little mnemonic to help you remember which one is which.
So, the first one is going to be Synagis. That's the trade name. And this is the RSV monoclonal antibody that has traditionally been used over, you know, the last few decades to help protect babies, especially high-risk babies from RSV infection.
And Synagis, the generic name for it is palivizumab. And so, you're going to hear palivizumab a lot during this podcast. It starts with pal.
So, I like to think of it as Synagis is my old pal because that's the one we used to use. And we used it, you know, year after year, after year, after year. So, it's like an old pal.
The new one is Beyfortis. And this one, the generic name for Beyfortis is nirsevimab. Okay.
nirsevimab. So, it starts with nurse. And so, I just think, well, the better one today that the nurses ought to be giving to babies to help prevent RSV is nirsevimab or the Beyfortis.
So palivizumab, that's our pal. That's the old Synagis. nirsevimab is Beyfortis.
That's the newer one. So, as we go along, as you hear, listen for pal or nurse at the end, if it's pal, it's the old Synagis. It's our old pal.
If it's nurse, it's the one that we are primarily using this RSV season. And it's the one that the nurses are giving. So, I don't know.
I had to use that mnemonic to help myself and maybe it'll help you as well. After listening to this episode, make sure you do claim your free category one credit. Really easy to do.
Just head over to the show notes for this episode over at pdacastcme.org. You'll find a link to the post-test in the show notes. Follow that link to Cloud CME, click on the materials tab taken past the post-test and the category one credit is yours.
And as I previously mentioned, we do offer credit to many pediatric professionals since we have joint accreditation. And that includes physicians, nurse practitioners, PAs, nurses, pharmacists, psychologists, social workers, and dentists. These are the credits they're category one credits.
So, they're the ones you need to fulfill your state's continuing medical education requirements. Of course, you want to be sure the content of this episode matches your scope of practice, which it probably does given that RSV is a, is so common and can be so devastating for, for many babies, including healthy ones. And so, it's something we definitely want to prevent and educate folks about.
So, I think it's one is going to be one that's pretty much important for anyone who takes care of kids. Complete details on the continuing medical education credit is available over at pdacastcme.org. Also want to remind you the information presented in our podcast is for general educational purposes only.
We do not diagnose medical conditions or formulate treatment plans for specific individuals. Also, your use of this audio program is subject to the PediaCast CME Terms of Use Agreement, which you can find at pdacastcme.org. So, let's take a quick break.
We'll get our expert panel settled into the studio, and then we will be back to talk about respiratory syncytial virus. It's coming up right after this.
[Dr Mike Patrick]
We have a trio of clinical pharmacists joining us this week, Colleen Djordjevich and Jackie Magers are clinical pharmacists with the Newborn Intensive Care Unit at Nationwide Children's Hospital.
And Megan Lewis is a clinical pharmacist with the Cardiothoracic Transplant and Heart Center also at Nationwide Children's. We also have a neonatal infectious disease expert with us today, Dr. Pablo Sanchez. He's a perinatal researcher at Nationwide Children's and a professor of pediatrics at the Ohio State University College of Medicine.
All four have a passion for supporting babies and families impacted by RSV and the prevention of these infections, especially in high-risk babies. That's what they're here to talk about, RSV infections and their prevention. Before we dive in, let's offer a warm PediaCast welcome to our guests.
Thank you all so much for joining us today. Really appreciate you being here. And then we also have a guest host with us who's going to guide the conversation this week.
Lindsey Glaze is an inpatient pharmacy educator at Nationwide Children's Hospital. She put lots of hard work into this episode, as did all of our guests. And we are so grateful for all of those efforts.
So, without further ado, let's hand the reins over to Lindsey Glaze. Thanks so much for being here, Lindsey.
[Lindsey Glaze]
Hi, Dr. Mike. Thanks so much for those introductions. Let's just get started here off the bat.
And Colleen, would you be able to explain to us what exactly is RSV?
[Colleen Djordjevich]
Yeah, of course. Before we start talking about the prevention, it is important that we kind of understand that RSV is a single-stranded RNA virus. And it's actually one of the most common respiratory pathogens in infants and young children.
So, it actually does account for greater than 80% of all the lower respiratory tract infections in infants younger than one year of age. And it's by far the most frequent cause of pediatric bronchiolitis and pneumonia. Okay.
And how does, how do these babies get RSV? So, transmission occurs through respiratory secretions from infected individuals. The incubation period does range from two to eight days.
However, it is important to note that immunocompetent individuals can actually shed the virus for up to three weeks. However, the average is about eight days. So those respiratory secretions coming from the upper respiratory tract, and then additionally that shedding of the epithelial layers in the lower respiratory tract, some of the signs and symptoms are rhinorrhea, cough, respiratory distress, fever, and malaise.
So those are some symptoms to look out for when thinking about RSV.
[Lindsey Glaze]
Okay. And then who is at risk for RSV?
[Colleen Djordjevich]
There are actually several risk factors. So, prematurity is one that we'll focus on mostly, however, being less than 12 weeks of age, the male sex, if the infant has a lack of breastfeeding, also if they have any other congenital anomalies, such as cardiac disease, cystic fibrosis, chronic lung disease of prematurity. Additionally, if in the household there was any utero or postnatal cigarette smoke exposure, that can also be a risk factor.
As I mentioned before that history of prematurity, that really does increase the morbidity and mortality of RSV. In these premature infants, just due to the fact that they have a reduced humoral protection and inefficient T-cell mediated response. And one other thing to mention too, I know we did talk about prematurity, but it is important to note that all infants, whether you were premature or born term are at severe risk for hospitalization with RSV.
So that's basically any infant who is less than one year of age.
[Dr Mike Patrick]
If I can interrupt really quickly, I just wanted to point out another term with RSV that a lot of folks hear is bronchiolitis. And so, RSV is, you know, a specific organism that causes infection. And when we see that spectrum of symptoms that go along with RSV, we call that bronchiolitis and there are other viruses that can also cause bronchiolitis.
So, we're really focused on RSV for this episode, but it is important to know other viruses can do it. And, you know, in some folks you get RSV and it's just a bad cold, but then in others, especially in babies, and we can say, well, there's high risk, but even healthy babies are still at risk because RSV is one of the leading causes of hospitalizations for babies worldwide.
[Lindsey Glaze]
Now that we kind of went through signs and symptoms and who is at risk, Megan, are you able to kind of speak to the complications of RSV that we've been seeing?
[Megan Lewis]
Of course. So, kind of as Dr. Mike mentioned, in more mild cases, you can really, it can act like the common cold for most children. They can have upper respiratory symptoms.
They might have a low-grade fever. However, in our patients that are less than one year of age and in others as well, more severe cases, they can have bronchiolitis, they can have pneumonia. They can have the inability to maintain normal hydration.
And for all of these reasons, these children can be hospitalized, require oxygen supplementation, need IV fluids, and in our most severe cases, they might even need mechanical ventilation and as well as in our severest cases, ECMO. So, kind of a broad range of, broad spectrum of.
[Lindsey Glaze]
You work in the cardiothoracic ICU and also with some of the transplant patients there. In your immunocompromised patients, are there any different management strategies than those that you've already discussed?
[Megan Lewis]
Yeah. So overall, supportive care is one of the biggest strategies for management. Kind of take it a step further in my immunocompromised patients.
And it's really those additional therapies are tailored based on the specific patient and usually in consult with our host defense infectious disease team. So, it can be based on the organ that's transplanted. So, for our lung transplant patients in particular, those patients are particularly prone to severe complications from any respiratory virus, RSV included.
Those can cause bronchiolitis obliterans syndrome or chronic lung allograft dysfunction. So, in those patients, we treat them much more aggressively. Ribavirin, oral or inhaled, is one of the only FDA approved therapies.
It's an antiviral medication. It is FDA approved, like I mentioned, for RSV. Particularly in adult patients, so we don't have any FDA approved therapies in our pediatric patient population.
We just extrapolate those from the adult patient population. We also typically use steroids, either oral or IV. We use IVIG.
And then as salvage therapy, we actually use palivizumab, which is also called Synagis, which some of you have may have heard before. And that was kind of our old monoclonal antibody used to prevent RSV. And we can use it as salvage treatment in our immunocompromised patients.
[Lindsey Glaze]
So, it definitely sounds like it'd be better to avoid it. What are our options for kind of preventing RSV?
[Megan Lewis]
So, one of the best ways to prevent RSV is really standard precautions. So, avoiding sick contacts and good hand hygiene when you're out in the community. For hospitalized patients, we put those patients on contact droplet precautions to protect them and to protect others from spreading RSV once they're admitted to the hospital.
Immunoprophylaxis has been shown to decrease RSV associated hospitalizations and our high-risk inference from anywhere from 39 to 82 percent. And what we use for that historically was palivizumab or Synagis, which I had mentioned before, which is a monoclonal antibody used to prevent RSV associated hospitalizations. Generally, we had given it prior to discharge for NICU patients and in other select patients to prevent RSV following AAP recommendations, which Colleen had briefly mentioned before.
So, patients born prematurely, patients less than 12 months with lung disease of prematurity, and then in other patients, a lot of my cardiac patients with congenital heart defects would get it as well.
[Lindsey Glaze]
You mentioned the historical perspective of using palivizumab. What are the new treatments available then for prevention of RSV?
[Megan Lewis]
Yeah, so last season we had a new monoclonal antibody called Nirsevimab or Beyfortis. That's a long acting MOND-24 RSV season. It replaced Synagis.
It reduced the cost and kind of extended eligibility for many more patients. So, anybody less than eight months of age entering their first RSV season was eligible versus some of the more high-risk patients that were eligible for Synagis. Colleen will discuss some more details in a bit.
And then there's also maternal RSV vaccines that Pablo will discuss later as well.
[Lindsey Glaze]
So, when is RSV season and then when do we begin prophylaxis?
[Megan Lewis]
So historically, RSV season began in the winter months and extended into spring. So anywhere from November to April was like our typical season. After the COVID-19 pandemic, it's been pretty difficult to predict when the season would be.
Rates were abnormally low in the 2020-2021 season. And then since then, they've kind of risen during unseasonal times, often earlier than the traditional season. So here at NCH, we monitor RSV rates in the community, and we start nirsevimab prophylaxis when RSV rates are greater than 5% for two consecutive weeks, score on October 1st.
Okay, so we are in RSV season officially then.
[Dr Pablo Sanchez]
We're at 6% last week and the previous week was 5%. So, I'm glad that we're providing nirsevimab currently to all of our infants and high-risk children.
[Lindsey Glaze]
So, let's talk more about nirsevimab and Beyfortis, this new therapy that became available last year. Colleen, can you tell me a little bit more about nirsevimab?
[Colleen Djordjevich]
Sure. So nirsevimab is like Palivizumab in that it is a monoclonal antibody. It's just modified in the FC region of that antibody.
So, it provides a longer half-life. So, you can think of it like Synagis, except we just have to give one dose in order for these infants to be covered. Another point about nirsevimab that I want to make is this is passive immunity against RSV.
So, it's really important when we're educating our family members or parents who potentially may want to give their baby nirsevimab that this is not a vaccine. This is a monoclonal antibody that does provide that passive immunization. It actually was approved by the FDA in July of 2023, and then it started being recommended by the CDC in August of 2023.
So, it's just that extended half-life that we only provide one dose in order for our infants to be covered.
[Dr Mike Patrick]
Colleen, if I can jump in really quick, why is it that we only have to give it once during the season, whereas Synagis we had to give every month?
[Colleen Djordjevich]
Yeah, that can get a little bit confusing. So, because Synagis, it had a shorter half-life. So, like a vaccine where we're creating our own antibodies if we get in contact with that virus, whereas for this passive immunity, we're just providing these antibodies that are just going to be in our bloodstream ready in case we happen to get in contact with that virus, we have that immunity there for us.
So, because Synagis had a shorter half-life, we had to give five doses in order to keep boosting that antibody amount, or that serum level amount of antibody that we had in our bloodstream. So, because nirsevimab has that longer half-life, those antibodies are staying longer in our serum level so that we don't have to give.
[Dr Mike Patrick]
And do we have any idea why that is? I'm sure it's complex microbiology. I mean, that difference in half-life.
Pablo, I'm sure you could add some insight here.
[Dr Pablo Sanchez]
So nirsevimab is a recombinant human immunoglobulin, like Colleen mentioned. It is completely recombinant, but the FC region of the molecule of the antibody was modified, and that is why we have such an extended half-life, and that's why only one dose is needed, and it lasts at least 150 days, whereas previously with Palivizumab, we had, as Colleen mentioned, we had to give it monthly. What's really interesting also, and important, is that there's no decline in its activity through at least 150 days.
So, it is as active on day 150 as it was after giving it on day one. The neutralizing activity of nirsevimab is superior to Palivizumab. So, it is not only longer lasting, but it is overall a better agent to neutralize the virus and prevent the virus from fusing to the host cells and cause the disease.
There actually is a new monoclonal that also has an extended half-life, Clostrofimab, that does get into the nasal mucosa, and so we may be seeing even further improvements in these monoclonal antibodies in efforts to not only prevent lower respiratory tract infection, but even the upper respiratory tract.
[Lindsey Glaze]
So right now, who qualifies for Nirsevimab administration?
[Colleen Djordjevich]
Sure. So unlike Synagis with our medical audience, they may have before said we had these specific criteria of who would qualify. This is now all infants under eight months of age entering their first RSV season.
Those infants do qualify. So, this is any premature infant term, you know, all babies less than eight months of age entering their first RSV. Now for the second season, any patients eight to 19 months who are at an increased risk for RSV.
So, these would be our patients who kind of similar to Synagis, who are severely immunocompromised, any high-risk children with bronchopulmonary disease or cystic fibrosis, so that is entering their second season would get Nirsevimab. And so, a dose is based on their weight. So, if you're less than five kilos, they would receive the 50-milligram dose, and then anyone greater than or equal to five kilos would receive a hundred milligram dose.
[Lindsey Glaze]
And is that the same dosing then for the second season as well? Can you tell us about the clinical studies that led to the FDA approval of this kind of like groundbreaking therapy?
[Colleen Djordjevich]
Sure. So, there's actually two studies that I really wanted to highlight today for our audience. And the first one is a phase 2B trial.
So, this looked at our preterm infants. So that was anyone who was 29 weeks to 34 weeks plus, and the primary endpoint was any medically attended RSV infection through those 150 days. So that five-month mark that we keep talking about post the Nirsevimab injection.
So, this study included around 1,400 infants from November of 2016 through November of 2017, and there were 900 or so infants who received Nirsevimab, and then close to 500 infants who received a placebo. So, after their injection, they looked at the incidence of the medically attended RSV infection. So, they actually found only 2.6% in the Nirsevimab group versus 9.5% in the control group. And that was a 95% confidence interval with a P value of less than 0.01. This did come out to a number needed to treat for these infants to 14. They also looked at hospitalizations, which is really important too. And they found that in the Nirsevimab group, so the infants who received Nirsevimab, it was 0.8% for hospitalizations versus 4.1% in the placebo group, which comes out to a number needed to treat of about 30. So that's sort of our like premature infant group. There is a phase three trial though that I want us to talk about too, which is the late preterm to term. So, this looked at any infants 35 weeks or greater.
Again, there were about 1500 infants who were included in this trial. And it took place between July of 2019 through November of 2019. And close to 1000 infants received Nirsevimab and close to 500 infants received placebo.
Again, this trial also looked at the incidence of any medically attended RSV infection and found 1.2% of infants in the Nirsevimab group versus 5% of infants in that placebo. So that wasn't also a 95% confidence interval and a P-value of less than 0.001. This calculates out to a number needed to treat of 26. And this study as well looked at the incidence of hospitalizations and found 0.6% in the Nirsevimab group versus 1.6% in the placebo group, which comes out to a number needed to treat of about 100. So really great for our preterm and our late preterm and term infants, which is why we have approval for all infants less than eight months of age entering their first RSV season to receive Nirsevimab. And also too, I did want to mention, you know, with any clinical trial and phase two and three trials, we want to look at any serious adverse events or hypersensitivity reactions. And the clinical trials did report no serious category of a serious event considered to be related to the trial regimen.
And they also did not report any hypersensitivity reaction.
[Dr Pablo Sanchez]
Thank you. So that was a great overview, Colleen. And I just want to also state that the Nirsevimab, once it became available last year, it became widely used in the United States even though there were shortages.
But importantly, there's been global use of Nirsevimab. And in the United States, the Centers for Disease Control, the new vaccine surveillance network of seven pediatric academic centers noted a 90% effectiveness against RSV hospitalization. Nirsevimab has been used extensively in Spain, and they're also reporting superb effectiveness, anywhere from 70 to 88%.
France recently reported a 3% effectiveness against RSV hospitalization. And the preliminary data also from the southern hemisphere, from Chile, is also extremely encouraging. So, this is really a boon to our infants for prevention of RSV infection.
[Lindsey Glaze]
So, there is going to be a lot of demand then for this monoclonal antibody. And we saw that last year with the first season for nirsevimab administration. Jackie, are you able to talk about were there any about the supply chain issues that we've had and kind of what did we do last year to kind of prevent that from happening for all of our infants?
[Jackie Magers]
Sure. As you can imagine, how Synergist was just meant for more for the preemie babies and now how with nirsevimab being available for all neonates, you know, up to eight months of age for the first season, that the population was a lot bigger. And so, it was kind of hard, I think, for the manufacturer, Sanofi, to kind of really, truly get a good, accurate prediction.
So, there was some difficulty keeping up with the demand in that first season, particularly with the 100-milligram dosing. But fortunately, here at Nationwide Children's, our inventory purchasing department is top notch. So, we really were very fortunate where we didn't have to run into using other alternative agents.
[Lindsey Glaze]
Did we put in place any restrictions on who could receive the monoclonal antibody?
[Jackie Magers]
No, typically we tried to follow the guidelines as best as we can. If we were running out of certain dosing strategies, then we did have Synergist as a backup plan, as a contingency plan for those patients that may not have been able to get their nirsevimab either at their before discharge from here.
[Dr Pablo Sanchez]
I would just like to add that we, unlike other centers around the country, we did not experience any nirsevimab shortage and we gave them to all eligible infants and high-risk children. And I just want to give a shout out to Mike Storey from Pharmacy because he did a superb job of keeping, of having us have that supply.
[Lindsey Glaze]
Yes, we appreciate Mike and all of the inventory team working tirelessly to make sure that we were able to get the supply that we needed. Do we anticipate these same issues for this RSV season?
[Jackie Magers]
Hopefully not. Bay Fortis did work with the American Academy of Pediatrics and the CDC this year to ensure measures were in place to hopefully meet the demand for this upcoming season. So, they've tried to be a little more proactive as best as they could based off of usage from the 2023-2024 season.
So, fingers crossed that we don't run into issues this year.
[Lindsey Glaze]
So, assuming that we are not going to have any supply issues, when will patients at NCH receive nirsevimab?
[Jackie Magers]
So as my colleagues previously mentioned, we started doing that starting October 1 of this year. And typically, at least on the NICU side of things, we will give our nirsevimab injection right before they go home or if the baby is due for some other immunizations around that same time, we try to cluster them together just to minimize the number of painful procedures. So, but an exception to this rule is if we have a kiddo who had previously received nirsevimab but then has since required ECMO or cardiopulmonary bypass.
If that occurs, then the patient needs to get repeat or a subsequent dose, and that's typically done when the patient is deemed clinically stable. Currently, majority of birthing hospitals are not offering nirsevimab upon discharge for babies being discharged from the well-baby nursery. So, it's recommended that those patients get their nirsevimab injection when they go to their first primary care physician appointment within that first week.
[Dr Mike Patrick]
And I think that's really an important point for the primary care docs in our audience to understand that just, you know, don't assume that the hospital from which a baby was discharged received the first dose. And so, it's definitely something that you want to bring up with families and find out did they get it? And if they didn't, you know, presenting the option of it, but explaining that, you know, the benefits are very high, you know, as we as compared to any risks that may be associated with it.
And we have really good evidence from the last couple of years that it's fine to give it with along with all the other childhood immunizations at the same time. Correct, Dr. Sanchez? Yes, absolutely.
It can be given.
[Dr Pablo Sanchez]
This medication can be given at the same time that other that any vaccine is given, including hepatitis B in the newborn period. I just want to comment, though, that in Columbus, none of the birthing hospitals are providing nursing in the newborn nursery. There are other hospitals around the country and around the world that are providing it because it is safe to give it in the immediate newborn period before discharge.
Many of those hospitals have joined the Vaccines for Children program and they've been able to give it through that channel. However, we are still working through here in Columbus to see how we could eventually give it before nursery discharge. If the baby goes to the NICU and then goes back to the parents, we here at Ohio State University Wexner Medical Center, we are also providing nurse at the time of the NICU discharge back to the mother so that baby will be protected once he's discharged.
[Colleen Djordjevich]
And I would say that's true for our other birthing hospitals as well. So, at Riverside or Dublin, they would also give that to a pundit.
[Dr Mike Patrick]
But the primary care docs out there ask and, you know, make sure that they got it. And if they didn't, you know, educate the parents about it and hopefully get that child protected.
[Dr Pablo Sanchez]
I tell you, I just got as an aside, I just came back from Dallas where I was there for 25 years and their county hospital, which has about 13 to 15 thousand deliveries a year. They're giving them all in the newborn nursery. It's amazing.
However, it's a VFC managed program. Anyway, just as an aside, it was amazing.
[Lindsey Glaze]
OK, I want to kind of pivot and talk about, you know, what the AAP recommendations are. So, Jackie, can you tell us what AAP recommends for RSV prevention and how these guidelines may have changed over time with the previously with palivizumab now versus with nirsevimab?
[Jackie Magers]
Sure. The AAP first guidelines for RSV came out in 1998 and then has since then been revised four times, with the most recent one being released in 2014. Those were then again revalidated in 2023, but that basically was still supporting the use of the synergists.
And what Megan, I think, has commented on earlier was basically the five doses once a month during the RSV season. And then the earlier ones also had a select premature infants who only got three doses based on various risk factors. So, it has gradually changed from time to time.
So, the most recent guidelines for synergists, like I mentioned, were last published and updated in 2014 and agreed upon again in 2023. But basically, those are those premature infants less than 32 weeks, and they had an oxygen requirement of greater than 21 percent for at least the first 28 days of life. And then there were also those patients with a cyanotic congenital heart disease or those who had moderate to severe pulmonary hypertension.
Those kiddos, they did qualify for the first season, but not necessarily the second season. But our kids with chronic lung disease or BPD, if they were still requiring medical support, so chronic systemic steroids, diuretic therapy or supplemental oxygen, they could receive a synergist during the second RSV season.
[Lindsey Glaze]
And then this is kind of going back to the point that we talked about with the shortage last year. We didn't really see this here at NCH, but do you know, how did Palivizumab kind of fit into prevention last year during if other hospitals had shortages where they weren't able to get nirsevimab? And do you think that may also be the case this year if there's any shortage issues?
[Jackie Magers]
I'm hoping with some of the pre-work like the AAP and the CDC have done, worked with Sanofi this year that hopefully we don't have to employ those measures again. But at least at NCH, our contingency plan was to use synergists. But as we've already talked about, we were very fortunate where we didn't have any shortage type issues.
The handful of times that was used was mostly for treatment of diagnosed RSV disease and not necessarily for prophylaxis. So, for this upcoming season, I would imagine it would be the same thing, more for a treatment and not necessarily the prophylaxis use.
[Lindsey Glaze]
OK, so we've talked about historical data with RSV treatment, how palivizumab fit into that picture. But now that nirsevimab is here, let's kind of just recap exactly things that our audience members need to know going forward. So, Dr. Sanchez, can you describe again how often we're using nirsevimab, how often you give nirsevimab during RSV season?
[Dr Pablo Sanchez]
So nirsevimab is only given once during the RSV season. For infants less than eight months of age, they must be less than eight months of age at the time of its administration. And for infants who are eight months to 19 months of age, then also only once at the beginning or during the RSV season.
[Lindsey Glaze]
And then we've talked about how this is significantly better than with Synergist where it was, you know, five doses per season. Are there any other differences between the two that our audience should be aware of?
[Dr Pablo Sanchez]
Well, nirsevimab certainly has higher neutralizing activity against RSV than palivizumab. The administration of only a single dose during the season or before the season has so much advantage that currently we need to forget that palivizumab exists. We need to focus on the administration of nirsevimab to all babies.
This has been a huge, huge, huge boon. We've been waiting, waiting and anticipating the day that we could say that we could prevent RSV hospitalization in the normal child, not just the high-risk one. And with effectiveness of over 80 to 90 percent, we can be there if we are able to get this product into all infants less than eight months of age in their first season and eight months to 19 months of age in the second season who are high risk.
[Lindsey Glaze]
I've also heard about maternal RSV vaccines, Abrysvo and Arexvy. Are you able to kind of describe how that also is helping with prevention of RSV and who qualifies or just tell us a little bit more about both of those vaccines?
[Dr Pablo Sanchez]
So now we have a double approach to RSV prevention in infants. And one, as you've mentioned, has been the nirsevimab, but now we also have the availability of a maternal vaccine. It is a bivalent vaccine that targets both RSV A and B.
It is given from 32 to 36 weeks of pregnancy. It is a seasonal vaccine, so it is administered to pregnant women from September through January when it would be expected that the baby would be born right before or during the RSV season. So currently there is one maternal Refusion F protein-based RSV vaccine that is manufactured by Pfizer.
And this vaccine was approved by the FDA in August of 2023, recommended by the Advisory Committee of Immunizations of the CDC and by CDC on 9-22-2023. And then, very importantly, the official recommendations are published in the Morbidity and Mortality Weekly Report in October of 2023, which made it a formal recommendation that insurance carriers needed to cover at least within the year following its approval and publication in the Morbidity and Mortality. So, this maternal vaccine, Pfizer vaccine, the pre-F fusion vaccine, was studied in a randomized trial where it was administered to pregnant women from 24 to 36 weeks of pregnancy.
The vaccine efficacy at 180 days after birth was approximately 70%. And overall, it was well tolerated and safe, except that there was an imbalance of premature births in the women who received the vaccine, 5.1 versus 4.1 in the women who had received the placebo. It was not statistically significant, but because of that concern, the FDA only licensed the vaccine for administration from 32 to 36 weeks.
At the same time, there was another RSV pre-fusion F-protein vaccine that was developed by GlaxoSmithKline, and in that trial, there was a significant increase in premature births following the administration compared to women who had received the placebo. Because of that, the GlaxoSmithKline vaccine was, the study was stopped, and it's no longer available or approved for administration to pregnant women. It is available though, for people who are 75 years of age or older, because RSV infection is more severe and can be more severe in the eldered.
[Dr Mike Patrick]
And I just want to point out a couple of things with that series of facts that you shared, Dr. Sanchez. First, that this is important to medicine, that we make sure that the things that we're giving and recommending are safe. And so especially during the pandemic, and there's a lot of misinformation out there about various vaccines and therapies, that we really, it is important to us that we are not doing harm, that we are actually doing something that's going to be beneficial for children.
And so, I think when you say like we stopped giving it because we saw this possible association, and of course, in senior Americans, that's not as big of an issue because they're not getting pregnant. And so, we don't have to worry about preterm births in those adults. The other thing I wanted to mention is just, and I guess it's a little different since this was a controlled trial with a placebo, but you know, you could argue if you know it's a high-risk pregnancy, you may be more likely to say, oh, let's remember to give this vaccine to help prevent RSV to the baby.
And so there could be a sampling effect where the more high-risk people are getting it for sure, and then you're going to see more preterm births, not necessarily because of the vaccine, but because we preferentially gave the vaccine to people who are at higher risk to have a premature birth. But it sounds like if there was a placebo involved, then maybe that's not as big of an issue. And I only bring this up because we do have to think about all of the data when we think about trials and their results and make sure that we really are finding a causation, not just an association, if that makes sense.
[Dr Pablo Sanchez]
Yeah, the association with preterm births in the MATIS trial, which is the pre-F vaccine of Pfizer's, was called MATIS. That association and preterm births, the preterm births occurred more than 30 days after the administration of the vaccine, which makes it less likely to be causal. And also, the preterm birth, even in both groups, was 4-5%, which is substantially lower than preterm births on a global basis, which are in the order of 8-12%.
So that population, if anything, probably may have been a little bit healthier. Regardless of that, though, the FDA approved the licensure of this vaccine to pregnant women at 32-36 weeks, but they also recommended and post-marketing surveillance for preterm births as well as hypertensive disorders of pregnancy. And importantly, there was a recent study performed at two hospitals in New York City, whereby post-marketing surveillance, they did not find an association with preterm births whatsoever, but there was an association with hypertensive disorders.
So, I think that we still are needing to monitor these women who receive the vaccine. And however, I think that the vaccine will be a major boon on a global scale.
[Colleen Djordjevich]
And one thing I just wanted to mention too, as we get questions a lot as neonatal pharmacists, if the mom received the vaccine, does her baby still qualify for Beyfortis or nirsevimab? So, one thing that's important to mention too is if the mother received the vaccine and the baby was born within 14 days after the mom received the vaccine, we still would want to give that infant Beyfortis.
[Dr Pablo Sanchez]
Less than 14 days.
[Colleen Djordjevich]
Yes. Yeah. If the baby was born within those 14 days, then you would still receive it.
[Dr Mike Patrick]
But if it was given more than 14 days ago, then you may not need it?
[Colleen Djordjevich]
Correct. Yeah. So, if the mother received the vaccine greater than 14 days, then you would not receive the Nirsevimab.
[Dr Pablo Sanchez]
I don't want to be a stickler, but it's 14 days or greater. So, remember that the mother gets vaccinated. She needs to produce IgG antibodies against the fusion protein.
And those proteins, those antibodies need to cross the placenta and get into the fetus. And that will take approximately, it can take up to 14 days. But if the mother received the vaccine and the baby is born 14 or more days after she received it, then the baby does not need nirsevimab unless there are other high-risk conditions.
So nirsevimab is recommended to infants less than eight months of age if their mother received the RSV-PF vaccine during the pregnancy at the appropriate time, if the infant is born to a mother who is infected with HIV. HIV, maternal HIV infection may impact the transfer of antibodies through the placenta. And so, because of that uncertainty, we want to cover the baby and protect the baby.
So those babies, even if the mother received the vaccine at the appropriate time and over 14 or more days after, was born 14 or more days afterwards, that baby should get nirsevimab. Also, if the mother received the vaccine and she was immunocompromised, we're not sure also what her immune response, how adequate it was and whether the fetus had received a sufficient antibody so that baby would also receive nirsevimab. And then those infants who are at really very high risk for severe RSV infection, such as those who have hemodynamically significant cyanotic or acyanotic congenital heart disease, even if the mother received the vaccine, we would also give the baby a dose of nirsevimab to optimize protection.
[Lindsey Glaze]
I think we might also get asked the question, is there any guidance for baby number two? So, with mothers of multiple pregnancies, they're recommended to get Tdap with every pregnancy to pass on the testis immunity. Do we have any guidance for the…
[Dr Pablo Sanchez]
That is an important question. That is an important issue. So currently, there is no recommendation for providing RSV vaccine to any future pregnancy if the mother has received it already with a previous pregnancy.
In adults greater than 65 years of age, RSV antibodies last after one-time vaccination, RSV antibodies last for at least three years. We do not have any data on safety of repeating the vaccine at a subsequent pregnancy. We also don't know whether it's even needed.
So, until those trials are done, and until we have more information as to the transplacental passage of antibodies in a future pregnancy, and also with safety, we really only recommend it in one pregnancy. A future pregnancy, the mother does not get vaccinated, but the baby receives nirsevimab. I think a lot of that recommendation also comes because we do have another modality, another very effective way of protecting a subsequent child against severe RSV test.
[Lindsey Glaze]
Okay. Thank you all so much for our discussion today on RSV and especially for introducing and discussing nirsevimab. Any other thoughts from the group that you would like the audience to know?
[Dr Pablo Sanchez]
You know, a frequent question that comes up is we have two modalities. We have the maternal pre-F RSV vaccine, and we have nirsevimab for the baby. We've already discussed that in some instances, both the mother gets the vaccine and the infant gets nirsevimab, but which one's better?
And I just want to say that both are highly effective at preventing RSV hospitalization. There is no study that has evaluated each one together, so there is no head-to-head trial comparing nirsevimab versus maternal RSV vaccine. Both have shown high effectiveness and so it really comes down to personal considerations as to whether the mother receives it or she prefers that the infant receive the medication, nirsevimab.
Certainly, if nirsevimab were to be in shortage, certainly we would want the mother to get the vaccine as long as it's in good supply as well. So, I think we have two strategies that can complement each other and really requires a dialogue between the mother, parent, the father, and the healthcare professional as to how best to proceed.
[Dr Mike Patrick]
One of the things that may come up with parents, and Colleen, you may see this in the NICU, is the question of, is this a blood product? Since it's a monoclonal antibody, is that a consideration? Because if it were for a particular family, then maybe, as Pablo said, the personal choice, the mother may want the vaccine rather than the baby getting what could possibly be considered a blood product, or is it?
[Colleen Djordjevich]
That's a great question. I don't believe that we do consider it a blood product like we would with IVIG. This is a developed antibody, so we wouldn't consider it a blood product like other healthcare providers may have heard of, like IVIG, for example.
[Dr Mike Patrick]
Great, and that's something I think that primary care folks also need to understand that so that they can, you know, if you're going to do it in your office, I'm sure that's a question that comes up and we'd want to let folks know that no, it is not a blood product.
[Dr Pablo Sanchez]
This is a completely recombinant, laboratory-made product, medication. Absolutely nothing to do with any blood product or has not been obtained from blood donors or nothing whatsoever. It is completely safe with respect.
[Dr Mike Patrick]
Great, good to know. Well, this has been a really fantastic conversation, and I'm just so appreciative for all the hard work that all of you put in to bringing this together. So, once again, Colleen Djordjevich, Clinical Pharmacist with Neonatal Intensive Care, and Jackie Magers, also with Neonatal Intensive Care, and Megan Lewis, Clinical Pharmacist with the Cardiothoracic Transplant and Heart Center, and Dr. Pablo Sanchez, Pediatric Infectious Diseases and Neonatology at Nationwide Children's Hospital. And of course, thank you to all of you for taking time out of your day and making a PediaCast CME part of it. Really appreciate it. And then, of course, extra thanks to Lindsey Glaze, who is our guest host today and guided a wonderful conversation. Thanks so much for that, Lindsey.
[Dr Mike Patrick]
We are back with just enough time to say thanks, once again, to all of you for taking time and making PediaCast CME a part of your day. Really do appreciate that.
Also, thanks again to our guests this week, Colleen Djordjevich and Megan Lewis and Jackie Magers, all Clinical Pharmacists at Nationwide Children's Hospital. Dr. Pablo Sanchez, Pediatric Infectious Disease Expert and Neonatologist, also at Nationwide Children's. And thanks again to our guest host, Lindsey Glaze, Inpatient Pharmacy Educator at Nationwide Children's Hospital.
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