TrueCare DPC
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Introduction
On April 20, 2023, the New England Journal of Medicine (NEJM) published a phase 3 trial for Pfizer’s new RSV vaccine titled “Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants.” The study reported vaccine efficacy of approximately 57.1% [1] and on August 21, 2023, the vaccine received FDA approval for pregnant mothers between 32 and 36 weeks of pregnancy to prevent RSV in infants. [2]
Is ABRYSVO, Pfizer’s new RSV Vaccine (henceforth just “Vaccine”) right for you or your loved ones? To answer that, I believe we should first answer a few other questions. These three questions are questions that I believe every patient is entitled to know the answers to prior to deciding on whether or not any vaccine is right for them.
1. How common is the actual infection we’re vaccinating against and what are the chances that I or my child will catch it?
2. What is the absolute risk reduction of the vaccine compared to placebo?
3. How many people would need to receive the vaccine before someone is harmed and how many people need to receive the vaccine in order to protect one person from the infection we’re trying to prevent?
Let’s go ahead and address each of these questions one at a time.
How Common is RSV?
To understand how common a disease is, we can ask what its prevalence or its incidence rate is. Incidence rate tells us not only how common, but also how fast the rate of a disease is over a specified time. Prevalence, on the other hand, is a way to describe how common a specific health condition or characteristic is within a group of people within a specific window of time. For example, if we say the prevalence of RSV in the United States over the last 5 years is 5%, it means that 5 out of every 100 people in the country would have experienced RSV infection in the last 5 years.
Absolute risk is an attempt to determine the probability of something happening. It’s how we try and understand the likelihood that a certain population may experience “an event” over a certain period of time. For example, if the absolute risk (AR) of infants younger than 12 months old contracting an RSV lower respiratory tract infection (RSV-LRTI) is 3%, that means that 1 in every 33 infants younger than 12 months old has a chance of contracting RSV-LRTI.
So, when you ask your practitioner “over the last 3-5 years, how common is RSV among infants younger than 12 months and what is the absolute risk that my own child will have an RSV-LRTI?” you’re asking them, “looking at just the last 3-5 years, what is the prevalence of RSV infection in infants younger than 12 months, and what is the absolute risk of RSV-LRTI?”
In our discussion of RSV, we want to understand how common the infection is. But not just how common it is, how common is it for RSV infection to be severe? Now, global estimates state the disease burden is substantial. [3,4,5] It’s recognized globally as the leading cause of death in infants younger than 6 months of age, especially in low- and middle-income countries. But because my patient population is in the United States, my patients don’t need to know the impact RSV is having overseas, but rather its impact here at home.
To answer that question, I’ve taken a look at six studies, one of which is the Pfizer study, and broken down what they reported regarding the prevalence and absolute risk of RSV. Now, the individual breakdown can be pretty lengthy. So, I’ve summarized the findings here and provided a link to go to the individual results and original references for those of you who are curious and desire to get into the nitty gritty. Note: I’ve focused on studies that specifically report on US babies that are younger than 12 months of age.
We can break out how common RSV is and the absolute risk (AR) of infection into three separate buckets:
1. Outpatient treatment – how often does an RSV infection lead to a clinic visit where the child is examined and then sent home to recover?
2. Emergency Department (ED) visits – how often does an RSV infection lead to a visit to the ED?
3. Hospitalization – How often does an RSV infection require baby to be hospitalized?
Based on the studies I’ve reviewed; here’s how the numbers pan out [3,4,5,7]:
1. Outpatient treatment – Rates ranged from 2.34 – 2.8%
2. ED visits – Rates ranged from .025 – 4.74%
3. Hospitalization – rates ranged from .252 – 2.37%
What this means is that depending on the study, which vary based on how data was gathered, what years of data were included, and how the analysis was conducted, the approximate AR of your little one needing to see a clinic for RSV is between 2.34% and 2.8%, needing an ED visit for RSV is between .025% and 4.74%, and being hospitalized for RSV is between .252% and 2.37%.
But let’s say little one does end up being one of the unlucky few who have a severe RSV infection. What is the absolute risk that little one will succumb to his or her infection and we experience a tragedy? How fatal is RSV for children less than 12 months old in America?
I was only able to find one study that looked at that very specific question. Reichert et al. published their findings in the Journal of Infectious Diseases in 2022 using data spanning from 1999 to 2018. [6] They reported that within the span of those 20 years, there were 561 infant deaths attributed to RSV. They calculated that on average, 28 children would pass away from an RSV infection every year. This, according to the authors, would mean that the average mortality rate was 6.9 deaths for every 1,000,000 live births or 0.00069%.
Is this a lot? Well, that’s honestly up to you to decide! That’s why I think having this information is so important because it’s useful in helping you gauge whether or not you want/need the vaccine.
But now that we have a sense of how common RSV infection is and what the approximate absolute risk is to our children, let’s move on to our next question.
What is the Absolute Risk Reduction of the Vaccine?
For this question we can turn specifically to the Pfizer study. When determining absolute risk reduction, we first need to look at the different groups included in the study and calculate the absolute risk for each.
In the Pfizer study, there were 3676 mothers who received placebo and 117 infants contracted an RSV infection within 180 days of birth. This makes the AR of contracting RSV in the placebo group 3.19%. There were 3682 mothers who received vaccine and 57 infants contracted an RSV infection within 180 days of birth. This makes the AR of contracting RSV in the vaccine group 1.55%. This means that the absolute risk reduction (ARR) of the vaccine is 1.64% (3.19% minus 1.55%). In other words, according to the Pfizer study, if you were to get the Pfizer vaccine as a pregnant mother, the risk of your infant experiencing an RSV infection within 180 days goes from a 3.19 out of 100 chances to a 1.55 out of 100 chances.
What about a severe infection? What is the absolute risk reduction of the vaccine compared to placebo for a severe RSV infection?
Well, the AR in the study for severe infection in the placebo group was 1.68% This meant that there were 62 cases of infants with severe infection in the first 180 days of life whose mothers received placebo. In the vaccine group the AR was .516% or 19 cases of infants with severe infection in the first 180 days of life. Therefore, the absolute risk reduction for severe infection is 1.164%. Again, this means that if you are a pregnant mother receiving the Pfizer vaccine, you take your infant’s risk of severe infection from 1.68 out of every 100 to .516 out of every 100. So, given this, is it worth getting the vaccine? Let’s take a moment to consider two final factors addressed by our last question.
What is the Number Needed to Harm and Number Needed to Vaccinate?
Now, to be clear, the number needed to harm (NNH) is not a direct measure of safety, per se. Instead, what this calculation allows us to do is put a number to the question “how many people need to receive the treatment before we can expect someone to have an adverse event that is possibly associated with the treatment?” There is no set value that determines safety. Meaning, an NNH of 100 is not necessarily safe or unsafe. We can say that an NNH of 5 compared to 10 indicates that the lower NNH is probably less likely to cause an adverse event. But that doesn’t automatically mean the treatment with an NNH of 5 is necessarily safe.
Similarly, we use number needed to vaccinate (NNV) or number needed to treat (NNT) to help us estimate how effective a treatment/therapy/intervention may be. Like NNH, there is no set number that automatically says something is effective. But we can use this as a comparison to help us in trying to determine if a treatment is worth it for us and our patients.
With that in mind, let’s take a look at the NNH for the Pfizer vaccine. I’ll give you the bottom line upfront here and you can go to the detailed breakdown to see the details of how this was calculated.
Now, the investigators of the Pfizer study reported on adverse events in the first month of life and serious adverse events in the first 24 months of life. They also reported on total number of RSV cases in the first 180 days of life and severe RSV infections for the first 180 days. Using these reported figures and the data provided in the study’s Supplementary Appendix, the NNVs and NNH are as follows:
The NNH in the first month of life is 43.73.
The NNV to prevent any case of RSV in the first 180 days is 61.17
NNV to prevent severe infection is 85.43.
The NNH to potentially cause a serious adverse event in the first 24 months of life is 149.65.
Again, NNV to prevent any case of RSV in the first 180 days is 61.17
NNV to prevent severe infection is 85.43.
So, what does this mean in English?
It means that based on the data provided, if we gave about 44 pregnant mothers at between 32 and 36 weeks of pregnancy the Vaccine, there is a chance that one infant would experience an adverse event in the first month of life that may be attributed to the vaccine. In contrast, in order to potentially prevent an RSV infection during the first 180 days, we would need to vaccinate about 61 to 62 mothers and in order to potentially prevent a serious RSV infection, we would need to vaccinate between 85 and 86 pregnant mothers.
When looking at the vaccine’s potential for serious harm, we would need to give approximately 150 pregnant mothers the vaccine before an infant might experience a serious adverse event that could be attributed to the vaccine. Again, this is in comparison with the NNV of 61.17 for preventing any RSV infection and NNV of 85.43 to prevent a serious RSV infection.
Again the detailed breakdown of this can be found here.
Summary
In summary, what have we learned, and what can we do with this information?
In the US, RSV is by definition deadly. In the past, it has killed an average of 28 American babies a year. There is between a .025 to a 4.74% chance that RSV will lead to a clinic visit, ED visit, or hospitalization in little ones less than 12 months old. The Pfizer RSV vaccine has been shown to reduce this risk by 1.64%. If we gave the vaccine to 44 mothers, there’s a chance one baby would be harmed in the first month of life. If we gave the vaccine to 150 mothers, there’s a chance that one baby would be seriously harmed by it in the first 2 years of life. In contrast, we would need to give about 61 mothers the vaccine before protecting one baby from RSV in the first 6 months of life, and 85 mothers the vaccine before protecting one baby from a serious RSV infection.
So, should you or your loved one get the new Pfizer ABRYSVO Bivalent Prefusion F vaccine? That is up to you! I recommend you take this information to your primary care practitioner and discuss it in detail with them. If you don’t have one, good news! I’m enrolling patients at my practice, and I would be more than happy to go over all this with you!
References
1. Kampmann B, Madhi SA, Munjal I, Simões EAF,et al; MATISSE Study Group. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants. N Engl J Med. 2023 Apr 20;388(16):1451-1464. doi: 10.1056/NEJMoa2216480. Epub 2023 Apr 5. PMID: 37018474.
2. US FDA. FDA Approves First Vaccine for Pregnant Individuals to Prevent RSV in Infants. FDA News Release. 2023 Aug 21. Accessed on 2024 Feb 4 at https://www.fda.gov/news-events/press-announcements/fda-approves-first-vaccine-pregnant-individuals-prevent-rsv-infants
3. Gantenberg JR, van Aalst R, Zimmerman N, et al. Medically Attended Illness due to Respiratory Syncytial Virus Infection Among Infants Born in the United States Between 2016 and 2020. J Infect Dis. 2022 Aug 15;226(Suppl 2):S164-S174. doi: 10.1093/infdis/jiac185. PMID: 35968869; PMCID: PMC9377038.
4. Langley JM, Bianco V, Domachowske JB, et al. Incidence of Respiratory Syncytial Virus Lower Respiratory Tract Infections During the First 2 Years of Life: A Prospective Study Across Diverse Global Settings. J Infect Dis. 2022 Aug 26;226(3):374-385. doi: 10.1093/infdis/jiac227. PMID: 35668702; PMCID: PMC9417131.
5. Suh M, Movva N, Jiang X, Reichert H, et al. Respiratory Syncytial Virus Burden and Healthcare Utilization in United States Infants <1 Year of Age: Study of Nationally Representative Databases, 2011-2019. J Infect Dis. 2022 Aug 15;226(Suppl 2):S184-S194. doi: 10.1093/infdis/jiac155. PMID: 35968879; PMCID: PMC9377028.
6. Reichert H, Suh M, Jiang X, et al. Mortality Associated With Respiratory Syncytial Virus, Bronchiolitis, and Influenza Among Infants in the United States: A Birth Cohort Study From 1999 to 2018. J Infect Dis. 2022 Aug 15;226(Suppl 2):S246-S254. doi: 10.1093/infdis/jiac127. PMID: 35968877; PMCID: PMC9377030.
7. McLaughlin JM, Khan F, Schmitt HJ, et al. Respiratory Syncytial Virus-Associated Hospitalization Rates among US Infants: A Systematic Review and Meta-Analysis. J Infect Dis. 2022 Mar 15;225(6):1100-1111. doi: 10.1093/infdis/jiaa752. PMID: 33346360; PMCID: PMC8921994.