I had a preemie born at 33 weeks in October and nothing was offered. That particular year we did have some sort of LRTI at around 37 weeks? (He'd been home a few weeks when he got sick.) We never saw a doctor and managed it at home without complication. Given what we know about the risk of RSV to the frail elderly when the immune system starts to wane in old age, I'd question if there is lifetime risk to this intervention and how the development of natural immunity to an ubiquitous virus is impacted by the mass administration of something like this.
I don't feel comfortable with mass administration of something like this without a whole lot more data points - what happens immediately after is just one part of the picture. What happens by the time they're 5, 6, 10, 30 years old? It seems lately that medicine has a habit of short term gain focus, without concern for long term risk. And yet we all hope to live into the long term, so it would seem to me that this is a really risky approach.
I definitely share those concerns, I added an addendum to the post that addresses some of it. I don't think we can expect decades of follow-up data prior to approval, but we should definitely have more than is provided. I think at minimum there should be something like 5X the number of infants and they should be followed for multiple subsequent seasons with active monitoring to see if infections, immune response, etc. in those seasons has changed. There was some of that follow-up data, but not as much as I think would be required to justify a blanket recommendation. We will see what happens with approval, recommendation, etc.
Thank you for this analysis. I have several concerns that you didn't mention.
35-37 week EGA infants are not equivalent to term infants in terms of risk of severe RSV illness. I don't find cases or severe cases broken out by gestational age, including in the supplement. Maybe I missed that?
Although the relative risk reduction numbers are large, the actual numbers for risk reduction are small. The primary endpoint of medically attended LRTI is defined as a baby who comes into an outpatient setting coughing, with rales or wheezing. The vast majority of those babies recover uneventfully after several days of supportive care at home. Reducing the number of babies who experience that from a single digit percent to a lower single digit percent may ultimately be considered valuable enough, but doesn't seem sufficient to warrant a universal recommendation for a new therapy. Very severe medically attended LRTI is defined as any child who received supplemental O2 or IV fluids in hospital, basically just about any child admitted for bronchiolitis. (Severe, maybe, but the "very" seems like a sales pitch:) Again a decrease in this from 1.7% to 0.3% doesn't seem to warrant a universal, new, likely expensive drug. More data on length of stay in the severe cases, ICU admission and gestational age would have been helpful. Based on long experience as a pediatrician, I would guess that most stays were 2-4 days, and the longer stays with ICU time were predominantly late preterm infants. Again, using data including preterm infants to justify recommendation of this treatment for term infants seems pretty tenuous.
Like the previous commenter, I would also have concerns about the population impact of kicking the first RSV illness down the road a year in healthy children, though it will just happen the next year not 5 or more years later. This is obviously good for very high risk children, but may not be for healthy infants. Maybe it's better to get your first RSV when you still have maternal antibodies around? We don't know yet.
Cynically, I'm braced for a big push for more RSV testing and maybe a declaration of public health emergency to drive quick uptake of this when it should be assessed more carefully. More fear and disruption for parents, as well as a big economic investment for small gains may be the major adverse effects.
Thank you for the comment! I agree with a lot of it, I actually just did an addendum on the end of the post because I thought it would be an easier way to address some of those concerns
I'm commenting on this 6 months after you posted it, so I hope you see this! My sister had a baby last month at 37 weeks after an emergency C-section. He's healthy and gaining weight. My toddler niece brought home RSV from daycare and the whole household had it last week. Now baby has a slight cough. Mom is breastfeeding and passing along her antibodies, and there's no cause for alarm at this stage. She and baby went in today for a checkup and the doc pushed the monoclonals hard. She texted me, unsure of what to do. I said, "Aren't you already passing him antibodies in your breast milk? How/why are the antibodies in the shot different or better?" The doc responded that because she didn't get the RSV vaccine while pregnant, that she doesn't have the same antibodies. That seems insane to me. Looking at the study, I see that babies who were already infected were excluded from the study. My sister decided to go ahead with the shot under pressure, but I have misgivings. Do you have any insight here, Dave? I appreciate you and your analysis.
Hello, thank you for reaching out! I hope your family is all doing well and has recovered at this point. I'm not qualified to give medical advice, seeing as I am still a medical student and don't have my license. I would also add that I would not presume to question the decision of an experienced physician that is close to the details of a specific case. With that being said, I'm happy to speculate on some of the thoughts that the physician may have had at that time. I assume the monoclonal was nirsevimab (there is another, older monoclonal available, palivizumab, and I don't know which one was given in this case.)
It sounds like baby may have been born early enough to be considered high risk for a severe infection with RSV. Your point regarding antibodies being passed through breast milk is true, but there are some complicating issues that don't make it a simple decision.
The exposure of RSV at home was at the same time, meaning your sister and her child were exposed to RSV when the toddler came home. Assuming your sister was infected, antibodies can take time to develop and be passed on. The monoclonal delivers the antibodies directly, which would theoretically be helpful almost immediately if there was a recent exposure. It's also possible that your sister wasn't infected and the infant was, so it's hard to just assume they both were.
Assuming she was infected, I think you are correct that your sister developed antibodies, maybe even within a couple days, assuming her immune system has seen RSV many times before. The decision to recommend nirsevimab seems reasonable to me, especially given the likely high risk of such a young infant being exposed after being born prematurely.
Please let me know if you have any other questions about this, my apologies for the delay. I hope you and your family are thriving in the new year and this is now a forgotten concern.
Thank you, Dave! All is indeed well now. My baby nephew's symptoms did worsen after the shot, and he had a couple of days of tough congestion, intense coughing, and vomiting. Luckily he never spiked a fever or stopped eating, and he has since gotten much better. Appreciate your feedback and your kind words!
Recommended unanimously by ACIP for universal use in newborns as of yesterday. ACIP called it both a vaccine and a therapeutic at various points. Definitely not a vaccine in the usual sense, since passive. I don't know of any other Ab products categorized as vaccines. I don't fully understand the laws, but I think calling it a vaccine may force insurance coverage, and it allows VFC inclusion. It's a therapeutic for AE reporting, so adverse effects, if significant, won't be in VAERS. It's expensive ($445/dose for the universally recommended dose, twice that for second season high risk infants). I assumed the next step was pre-declaring an RSV emergency to force insurance coverage or allow federal coverage, but maybe that's not needed when calling it a pediatric vaccine. There's no non-Pharma sponsored data to support this universal recommendation, number of infants studied was small and so is absolute effect size. Definitely get the sense infants are being used as a sink for an expensive pharmaceutical product before we know for sure that it's valuable and safe. An RSV emergency will help with uptake, so probably one will be declared as early as possible in this year's viral season, with lots of associated media coverage.
Anticipate spending a lot of time talking about nuances of this with parents this fall, while remaining NOT anti-vax and NOT FOR infants being in hospital with breathing problems. I'll keep trying to be the backstop/source of information for my patients and their parents that institutional pediatrics and the regulatory agencies have decided not to be. This is not the pediatric profession I used to know.
That's unfortunate, I expect the decision re: maternal Abrysvo to come out this month as well. I agree it makes no sense to consider it a vaccine, unless they consider all mAbs vaccines. I was disappointed to see they recommended it for all infants under 8 months.
I had a preemie born at 33 weeks in October and nothing was offered. That particular year we did have some sort of LRTI at around 37 weeks? (He'd been home a few weeks when he got sick.) We never saw a doctor and managed it at home without complication. Given what we know about the risk of RSV to the frail elderly when the immune system starts to wane in old age, I'd question if there is lifetime risk to this intervention and how the development of natural immunity to an ubiquitous virus is impacted by the mass administration of something like this.
I don't feel comfortable with mass administration of something like this without a whole lot more data points - what happens immediately after is just one part of the picture. What happens by the time they're 5, 6, 10, 30 years old? It seems lately that medicine has a habit of short term gain focus, without concern for long term risk. And yet we all hope to live into the long term, so it would seem to me that this is a really risky approach.
I definitely share those concerns, I added an addendum to the post that addresses some of it. I don't think we can expect decades of follow-up data prior to approval, but we should definitely have more than is provided. I think at minimum there should be something like 5X the number of infants and they should be followed for multiple subsequent seasons with active monitoring to see if infections, immune response, etc. in those seasons has changed. There was some of that follow-up data, but not as much as I think would be required to justify a blanket recommendation. We will see what happens with approval, recommendation, etc.
Thank you for this analysis. I have several concerns that you didn't mention.
35-37 week EGA infants are not equivalent to term infants in terms of risk of severe RSV illness. I don't find cases or severe cases broken out by gestational age, including in the supplement. Maybe I missed that?
Although the relative risk reduction numbers are large, the actual numbers for risk reduction are small. The primary endpoint of medically attended LRTI is defined as a baby who comes into an outpatient setting coughing, with rales or wheezing. The vast majority of those babies recover uneventfully after several days of supportive care at home. Reducing the number of babies who experience that from a single digit percent to a lower single digit percent may ultimately be considered valuable enough, but doesn't seem sufficient to warrant a universal recommendation for a new therapy. Very severe medically attended LRTI is defined as any child who received supplemental O2 or IV fluids in hospital, basically just about any child admitted for bronchiolitis. (Severe, maybe, but the "very" seems like a sales pitch:) Again a decrease in this from 1.7% to 0.3% doesn't seem to warrant a universal, new, likely expensive drug. More data on length of stay in the severe cases, ICU admission and gestational age would have been helpful. Based on long experience as a pediatrician, I would guess that most stays were 2-4 days, and the longer stays with ICU time were predominantly late preterm infants. Again, using data including preterm infants to justify recommendation of this treatment for term infants seems pretty tenuous.
Like the previous commenter, I would also have concerns about the population impact of kicking the first RSV illness down the road a year in healthy children, though it will just happen the next year not 5 or more years later. This is obviously good for very high risk children, but may not be for healthy infants. Maybe it's better to get your first RSV when you still have maternal antibodies around? We don't know yet.
Cynically, I'm braced for a big push for more RSV testing and maybe a declaration of public health emergency to drive quick uptake of this when it should be assessed more carefully. More fear and disruption for parents, as well as a big economic investment for small gains may be the major adverse effects.
Thank you for the comment! I agree with a lot of it, I actually just did an addendum on the end of the post because I thought it would be an easier way to address some of those concerns
I'm commenting on this 6 months after you posted it, so I hope you see this! My sister had a baby last month at 37 weeks after an emergency C-section. He's healthy and gaining weight. My toddler niece brought home RSV from daycare and the whole household had it last week. Now baby has a slight cough. Mom is breastfeeding and passing along her antibodies, and there's no cause for alarm at this stage. She and baby went in today for a checkup and the doc pushed the monoclonals hard. She texted me, unsure of what to do. I said, "Aren't you already passing him antibodies in your breast milk? How/why are the antibodies in the shot different or better?" The doc responded that because she didn't get the RSV vaccine while pregnant, that she doesn't have the same antibodies. That seems insane to me. Looking at the study, I see that babies who were already infected were excluded from the study. My sister decided to go ahead with the shot under pressure, but I have misgivings. Do you have any insight here, Dave? I appreciate you and your analysis.
Hello, thank you for reaching out! I hope your family is all doing well and has recovered at this point. I'm not qualified to give medical advice, seeing as I am still a medical student and don't have my license. I would also add that I would not presume to question the decision of an experienced physician that is close to the details of a specific case. With that being said, I'm happy to speculate on some of the thoughts that the physician may have had at that time. I assume the monoclonal was nirsevimab (there is another, older monoclonal available, palivizumab, and I don't know which one was given in this case.)
It sounds like baby may have been born early enough to be considered high risk for a severe infection with RSV. Your point regarding antibodies being passed through breast milk is true, but there are some complicating issues that don't make it a simple decision.
The exposure of RSV at home was at the same time, meaning your sister and her child were exposed to RSV when the toddler came home. Assuming your sister was infected, antibodies can take time to develop and be passed on. The monoclonal delivers the antibodies directly, which would theoretically be helpful almost immediately if there was a recent exposure. It's also possible that your sister wasn't infected and the infant was, so it's hard to just assume they both were.
Assuming she was infected, I think you are correct that your sister developed antibodies, maybe even within a couple days, assuming her immune system has seen RSV many times before. The decision to recommend nirsevimab seems reasonable to me, especially given the likely high risk of such a young infant being exposed after being born prematurely.
Please let me know if you have any other questions about this, my apologies for the delay. I hope you and your family are thriving in the new year and this is now a forgotten concern.
Thank you, Dave! All is indeed well now. My baby nephew's symptoms did worsen after the shot, and he had a couple of days of tough congestion, intense coughing, and vomiting. Luckily he never spiked a fever or stopped eating, and he has since gotten much better. Appreciate your feedback and your kind words!
Recommended unanimously by ACIP for universal use in newborns as of yesterday. ACIP called it both a vaccine and a therapeutic at various points. Definitely not a vaccine in the usual sense, since passive. I don't know of any other Ab products categorized as vaccines. I don't fully understand the laws, but I think calling it a vaccine may force insurance coverage, and it allows VFC inclusion. It's a therapeutic for AE reporting, so adverse effects, if significant, won't be in VAERS. It's expensive ($445/dose for the universally recommended dose, twice that for second season high risk infants). I assumed the next step was pre-declaring an RSV emergency to force insurance coverage or allow federal coverage, but maybe that's not needed when calling it a pediatric vaccine. There's no non-Pharma sponsored data to support this universal recommendation, number of infants studied was small and so is absolute effect size. Definitely get the sense infants are being used as a sink for an expensive pharmaceutical product before we know for sure that it's valuable and safe. An RSV emergency will help with uptake, so probably one will be declared as early as possible in this year's viral season, with lots of associated media coverage.
Anticipate spending a lot of time talking about nuances of this with parents this fall, while remaining NOT anti-vax and NOT FOR infants being in hospital with breathing problems. I'll keep trying to be the backstop/source of information for my patients and their parents that institutional pediatrics and the regulatory agencies have decided not to be. This is not the pediatric profession I used to know.
That's unfortunate, I expect the decision re: maternal Abrysvo to come out this month as well. I agree it makes no sense to consider it a vaccine, unless they consider all mAbs vaccines. I was disappointed to see they recommended it for all infants under 8 months.