November 1, 2023 • 42 mins
Dr. Rupeena Purewal welcomes Dr. Zain Chagla, associate professor at McMaster University, to discuss the upcoming respiratory season and the RSV vaccine.
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Episode Transcript
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Thanks for joining us again at the Canadian Breakpoint, a Canadian infectious diseases
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podcast by Canadian infectious diseases physicians.
I'm Summer Stewart, back again with Dr. Rupeena Purewal, pediatric infectious diseases physician
from Saskatoon.
In this episode, we invite Dr. Zain Chagla, associate professor at McMaster University,
co medical director of infection control at St. Joseph's Healthcare in Hamilton, and a
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consultant in infection control at Woodstock General Hospital to discuss the upcoming respiratory
season and the RSV vaccine.
Dr. Purewal.
All right, welcome everyone to another episode of our podcast, the Canadian Breakpoint.
Today we have a very special guest and many of you may actually know him.
It's Dr. Zain Shagla.
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We'll be speaking about the respiratory season with us today and a lot of new information
on RSV.
So without further ado, let me introduce Dr. Shagla.
Dr. Shagla is an associate professor at McMaster University and an infectious diseases consultant.
He is the medical director of infection control, head of infectious diseases service, and the
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interim senior medical director of clinical operations at St. Joseph's Healthcare Hamilton.
He's a member of the Institute for Infectious Diseases Research at McMaster University and
a council member of AMI Canada.
Dr. Shagla holds a BSc and MD from Queen's University, an internal medicine residency
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from Western University, an infectious diseases fellowship at McMaster University, and a master's
of science infectious diseases, and a diploma in tropical medicine from the London School
of Hygiene and Tropical Medicine.
So it's fantastic with all those credentials.
I'm super excited to speak with you today, Dr. Shagla, for a really important topic.
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We're kind of entering the respiratory season that we have been expecting for a few months
now and I think all of us experts have been talking about this and a bit dreaded respiratory
season.
So, but we also have a lot of new information for this respiratory season.
So that's kind of what we're going to focus on today.
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Why don't we start a little bit about what is this season looking like?
What population is most affected?
And really for our listeners who, you know, are general practitioners, nurses, nurse practitioners
have family members that are probably going to ask them a dozen questions.
And so why don't we give our listeners a bit of an overview of what we might be dealing
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with this respiratory season?
Yeah, absolutely.
And first off, thanks for having me.
I hope we can go by first names here for the sake of it.
It's a whole lot more fun.
So, you know, no one wants respiratory season to come.
I think that's, you know, if we could get rid of it, we would get rid of it.
But at the same time, especially in a climate with four seasons.
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So you know, I wish we didn't have a respiratory season, but we did.
And it's eventuality of every year that this is a tough season, tough season for individuals,
for families, for people who have vulnerable people in their house, for people with kids.
It's tough for, you know, society, workplaces, lots of absenteeism.
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And it's tough for health care.
And that, you know, in that context that there are just a lot of patients, not only with
respiratory disease itself, but flare ups of their underlying disease states, often
from respiratory infections.
And so, you know, it's even pre pandemic, it was a problem.
And it was always a time when health care workers knew that things would be stretched.
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And come 2023, 2024, we've added another virus to the mix, even in the best of seasons.
It wasn't a great time.
And now we've added another virus that's here as a contributor to all of this.
So you know, I think we will see obviously a respiratory season.
Last year, we probably had one of our worst respiratory seasons on record.
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This year, there's a lot of speculation about what's exactly going to happen.
But you know, recognizing even in the best case scenario, where we come in with a regular
influenza season, a regular RSV season and add COVID-19 in the mix, it's still going
to be pretty tight.
And it's still going to be pretty hard for some health care systems to compensate for
it.
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Yeah, definitely.
And you know, kind of when we talk about this new virus, RSV in a population that we don't
normally, you know, prior, I would say pre pandemic, but it probably is just prior to
the last few years in general, you know, we would see RSV in pediatric populations quite
frequently.
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And that was my kind of area for months and months, you know, this fall to spring, but
not only that, like the patterns have changed in our pediatric populations too, for some
of these viruses where we're seeing less of the seasonal and this kind of constant viral
activity, which we've been picking up with a lot of our surveillance programs.
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So you mentioned, I mean, obviously there's vulnerable populations.
So I think age groups, like I know for RSV classically, it's at less than six months
old, that's really getting affected to getting into hospitals.
And then in, I think adults, that would be the elderly population more so.
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So RSV in adults.
So it's interesting, you know, I think last year was the season where everyone learned
about RSV, right?
Everyone over the last five years is getting infectious diseases and virology lessons left
and right, and RSV became chapter two after COVID-19.
And it was the pediatric system, obviously, that introduced it.
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You know, RSV has been an issue in adults for a long time.
It's interesting because I think healthcare providers see it, you know, certainly as an
internist and as a resident, as an ID physician, you see it often enough, but I think there's
just been a lot of apathy towards it in the adult population, recognizing it's, you know,
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one of the respiratory viruses that makes people sick.
We had zero tools to offer for it.
It strikes down the same individuals that have issues with other respiratory viruses,
you know, and there was a lot of focus on influenza because it was the one that had
solutions in terms of vaccine campaigns, potentially therapeutics and other pieces.
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You know, if you look at RSV across the sector, you know, in many different studies, the impacts
are actually pretty similar in the adult population to influenza.
So you know, in the adult sector, for example, for long-term care costs, RSV, in the US,
there's Medicare data suggesting it's actually pretty similar to influenza in terms of hospital
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care and specific care to long-term care patients.
There's data from Alberta actually in terms of healthcare costs for adults with RSV and
it's sizable.
Like an RSV hospitalization costs about $12,000 to the system.
It's about $40,000 at a year, which is actually pretty similar to influenza.
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Total budgets are actually not that far off in that sense.
And if you look at patients, even what happens to them in hospital when they get RSV and
you know, the rates of things like bacterial pneumonia, cardiac complications, death are
actually pretty similar.
So you know, I think it's one of these diseases that did affect adults.
I think we didn't talk about it much because there wasn't really much we could offer, but
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I think, you know, leveraging on A, the global education that was given last year around
RSV and the impacts, especially when it raced back into a population after being naive to
it for a few years and B, the fact that we have actual now vaccines for RSV, which is
a huge medical advance, you know, it's something that really should be brought to the forefront
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to talk about as a potential vaccine-mitigatable disease in that sense.
Yeah, exactly.
And I think you made a very important point here is that usually we don't talk about a
lot of these things because we don't have solutions.
But fortunately entering into a respiratory season where we're anticipating a lot of RSV,
a lot of influenza, a lot of COVID, you know, all over respiratory viruses in general.
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I think this year, you know, seeing that we do have some new updates for people to counsel,
not just to say lift your sleeves and let's get influenza and COVID vaccines, but for
some of our populations, we actually have a new RSV vaccine.
And so why don't we discuss a little bit, because I know there's going to be a lot of
questions for family doctors and other upfront general practitioners and healthcare professionals
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where they're probably going to get questions around indications, contraindications.
So why don't we dive into a little bit about the RSV vaccine and really when was it approved
and all of the wealth of information that you can give us today.
Yeah, absolutely.
So, you know, the RSV vaccine story is a huge success over the last few years.
And we talked about, I think about the burden of RSV in adults being not trivial.
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And so the big question is why don't we have, why didn't we have an RSV vaccine until now?
We've had influenza vaccine, we saw in the pandemic, we could develop a COVID-19 vaccine
very quickly.
Why isn't there an RSV vaccine?
And the answer was, there was, there were trial targets of RSV vaccines back in the
60s and 70s.
The issue is, you know, the epitopes and the antigen were not well developed.
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And RSV has a fusion protein, which is kind of what binds the virus, similar to spike
protein, what binds the virus to the target cells within the respiratory tract.
That fusion protein was thought to be very well conserved between both RSV and B, the
two subtypes.
So really good immunogenic target.
The issue was, is that when RSV is in its natural state, the fusion protein goes into
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a post-fusion confirmation.
So this, this, you know, more oblong looking protein, which helps with its function, but
it is not very immunogenic.
And then the binding sites for neutralizing antibodies are actually quite covered up.
This actually creates two problems.
One is that you don't get a good vaccine response.
But secondly, you may develop antibodies which are not sterilizing, don't have effects on
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the virus.
And then when exposed to the virus, you're already primed to make that immune response
with those antibodies.
And in fact, you know, some of those early vaccine trials not only showed that these
vaccines weren't effective using the post-fusion protein and lysed viral components, but they
actually may have been deleterious in the context of increasing susceptibility to severe
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COVID, severe RSV in that context.
And so they were largely abandoned and there was a lot of work done over the last few decades
to kind of figure out, okay, where is the immune target?
What can we find that stable?
And how does that relate to, you know, eventual development of a vaccine?
The last 10, 15 years, there's been this recognition that the pre-fusion state, so before the fusion
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protein binds to the cell, is not the stable state for the protein, but actually does open
up some very potent neutralizing antibody binding sites.
So that was piece number one to the puzzle.
And then piece number two is really work over the last few years is how to actually keep
the protein in that stable confirmation.
So let's keep it in that pre-fusion state.
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And once that was really developed, we saw three companies, in fact, multiple companies,
develop RSV vaccines based on that construct, two of them using a protein-based method with
an adjuvant and one using an mRNA method, but really using that pre-fusion protein and
that immune response for the pre-fusion protein to then develop vaccines.
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And so GSK developed the RxV vaccine, which is the one approved in Canada.
Pfizer developed a vaccine not approved in Canada yet, but going through HealthCan approval,
and Moderna developed a vaccine again, going through HealthCan approval currently.
So these work essentially with that pre-fusion protein and an adjuvant.
So adjuvant is a molecule that's used to really trigger potent immune responses.
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They're part of most protein-based vaccines.
And the adjuvant is actually pretty similar to one that we have on the market.
It's actually the same as one that's in the Shingrix vaccine.
So this AS01 adjuvant, which is for the Shingles vaccine, a very, very potent vaccine.
It gives very, very good immune responses.
And so using that technology in this vaccine.
They took the, and I'll talk about the GSK vaccine mainly because it's the one that's
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approved on the Canadian market.
So they took about 12,500 individuals.
They gave them this vaccine versus placebo, and they looked at lower respiratory tract
disease.
They did this trial actually during the pandemic, which is remarkable considering there wasn't
a lot of respiratory virus spread, but they saw about an 80% reduction in lower respiratory
tract disease with RSV, about a 90% reduction in severe lower respiratory tract disease,
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and even about a 70% reduction in acute respiratory symptoms.
So just like a sore throat, minor symptoms, but having RSV with minor symptoms.
So really big benefits.
This was a population that was over 60, and it was a population where about 30, 40% of
them had comorbid diseases like cardiac disease, lung disease, diabetes, obesity, and a few
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of them that were actually not frail, but what we consider pretty frail.
So people that had functional issues and may have been even higher risk for severe disease
in that sense.
So really, really good data, and that's really what led to the approval of this vaccine and
now the availability of this vaccine actually across the country for populations over the
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age of 60.
Well, it's fantastic.
Yeah.
I mean, those efficacy rates are very high and definitely the population, you know, it's
always the strength of the study when the population that's tested is that high risk
population.
So because that's what we're talking about with those comorbidities and the respiratory
season, because those are the patients that we would see that would enter the hospital
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and have very severe morbidity and mortality from RSV.
So Zane, in terms of all of this research is out there, is it a one dose?
Is it two doses?
So what's kind of the administration requirements and can this be given at a physician's office?
Yeah.
So for the first question, it's a really good question.
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And, you know, when we think about COVID-19 vaccines, you know, we weren't sure about
the dosing, the virus continues to evolve.
And the other part of COVID-19 vaccines is a lot of people that got COVID-19 vaccines
have never seen COVID-19 before, right?
So this is really priming the initial immune response.
Influenza vaccines, they often have to be tweaked to deal with the antigenic drift.
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So kind of different subtypes of influenza circulating globally and try to match appropriately.
RSV vaccine is a little bit different.
So number one, this is an infection, especially in the six year old population, which people
have probably seen five to 10 times during their lifetime.
They have some preexisting immunity.
It's clearly not enough to keep them out of hospital and keep them from getting sick.
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But there is some preexisting immunity.
And number two is a virus that is relatively antigenically stable.
So not seeing that much of the drift in that sense.
There's RSV, A and B and the GSK trial showed that similar effects in both, but relatively
you're not seeing the viral evolution we see with influenza and COVID-19.
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So all of the trials have incorporated not only the initial one shot versus no shot one
year clinical data, but are actually ongoing looking at what year two looks like for these
people, what year three looks like for these people.
And in the GSK trial, they actually gave a subset of people who got the shot in year
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one, a shot in year two versus not getting a shot in year two.
So really now we have a little bit of year two data and interim data analysis that looks
at two shots versus one shot versus zero shots in year two of the respiratory season.
And the bottom line is efficacy is still pretty preserved.
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It's about 77, 78% for medically attended or respiratory tract infection.
And two shots right now looks as good as one shot.
So that 78% number is similar, essentially not different between two shots and one shot.
So for the moment, this vaccine is currently only recommended as a single dose because
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we do now have two seasons data suggesting that a single dose has the effects for two
seasons that multiple doses would have as well.
And so that's really a good piece that we may have a vaccine that, similar to others,
where it's more of a staggered strategy of immunization, not a yearly strategy.
And so when people go and roll up their sleeves, they can get some assurance that the protection
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isn't just going to be for every season I need to update it, but maybe actually for
a decent amount of time afterwards.
The second part to your question was who can administer it?
So this is a new vaccine.
And so that creates a little bit of logistical challenges across the board.
It isn't very different than, say, Shingles vaccine or hepatitis B vaccine in the context
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of what it's constituted with.
So in certain provinces, like the Western provinces, pharmacists have the ability to
administer either with or without a physician's order, depending on the province and the scope
of practice.
In places like Ontario, it's really just physician discretion right now, but there is a lot of
work ongoing to make sure that that's a bit more open and matches.
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Because again, I presume a pharmacist in British Columbia is pretty similar to a pharmacist
in Ontario in terms of their ability to deal with a vaccine.
And so there is a lot of work that's being done to really try to make sure that it's
more accessible to people, recognizing the challenges in primary care.
This is still a vaccine outside of one province that's publicly funded it for long-term care
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in Ontario.
This is still a vaccine that's also privately paid because there's not really a nasty recommendation
for it yet, which is often a trigger to then look at cost effectiveness and public versus
private payers.
So Ontario has invested in long-term care facilities, recognizing that there's probably significant
benefit there.
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But outside of that, it's privately funded.
It may be funded through private insurance plans, but that also creates a logistical
challenge because now you actually have to buy the product and administer it.
So again, hopefully more advocacy around getting it in pharmacies and more spots that can do
it appropriately that put less barriers at that patient level.
And generally, do we know if like, let's say patients are asking about costs, do we know
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roughly maybe it's a little bit different?
Yeah, the manufacturer cost is 230 Canadian.
In the US, it's $280 American.
So there is a discount being north of the border.
That is not necessarily the cost to patient.
There's obviously costs the pharmacy has to take for bringing it in, injection costs,
et cetera.
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But that's the baseline cost plus probably a little bit on the pharmacy end or the provider
end in that standpoint.
And then just like any new rollout for vaccines, I know there's always questions in regards
to safety.
So what, you know, we talked about the efficacy, we talked about the administration of this
vaccine in those similar trials, I would assume, especially at the second year for sure, but
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initially as well, safety was looked at.
So what can we tell our some of our listeners about that?
Yeah, absolutely.
So the GSK vaccine, the Eurexia vaccine, you know, it has a Shingrix adjuvant.
For those who have taken Shingrix or administered Shingrix, it gives people a sore arm and a
lot of swelling.
And so that was seen in the clinical trials, a lot of, you know, compared to placebo swelling,
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fever, malaise, nausea, injection site redness, you know, those were higher in the group that
got the RSV vaccine versus the group that got placebo.
That's not necessarily a harm, but it's just a recognizable side effect of that adjuvant
being very, very immunogenic.
Unfortunately, it leaves people with a bit of immunogenic side effects.
Most of these SAEs were dealt with in 40 to 72 hours.
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Sorry, these AEs, sorry, were dealt with in 40 to 72 hours.
In terms of SAEs, serious adverse events in the registration clinical trial, there was
none higher than placebo.
On the product monograph, there are two descriptions of Guillain-Barre-like cases associated with
the vaccine.
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One was associated with co-administration with the influenza vaccine.
So it's not clear exactly what the source was.
And there's one that probably is temporally related to the vaccine in a separate clinical
trial, wasn't actually in this clinical trial.
So there is that indication.
And certainly part of post-marketing surveillance is looking for it.
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But at the same time, outside of that, and these Guillain-Barre events are also difficult
to adjudicate just because they're spontaneous events in a baseline risk in the population
and a risk associated with respiratory tract infections too.
We have actually data around, for example, natural influenza and Guillain-Barre syndrome,
which is about 1 in 100,000, that risk and benefit discussion in that context.
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And hopefully, as again, more global administration happens, we get more global data if this is
a real trend and what the prevalence is.
But really, outside of that issue, there really isn't major SAEs that were noted.
And again, other than the side sore arm, which for some people could be considered, it feels
lousy, but at least means it's working in that sense.
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Right?
Yeah.
Right.
So I know in pediatrics, we always talk about co-administration of vaccines because our
vaccine schedules are so detailed and intricate.
There's multiple vaccines that are given.
So in this adult population over 60, I know that a lot of people are now getting that
text message where influenza vaccines are rolling out.
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We know that there is a new COVID vaccine covering the Armicon variant that was released
by Moderna.
So in terms of with RSV and in the study, like you mentioned that some of the co-administration
with RSV and influenza led to, let's say an incident like Yomber, so did they discuss
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co-administration of all the other vaccines that maybe even shingles, I guess, because
a lot of that population would also be exposed to such a vaccine?
Yeah, absolutely.
So the trial that had the single case with co-administration, there was actually a trial
that looked at co-administration with both high dose quadrivalent vaccine for influenza
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and adjuvanted influenza vaccine.
At least outside of H3N2 titers with, I believe, the adjuvanted vaccine, there was non-inferiority
in terms of individuals who got influenza alone versus influenza plus the RSV vaccine.
And safety wise, there was no concerns other than the single case and even then it was
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hard to say where it was adjudicated.
So at least we have some co-administration data.
Even that lower level of H3N2 antibodies, it's not clear what that clinically still
developed antibodies that were slightly lower than pre-specified margin.
Does that mean there's less protection or does that mean the protection is the same?
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If you were exposed, it's not really clear.
The ACIP in the US, which is probably the guideline organization we rely on, just kind
of said consider co-administration if it's easier for the patient, the risks and benefits,
losing patients, et cetera, and consider if there's factors that may want people to space
things out, they're a bit more predisposed to side effects, they're worried about side
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effects, then space them out.
And if you have good patient follow-up, then that's not an unreasonable issue.
And obviously consider where you are in the respiratory season.
If we're talking about doing this in May, probably fine to space things out.
If RSV is surging, then you might want to have some second thoughts about spacing things
out if you're going to lose the patient in that couple of weeks.
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The other vaccines like herpes zoster, pneumococcal, COVID-19 vaccines, there's no data and there
wasn't co-administration data in clinical trials.
I would say there are some organizations, the Ontario Advisory Council on Immunization,
for example, that said maybe for the first little while, give a couple of weeks between
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vaccines, not for any safety issue, but just for the fact that you could actually attribute
if there is an adverse event where what vaccine it's associated with.
But at the same time that the ACIP had really come out with a recommendation to say, think
about your patient, their demographics, their risks, their benefits of getting co-administration
versus non-benefits of getting co-administration and make a discussion.
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There's not a yes or no.
You can certainly co-administer if you want, but really consider that patient.
The only other thing I would say is if you're going to use adjuvanted vaccines like the
adjuvanted influenza vaccine or the adjuvanted herpes zoster vaccine, give it in separate
arms to that patient so that you don't have a huge amount of adjuvant in one side.
Not dangerous, but they're going to have a lot of pain on that side if you keep pushing
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it in that sense.
Yeah.
And then I guess seeing we should probably let our listeners know that with RSC this
vaccine is inactivated.
And so that would be important.
I know that's always a question when vaccines roll out.
And so like influenza, obviously we have active and inactive formulations, but specifically
unless I'm wrong.
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So this is a protein based vaccine.
And so for immunocompromised populations and their families, there's no issues with potential
spread or again, being immunocompromised.
And we do know RSC is a big issue in immunocompromised patients and is actually a population of concern.
So especially if they're over 60, that is a population of really, really consider vaccination.
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We have good data from herpes zoster that this adjuvant really does a good job at triggering
immune responses.
And in bone marrow transplant individuals, there's no contraindication in immunocompromised
person.
And in fact, probably a good amount of benefit in that context.
I think it's also fantastic that it's a one shot, right?
So I mean, probably the benefits of being conjugated and also that if we get it early
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on in the season, then it will last you the season.
And who knows what the respiratory season, how long the respiratory season will be?
Because I know in pediatrics, for instance, we saw this early fall, late spring was our
RSV season.
And then now it's just turning into kind of that less seasonal pattern.
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So I think it's reassuring to people as well that this isn't something that's only going
to last you four or five months, but the hope is that it lasts you the entire season and
longer.
Yeah, absolutely.
And you know, in those discussions around costs, like we know cost is an issue.
People have cost containment issues and the need to afford medications.
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You know, think about it as amortizing it over at least two years, maybe even longer.
And so, you know, this is not just a cost upfront today.
It's probably a cost for two years or three years, depending on the data that we see coming
out.
You know, there may be that frame of mind that this is more of a long term intervention
than a short term intervention.
I know there's a lot of discussion around RSC in general, even in the pediatric population.
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So like we talked about the disease burden.
So in the past, we've really, I mean, even now we don't have like an RSC specific vaccine
in pediatric patients.
There is some discussions around rollouts in pregnant women and other high risk populations.
Like we've already fortunate to see that at least one came out in elderly population with
(28:18):
comorbidities.
But just so our listeners know, like there isn't a pediatric formulation of this yet.
We, they will be hearing a little bit more about some of the monoclonal antibodies.
Historically, we've had Pellivizumab on the market for a long, long time, as long as I
can remember practicing and learning about it.
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And so I think there will be some newer data coming out from PHAC for sure in a few short
months here in terms of Nercivumab, which I think a lot of our listeners probably tuned
into some of the information and probably will be hearing from their RSC programs locally.
It is obviously jurisdiction, inter-jurisdictional differences.
(29:03):
We know that with all vaccines and healthcare in general, and you know, once like Health
Canada definitely has approved this.
And so with the rollout of Nercivumab, we don't know exactly which populations to target.
I know the US has definitely given us more information in terms of a wide group patients,
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but just for our listeners to be aware that some of that data isn't as particular, you
know, rolled out yet for Canada, but should be on the way.
But just to discuss a little bit about what we're seeing with RSV.
So obviously through some of our impact surveillance data, similarly to what other groups have
seen in other populations, like you mentioned in the adult population as well, is that we
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didn't actually have a season for RSV back in 2020 to 2021, which was a bit strange for
us in pediatrics because prior to that and then after that, we've seen peak numbers of
RSV and really affects kind of the young comorbidities definitely.
So if anybody has chronic or congenital heart conditions, chronic lung disease, and that's
(30:13):
kind of our same population.
Now we haven't seen much of a difference in terms of the actual morbidity that's changed.
So that's been very similar, but we have seen a rise in our hospitalizations.
And so that's gone up significantly and still affecting less than six months old, primarily.
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And so I think that's still, whenever we talk about extremes of age, I think that's very
common in medicine, right?
So extremes of age, less than six months, I mean, even probably up to a year, we worry
about that with RSV and then 60 and older is kind of what we're talking about in the
elderly population.
So I think some of these things are towards preventative, right?
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That's what our actions are towards.
And that's what Nercifimab and even Pellivizumab in the past.
So I think some of the differences, I won't go into all the details of that today for
time's sake.
And, but definitely once PHAC gives us some more information, I think we'll probably do
another episode on Nercifimab because I think it's worthy of its own episode for sure.
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It's a difficult file, right?
Because vaccinations are kind of pretty straightforward in terms of, you give it, that's it.
There's a cost associated, there's a burden associated.
And the demand drives the vaccination in terms of the disease state.
This is a tricky file, right?
Because there's a cost effectiveness component in terms of the number of hospitalizations
(31:38):
averted.
There's lots of ways that we measure cost effectiveness in terms of quality adjusted
life years and that type of thing.
And so this is where some of these discussions are happening.
This is where the one decision could be made in the US, one decision could be made in Canada
that are polar opposites.
And again, it's not as simple as saying yes or no.
(32:00):
The drug's approved, it's just how do we roll this out effectively to the most individuals
that are at risk and get the biggest value for it in that sense, right?
Yeah.
And just like you mentioned, Zane, we're entering into programs that are already established,
right?
So we already have these RSV programs and multiple centers.
And so kind of figuring out the logistics of the change as well.
(32:22):
And I think it rolled out in a time where RSV is just around the corner too.
So but definitely new information, a lot of updates.
And so all of this along with other preventative measures that we've seen being implemented
in the last few years, I think we're on the right track.
That's probably the most fortunate take back from this.
(32:44):
Even though it's a dreaded respiratory season, we have more options.
So with this upcoming respiratory season, what's our future?
Do we think that we're seeing an uptick in general?
Are we already seeing this uptick?
Yeah.
I mean, I think COVID-19 obviously is one that it's hard to predict, right?
If you could tell what could happen, you'd probably make a lot of money and be able to
(33:08):
go through it.
But at the same time, we do see COVID transmission.
It is translating into some degree of hospitalizations and unfortunately is translating into nosocomial
activity.
But in the same context, there has been a rapid, rapid decline in severe complications
with COVID-19 and that's really due to COVID-19 and therapeutics.
Influenza is probably, as we saw in some of the other Southern jurisdictions, is probably
(33:33):
going to have more of a typical seasonal pattern.
Maybe a bit of a higher peak, it's not clear.
A little bit more reassuring from last year, it doesn't seem to have taken off just yet.
It's kind of at the beginning.
So it's probably a little bit more hopefully predictable.
RSV, again, I think we're starting to see the uptick a little bit earlier, not as bad
(33:54):
again as last season's uptick, but starting.
All the other respiratory viruses obviously come around to adenovirus and rhinovirus,
that's typically earlier in the year, parainfluenza, human beddenumovirus in the spring, all that.
I think the one thing that is probably new-ish and one of the directions on improving vaccinations
(34:15):
is also a significant recognition of the chronic disease states that get exacerbated by underlying
viral diseases.
I'll give one example of coronary artery disease or cardiovascular disease.
It's always been known, I mean, we see it in the winter, right?
That heart attacks go up and people often complain of a viral illness before their MI.
(34:35):
These are pure MIs, chest pain MIs, not I have a cough and I have no troponin, this
is people who have plaque disruption and need an intervention.
There's been a lot of data across the country, Jeff Kwong's group here in Ontario has really
studied this quite a bit and saw, for example, the rate of incident MI after influenza is
(34:57):
six times higher in the seven days post-influenza diagnosis than it is before having influenza
or even seven days after having influenza.
That's an important concept.
We actually have our first randomized clinical trial of influenza vaccine in cardiac prevention
and it's pretty landmark trial.
It's actually one that isn't discussed much, but this was by Mark Loeb, who's a colleague
(35:21):
of mine here.
They went to some low-income countries where influenza vaccine was not standard of care.
So it was really kind of an altruistic trial to get some people influenza vaccine.
They gave influenza vaccine versus placebo to individuals who had cardiac risk.
They looked in the influenza season and they saw about a 19% relative risk reduction in
(35:45):
incident fatal or non-fatal myocardial infarction or stroke as a composite outcome in individuals
who got an influenza vaccine versus not.
This isn't that they get influenza, this isn't that they get pneumonia, did they end up hospitalized?
It's literally, did they have a heart attack or a stroke and they saw a decline.
So that's an important intervention, right?
(36:05):
For those primary care specialists who deal with high-risk cardiac patients, we have agonizing
discussions about antiplatelet agents, anticoagulation, statin, glycemic control, hypertension control.
We rarely have discussions of, hey, are you up to date with your immunizations?
(36:26):
But I think that paradigm has shifted to say, actually, I need to talk to you if you're
up to date on your immunizations because that's just important as the antiplatelet discussion
we need to have or the statin discussion or the hypertension discussion we need to have.
So really groundbreaking, but a concept that I think has been going on for a while, but
recognizing again that there is a probably chronic disease burden from viral infections
(36:49):
that needs much more intervention from those in that sense.
So really emphasizing preventative measures alongside other preventative risk-modifying
disease methods that they're using.
So I think for some of our cardiologists listening out there, I think that's good to implement
into our day-to-day counseling because I think it's important to have that whole framework,
(37:14):
right?
So we have to cover all aspects and presenting some of this data to your patients.
I think that's really important because I think a lot of information, there's a lot
of information out there, but really having some of that evidence-based and trial information,
I think is very helpful for patients to understand.
It's not just that we're preventing you from getting a common cold, but there's actually
(37:37):
other benefits.
Absolutely.
And it's a group discussion, right?
So all healthcare providers need to be involved with immunization.
It's not just primary care.
It's not just pharmacy.
It's not just infectious diseases.
It's everyone has a role to play.
Again, a cardiologist has just as much skin in the game to make sure that person's immunized
as the primary care physician.
Yeah.
(37:58):
And I think just making it routine.
And I know there's a lot of discussion around, there's obviously vaccine hesitancy, but there's
also vaccine fatigue, right?
So we are seeing people from the last few years, all we talk about is vaccines, vaccines,
vaccines, and I can imagine for patients and for their families and for people who are
(38:21):
trying to raise their families, it's challenging, right?
There's always something new.
There's always something that we're talking about, but I think this is just the spread
of information is very different nowadays than it was before.
And so I think just counseling your patients is really important, reminding them that we're
not going to talk about this all the time, not in July and August, but right now as we're
(38:44):
having peak respiratory season, that's why you're hearing more about this.
And so really taking on those preventive measures.
That's fantastic, Zane.
I'm really excited about this RSV vaccine because I want to see some of the post-marketing
surveillance.
I think it'll be interesting to see some of the data through there.
(39:05):
So what's the future currently?
Are there enrollments for trials that physicians should be thinking about?
Is there a future combined vaccines that are coming out?
And maybe we can prep our patients for anything that's on your end.
So definitely the combined vaccine is a big issue.
(39:25):
And certainly there's a lot of work being done, COVID-19, RSV and influenza, bundling
them, not only having them separate, but bundling them up, recognizing it's a challenge.
The data cuts from year two and year three of these studies are also going to start coming
out so we can probably get a bit more sense of what long-term efficacy of these vaccines
are.
There is a lot of work being done.
(39:46):
And again, we'll probably see real-world implementation data.
And similar to the journey of the herpes zoster vaccine, we start seeing what happens in real-world
populations, right?
So long-term care populations, majorly immunocompromised populations.
I think the data will be good, but I think, again, it gives more push for, A, public funding
models, but B, really the benefits of these vaccines.
(40:09):
Yeah.
So a lot to look forward to, but let's all be safe this respiratory season.
So I think we have some preventative options.
The vaccines have started to roll out.
So reach out to your local pharmacists and pharmacies and physicians if you need more
information.
And so I think really important is along with prevention.
(40:30):
We do this in pediatrics all the time.
I counsel everybody about hand washing and if you're sick, stay home, masking, that type
of thing.
So we know that all of these preventative measures along with vaccines are effective.
And so is there any last few words you want our listeners to know about?
Yeah.
(40:50):
No, it's just, look, we live in a, it's a terrible time that we have to deal with respiratory
season, but think about it.
This year is very different than 2018.
We have multiple vaccines, we have therapeutics.
We have lots of different ways to make sure people are safer during respiratory season.
You know, it's time, you know, I think providers are really willing to have those discussions
with patients.
And so, you know, have that discussion with your provider because again, it's important.
(41:14):
And again, it's really the scientific progress, which has been great.
Exactly.
And I think we're very fortunate that all of this is rolling out at a very good speed.
So definitely timely for the respiratory season as well.
That's fantastic.
So before we go, I just want to let everybody know that this podcast is only for informational
purposes and not to endorse a product or a vaccine product or any information.
(41:39):
Pleasure to have you on our podcast today and, you know, talk about such a pressing
issue that's, you know, just around the corner for most of us.
And so I think with all of this advice and information that you've given us today, I
think we're setting ourselves up for a successful, although dreaded respiratory season.
(42:00):
Thanks for having me.
Thanks, Sain.
Thank you, Dr. Purwall and Dr. Shagla.
Have a topic suggestion?
Email us at thecanadianbreakpoint at gmail.com and follow us on ex, formerly Twitter, at
CA Breakpoint.
See you again soon at the Canadian Breakpoint.
Thanks for joining us again at the Canadian Breakpoint, a Canadian infectious diseases
(00:12):
podcast by Canadian infectious diseases physicians.
I'm Summer Stewart, back again with Dr. Rupeena Purewal, pediatric infectious diseases physician
from Saskatoon.
In this episode, we invite Dr. Zain Chagla, associate professor at McMaster University,
co medical director of infection control at St. Joseph's Healthcare in Hamilton, and a
(00:33):
consultant in infection control at Woodstock General Hospital to discuss the upcoming respiratory
season and the RSV vaccine.
Dr. Purewal.
All right, welcome everyone to another episode of our podcast, the Canadian Breakpoint.
Today we have a very special guest and many of you may actually know him.
It's Dr. Zain Shagla.
(00:54):
We'll be speaking about the respiratory season with us today and a lot of new information
on RSV.
So without further ado, let me introduce Dr. Shagla.
Dr. Shagla is an associate professor at McMaster University and an infectious diseases consultant.
He is the medical director of infection control, head of infectious diseases service, and the
(01:16):
interim senior medical director of clinical operations at St. Joseph's Healthcare Hamilton.
He's a member of the Institute for Infectious Diseases Research at McMaster University and
a council member of AMI Canada.
Dr. Shagla holds a BSc and MD from Queen's University, an internal medicine residency
(01:37):
from Western University, an infectious diseases fellowship at McMaster University, and a master's
of science infectious diseases, and a diploma in tropical medicine from the London School
of Hygiene and Tropical Medicine.
So it's fantastic with all those credentials.
I'm super excited to speak with you today, Dr. Shagla, for a really important topic.
(01:59):
We're kind of entering the respiratory season that we have been expecting for a few months
now and I think all of us experts have been talking about this and a bit dreaded respiratory
season.
So, but we also have a lot of new information for this respiratory season.
So that's kind of what we're going to focus on today.
(02:21):
Why don't we start a little bit about what is this season looking like?
What population is most affected?
And really for our listeners who, you know, are general practitioners, nurses, nurse practitioners
have family members that are probably going to ask them a dozen questions.
And so why don't we give our listeners a bit of an overview of what we might be dealing
(02:43):
with this respiratory season?
Yeah, absolutely.
And first off, thanks for having me.
I hope we can go by first names here for the sake of it.
It's a whole lot more fun.
So, you know, no one wants respiratory season to come.
I think that's, you know, if we could get rid of it, we would get rid of it.
But at the same time, especially in a climate with four seasons.
(03:04):
So you know, I wish we didn't have a respiratory season, but we did.
And it's eventuality of every year that this is a tough season, tough season for individuals,
for families, for people who have vulnerable people in their house, for people with kids.
It's tough for, you know, society, workplaces, lots of absenteeism.
(03:25):
And it's tough for health care.
And that, you know, in that context that there are just a lot of patients, not only with
respiratory disease itself, but flare ups of their underlying disease states, often
from respiratory infections.
And so, you know, it's even pre pandemic, it was a problem.
And it was always a time when health care workers knew that things would be stretched.
(03:49):
And come 2023, 2024, we've added another virus to the mix, even in the best of seasons.
It wasn't a great time.
And now we've added another virus that's here as a contributor to all of this.
So you know, I think we will see obviously a respiratory season.
Last year, we probably had one of our worst respiratory seasons on record.
(04:10):
This year, there's a lot of speculation about what's exactly going to happen.
But you know, recognizing even in the best case scenario, where we come in with a regular
influenza season, a regular RSV season and add COVID-19 in the mix, it's still going
to be pretty tight.
And it's still going to be pretty hard for some health care systems to compensate for
it.
(04:31):
Yeah, definitely.
And you know, kind of when we talk about this new virus, RSV in a population that we don't
normally, you know, prior, I would say pre pandemic, but it probably is just prior to
the last few years in general, you know, we would see RSV in pediatric populations quite
frequently.
(04:51):
And that was my kind of area for months and months, you know, this fall to spring, but
not only that, like the patterns have changed in our pediatric populations too, for some
of these viruses where we're seeing less of the seasonal and this kind of constant viral
activity, which we've been picking up with a lot of our surveillance programs.
(05:13):
So you mentioned, I mean, obviously there's vulnerable populations.
So I think age groups, like I know for RSV classically, it's at less than six months
old, that's really getting affected to getting into hospitals.
And then in, I think adults, that would be the elderly population more so.
(05:33):
So RSV in adults.
So it's interesting, you know, I think last year was the season where everyone learned
about RSV, right?
Everyone over the last five years is getting infectious diseases and virology lessons left
and right, and RSV became chapter two after COVID-19.
And it was the pediatric system, obviously, that introduced it.
(05:56):
You know, RSV has been an issue in adults for a long time.
It's interesting because I think healthcare providers see it, you know, certainly as an
internist and as a resident, as an ID physician, you see it often enough, but I think there's
just been a lot of apathy towards it in the adult population, recognizing it's, you know,
(06:19):
one of the respiratory viruses that makes people sick.
We had zero tools to offer for it.
It strikes down the same individuals that have issues with other respiratory viruses,
you know, and there was a lot of focus on influenza because it was the one that had
solutions in terms of vaccine campaigns, potentially therapeutics and other pieces.
(06:40):
You know, if you look at RSV across the sector, you know, in many different studies, the impacts
are actually pretty similar in the adult population to influenza.
So you know, in the adult sector, for example, for long-term care costs, RSV, in the US,
there's Medicare data suggesting it's actually pretty similar to influenza in terms of hospital
(07:01):
care and specific care to long-term care patients.
There's data from Alberta actually in terms of healthcare costs for adults with RSV and
it's sizable.
Like an RSV hospitalization costs about $12,000 to the system.
It's about $40,000 at a year, which is actually pretty similar to influenza.
(07:23):
Total budgets are actually not that far off in that sense.
And if you look at patients, even what happens to them in hospital when they get RSV and
you know, the rates of things like bacterial pneumonia, cardiac complications, death are
actually pretty similar.
So you know, I think it's one of these diseases that did affect adults.
I think we didn't talk about it much because there wasn't really much we could offer, but
(07:47):
I think, you know, leveraging on A, the global education that was given last year around
RSV and the impacts, especially when it raced back into a population after being naive to
it for a few years and B, the fact that we have actual now vaccines for RSV, which is
a huge medical advance, you know, it's something that really should be brought to the forefront
(08:10):
to talk about as a potential vaccine-mitigatable disease in that sense.
Yeah, exactly.
And I think you made a very important point here is that usually we don't talk about a
lot of these things because we don't have solutions.
But fortunately entering into a respiratory season where we're anticipating a lot of RSV,
a lot of influenza, a lot of COVID, you know, all over respiratory viruses in general.
(08:35):
I think this year, you know, seeing that we do have some new updates for people to counsel,
not just to say lift your sleeves and let's get influenza and COVID vaccines, but for
some of our populations, we actually have a new RSV vaccine.
And so why don't we discuss a little bit, because I know there's going to be a lot of
questions for family doctors and other upfront general practitioners and healthcare professionals
(09:03):
where they're probably going to get questions around indications, contraindications.
So why don't we dive into a little bit about the RSV vaccine and really when was it approved
and all of the wealth of information that you can give us today.
Yeah, absolutely.
So, you know, the RSV vaccine story is a huge success over the last few years.
And we talked about, I think about the burden of RSV in adults being not trivial.
(09:29):
And so the big question is why don't we have, why didn't we have an RSV vaccine until now?
We've had influenza vaccine, we saw in the pandemic, we could develop a COVID-19 vaccine
very quickly.
Why isn't there an RSV vaccine?
And the answer was, there was, there were trial targets of RSV vaccines back in the
60s and 70s.
The issue is, you know, the epitopes and the antigen were not well developed.
(09:51):
And RSV has a fusion protein, which is kind of what binds the virus, similar to spike
protein, what binds the virus to the target cells within the respiratory tract.
That fusion protein was thought to be very well conserved between both RSV and B, the
two subtypes.
So really good immunogenic target.
The issue was, is that when RSV is in its natural state, the fusion protein goes into
(10:16):
a post-fusion confirmation.
So this, this, you know, more oblong looking protein, which helps with its function, but
it is not very immunogenic.
And then the binding sites for neutralizing antibodies are actually quite covered up.
This actually creates two problems.
One is that you don't get a good vaccine response.
But secondly, you may develop antibodies which are not sterilizing, don't have effects on
(10:43):
the virus.
And then when exposed to the virus, you're already primed to make that immune response
with those antibodies.
And in fact, you know, some of those early vaccine trials not only showed that these
vaccines weren't effective using the post-fusion protein and lysed viral components, but they
actually may have been deleterious in the context of increasing susceptibility to severe
(11:05):
COVID, severe RSV in that context.
And so they were largely abandoned and there was a lot of work done over the last few decades
to kind of figure out, okay, where is the immune target?
What can we find that stable?
And how does that relate to, you know, eventual development of a vaccine?
The last 10, 15 years, there's been this recognition that the pre-fusion state, so before the fusion
(11:28):
protein binds to the cell, is not the stable state for the protein, but actually does open
up some very potent neutralizing antibody binding sites.
So that was piece number one to the puzzle.
And then piece number two is really work over the last few years is how to actually keep
the protein in that stable confirmation.
So let's keep it in that pre-fusion state.
(11:49):
And once that was really developed, we saw three companies, in fact, multiple companies,
develop RSV vaccines based on that construct, two of them using a protein-based method with
an adjuvant and one using an mRNA method, but really using that pre-fusion protein and
that immune response for the pre-fusion protein to then develop vaccines.
(12:11):
And so GSK developed the RxV vaccine, which is the one approved in Canada.
Pfizer developed a vaccine not approved in Canada yet, but going through HealthCan approval,
and Moderna developed a vaccine again, going through HealthCan approval currently.
So these work essentially with that pre-fusion protein and an adjuvant.
So adjuvant is a molecule that's used to really trigger potent immune responses.
(12:34):
They're part of most protein-based vaccines.
And the adjuvant is actually pretty similar to one that we have on the market.
It's actually the same as one that's in the Shingrix vaccine.
So this AS01 adjuvant, which is for the Shingles vaccine, a very, very potent vaccine.
It gives very, very good immune responses.
And so using that technology in this vaccine.
They took the, and I'll talk about the GSK vaccine mainly because it's the one that's
(12:57):
approved on the Canadian market.
So they took about 12,500 individuals.
They gave them this vaccine versus placebo, and they looked at lower respiratory tract
disease.
They did this trial actually during the pandemic, which is remarkable considering there wasn't
a lot of respiratory virus spread, but they saw about an 80% reduction in lower respiratory
tract disease with RSV, about a 90% reduction in severe lower respiratory tract disease,
(13:22):
and even about a 70% reduction in acute respiratory symptoms.
So just like a sore throat, minor symptoms, but having RSV with minor symptoms.
So really big benefits.
This was a population that was over 60, and it was a population where about 30, 40% of
them had comorbid diseases like cardiac disease, lung disease, diabetes, obesity, and a few
(13:43):
of them that were actually not frail, but what we consider pretty frail.
So people that had functional issues and may have been even higher risk for severe disease
in that sense.
So really, really good data, and that's really what led to the approval of this vaccine and
now the availability of this vaccine actually across the country for populations over the
(14:05):
age of 60.
Well, it's fantastic.
Yeah.
I mean, those efficacy rates are very high and definitely the population, you know, it's
always the strength of the study when the population that's tested is that high risk
population.
So because that's what we're talking about with those comorbidities and the respiratory
season, because those are the patients that we would see that would enter the hospital
(14:25):
and have very severe morbidity and mortality from RSV.
So Zane, in terms of all of this research is out there, is it a one dose?
Is it two doses?
So what's kind of the administration requirements and can this be given at a physician's office?
Yeah.
So for the first question, it's a really good question.
(14:47):
And, you know, when we think about COVID-19 vaccines, you know, we weren't sure about
the dosing, the virus continues to evolve.
And the other part of COVID-19 vaccines is a lot of people that got COVID-19 vaccines
have never seen COVID-19 before, right?
So this is really priming the initial immune response.
Influenza vaccines, they often have to be tweaked to deal with the antigenic drift.
(15:07):
So kind of different subtypes of influenza circulating globally and try to match appropriately.
RSV vaccine is a little bit different.
So number one, this is an infection, especially in the six year old population, which people
have probably seen five to 10 times during their lifetime.
They have some preexisting immunity.
It's clearly not enough to keep them out of hospital and keep them from getting sick.
(15:28):
But there is some preexisting immunity.
And number two is a virus that is relatively antigenically stable.
So not seeing that much of the drift in that sense.
There's RSV, A and B and the GSK trial showed that similar effects in both, but relatively
you're not seeing the viral evolution we see with influenza and COVID-19.
(15:49):
So all of the trials have incorporated not only the initial one shot versus no shot one
year clinical data, but are actually ongoing looking at what year two looks like for these
people, what year three looks like for these people.
And in the GSK trial, they actually gave a subset of people who got the shot in year
(16:10):
one, a shot in year two versus not getting a shot in year two.
So really now we have a little bit of year two data and interim data analysis that looks
at two shots versus one shot versus zero shots in year two of the respiratory season.
And the bottom line is efficacy is still pretty preserved.
(16:31):
It's about 77, 78% for medically attended or respiratory tract infection.
And two shots right now looks as good as one shot.
So that 78% number is similar, essentially not different between two shots and one shot.
So for the moment, this vaccine is currently only recommended as a single dose because
(16:51):
we do now have two seasons data suggesting that a single dose has the effects for two
seasons that multiple doses would have as well.
And so that's really a good piece that we may have a vaccine that, similar to others,
where it's more of a staggered strategy of immunization, not a yearly strategy.
And so when people go and roll up their sleeves, they can get some assurance that the protection
(17:14):
isn't just going to be for every season I need to update it, but maybe actually for
a decent amount of time afterwards.
The second part to your question was who can administer it?
So this is a new vaccine.
And so that creates a little bit of logistical challenges across the board.
It isn't very different than, say, Shingles vaccine or hepatitis B vaccine in the context
(17:34):
of what it's constituted with.
So in certain provinces, like the Western provinces, pharmacists have the ability to
administer either with or without a physician's order, depending on the province and the scope
of practice.
In places like Ontario, it's really just physician discretion right now, but there is a lot of
work ongoing to make sure that that's a bit more open and matches.
(17:58):
Because again, I presume a pharmacist in British Columbia is pretty similar to a pharmacist
in Ontario in terms of their ability to deal with a vaccine.
And so there is a lot of work that's being done to really try to make sure that it's
more accessible to people, recognizing the challenges in primary care.
This is still a vaccine outside of one province that's publicly funded it for long-term care
(18:21):
in Ontario.
This is still a vaccine that's also privately paid because there's not really a nasty recommendation
for it yet, which is often a trigger to then look at cost effectiveness and public versus
private payers.
So Ontario has invested in long-term care facilities, recognizing that there's probably significant
benefit there.
(18:41):
But outside of that, it's privately funded.
It may be funded through private insurance plans, but that also creates a logistical
challenge because now you actually have to buy the product and administer it.
So again, hopefully more advocacy around getting it in pharmacies and more spots that can do
it appropriately that put less barriers at that patient level.
And generally, do we know if like, let's say patients are asking about costs, do we know
(19:04):
roughly maybe it's a little bit different?
Yeah, the manufacturer cost is 230 Canadian.
In the US, it's $280 American.
So there is a discount being north of the border.
That is not necessarily the cost to patient.
There's obviously costs the pharmacy has to take for bringing it in, injection costs,
et cetera.
(19:25):
But that's the baseline cost plus probably a little bit on the pharmacy end or the provider
end in that standpoint.
And then just like any new rollout for vaccines, I know there's always questions in regards
to safety.
So what, you know, we talked about the efficacy, we talked about the administration of this
vaccine in those similar trials, I would assume, especially at the second year for sure, but
(19:47):
initially as well, safety was looked at.
So what can we tell our some of our listeners about that?
Yeah, absolutely.
So the GSK vaccine, the Eurexia vaccine, you know, it has a Shingrix adjuvant.
For those who have taken Shingrix or administered Shingrix, it gives people a sore arm and a
lot of swelling.
And so that was seen in the clinical trials, a lot of, you know, compared to placebo swelling,
(20:10):
fever, malaise, nausea, injection site redness, you know, those were higher in the group that
got the RSV vaccine versus the group that got placebo.
That's not necessarily a harm, but it's just a recognizable side effect of that adjuvant
being very, very immunogenic.
Unfortunately, it leaves people with a bit of immunogenic side effects.
Most of these SAEs were dealt with in 40 to 72 hours.
(20:31):
Sorry, these AEs, sorry, were dealt with in 40 to 72 hours.
In terms of SAEs, serious adverse events in the registration clinical trial, there was
none higher than placebo.
On the product monograph, there are two descriptions of Guillain-Barre-like cases associated with
the vaccine.
(20:53):
One was associated with co-administration with the influenza vaccine.
So it's not clear exactly what the source was.
And there's one that probably is temporally related to the vaccine in a separate clinical
trial, wasn't actually in this clinical trial.
So there is that indication.
And certainly part of post-marketing surveillance is looking for it.
(21:14):
But at the same time, outside of that, and these Guillain-Barre events are also difficult
to adjudicate just because they're spontaneous events in a baseline risk in the population
and a risk associated with respiratory tract infections too.
We have actually data around, for example, natural influenza and Guillain-Barre syndrome,
which is about 1 in 100,000, that risk and benefit discussion in that context.
(21:39):
And hopefully, as again, more global administration happens, we get more global data if this is
a real trend and what the prevalence is.
But really, outside of that issue, there really isn't major SAEs that were noted.
And again, other than the side sore arm, which for some people could be considered, it feels
lousy, but at least means it's working in that sense.
(21:59):
Right?
Yeah.
Right.
So I know in pediatrics, we always talk about co-administration of vaccines because our
vaccine schedules are so detailed and intricate.
There's multiple vaccines that are given.
So in this adult population over 60, I know that a lot of people are now getting that
text message where influenza vaccines are rolling out.
(22:22):
We know that there is a new COVID vaccine covering the Armicon variant that was released
by Moderna.
So in terms of with RSV and in the study, like you mentioned that some of the co-administration
with RSV and influenza led to, let's say an incident like Yomber, so did they discuss
(22:43):
co-administration of all the other vaccines that maybe even shingles, I guess, because
a lot of that population would also be exposed to such a vaccine?
Yeah, absolutely.
So the trial that had the single case with co-administration, there was actually a trial
that looked at co-administration with both high dose quadrivalent vaccine for influenza
(23:05):
and adjuvanted influenza vaccine.
At least outside of H3N2 titers with, I believe, the adjuvanted vaccine, there was non-inferiority
in terms of individuals who got influenza alone versus influenza plus the RSV vaccine.
And safety wise, there was no concerns other than the single case and even then it was
(23:28):
hard to say where it was adjudicated.
So at least we have some co-administration data.
Even that lower level of H3N2 antibodies, it's not clear what that clinically still
developed antibodies that were slightly lower than pre-specified margin.
Does that mean there's less protection or does that mean the protection is the same?
(23:48):
If you were exposed, it's not really clear.
The ACIP in the US, which is probably the guideline organization we rely on, just kind
of said consider co-administration if it's easier for the patient, the risks and benefits,
losing patients, et cetera, and consider if there's factors that may want people to space
things out, they're a bit more predisposed to side effects, they're worried about side
(24:12):
effects, then space them out.
And if you have good patient follow-up, then that's not an unreasonable issue.
And obviously consider where you are in the respiratory season.
If we're talking about doing this in May, probably fine to space things out.
If RSV is surging, then you might want to have some second thoughts about spacing things
out if you're going to lose the patient in that couple of weeks.
(24:35):
The other vaccines like herpes zoster, pneumococcal, COVID-19 vaccines, there's no data and there
wasn't co-administration data in clinical trials.
I would say there are some organizations, the Ontario Advisory Council on Immunization,
for example, that said maybe for the first little while, give a couple of weeks between
(24:56):
vaccines, not for any safety issue, but just for the fact that you could actually attribute
if there is an adverse event where what vaccine it's associated with.
But at the same time that the ACIP had really come out with a recommendation to say, think
about your patient, their demographics, their risks, their benefits of getting co-administration
versus non-benefits of getting co-administration and make a discussion.
(25:19):
There's not a yes or no.
You can certainly co-administer if you want, but really consider that patient.
The only other thing I would say is if you're going to use adjuvanted vaccines like the
adjuvanted influenza vaccine or the adjuvanted herpes zoster vaccine, give it in separate
arms to that patient so that you don't have a huge amount of adjuvant in one side.
Not dangerous, but they're going to have a lot of pain on that side if you keep pushing
(25:40):
it in that sense.
Yeah.
And then I guess seeing we should probably let our listeners know that with RSC this
vaccine is inactivated.
And so that would be important.
I know that's always a question when vaccines roll out.
And so like influenza, obviously we have active and inactive formulations, but specifically
unless I'm wrong.
(26:02):
So this is a protein based vaccine.
And so for immunocompromised populations and their families, there's no issues with potential
spread or again, being immunocompromised.
And we do know RSC is a big issue in immunocompromised patients and is actually a population of concern.
So especially if they're over 60, that is a population of really, really consider vaccination.
(26:24):
We have good data from herpes zoster that this adjuvant really does a good job at triggering
immune responses.
And in bone marrow transplant individuals, there's no contraindication in immunocompromised
person.
And in fact, probably a good amount of benefit in that context.
I think it's also fantastic that it's a one shot, right?
So I mean, probably the benefits of being conjugated and also that if we get it early
(26:50):
on in the season, then it will last you the season.
And who knows what the respiratory season, how long the respiratory season will be?
Because I know in pediatrics, for instance, we saw this early fall, late spring was our
RSV season.
And then now it's just turning into kind of that less seasonal pattern.
(27:12):
So I think it's reassuring to people as well that this isn't something that's only going
to last you four or five months, but the hope is that it lasts you the entire season and
longer.
Yeah, absolutely.
And you know, in those discussions around costs, like we know cost is an issue.
People have cost containment issues and the need to afford medications.
(27:33):
You know, think about it as amortizing it over at least two years, maybe even longer.
And so, you know, this is not just a cost upfront today.
It's probably a cost for two years or three years, depending on the data that we see coming
out.
You know, there may be that frame of mind that this is more of a long term intervention
than a short term intervention.
I know there's a lot of discussion around RSC in general, even in the pediatric population.
(27:57):
So like we talked about the disease burden.
So in the past, we've really, I mean, even now we don't have like an RSC specific vaccine
in pediatric patients.
There is some discussions around rollouts in pregnant women and other high risk populations.
Like we've already fortunate to see that at least one came out in elderly population with
(28:18):
comorbidities.
But just so our listeners know, like there isn't a pediatric formulation of this yet.
We, they will be hearing a little bit more about some of the monoclonal antibodies.
Historically, we've had Pellivizumab on the market for a long, long time, as long as I
can remember practicing and learning about it.
(28:39):
And so I think there will be some newer data coming out from PHAC for sure in a few short
months here in terms of Nercivumab, which I think a lot of our listeners probably tuned
into some of the information and probably will be hearing from their RSC programs locally.
It is obviously jurisdiction, inter-jurisdictional differences.
(29:03):
We know that with all vaccines and healthcare in general, and you know, once like Health
Canada definitely has approved this.
And so with the rollout of Nercivumab, we don't know exactly which populations to target.
I know the US has definitely given us more information in terms of a wide group patients,
(29:26):
but just for our listeners to be aware that some of that data isn't as particular, you
know, rolled out yet for Canada, but should be on the way.
But just to discuss a little bit about what we're seeing with RSV.
So obviously through some of our impact surveillance data, similarly to what other groups have
seen in other populations, like you mentioned in the adult population as well, is that we
(29:49):
didn't actually have a season for RSV back in 2020 to 2021, which was a bit strange for
us in pediatrics because prior to that and then after that, we've seen peak numbers of
RSV and really affects kind of the young comorbidities definitely.
So if anybody has chronic or congenital heart conditions, chronic lung disease, and that's
(30:13):
kind of our same population.
Now we haven't seen much of a difference in terms of the actual morbidity that's changed.
So that's been very similar, but we have seen a rise in our hospitalizations.
And so that's gone up significantly and still affecting less than six months old, primarily.
(30:34):
And so I think that's still, whenever we talk about extremes of age, I think that's very
common in medicine, right?
So extremes of age, less than six months, I mean, even probably up to a year, we worry
about that with RSV and then 60 and older is kind of what we're talking about in the
elderly population.
So I think some of these things are towards preventative, right?
(30:55):
That's what our actions are towards.
And that's what Nercifimab and even Pellivizumab in the past.
So I think some of the differences, I won't go into all the details of that today for
time's sake.
And, but definitely once PHAC gives us some more information, I think we'll probably do
another episode on Nercifimab because I think it's worthy of its own episode for sure.
(31:18):
It's a difficult file, right?
Because vaccinations are kind of pretty straightforward in terms of, you give it, that's it.
There's a cost associated, there's a burden associated.
And the demand drives the vaccination in terms of the disease state.
This is a tricky file, right?
Because there's a cost effectiveness component in terms of the number of hospitalizations
(31:38):
averted.
There's lots of ways that we measure cost effectiveness in terms of quality adjusted
life years and that type of thing.
And so this is where some of these discussions are happening.
This is where the one decision could be made in the US, one decision could be made in Canada
that are polar opposites.
And again, it's not as simple as saying yes or no.
(32:00):
The drug's approved, it's just how do we roll this out effectively to the most individuals
that are at risk and get the biggest value for it in that sense, right?
Yeah.
And just like you mentioned, Zane, we're entering into programs that are already established,
right?
So we already have these RSV programs and multiple centers.
And so kind of figuring out the logistics of the change as well.
(32:22):
And I think it rolled out in a time where RSV is just around the corner too.
So but definitely new information, a lot of updates.
And so all of this along with other preventative measures that we've seen being implemented
in the last few years, I think we're on the right track.
That's probably the most fortunate take back from this.
(32:44):
Even though it's a dreaded respiratory season, we have more options.
So with this upcoming respiratory season, what's our future?
Do we think that we're seeing an uptick in general?
Are we already seeing this uptick?
Yeah.
I mean, I think COVID-19 obviously is one that it's hard to predict, right?
If you could tell what could happen, you'd probably make a lot of money and be able to
(33:08):
go through it.
But at the same time, we do see COVID transmission.
It is translating into some degree of hospitalizations and unfortunately is translating into nosocomial
activity.
But in the same context, there has been a rapid, rapid decline in severe complications
with COVID-19 and that's really due to COVID-19 and therapeutics.
Influenza is probably, as we saw in some of the other Southern jurisdictions, is probably
(33:33):
going to have more of a typical seasonal pattern.
Maybe a bit of a higher peak, it's not clear.
A little bit more reassuring from last year, it doesn't seem to have taken off just yet.
It's kind of at the beginning.
So it's probably a little bit more hopefully predictable.
RSV, again, I think we're starting to see the uptick a little bit earlier, not as bad
(33:54):
again as last season's uptick, but starting.
All the other respiratory viruses obviously come around to adenovirus and rhinovirus,
that's typically earlier in the year, parainfluenza, human beddenumovirus in the spring, all that.
I think the one thing that is probably new-ish and one of the directions on improving vaccinations
(34:15):
is also a significant recognition of the chronic disease states that get exacerbated by underlying
viral diseases.
I'll give one example of coronary artery disease or cardiovascular disease.
It's always been known, I mean, we see it in the winter, right?
That heart attacks go up and people often complain of a viral illness before their MI.
(34:35):
These are pure MIs, chest pain MIs, not I have a cough and I have no troponin, this
is people who have plaque disruption and need an intervention.
There's been a lot of data across the country, Jeff Kwong's group here in Ontario has really
studied this quite a bit and saw, for example, the rate of incident MI after influenza is
(34:57):
six times higher in the seven days post-influenza diagnosis than it is before having influenza
or even seven days after having influenza.
That's an important concept.
We actually have our first randomized clinical trial of influenza vaccine in cardiac prevention
and it's pretty landmark trial.
It's actually one that isn't discussed much, but this was by Mark Loeb, who's a colleague
(35:21):
of mine here.
They went to some low-income countries where influenza vaccine was not standard of care.
So it was really kind of an altruistic trial to get some people influenza vaccine.
They gave influenza vaccine versus placebo to individuals who had cardiac risk.
They looked in the influenza season and they saw about a 19% relative risk reduction in
(35:45):
incident fatal or non-fatal myocardial infarction or stroke as a composite outcome in individuals
who got an influenza vaccine versus not.
This isn't that they get influenza, this isn't that they get pneumonia, did they end up hospitalized?
It's literally, did they have a heart attack or a stroke and they saw a decline.
So that's an important intervention, right?
(36:05):
For those primary care specialists who deal with high-risk cardiac patients, we have agonizing
discussions about antiplatelet agents, anticoagulation, statin, glycemic control, hypertension control.
We rarely have discussions of, hey, are you up to date with your immunizations?
(36:26):
But I think that paradigm has shifted to say, actually, I need to talk to you if you're
up to date on your immunizations because that's just important as the antiplatelet discussion
we need to have or the statin discussion or the hypertension discussion we need to have.
So really groundbreaking, but a concept that I think has been going on for a while, but
recognizing again that there is a probably chronic disease burden from viral infections
(36:49):
that needs much more intervention from those in that sense.
So really emphasizing preventative measures alongside other preventative risk-modifying
disease methods that they're using.
So I think for some of our cardiologists listening out there, I think that's good to implement
into our day-to-day counseling because I think it's important to have that whole framework,
(37:14):
right?
So we have to cover all aspects and presenting some of this data to your patients.
I think that's really important because I think a lot of information, there's a lot
of information out there, but really having some of that evidence-based and trial information,
I think is very helpful for patients to understand.
It's not just that we're preventing you from getting a common cold, but there's actually
(37:37):
other benefits.
Absolutely.
And it's a group discussion, right?
So all healthcare providers need to be involved with immunization.
It's not just primary care.
It's not just pharmacy.
It's not just infectious diseases.
It's everyone has a role to play.
Again, a cardiologist has just as much skin in the game to make sure that person's immunized
as the primary care physician.
Yeah.
(37:58):
And I think just making it routine.
And I know there's a lot of discussion around, there's obviously vaccine hesitancy, but there's
also vaccine fatigue, right?
So we are seeing people from the last few years, all we talk about is vaccines, vaccines,
vaccines, and I can imagine for patients and for their families and for people who are
(38:21):
trying to raise their families, it's challenging, right?
There's always something new.
There's always something that we're talking about, but I think this is just the spread
of information is very different nowadays than it was before.
And so I think just counseling your patients is really important, reminding them that we're
not going to talk about this all the time, not in July and August, but right now as we're
(38:44):
having peak respiratory season, that's why you're hearing more about this.
And so really taking on those preventive measures.
That's fantastic, Zane.
I'm really excited about this RSV vaccine because I want to see some of the post-marketing
surveillance.
I think it'll be interesting to see some of the data through there.
(39:05):
So what's the future currently?
Are there enrollments for trials that physicians should be thinking about?
Is there a future combined vaccines that are coming out?
And maybe we can prep our patients for anything that's on your end.
So definitely the combined vaccine is a big issue.
(39:25):
And certainly there's a lot of work being done, COVID-19, RSV and influenza, bundling
them, not only having them separate, but bundling them up, recognizing it's a challenge.
The data cuts from year two and year three of these studies are also going to start coming
out so we can probably get a bit more sense of what long-term efficacy of these vaccines
are.
There is a lot of work being done.
(39:46):
And again, we'll probably see real-world implementation data.
And similar to the journey of the herpes zoster vaccine, we start seeing what happens in real-world
populations, right?
So long-term care populations, majorly immunocompromised populations.
I think the data will be good, but I think, again, it gives more push for, A, public funding
models, but B, really the benefits of these vaccines.
(40:09):
Yeah.
So a lot to look forward to, but let's all be safe this respiratory season.
So I think we have some preventative options.
The vaccines have started to roll out.
So reach out to your local pharmacists and pharmacies and physicians if you need more
information.
And so I think really important is along with prevention.
(40:30):
We do this in pediatrics all the time.
I counsel everybody about hand washing and if you're sick, stay home, masking, that type
of thing.
So we know that all of these preventative measures along with vaccines are effective.
And so is there any last few words you want our listeners to know about?
Yeah.
(40:50):
No, it's just, look, we live in a, it's a terrible time that we have to deal with respiratory
season, but think about it.
This year is very different than 2018.
We have multiple vaccines, we have therapeutics.
We have lots of different ways to make sure people are safer during respiratory season.
You know, it's time, you know, I think providers are really willing to have those discussions
with patients.
And so, you know, have that discussion with your provider because again, it's important.
(41:14):
And again, it's really the scientific progress, which has been great.
Exactly.
And I think we're very fortunate that all of this is rolling out at a very good speed.
So definitely timely for the respiratory season as well.
That's fantastic.
So before we go, I just want to let everybody know that this podcast is only for informational
purposes and not to endorse a product or a vaccine product or any information.
(41:39):
Pleasure to have you on our podcast today and, you know, talk about such a pressing
issue that's, you know, just around the corner for most of us.
And so I think with all of this advice and information that you've given us today, I
think we're setting ourselves up for a successful, although dreaded respiratory season.
(42:00):
Thanks for having me.
Thanks, Sain.
Thank you, Dr. Purwall and Dr. Shagla.
Have a topic suggestion?
Email us at thecanadianbreakpoint at gmail.com and follow us on ex, formerly Twitter, at
CA Breakpoint.
See you again soon at the Canadian Breakpoint.
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