Efficacy Differences, Adherence Challenges Between mRNA-1273 and BNT162b2 Vaccines for Immunocompromised Populations

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Welcome back to PopHealth Perspectives, a conversation with the Population Health Learning Network where we combine expert commentary and exclusive insight into key issues in population health management and more. 

In this episode, Dr Gary Owens discusses the factors contributing to lower vaccine adherence among immunocompromised patients and compares the efficacy rates of mRNA-1273 and BNT162b2 vaccines, providing insights into vaccine choices for immunocompromised individuals.  

Could you please introduce yourself by sharing your name, your title, organization, and experience?

Yes. I'm Gary Owens, and I'm president of Gary Owens Associates, which is a consulting organization around new technology and pharmaceutical issues. I am a family physician by background, and had about 14 years in clinical practice, then spent another couple of decades working in the payer world. And the last decade-plus, in the consulting world. So it's a pleasure to join you this afternoon. 

Can you explain the distinct factors contributing to lower vaccine adherence among patients who are immunocompromised? 

That's a very interesting issue. A little bit has been written about it. One would think, especially if you are immunocompromised, that the vaccine rate would be higher rather than not as high as we anticipated. And, in fact, at one point it was the case. There was a really good study published by Sara Tartof and our colleagues from Kaiser that at the beginning of the COVID pandemic with the stressing of COVID vaccination the immunocompromised actually, their vaccination rates, exceeded those rates of the general public approaching 90%. 

However, then we began to [place] a fairly large emphasis on vaccination of the general public after we had prioritized some of the chronically ill and immunocompromised. And I think maybe there was even some confusion about immunocompromised patients having received, probably, by the time we were publicizing the need for a third immunization they had received their third immunization perhaps not realizing that guidelines may have recommended even a fourth or a fifth one. 

I think another reason that maybe their rates had gotten a bit lower, and then parallel with I think the general public a bit of COVID fatigue after the peak of the pandemic in 2020 and 2021 into 2022. I think there is a little bit of COVID fatigue, maybe even on the part of providers. And quite honestly, there's some conflicting recommendations about how many doses the CDC does update on their website, the vaccines that are useful in people who are immunocompromised, and they specifically call out to the Pfizer-BioNTech vaccine, Moderna, Novavax's vaccine. But then they give somewhat differing recommendations for the 3 different vaccines. So there's a lot of room for confusion, and, as we all know sometimes, when medical routines become more complex, it becomes more difficult to adhere to them. 

There is a fair amount of misinformation, and sometimes it is very difficult for people who don't have a scientific or medical background to begin to glean reliable sources versus unreliable sources. And unfortunately, medical misinformation has become a huge issue that we're beginning to see a lot of publicity about it in mainstream medical journals, and including some recent articles that I read in the Journal of the American Medical Association. 

A meta-analysis revealed mRNA-1273 demonstrated a notable decrease in the risk of SARS-CoV-2 infection, severe infection, hospitalization, and mortality in immunocompromised populations when compared to BNT162b2. Given mRNA-1273’s efficacy in patients who are immunocompromised, what is your experiential comparison of mRNA-1273 and BNT162b2? 

Unfortunately, I think, especially in the payer world where I spend most of my time, we don't really have a good source of data on this differentiation. Certainly, payer databases may be ripe for gleaning that because we should have which vaccine the patient's got as well as a history subsequent to the vaccine. But this was a reasonably well-done meta-analysis. Eventually they called it down to about 34 studies that they looked out of which 17 they used to make the analysis. Their data, again subject to the limitations, are reasonably convincing that there was a difference in outcomes.  

And, as you pointed out, those differences not only were in reduction in risk of COVID infection, but also a reduction in hospitalization, and a relatively small rate reduction in the risk of death. I think it was, I believe if I remember the number correctly, it was somewhere around 15 deaths could be prevented per 100,000. Not insignificant, but still a relatively small number. So, I think this is the first study of this kind that I've seen. And the reality is we're almost going to have to rely on real-world studies like this to help choose.  

Now that I've said that if we go back to my first statement where we're seeing now under vaccination of the immunocompromised, I think public health efforts probably still need to focus on getting them vaccinated. Not necessarily which vaccine they get, because we know both vaccines confer substantial protection. And yes, if you had your druthers, you want to use the one that has the data. But this is simply one metanalysis, so we're still limited in the amount of data that we have. 

Are there specific factors that patients who are immunocompromised should consider when choosing between these two vaccines?

Certainly, if they have the wherewithal to choose, or the physicians have the wherewithal to choose. And since we know that the safety profiles of these 2 vaccines are somewhat similar. There's some subtle differences. And if one vaccine has some data showing it's more effective in the immunocompromised, you might want to go in that direction. But then the other big factor is availability. If your particular provider only stocks one vaccine, again, I think I would err in favor of getting that vaccine rather than procrastinating and perhaps not getting the vaccine at all and putting oneself at increased risk. So again, if you have a choice of vaccines, maybe you go with the mRNA-1273 vaccine. But again, as I talk to providers, as I talk to pharmacists who administer a lot of these vaccines, most patients aren't even asking. They're simply coming in. 

You know, and we have similar things in flu vaccines. You know, there are a number of manufacturers in flu vaccines. But generally most of us, myself included, don't ask which manufacturer I'm getting. I simply say to my primary care doc, “Hey! It's time for the flu vaccine. Do you have it in stock so I can get it today?”

The evidence certainty among the comparisons in the meta-analysis was classified as type 3 (low) and 4 (very low). Considering the potential biases in observational studies, how confident can we be in the conclusions drawn from this meta-analysis regarding efficacy rates for both vaccines? 

I think we can be moderately confident, mainly because I don't think you are ever going to see a randomized, prospective head-to-head trial of the existing COVID vaccines. I just think that would not be practical. As the authors of this study pointed out, it would be a relatively large study in order to show the relatively small differences. So I think we can be reasonably confident. There were some limitations. The authors pointed out, for instance, that they only use studies done in English language. I believe a preponderance of studies done in the US. And certainly, even though they described the methodology for finding the studies that they use the in this meta-analysis, I think it would need, or we would need, to see at least one or maybe a couple of more separate analytics.  

The one thing that always raises a little bit of a skeptical eyebrow, and of course that's just the payer and me coming out, is this study was funded by one of the manufacturers of one of the vaccines. And one always has at least a slight level of concern: “Was the data massaged until it confessed the right answer?” They'll torture the data until it tells you what you want. I'm not accusing the authors of that by any means, but it just does raise that small element of skepticism. 

Again, I'll point out the study that was published about a year ago this time in the JAMA network. That analysis of COVID vaccine uptake among, you know, immunocompromised folks came from a Kaiser database of over 42,000 people, and I think we need to see more of those kinds of studies perhaps done by someone independent of a developer of the vaccine. But again, that study only looked at vaccination rates and explored some of those things that we talked about as reasons why the vaccination rate fell off over time in the immunocompromised. Perhaps the next study is one that I talked about a bit earlier, is using a large integrated delivery network database, or maybe a multi-health plan database to glean similar data that should be readily available to know which vaccine the patient received and then their subsequent medical claims history, which is where most of these data could come from. 

Have you observed any differences in treatment outcomes between the mRNA-1273 and BNT162b2 vaccines in immunocompromised individuals in your clinical experience? 

In my clinical experience, being only vicariously through the payers and the databases I work with, I can’t say I have. So in one sense, this meta-analysis was a bit eye-opening and stimulates thoughts for further research. But I'll be perfectly honest and say heretofore I have not looked for any differences. Again, much more concerned about vaccine rates and patients getting boosters, and especially those patients who have chronic diseases over the age of 60 or those immunocompromised getting a COVID-19 vaccine, not yet as concerned about which COVID-19 vaccine.

Are there any limitations or factors that should be taken into consideration when interpreting the results of this meta-analysis in the context of real-world clinical practice? 

Well, I think the authors recognize many, many of the limitations of this study. They pointed out it's still a relatively small number of studies that they are able to look at, they use basically studies that were published in the English language, and the databases you have to use came from observational studies. And of course, observational studies, as we've already discussed, are generally considered lower quality of evidence even though practically, that's the type of evidence we're going to need here. So those things do limit a study like this. I don't think they are what I would call ones that would invalidate this study. I think overall this was a reasonably well-done paper and the authors did acknowledge the limitations. But I think the big thing it potentially calls for, as we've already discussed, perhaps more work in more validation of what they found here.

What further research is necessary to enhance our comprehension of how these vaccines work in individuals who are immunocompromised and to effectively address vaccine hesitancy within this population?

Yeah, I think the first thing is to address the vaccine hesitancy. One of which, I think, does need to be continuing and a health care system, I'll literally say, the war on misinformation. Again I think there's so much misinformation out there. I recently read an article that attributed the vast majority of COVID information to a term that I've not seen before: the misinformation dozen. A small handful of people who are ultimately responsible for spreading a lot of COVID misinformation. So as health care systems payers, integrated delivery networks, and even physician groups, I think we need to first and foremost combat that misinformation and get the word out about the recommendations for immunizing the immunocompromised. And again, the CDC does a good job in their COVID-19 information of publishing the most recent recommendations. Perhaps if there's a way to simplify those recommendations based on future data, it'll make it easier for all of us, both providers and patients included, to be able to advise patients on the right thing.  

And I think last, but not least, maybe an integrated delivery system, or a health plan, or even an independent third-party researcher at a university doing a similar type of prospective (well, you can't do it prospectively, because it's an observational) but retrospective observational study that might help validate this. All of which would make for, I think, more ability to rely on whether or not there are differences between the mRNA-1273, and the BNT162b2 vaccines. 

I think my final message here would be this is the type of original research, the type of observational research, that we probably not only need, and I'm sure it's ongoing in immunocompromised patients, but perhaps even in the healthy adult, even these things stratified by age and even, maybe, perhaps tying some of this research to the risk of long COVID and vaccination that we still don't know enough about. 

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