Transcription:
COVID-19 Vaccination and Rheumatic Disease

Melanie Cole (Host): This is Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole, and I invite you to join us as we discuss the COVID-19 vaccination and rheumatic disease. Joining me is Dr. Eric Ruderman. He's an Associate Chief and Professor of Medicine in the Division of Rheumatology at Northwestern Medicine. Dr. Ruderman, it's a pleasure to have you join us, as this is a really interesting topic. Can you start by telling us a little bit about the initial studies of the vaccine and why there were gaps for immunocompromised people?

Eric Ruderman, MD (Guest): Sure. I think you have to remember what was going on back in the spring and summer of 2020, when those studies were done. The goal was to try to identify a vaccine as quickly as possible. You know, the world was a very different place and the initial studies really sort of took all comers. I don't think they excluded anybody, except people with really serious underlying diseases where they were concerned about potential problems, but there were people with rheumatoid arthritis in those studies, there were people with other rheumatologic diseases, but they weren't specifically called out.

So, the studies weren't stratified to look at that group of patients, at those people, with those diseases. And I think that, that left everybody wondering afterwards, these vaccines work, they work very well, but maybe there's a difference in some of those people with certain diseases or on certain medications and the original studies really just weren't designed to ask that question. They were more aimed at sort of getting the big picture so that they could get the information they needed to get these vaccines out there as soon as they could.

Host: Well then Dr. Ruderman research presented at the ACR Convergence 2021 in November, looked at rheumatic disease following COVID vaccination. What did you learn? How did the researchers find out more about the safety of the vaccines in patients with rheumatic disease?

Dr. Ruderman: It's a great question. And it's a question we've been really asking from day one in Rheumatology. From back in the spring of 2020, there was a lot of interest in understanding really two things, how is this disease affecting our patients and are our patients with specific rheumatologic diseases doing worse? Patients on specific medications, are they doing worse? And then when the vaccines came along, the obvious question was, will the vaccine be as protective in those people as they are in the general population? And there's been increasing data that I think has helped us hone in on that question. And we've learned that by and large, our patients do pretty well but there are just a few medications that seem to impact interestingly, both response to the disease and response to the vaccine. And one of the ones that has been a big issue, and there was some data presented at ACR meeting on this has been rituximab, which is a monoclonal antibody that targets B cells. And since the B cells, the B lymphocyte cells are the ones that are really important in generating the immune response in response to a vaccination; it stands to reason that if you're on a medication that affects those cells, you may see a difference in response. And that's exactly what we've seen. And we've found that early on patients who received vaccination, who were taking rituximab, did not generate the kind of antibody response that everybody else did.

So, what we did was we responded by saying, well, let's try to separate when they get the vaccine from when they get the rituximab, can they afford a break in therapy for a while? And it's a challenging question because on the one hand, you want to see people respond to vaccine. But you also don't want to stop their therapy because you don't want their disease to get worse.

And so it's a challenge. One of the things that did show up at the ACR meeting this year was in patients who had not responded, or at least didn't have antibodies after the first two doses of vaccine, there was at least a subset who responded to the booster, either with antibodies or with some T cell mediator response, which gave us reassurance that there was at least some benefit, that we weren't wasting our time vaccinating these patients. But I think we're still very concerned that these people are not as protected as everybody else. And at the same time we've had data that's come along from the beginning of the pandemic that says one of the key factors that influences who does poorly with a COVID infection is how active their underlying rheumatologic disease is, perhaps as much or more so than many of the medications.

And so, we're sort of stuck between a rock and a hard place. If you stop the rituximab so they respond more to the vaccine, but their disease flares, are you doing them any good if they develop COVID, if they are exposed to and get infected? So, it's been a challenge all along. I think one of the reassuring things we learned from the meeting was some data not definitive, but preliminary that says, it's not all or nothing. And that patients, even on a drug like rituximab who may have less of a response, do at least get some benefit from the vaccination.

Host: So, then let's talk about the risk of an auto-immune flare up from the vaccine, but conversely, do those immunosuppressive medications affect the vaccine effectiveness? Have we looked at that?

Dr. Ruderman: We have. There's not great data. Some of it is extrapolated from other vaccines. We've had a lot of data over the years in other vaccines, flu vaccine, pneumococcal vaccine, shingles vaccine, and by and large, a lot of the drugs that we use have some impact on effectiveness, but they don't, completely block it.

So, it isn't as though the vaccine is a waste of time. And I think we've all been pleased at with the really remarkable effectiveness, particularly these mRNA based vaccines, that if you lose a little of that, you're still pretty well-protected. And so we think that's been pretty good, but there's been some recommendations and some guidance based on other vaccines.

So, as an example, there was an interesting study a few years ago, looking at flu vaccine in patients on methotrexate. And they found that if patients skip their methotrexate for a couple of weeks after getting the flu vaccine, they actually mounted a better response to the vaccine. And so that led us to make that same recommendation for the COVID vaccine. Whether that really is true or not, I don't think we have data to back that up, but the logic behind that is that missing a dose or two of the methotrexate after getting vaccinated, is not likely to have a huge impact on disease activity and they're not likely to flare. So, there really isn't a lot of downside and if there's benefit, it makes sense.

Host: Well, that's very interesting, which leads well into my next question. Is there issues or protocols for timing and use considerations for immunomodulary therapy in relation to the vaccination? And do we have some contraindications to the vaccinations for patients with rheumatic disease?

Dr. Ruderman: I think the first answer to the second part of your question is no, that by and large, the contraindications to vaccination in our patients are really the same as for anybody else. And that's for people who've had a serious allergic reaction to either a prior COVID vaccine or a different vaccine. Those are people you're a little bit cautious about. But we have not really had any reason to suspect that there's a contraindication for any of our patients with any of our specific diseases. And by and large, from the very beginning, the rheumatology community has felt that the benefit of being vaccinated far outweighs any theoretical risks that could be seen in some of these folks. And so we've really recommended that everybody get vaccinated. Now, in terms of timing, there are some recommendations. The American College of Rheumatology had put out some recommendations last year and they update them regularly. Much of it is not really database specifically because those studies haven't been done, but it's sort of an expert analysis and it's based on some data from other vaccines, as I mentioned.

And so things like skipping a dose of methotrexate after getting vaccinated, skipping a dose of sulfasalazine, holding a dose of a JAK inhibitor, another oral agent that we use in rheumatoid arthritis for a week in the hopes of making sure that people get a better response. The trickiest ones have been the B cell directed therapies.

And there are a number of drugs that affect how B cells work. The rituximab, I mentioned already. There's a drug called belimumab that's used in lupus. There's a drug called abatacept that we use in rheumatoid arthritis that affects B-cell and T-cell interaction. And so there've been recommendations to treat, time the vaccine so that they're not at the peak effectiveness of the drug. So, any impact that drug has on those B cells, maybe somewhat lessened to try to maximize the response that those patients are going to get to the vaccine. Honestly, we don't have a lot of data to show how well that has worked, but that's been the way we've approached those drugs.

And it changes as we go along. So early on, back in early 2021, the goal was to get everybody or as many people vaccinated as soon as we could. And so we really were kind of hesitant to say, well, you just took this medication and let's wait a few months before you get vaccinated because the potential consequences of that were tremendous. Now with boosters and other doses, I think there's a little bit more leeway to time it because we figure people are protected already. We want to increase their protection with the booster. And if we can do a better job with that, by trying to time it and delay it a little bit around medication dosing, that, that makes a little bit more sense than it did early on when the goal was really to get vaccine in as many people as we could, as quickly as we could.

Host: That is so interesting, Dr. Ruderman. And is your team doing any research in this area at Northwestern Medicine that you'd like other providers to know about?

Dr. Ruderman: Well, we've been monitoring our patients and we've been following them. And I think, where we're looking at right now, is trying to see responses in some of our patients on some of these drugs that might mitigate their response to the vaccine and try to understand are there ways around that.

And that's been important recently as we've sort of looked at some of these antiviral therapies, both the monoclonal antibodies and the oral agents that are targeted against the COVID virus. And the idea of using some of these almost as a preventative agent. In other words, not giving them to people after they've gotten sick, but ahead of time to sort of prevent them from getting sick.

And we've been trying to look at ways of using those agents in our patients who we think maybe have had a lower response to vaccine and to protect them. It's challenging because all of those drugs, both the monoclonal antibodies and the specific antiviral drugs are in very short supply. And so the big need for those drugs right now is in people who have the infection and are potentially going to get very sick and you want to keep them out of the hospital or keep them out of the ICU.

As that supply opens up, we're beginning to look more and more at the idea of using preventative therapy in some people who are potentially at much higher risk if they get infected and try to keep them from getting the infection in the first place.

Host: Dr. Ruderman what an important topic we're discussing today. As we wrap up, are there any other important considerations for providers caring for patients with rheumatic disease in this COVID time? Anything that you'd like to let them know or advice you'd like to share?

Dr. Ruderman: Sure. I, think there's two things. On the topic of vaccines, I think from the beginning, it has been very important to encourage our patients to get vaccinated. Even if in some instances, the vaccine may not be as effective as we would hope, it's better than doing nothing. And we do get a lot of patients who are sort of gun shy and they're worried about what the implications are. I should note that we really haven't seen the vaccine trigger flares of our underlying diseases. And there is some published data from other institutions that have looked at that both after the initial dosing and after the booster dosing. What we've seen is, many people who get these vaccines feel kind of crummy for a day or two afterwards, they get a low grade fever. They get some muscle aches, they get some joint aches, they get headache, and in some of our patients with rheumatic diseases, we see that some of their usual symptoms, their RA symptoms, the joints that are often involved in their rheumatoid arthritis, for example, may hurt more.

But we really haven't been seeing flares of their disease that necessitate changing their treatment or doing anything different. And so we've really encouraged people that, that's not a reason not to get vaccinated and our patients should get vaccinated because that's the way to protect against this virus.

The other key point is that we're learning more about which of our patients are particularly at risk. And I have patients who are treated with rituximab particularly, and my advice to them has been don't let your guard down. Those are people who should not be eating in a restaurant right now. Those are people who should not be socializing with large groups of people, some of whom may potentially not be vaccinated or not be protected. We're not there yet. And that's a particular group of people who really needs to take the precautions that we're all taking, but take them to the next level because their risk is so much higher.

Host: Thank you for such great information, Dr. Ruderman. What a fascinating topic this is, and I hope that you'll join us again to update us as we learn more. And to refer your patient or for more information, please visit our website at breakthroughsforphysicians.nm.org/rheumatology to get connected with one of our providers.

That concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians. Please always remember to subscribe, rate and review this podcast and all the other Northwestern Medicine podcasts. I'm Melanie Cole. Thanks so much for listening.