Alfred Kim, MD, PhD, on the COVID-19 Vaccine for Patients Who Are Immunosuppressed

In this podcast, Alfred Kim, MD, PhD, talks about the COVID-19 vaccine in rheumatology. He discusses the top concerns that rheumatologists and their patients have about the vaccine and how his new research initiative may shed light on the vaccines' safety and efficacy among patients who are immunosuppressed.

Alfred H. Kim, MD, PhD, is an assistant professor, Division of Rheumatology, School of Medicine, at Washington University in St. Louis. There, he is the founder and director of the Lupus Clinic.

TRANSCRIPT:

Hello, everyone. Welcome to another installment of the Autoimmune Learning Network podcast series. I'm your moderator, Colleen Murphy, with the Autoimmune Learning Network. The COVID-19 vaccination rollout is underway. While some Americans look forward to the day that they can receive their vaccination, others are more hesitant.

What are the climate among your patients? Are they excited to get vaccinated, or are they unsure about whether they should even get vaccinated, maybe due to their rheumatologic conditions or medications? Dr. Alfred Kim is with me today to talk about the COVID-19 vaccine in rheumatology.

Dr. Kim is an assistant professor of medicine in the Division of Rheumatology at Washington University in St. Louis. There, he directs the Lupus Clinic, which he also founded. Thanks for joining me, Dr. Kim.

Dr. Alfred Kim:  Thank you very much, Colleen, for inviting me.

Colleen Murphy:  Absolutely. Now, I saw on your Twitter that you recently received your vaccination. I'm sure that must have been a happy moment for you.

Dr. Kim:  Yeah. You feel a little bit like you're part of history. Obviously, the data from both Pfizer and Moderna vaccine trials are very impressive. No vaccine has ever reached the level of protection that they have, which is around 95%. Most vaccine is around 70%. I was just thrilled. I felt very fortunate to be able to get it.

Colleen Murphy:  Let's talk about the top concerns about the COVID-19 vaccine that you have heard from your patients as well as concerns that maybe other rheumatologists have had and shared with you or their patients. What do we know about these concerns? What are the knowledge gaps that still exist about them?

Dr. Kim:  That's a great way to start. The concerns and knowledge gaps, which are essentially overlapping, center around efficacy—how well does the vaccine work? Then safety—will someone get a side effect or worse? In terms of efficacy, the main question is, will it work in me? I am a patient who takes immunosuppressive medications.

There are data showing that less than optimal or maximal responses can be observed with certain types of medicines, mostly studied with rituximab, methotrexate, and abatacept. That is something that has been propagated. These are facts. The only caveat to this is that even if we have a reduction from maximal responses, are those responses still protective? That, we don't know.

This is the one thing we want to look at, was to try to measure the level of responses compared to maximum, in other words, what's seen in people not taking immunosuppressants and whether or not that's going to be effective.

Meanwhile, while that data is being generated, the other question that is corollary to this is, should I hold my medicines while I'm getting my vaccine?

There is data using rituximab that, comparing to optimal situations, which may not be required, that with methotrexate with an influenza immunization, that if you hold the two doses after you get your flu shot, then you're able to generate maximal flu responses.

There are other medicines, particularly rituximab, which has a much more dramatic effect on vaccine responses. If you get rituximab, the data demonstrates only about a quarter of these people generate vaccine responses. There's certain medicines that have a higher risk than others. There are other medicines like the anti-TNFs which appear to not have any effect.

That's in terms of, how well would this vaccine work with me? On the flip side, the questions that we're getting and the unmet need in terms of knowledge is regarding safety. Is it safe for me to get? There is absolutely no data to support one argument or another. Both the Moderna and Pfizer efforts did not have any immunosuppressed people within their trials.

I get why the rapid nature of how these trials had to be put together and the unbelievably urgent need to demonstrate whether or not these vaccines work and are safe, pretty much had to exclude many specific conditions, but it left patients with autoimmune diseases out in the cold, so to speak.

Then the other question we're getting from this is, will I flare on this type of vaccine? While most vaccines do not...Well, none of the vaccines that we typically give our autoimmune patients have been reported to, at the population level, generate flares.

I can tell you anecdotally that I do have some lupus patients, for example, where I give them the influenza vaccine and appears like they have a pretty substantial flare afterwards.

This is a low percentage, but nevertheless, it's not like zero. The problem is that each patient is thinking, "Which side am I going to land on? Am I going to flare or not flare?" We don't have any data to guide that.

Colleen Murphy:  That's interesting. You just mentioned some of the knowledge gap and questions that are still ending. I hear you have a research proposal for vaccination for COVID-19 among patients who are immunosuppressed. What does that research entail? Can you share a little bit about that?

Dr. Kim:  Absolutely. We recognized immediately after the reports that especially the Pfizer vaccine was demonstrating really nice data and good responses. We knew that we were going to need to better understand how the vaccine would impact patients with autoimmune diseases.

In early December, we loosely started some email chains with our gastroenterology colleagues who treat inflammatory bowel disease, our neurology colleagues who treat multiple sclerosis, and our dermatology colleagues who treat a wide variety of skin diseases that are immune-mediated such as psoriasis, and also our ophthalmologists who treat uveitis.

We've gone to discussions about whether any one of us knew any guidelines being put out by major organizations that represent our diseases. There were absolutely none, obviously, because there's no data.

We recognized that we had a unique opportunity to fulfill a substantial unmet need. We started this study called "COVID-19 Vaccine Responses in Patients with Autoimmune Disease," which I clumsily call COVIRIPAD.

The purpose of this study is to understand how well does this vaccine work. In other words, more specifically, how large of an immune response do you get to the vaccine? How well does that vaccine response protect against an infection? How durable are the vaccine responses in autoimmune patients? Also about safety, how safe is that by associating adverse events?

We have a second, more very heavily scientific arm where we are going to be examining the trajectory of immune responses at the cellular level in these type of patients. There are two major cell types, T cells and B cells that can help build vaccine responses.

Some work has been done with other vaccines but not in the autoimmune setting. This would be the first study to get very hardcore granular data on the evolution of immune responses to any vaccination.

Of course, the top tier is the basic unmet need. Does it work? Is it safe? Then the deeper one is going to be seen whether immunosuppressive medications alter the dynamics of vaccine responses.

Colleen Murphy:  That sounds great. Do you have any timeline on this when we can start expecting things to come from it?

Dr. Kim:   That's a question I ask myself every day. When the emails start flying around in early December, we knew that the vaccine was going to be rolled out for tier one in most states in mid-December. We had to get our forces together really quickly.

We started recruiting and consenting subjects in mid-December. Now, we’ve hit our 100th subject enrolled. The peak immune response for vaccination, at least with influenza, is about one week after the final booster.

In this case, it's going to be, for the Pfizer vaccine, day 28 after your first shot. Then this as a result will be day 7 after your second shot. Then for the Moderna vaccine, it'll be day 35, which is going to be also one week after that booster shot.

Based of our timeline, we should be able to report the first 100 patients in our study or get a full data sets back in about a month. Hopefully, within a couple of weeks, we'll be able to get our observations out, at least as a preprint. It'll be submitted to a peer-reviewed journal for additional rigor checks.

This is going to be something that we were hoping within a month to month and a half, we'll have something out for at least a preliminary early look.

Colleen Murphy:  All right, definitely something to look forward to there. I'll have to keep my eye on that. It brings me to the next question, because you did say this research can help with other vaccines as well. How does the discussion about the COVID-19 vaccine among rheumatology patients fit into the larger vaccination conversation for immunosuppressed patients?

For example, does it reflect a wide-sweeping vaccine hesitancy, the need for more patient education? What can you tell us about that?

Dr. Kim:  There are two tiers here. The first one you discussed is more of the public health perspective, hesitancy, patient education. This is a common issue, not just among autoimmune patients, rheumatic disease patients, but virtually everyone. There is a substantial amount of misinformation about vaccines.

The COVID vaccine, for example, when you go through patient websites, in the discussion, there's always several people advocating that what they're doing is they're putting chips into your brain so they can track you, which is kind of a silly argument because, A, that's not really feasible but second, if they have a phone with Facebook on it, it's already being done. [laughs]

It's an interesting argument with an impact that is not realizable but, at the same time, it hurts us at the public health level. The idea of making sure that we leave the notion that vaccines are safe and effective is critical. This is true for every vaccine that's out there.

The uptake for flu vaccine, for example, is generally very low. It's around 50%. We would love to have a much higher to 90%, but there's a lot of perception issues. The COVID-19 vaccination effort accelerates the timeline and gives us a deeper understanding of patient misperceptions and their fears. It's important to address those fears.

The second tier here is going to be about, how well do these vaccines work? I'm not going to say that the results of our study is going to be applicable to each vaccine. We already know that each vaccine has different types of issues with different medicines.

I mentioned earlier, with influenza virus vaccines, certain drugs like methotrexate, rituximab appear to have reduced responses. Other drugs like anti-TNF such as etanercept or Enbrel, or adalimumab which is Humira, they don't have any effect on influenza responses.

But interestingly enough, in hepatitis B vaccines, there is a substantial reduction with anti-TNF that's not observed with methotrexate, for example. So there is a lot of nuance in terms of which vaccine and which medicine, which makes it a lot more complicated in terms of trying to extrapolate what we see in COVID to other vaccine experiences.

This is something we recognize pretty early. We need a fair amount of granularity where we know how each drug works in each disease. That's going to require a fair number of subjects to enroll.

Colleen Murphy:  This has all been interesting. As we sign off today, are there any last remarks you'd like to leave the audience with?

Dr. Kim:  Amongst us, amongst numerous other patient-facing organizations, Lupus Foundation of America, Arthritis Foundation, National Psoriasis Foundation, we're all recommending that all of our patients get the COVID-19 vaccine.

We do not anticipate new safety issues emerging. There are obviously questions about how well it works in the context of immunosuppression. Of course, we're going to be studying this, but we do anticipate that the vaccine will largely be effective for most of the patients.

In terms of holding doses, every rheumatologist seems to be advising different things. I have been advising not to change your current medications. I think the risk of flare and the use of prednisone to treat that flare, in a way, may outweigh any harm about any reduction in the vaccine response if any reduction is realized.

I've been recommending do not hold any medications. Many rheumatologists have been recommending at least holding methotrexate because of the influenza vaccine experience. Some people have been telling their patients to hold everything for a couple weeks after the vaccine.

This is a very confusing field for patients because it's still very confusing for rheumatologists. This is going to be a discussion that you and your rheumatologist are going to have to have. It's fair for you, as the patient, to ask your rheumatologist—if it was me, for example—aren't you worried that the vaccine is not going to work? That's a fair question to ask me.

If your rheumatologist is saying hold everything, aren't you scared that I'm going to flare, and that I'm going to need prednisone? Then see how those answers jive with your overall belief about how your health should be treated. These are very personal discussions until we get more data.

Colleen Murphy:  All right. Dr. Kim, thank you again so much for your time.

Dr. Kim:  All right. Thank you.