ACR COVID-19 vaccine guidance weighs risk with 'no data': What to tell your patients
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Working with minimal data and the pressure of the pandemic, the American College of Rheumatology put together guidelines for COVID-19 vaccination in individuals with rheumatic and autoimmune diseases.
The document, which was published in Arthritis & Rheumatology, contains 76 guidance statements, 74 of which were agreed upon and two of which were not agreed upon. Of the agreed-upon group, 16 statements had “strong” consensus, while the rest were offered with “moderate” consensus.
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Some of the key considerations pertained to continuing or suspending medications around the time of vaccination.
The group acknowledged that vaccination in patients being treated with rituximab (Rituxan, Genentech) can be challenging. They recommended that individuals receiving this drug should, first and foremost, use COVID-19 preventive measures, such as self-isolation. However, if the vaccine is administered, it should be given approximately 4 weeks before the next scheduled rituximab cycle. After vaccination, if the patient’s disease activity level permits, clinicians should wait 2 to 4 weeks before administering the next rituximab dose.
Methotrexate should be withheld for 1 week after each dose in patients with poorly controlled disease. For patients with well-controlled disease, no modifications are necessary.
Subcutaneous abatacept doses should be held for the week before and the week following the first COVID-19 vaccine dose, with no interruption for the second dose.
For therapies ranging from sulfasalazine, leflunomide and mycophenolate mofetil (MMF), to azathioprine, oral cyclophosphamide, TNF inhibitors, interleukin-6R, IL-1, IL-17 and IL-12/23 inhibitors, no modifications are necessary.
Healio Rheumatology sat down with one of the document’s authors, Cassandra Calabrese, DO, who serves as associate staff in the department of rheumatic and immunologic disease in the department of infectious disease at the Cleveland Clinic Foundation. She provided a look at the guideline development process and perils of working under pressure in a space with minimal data.
Healio Rheumatology: Could you talk a bit about the process of developing this guideline?
Calabrese: This was a tall task. First and foremost, I have to give credit to Jeff Curtis (MD, MS, MPH, of the University of Alabama at Birmingham), who did most of the work. It is always challenging to throw together a guidance document, but even more so with no data, and in a space where there is such a big unmet need.
The task was to review everything that is out there to date, all of the information on all of the COVID-19 vaccines. But then we also needed to look at other data on preexisting vaccines — flu and pneumonia, among others — and how they perform in these immune-mediated diseases and in the setting of immunosuppression. It was a lot of homework, there were a lot of opinions in the group as we tried to make sense of all of this. We had to put our heads together and extrapolate from studies on preexisting vaccines because we had no data for our patients on immunosuppressive drugs.
Healio Rheumatology: Given that you had to extrapolate from other vaccines, what does that mean for the utility of these guidelines?
Calabrese: The overarching principle is that this document is meant to be a basis for shared and informed discussion between rheumatology providers and their patients. This is not the law. For example, withholding medications is not necessarily going to be the right choice for everyone. You have to consider the risks of COVID-19, which has considerably more complications and can kill you at much higher frequency than influenza.
Healio Rheumatology: Digging deeper into the recommendations for withholding medications, can you talk about the decisions to withhold methotrexate for 1 week after vaccination?
Calabrese: This is where the idea of extrapolating comes into play. The study by Park and colleagues with the flu vaccine showed that withholding methotrexate for 2 weeks could increase vaccine efficacy. Because two of the COVID-19 vaccines use a two-dose schedule, we decided to split the difference and recommend withholding methotrexate for 1 week after each dose, so that patients would not be withholding methotrexate for a total of 4 weeks after receiving a COVID-19 mRNA vaccine. We settled in the middle of the road, to make it easier for patients.
Healio Rheumatology: What was the decision-making process like for rituximab?
Calabrese: Of all the drugs we use, we know that rituximab has the biggest impact on vaccine effectiveness. We know this from data on influenza and pneumococcal vaccines. The discussion was particularly challenging given the two-dose schedule of the COVID mRNA vaccines, and because so many patients on this drug have forms of vasculitis and other diseases with end organ involvement where they just can’t miss or delay a dose. It is for this reason that it may be preferable for them to get the Johnson & Johnson vaccine, which is a single dose. This will allow doctors and patients to coordinate as best as possible.
Healio Rheumatology: How about the conversation surrounding MMF?
Calabrese: This was also especially difficult. We know there is a signal that it does reduce vaccine efficacy. However, patients taking MMF generally have severe organ disease, which is why we did not recommend fiddling with it. Also, there are no data that holding MMF after a vaccine increases vaccine responsiveness. This is certainly something to think about but, at present, there is much uncertainty surrounding the utility and risk/benefit ratio of having patients hold this drug after COVID-19 vaccine.
Healio Rheumatology: In order to arrive at more definitive answers to these questions, are patients being entered into trials or registries to track responses to the recommendations?
Calabrese: Many institutions are already looking at vaccine responses in patients with RMDs who are getting the COVID-19 vaccines. We are doing a study here at the Cleveland Clinic, and there are studies happening at Washington University in St. Louis. Jeff Curtis and Kevin Winthrop are conducting trials, and there is another group working on this at Johns Hopkins. We can expect to start seeing some of these data emerge soon.
Healio Rheumatology: Are there any recommendations/concerns for patients using over-the-counter NSAIDs in terms of vaccine efficacy?
Calabrese: There was a lot of discussion on this topic, as well. There were some older studies, mostly in infants, suggesting that prophylactic antipyretics could conceivably reduce vaccine efficacy. That is where all of these questions about Tylenol and NSAIDs come from. It is for that reason that it is recommended to not take these medications preemptively before getting the vaccine, to prevent side effects, but if patients develop reactogenicity post-vaccine — arm pain, fever, chills, etc. — then it is perfectly fine to take acetaminophen or NSAIDs.
Healio Rheumatology: Is there a risk of activation of autoimmune conditions or immune manifestations after vaccination or after COVID-19 itself?
Calabrese: I get asked this question a lot. At present, there are no solid data showing these trends. Of course, there have been case reports of unusual things happening after getting a vaccine, but these are anecdotes out of a very large denominator. But I try to remind myself, and my patients, that vaccines have been around for a long time with no evidence of causing flares of any immune-mediated or rheumatic disease. We feel these vaccines are comparably safe for our patients.
Healio Rheumatology: Can pregnant and nursing women receive the vaccine? Are there risks?
Calabrese: We recommend that this group get vaccinated, along with lactating women. Of course, pregnant women were not included in the vaccine trials. But our recommendation is supported by the CDC and the Society for Maternal Fetal Medicine, among other organizations.
Healio Rheumatology: What is the course of action for patients who develop symptoms following vaccination? Should they wait for negative symptoms or continue to second dose?
Calabrese: One reason a lot of patients cite for hesitancy is that their friends and family developed symptoms after getting the vaccine. I always explain to them that that is the immune system ramping up and making antibodies. This can come with fevers, chills, headaches and body aches, there can be redness or swelling at the injection site. It seems that this occurs more frequently after the second dose than the first. I tell my patients, “If this happens to you, which it probably will, it is a good thing.” I find that it helps to set these expectations.
Healio Rheumatology: Many guidelines these days are “living” documents, meaning they are meant to be updated as new data emerge and treatment paradigms evolve. Is this the case with this guideline?
Calabrese: Absolutely. We are already working on the next iteration.
For more information:
Cassandra Calabrese, DO, can be reached at 9500 Euclid Ave., Desk A50, Cleveland, OH 44195; email: calabrc@ccf.org.
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