Many unknowns remain regarding COVID-19 risks for patients with RA
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The intersection between COVID-19 and rheumatoid arthritis still carries considerable risks and unknowns more than 2 years into the pandemic, said Jeffrey Sparks, MD, MMSc, director of immuno-oncology and autoimmunity at Harvard Medical School.
Numerous studies over the last 2 years have shown that patients with RA are at considerably higher risk for poor outcomes from COVID-19. And while many rheumatologists are recommending fifth vaccine doses for patients with RA, those risks still remain at the forefront of RA treatment in the post-pandemic era.
In an interview with Healio, Sparks discussed the current state of COVID-19 and RA, what we’ve learned about how the two diseases interact, and how COVID-19 has changed the way RA is treated.
Healio: What is the current concern level regarding COVID-19 for patients with RA?
Sparks: Well, there's a lot to unpack there related to variants, vaccination and treatment. In some ways, there's a lot of positives because at this point, RA patients could qualify for up to five doses of vaccines. They may qualify for Evusheld as pre-exposure prophylaxis, there's outpatient treatment for COVID. In a way, there are a lot of positives. However, it seems that the vaccines were developed for the original viral strain. It seems clear that they really help against severe COVID-19. That's hospitalization or worse, but it seems like the vaccines are not helping as much related to transmission.
There are a lot of breakthrough cases in patients who have been vaccinated. And so I think we're in the stage now where we have a lot of tools to protect patients from staying out of the hospital and getting really sick. Certainly, there are a few patients that are still at risk for those outcomes. But by and large, most patients are getting COVID in the outpatient environment. So the goalposts have moved a bit related to some of the long-term outcomes where there's a lot of question marks in the general population and rheumatoid arthritis. Do the symptoms linger, does the actual viral shedding linger? Are there differences related to fatigue, cognitive dysfunction, shortness of breath, and maybe even fibrosis in the lung or other organs that already patients could be susceptible to? There are some answers, but there are still a lot of questions.
Healio: What kind of COVID-19 safety measures are you kind of recommending that patients with RA take moving forward at this stage?
Sparks: I think it's very confusing, honestly. And at some point, we'll probably just forget how to count, just because there's been so many doses. But just to make it clear, if we're talking about mRNA vaccines, that's Pfizer and Moderna. The first three doses are the initial series. The fourth dose is the first booster, the fifth dose is the second booster. So that is really the current standard now. It seems that every boost does help protect against severe COVID-19. Maybe it helps a bit with severity in the outpatient setting and maybe less with transmission, particularly if you've gotten infected pretty soon after your vaccination dose. I definitely am still recommending it. I think the other thing people are looking forward to are variant-specific vaccines and hopefully those will be available in the near future. But I would say that don't delay getting the vaccine, just to try to time it to when there's a peak or when there might be another vaccine available.
Healio: How has the treatment of RA changed since the start of the pandemic?
Sparks: Well, one thing is that untreated RA or RA that needs steroids, those patients are at risk for COVID and poor outcomes from COVID. So we really want to treat RA for many reasons and COVID is just yet another one. As far as the treatment choice, this has been a moving target as far as how the immune suppressants we use for RA affect COVID risk and severity. I think by and large, most classes are really safe to use, and the one medication where we still have a little trepidation about is related to rituximab (Rituxan, Genentech). Specific to RA, since there are so many other options, we might only use rituximab if all the other options have been exhausted or can't be used for some reason. That's probably the one caveat, is that rituximab seems to really affect the vaccine response and affects risk and severity of COVID-19.
Healio: Studies have shown that the mortality rate of COVID-19 and the risk of poor outcomes is higher in patients with RA. What is the current state of knowledge on why that is?
Sparks: I think a lot of the research was done prior to vaccines being available. It's very important to keep that in mind that it's sort of a different ballgame if you've been vaccinated. We know RA comes with a lot of comorbidities. The longer you've had RA the more likely those are to accrue. So certainly, one reason RA patients might have worse outcomes is that they're more likely to develop comorbidities that are established to be risk factors for severe outcomes for COVID-19. Other specific RA factors are just related to the altered immune system and some of that's intrinsic to RA by itself. Some of it is related to the medications. I think at this point, the two medications that we are still most worried about are corticosteroids such as prednisone and rituximab. And the last sort of RA-specific factor would be lung damage, particularly from interstitial lung disease. Certainly having damaged lungs to begin with. You have less reserve so if you do get a respiratory infection such as COVID, it might be enough to put things over the edge where poor outcomes can happen and those that can happen even in patients who are vaccinated related to just having preexisting lung damage.
Healio: Have there been any new kinds of strategies that have been developed to help treat RA since the pandemic started?
Sparks: Well, I think the availability of Evusheld, which are the neutralizing antibodies against COVID. Those came out at the very end of 2021, but weren't widely available until maybe 3 or 4 months ago. And at the very beginning, it was only really available for people who couldn't make a vaccine antibody response. So now there's more availability. That's been a really helpful development, particularly for rituximab patients, because it does sort of fill in the antibody response the vaccine can't give. Related to actual treatments for RA, there haven't been any new drugs approved in the COVID era. But certainly, just thinking forward, almost all the medications that we use for rheumatoid arthritis put people at risk for infection. And we've always known that, but I think it's going to be even more important to try to find a drug that can kind of modulate the immune system so that it doesn't suppress the immune system so much that it puts people at risk for infection. There's been a lot of interest in this and other rheumatic diseases, and I suspect it might happen with rheumatoid arthritis as well.
Healio: What areas of study are being developed regarding the intersection of COVID-19 and RA, and how we can safely treat RA with COVID-19 still out there?
Sparks: Some of these, we're doing ourselves. We've been doing a lot of research in COVID-19 specific to rheumatoid arthritis. And I think this is an opportunity to learn a lot about how the immune system responds to infections such as the virus. There's been a lot of talk about how the virus activates the immune system. It might put people at risk of developing inflammation, it might affect RA flares, it might increase antibody production, it might cause new auto antibodies against the body. And then you wonder about organ damage. In particular, RA patients are susceptible to fibrotic lung disease. Is this a trigger that might put patients at risk for fibrotic lung disease down the line? And then just thinking about the intersection about some of the features of COVID and RA, there's a lot of overlap related to pain, inflammation, hypercoagulability and blood clots, fibrosis. I think they're quite intertwined. We're going to learn a lot about this and hopefully it'll be to the point where we can understand how to protect patients against poor outcomes. It’s not just, ‘do you get hospitalized or not’; there are weeks and months of remodeling and reactions that the body has to a viral infection. This is an opportunity to help optimize the body's response to that.
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