One year after the start of the COVID-19 pandemic, what do we know about its effects on patients with immune-mediated inflammatory diseases such as psoriasis? Larry Green, MD, chats with Joel Gelfand, MD, MSCE, co-chair of the National Psoriasis Foundation COVID-19 Task Force, about the relationship between COVID-19 and psoriasis, from Task Force guidances to the evidence behind vaccine efficacy and safety in this patient population.
Dr Gelfand is a professor of dermatology and epidemiology, vice chair of clinical research and medical director of the dermatology clinical studies unit, and the director of the psoriasis and phototherapy treatment center at the University of Pennsylvania Perelman School of Medicine.
Dr Green is a clinical professor of dermatology at George Washington University School of Medicine in Washington, DC, and on the National Psoriasis Foundation Medical Board and the American Academy of Dermatology Board of Directors.
Transcript
Dr Larry Green: Hi, everyone. Welcome to another Dermatologist podcast. I'm Larry Green, clinical professor of dermatology at George Washington University School of Medicine in Washington DC, and on the editorial board of The Dermatologist. I'm very pleased today to have with me Dr Joel Gelfand, who's professor of dermatology and epidemiology at the University of Pennsylvania School of Medicine in Philadelphia. He is also director of the Psoriasis Treatment Center, to follow up a year later after COVID, to talk about what's new in COVID for patients with psoriasis and at the end we’re going to talk about vaccinations, especially the COVID vaccine and patients with psoriasis. So, Joel, happy have you here.
Dr Joel Gelfand: It's good to be back with you, Larry. Thanks for having me.
Dr Green: Joel, I'm sure people want to know about what you know and then listen to your expertise. Let's talk about our patients with psoriasis. First, what have we learned about the risk factors for COVID-19 infection outcomes in our patients with psoriasis?
Dr Gelfand: So let me take a step back, Larry, and let our listeners know that my role in this work has been to co-chair the National Psoriasis Foundation’s COVID-19 Task Force. We were established back in May of last year. We have 18 voting members. It's very multidisciplinary— dermatologist, rheumatologists, we had infectious disease doctors as well as pulmonary critical care people who are on the frontlines managing this pandemic.
We have Delphi process where we put out over 30 recommendations for our community about how to best manage psoriatic disease during the COVID pandemic. We constantly update these recommendations as new data comes out on the National Psoriasis Foundation COVID-19 Resource Center, so it's a good place to go.
Now, go back to your question, the first thing that patients want to know is, does having psoriasis and immune-mediated disease put them at increased risk of developing COVID-19 or having a more difficult course of illness of COVID-19?
Many months since the pandemic, I think we feel confident that having psoriasis itself is not a risk factor for having poor COVID-19 outcomes or being more likely to get COVID-19.
What seems to drive people's outcomes is risk factors like your age, sex, men do worse than women, and then certain underlying major comorbidities such as obesity, cardiovascular disease, advanced chronic kidney disease, and lung disease. Unfortunately, people with psoriasis tend to be very prone to these diseases. The more significant people has psoriasis, the more likely they tend to have kidney problems, and cardiovascular issues, and diabetes, and lung issues. As a group of patients, we know they probably are at higher risk for poor COVID outcomes, but it's not the psoriasis itself that's driving it. It's the underlying comorbidities.
Dr Green: That's so interesting that the comorbidities again come into play in our patients with psoriasis, and that's something we, as dermatologists, are trying to hone in when we see these patients and have them address these comorbidities that are main risk factors for poor COVID outcomes rather than the psoriasis itself. Interesting.
What about our patients with psoriasis and the worry about getting COVID and they're taking biologic or small molecule therapy, because they have severe psoriasis? Leaving the comorbidities aside for a second. What about these patients, if we take a biological small molecule, are they at risk for poorer outcomes or not?
Dr Gelfand: When the pandemic first came out, this was a real worry for our colleagues and for our patients. Many patients were self-discontinuing their biological medications for psoriatic disease out of fear that it might make them more prone to infection.
There's been several approaches to try and look at this problem. Some have been spontaneous reports to registries of patients with psoriasis, rheumatoid arthritis, or inflammatory bowel disease. Then,there's been cohort studies done at Spain and Italy, where centers have followed a bunch of patients on biologics and found out who got infected or not infected and compared to the general population. Then, there's been some studies using electronic medical record databases identifying lots of people in a population, if you will, and seeing what's happened to them. Generally speaking, these studies have been reassuring. We haven't seen any strong signals that the therapies we used to manage psoriatic disease, be they oral medications or injectable biologics, are major drivers of either getting sick with COVID or having poor COVID outcomes.
These data aren't perfect, for sure. More data is likely to emerge, but we think at this point based on what we know so far, it's unlikely that emerging data will suggest that these therapies are clinically meaningful in terms of increasing risk of infection or having a worst disease course. As a result, we recommend that most patients should maintain the psoriatic disease treatments. If they need to go on therapy for psoriatic disease, clinicians and patients should make the same choices that would make outside of a pandemic setting. The therapies aren't playing a major role in how the pandemic plays out for them.
That being said, there's always room for some shared decision making, and I think it's important that as clinicians we are humble in the advice we give patients, especially in a setting where data is so rapidly emerging. We don't want to over promise or oversimplify. In some individuals, if the patient is 65 or older and they have bad lung disease, and maybe their psoriasis is pretty mild, did that person need to go on systemic agents if there is some uncertainty? That's a shared decision-making thing to have between the doctor and the patient.
That being said, the experiences thus far both clinically and the literature has been that most patients who stopped therapy for psoriatic disease ultimately regretted it. Then, they would deal with not only the stress of the pandemic, but the stress of psoriatic disease flaring out of control and then trying to get back on the treatment and deal with insurance barriers and things of that nature.
Generally speaking, my perspective has been to try and help people control their psoriasis as best as possible to help them navigate these difficult times.
Dr Green: Yeah, I agree. A year ago, I did have a few patients who didn't contact me and they came back and saw me in the spring or the summer. They had decided on their own to stop biologic therapy, and they did regret it. Their psoriasis flared, they were very uncomfortable. They didn't get COVID, nobody got COVID infection, and they wanted to go back on therapy. Yes, my clinical experience certainly mirrors what you're saying.
So Joel, it seems that if we have a patient with severe psoriasis and they're flaring regardless of comorbidities, we want to start them on a biologic, it's a better choice in this day and age right now knowing what we know to start them on biologic therapy rather than having severe psoriasis in terms of risk record COVID outcome infection?
Dr Gelfand: I mean, we surely don't know if having bad psoriasis puts them at higher risk for bad COVID outcomes. In fact, the data seems to suggest that doesn't.
Clearly, having bad psoriasis leads to major impairments in health-related quality of life, other comorbidity problems, and it's a burdensome thing to deal with. We encourage patients that they should go ahead and treat their disease regardless of the pandemic.
We'll get into the vaccine story in a few minutes, but other patients at this stage now saying, "Well, I should pull up my psoriasis therapy because I got to wait to get vaccinated." That's also something we don't recommend. We recommend go ahead get your treatment for psoriatic disease and also get vaccinated as soon as you're eligible based on the local availability.
Dr Green: Yeah, we'll certainly delve into vaccinations in a few minutes. Let me ask you then, if you can, for a second, what are the effects of biologic therapies specifically that we want to call the infection in terms of TNF inhibitors, IL-17 and 23 inhibitors, etc?
Dr Gelfand: Today, none of them demonstrate signals of causing ill effects for getting sick with COVID to having worse outcomes. There's some data suggests in the field of rheumatoid arthritis or inflammatory bowel disease that patients who are in TNF inhibitors may have better outcomes from COVID compared to patients getting treatment with other therapies. There's also data that those who are on prednisone at doses 10 mg or higher to have worse COVID outcomes and patients not on prednisone at that dose.
The lessons for our population is, one, is if you have a patient with psoriatic disease who, for some reason, need to be on chronic prednisone, then the goal is to get that dose down under 10 mg as best you can. Some patients had bad psoriatic arthritis and need prednisone, but in general, we're trying to get that dose to the lowest dose needed to control their disease.
We don't have data currently to say that one therapy is more advantageous than another therapy in a setting of a pandemic. What should drive clinical decision making is what is the best therapy to control that patient's psoriatic disease?
Dr Green: Are there any recommendations specifically on methotrexate therapy in patients with COVID outcome?
Dr Gelfand: Yeah, so in the variety of studies have been done so far where people individually have methotrexate, people on that therapy don't seem that higher risks of getting hospitalized for COVID or having poor COVID outcomes.
There are some exceptions, but for the most part, this is going to be a major player. That said, there's some data in other vaccines, like the flu shot or pneumococcal vaccines, that suggests that people want methotrexate will have a less of an antibody titer response to the flu shot or pneumococcal vaccine.
We don't know if that reduction in antibody titer response is associated methotrexate therapy—this is largely people who have rheumatoid arthritis—whether that means they have more susceptible to getting the flu and getting pneumonia when they get those vaccines. But based on that data, we had recommended that people gain the Johnson & Johnson vaccine, which is a one-shot vaccine, they're 60 or older and have major comorbidities and their psoriatic disease is well-controlled. That may be a situation where, due to shared decision-making, you may want to consider holding the methotrexate for 2 weeks after getting the one-shot Johnson & Johnson vaccine, because hypothetically, they may get a better antibody titer response, but we don't know that's going to be clinically beneficial to the patient.
That guidance was put out in part due to ACR Guidance, which recommended with the two-shot vaccines, the mRNA vaccines, that people on methotrexate or tofacitinib, or certain other therapies, that they should hold those drugs for at least a week after each mRNA shot. There is no data to suggest that holding it for 1 week causes any meaningful benefits. Those vaccines are highly immunogenic with two shots. Our task force hasn't recommended holding any psoriatic disease therapy when you're getting an mRNA vaccine/ For one-shot J&J vaccine, in general, we recommend staying on your therapy and get your J&J shot. For a subgroup of people who are especially susceptible to poor outcomes, 60-year-old with comorbidities, that's maybe a group of methotrexate that may want to consider delaying it for 2 weeks.
Dr Green: We're talking about vaccines now, so let me take a step back. You mentioned it but I want to make sure it's clear for everybody. When it comes to the use of biologics or apremilast, the Task Force does not recommend any stopping therapy at all or any breaking therapy in receiving any of the vaccines for COVID-19.
Dr Gelfand: That's correct. The reason why is that although we have direct data for COVID vaccines, understanding the biology of how vaccines work and also having data extrapolate from the flu shot and pneumococcal vaccine, the therapies we use, outside of potentially methotrexate, don't really alter the vaccine response in individuals in terms of antibody titers.
Methotrexate is one example where we had this one trial done in Korea, with people with rheumatoid arthritis, where they were randomized to hold methotrexate for 2 weeks vs continue it, and they got the flu shot. Those who held methotrexate for 2 weeks, they had a marginally better antibody response of unknown clinical significance. Those patients still could have been protected from the flu. Bt that's the data that's driving the recommendations from the ACR, that's taking a step further from 2 weeks to 1 week in a different population and different vaccine.
From our perspective, we think it's unlikely it's going to make a clinically meaningful benefit, and making things overly complicated for patients just causes confusion and puts people at risk for not getting vaccinated because then they may delay their shot because they're afraid to get it or they think it won’t work, when in reality, these vaccines seem to be highly effective. In the clinical trials, the two mRNA vaccines, Pfizer and Moderna, and then the J&J adenovirus-based vaccine, not one patient who's in the immune window, a couple of weeks after their shot, got hospitalized for COVID-19 or died in COVID-19. That's the most important thing for us to try to prevent. People get sick. We don't want them to get sick, but we know that the existing vaccines, they're highly effective against the worst outcomes: being sick, to be hospitalized, or dying with disease.
Dr Green: I guess, in summary, for us, treating patients with psoriasis, even when it comes to methotrexate or tofacitinib, we don't want to withhold any doses of vaccine except maybe the J&J vaccine, or we want to hold the therapy for a week for J&J.
Dr Gelfand: That's exactly right, or 2 weeks extrapolating the data from Korea with methotrexate and the flu shot. That being said, we're limiting that to people who are the highest risk patients, who fit the 60-year-old or with a major comorbidity, where there were some hints from the J&J vaccine that maybe the vaccine didn't work as well on that patient population, so there's a little rationale there.
Even said, even though the vaccine didn't work as well protecting against mild to moderate illness or had a hint of that patient population, that one person 60 or older with a major comorbidity or outcomes in the J&J trial, who got vaccinated, died of COVID and got hospitalized with COVID, so even that high risk group still did well.
Dr Green: It's interesting. There's still so much misinformation about vaccines. I've had two patients in the last month call me, who use anti-TNF, that they're afraid to get the J&J vaccine because it's a live virus, and I had to tell them no.
Dr Gelfand: It's not a live virus, it’s not a live virus. These are not permanent things in your body. It’s sort of like Snapchat. Basically, they come in, you get the shot, they transiently express the spike protein of SARS-CoV-2 so your body can recognize the real virus if you become exposed to it. As soon as you get the vaccine, within a few days or a few weeks, it's completely out of your system. It's not able to continue propagating the protein. It goes away.
Contrast to natural infection. There are studies of people who are naturally infected recover fine, have a mild course of illness. You can still measure replicating virus in their GI tract months later. They're not ill. But that's how viruses behave. They're sneaky. They know how to get around our immune system and do things. It is much better to get immunity through a vaccine than trying to get natural immunity from a viral infection.
Dr Green: Joel, I was talking to Esther Friedman a few months ago. She was saying how long COVID patients or patients with chilblains, they've done biopsies, and this is months and months after infection, still see viral particles on electron microscopy in their COVID toes, which is fascinating that the virus can persist like that.
Dr Gelfand: Right. It's important that people remember that this is a new emerging infection. We don't fully understand the long-term implications.
The concerns I get from my patients is that we don't know the long-term safety of vaccines. The reality is for vaccines and how they work the history of vaccines, when people have side effects, they usually early on like within a week or two, or 3 or 4 weeks of getting the vaccine. You don't get side effects from a vaccine 6 months later. That's not how these things work because, as I mentioned earlier, they're in your body and they're gone. That should be, hopefully, be reassuring to patients. On the other hand, we certainly know that people have long-term problems from natural effects from COVID. The risk to benefit ratio is far in favor of being vaccinated.
I always tell my patients I got vaccinated as soon as I could. My wife was in health care. She got vaccinated as soon as she could. My daughter, who's 16, as soon as we're able to get her vaccinated, she will get vaccinated. Then, we hope to be able to go back to living a more normal life at that point in time.
Dr Green: Let me, for everyone's sake, summarize what you want to say about the NPF COVID-19 Task Force recommendations, the group that you chair, in terms of treatment for COVID and vaccination related to COVID for our patients with psoriasis.
Dr Gelfand: Key points that I want to make sure all my colleagues are aware of is, number one is that we should treat psoriatic disease, as if the pandemic is not going on. Our therapies aren't major drivers of getting infected or having poor outcomes and therefore, we should choose the therapy that we think is most likely to improve the psoriatic disease.
The second issue is that patients should get the first vaccine that they are eligible to receive. They all work quite well in preventing hospitalization from COVID or mortality from COVID. For most patients, they should stay on their psoriatic disease therapies during the vaccine period. There's no real evidence that delaying their psoriatic disease therapies is, again, meaningfully alter their response to the vaccines.
Then finally, patients should also know that even though they're psoriatic disease therapies don't seem to alter their risk of having a bad outcome from COVID-19, based on how the CDC has aligned things, if you're on a drug like apremilast or methotrexate or a biologic, that, at a minimum, puts you at category 1C, possibly category 1B, for prioritization. When you register with your local community health department or with a pharmacy, you want to let them know that you are on what's called an immune-weakening medication. In a way, our patients have the best of both worlds: get a priority for getting vaccinated, even though the reality is that these treatments don't seem to meaningfully alter that risk.
Finally, oftentimes as dermatologists, we're the only doctor that the patient's in contact with. For my patients at Penn, they know that if they get sick with COVID, we do have the ability to do infusions of these sort of antibody cocktails from Regeneron and Lilly. For high-risk patients, people who are 65 or older, who have major comorbidities, if they're coming down with symptoms of COVID, those are individuals that you want to urge to contact their providers or their local hospital to see if they are candidates who are getting one of these antibody cocktails to prevent them from having a tough course of disease.
Dr Green: Thank you. All great tips. Thanks, Dr Gelfand, for being with us on this podcast, "The Dermatologist," and talking about the latest recommendations for our patients with psoriasis in regards with COVID-19 infection vaccines. You guys can listen to this and give us your feedback on our website. We really appreciate that. Thank you for listening.
