RheumNow Podcast - The SARS-CoV-2 Update (8-14-20) Save

Fourteen August twenty twenty. This is the RheumNow podcast. Hi. I'm doctor Jack Cush, executive editor of roomnow.com. This week, unpronounceable new generic names, MRI of the knee, N O A, what does it all mean?

And a whole lot of COVID numbers. In essence, we might call this a COVID recap. But first, congratulations to doctor Ken Segg, who's been officially named as the new chief of the division of clinical rheumatology and clinical immunology and rheumatology at University of Alabama Birmingham. Ken's been there a long time, great guy, does a lot of interesting outcomes research, and now is gonna lead that division into its next generation of making leaders in rheumatology. Look to Ken and UAB for great things.

Great things are measured often in dollar sales amount. Well, the numbers are out for blockbuster drugs in 2019, and as has been the case in years past, rheumatology drugs are usually just jamming the list. At least in the top 10, we've got four drugs that we are known to prescribe. Leading the pack again is Humira. These are worldwide sales at 21,400,000,000.

Number three is still etanercept holding in there at 8,100,000,000. Number four and kinda moved up the list a little is Stellara, 6.6, enjoying use in psoriatic disease and spondylitis now. And still holding on at number 10, sound like Casey Case in there, is Remicade at $4,600,000,000 in sales. That's Remicade, not the generic. So I think if you added in the generics, the biosimilars of of Remicade, it might well be very high on the list.

All those other three drugs don't yet really have any substantial worldwide. Well, that's not true. Enbrel's got biosimilar sales outside of The US that are that are growing and looking good. So, a lot of good reports this week about ankylosing spondylitis, that are I think are relevant to practice. One study from the corona registry looked at almost five hundred patients with axial spondyloarthritis.

And in their cohort, twenty five percent of those patients had enthesitis. The interesting thing about that was that enthesitis was associated with, guess what, worse disease activity, worse quality of life. I mean patients don't do as well. This is true in a lot of diseases, but also especially in the spondyloarthropathies where the presence of comorbidities are associated with worse outcomes. The presence of these extra spinal manifestations are associated with worse outcomes.

I think this is a reason to step up and maybe not rely too long or too heavily on simple therapies that are probably not going to be as effective as some of our newer, more aggressive therapies. The other interesting thing that came out this week was Cosentyx, being effective, that's a secukinumab being effective in non radiographic axial spondyloarthritis. That was a nice and new interesting report. I had a case this week of someone with Behcet's and you know we all know about Behcet's and how to diagnose it and too much steroid use being used and we're very grateful with the FDA approval of Eprimelast for Behcet's. And we know that most of that data was really based on improvement of oral ulcerations.

My patients with Behcet's had, genital ulcers and orals and, was doing well on a premilast, not quite as well with the genital ulcers as the oral ulcers. Oral ulcers had totally resolved. So I looked up the the original, reports in the New England Journal article. As you know, Epimelast was approved for Behcetz in 2019. And its approval was based on two studies, a phase two and a large phase three showing significant improvement in area under the curve with regard to oral ulcers and their severity.

But in that study, the last study that was published, there was significant improvement in overall quality of life and some global measures of of Behcet's, but there was a non significant trend in improvement in genital ulcerations. Now the problem was that there are only seventeen patients and a few 100 patients who were enrolled with genital ulcers. That wasn't the point of the trial. So I think maybe we need more data. When I say non significant trend and only in seventeen patients, it still looked pretty good.

Seventy one percent resolution on a premilast versus, forty one percent on placebo. Forty one percent on placebo? How much that placebo cost? Again, the power of placebo is quite amazing. A study came out this week about the correlation of MRI in knee OA, and when looking at knee OA pain in two ninety four patients from the osteoarthritis initiative, these are patients who were followed at least six years with at least four repeat repetitive MRIs.

They found that the features that were best associated with knee OA pain on MRI were meniscal extrusion, meaning the pain is not from the OA, it's from meniscal disease, full thickness cartilage loss, that seems to make sense, and osteophytes. So there, in this case, there is some correlation between imaging and pain. As you know, the correlation between pain and, Kellgren Lorenz x-ray scores in knee OA is not that great. So pain is a multi modal, multi mess in trying to figure out in some patients who have knee OA. Bristol Myers Squibb announced the new name for its TYK2 inhibitor.

This is previously called BMS nine hundred eighty six thousand one hundred sixty five. It's been studied, I believe in the New England Journal report that was showed very impressive data in psoriasis about two years ago. It's in clinical trials for psoriasis, psoriatic arthritis, lupus and inflammatory bowel disease. It's been called the TYK2 inhibitor. As you know, TYK2 is one of the the intracellular mediators, the Janus kinase inhibitors.

TYK2 is one of the others that, is a potential target for drug therapy. And this is sort of a selective TYK2. And the data looked really good and what I've seen so far in sorry, mainly psoriatic disease, well, it's got a name. It's called ducravacitinib. Ducravacitinib.

All I know is that it's 15 letters long. I think that's a record in rheumatology. The do might have something to do with the two in tick two. The crave, nobody knows the origins of these drugs so maybe that's a whole one hour CME lecture at some point that I don't wanna sit through. Anyway, congratulations to BMS and ducravacitinib.

So we have a number of reports about COVID that I've been wanting to put out. Just this past week JAMA, has an I'm sorry, not JAMA, Annals of Internal Medicine reports that, on the issue of ACE inhibitors, and ARBs and whether or not that's a good thing or a bad thing in patients with COVID nineteen disease. As you know, the SARS CoV-two virus binds to, ACE inhibitors to gain access, and have undergo endocytosis into cells that it attaches to. So ACE is important in the pathogenesis of COVID, but would giving an ACE inhibitor or ARB somehow be a bad thing or would it be a good thing? No one really knows.

Well, now this report comes out. Based on this report, twenty three thousand five hundred sixty five, patients infected with, COVID nineteen, they showed that the use of ACE inhibitors and ARBs was not associated with more severe outcomes and that's fairly high certainty evidence looking at a number of different reports. So and moreover that, taking those drugs did not seem to change, test results for the SARS CoV two virus. So again, can continue to use ACE inhibitors and ARBs reasonably, and effectively in your patients without impairing their COVID outcomes. Obviously, there's a lot else that will impair COVID outcomes.

Speaking of COVID outcomes, maybe it's best just not get COVID. And who better to look at than healthcare workers who are constantly around COVID? There are two reports, both coming out of New York. The first report looked at almost three thousand patients who underwent, testing. These are hospital employees.

Most of them were antibody testing, some were PCR, some were both. Turns out that again, when you looked at the overall infection rate, not and that's just based on serologic positivity, not based on symptoms, it was nine point eight percent and that being sufficiently below the regional, comparative numbers, at least, about half as, as much. Again, a strong statement in favor of the many things that healthcare workers go through to avoid that virus, meaning PPE works, effective PPE works. This is mirrored by another study from, Northwell, University Hospitals where they tested forty six thousand of their patients through June, And overall, they found a similar number of seropositivity, that being a low number of thirteen point seven percent. And they showed a really good correlation when looking at just the serologic test for antibody and those who had PCR.

So the PCR positive ACP workers were about ninety four percent likely to be seropositive. Similarly or conversely, the PCR negative healthcare workers who were, again, PCR negative, they were about ninety percent likely to be seronegative by serologic testing. Again, both these reports say that what we do in healthcare is effective at, keeping those numbers low, and says a lot maybe for doing, the easier to do, serologic testing. The latest numbers that came out from the, CDC, again, this is a little bit behind what you see at Johns Hopkins and on CNN, but these are verified cases from the CDC. I haven't put a number up in a long time because you know it goes up like, you know, 10,000 a month, as we're on our way to, three hundred thousand infections in The United States.

But the most recent numbers, three hundred thousand deaths, I'm sorry. The most recent numbers here are, five point one million infections in The United States. Again, just shocking. When you look at deaths at at the time they did this, there's a hundred and sixty three thousand deaths, and that was on the day that this was produced, was midweek, there was twelve hundred new deaths on the day before. The this week we, we had a day of fifteen hundred deaths in a day, you know, at the peak of what was going wrong in New York City, it got as high as almost nine hundred a day in New York, but again, that New York is way down and other other states are way up.

My state of Texas had three hundred and fifty four deaths just the other day. But we have averaged over a thousand deaths for the last seventeen days. This is still a gigantic problem. The, states with the highest numbers are led by New York at 32,000, New Jersey at almost sixteen thousand, California at ten thousand, Massachusetts and Texas, around eighty seven hundred, not far behind is Florida, Arizona, Illinois, and Pennsylvania at, six to seven thousand deaths apiece. The good news is that of all these deaths and infections, there's not so many with amongst healthcare workers according to this the, CDC.

A hundred and thirty thousand, healthcare workers have been infected with the coronavirus, of whom six hundred and eighteen have died. So, I think that's encouraging data, although sad data. I had a number of reports for them specifically looking at, observations in our rheumatic disease and autoimmune patients and what happened when they got the COVID virus. They all showed the same thing, Meaning they showed a few very important points. And these echo the earlier report from Gianfrisco and Philip Robinson and, Yazdani and others from the Global Rheumatology Alliance that was published in ARD in July.

And that was that amongst the first 600 patients in the Global Rheumatology Alliance, those are your rheumatology patients who were, put into the database because they had a COVID infection, and when they looked at the risk of hospitalization, they showed that taking prednisone ten milligrams a day or more was associated with a two fold significantly increased risk of getting, a COVID infection. They showed there was really no outcome change when you looked at our patients who were taking biologics and or conventional DMARDs, except for those that were taking TNF inhibitors, where there was a significant reduction in COVID infections by sixty percent, odds ratio about zero point four. That's actually mirrored pretty well by these four reports that say number one, rheumatic disease patients, autoimmune disease patients are at risk for COVID infection if they're uncontrolled. Two of these four reports say the same thing. Patients with active disease, as judged by the clinician or by disease activity measures, are at a up to two fold higher risk of getting the infection.

But that they showed across the board, the use of DMARDs and biologics was not associated with worse outcomes or death, but that the steroids were associated with a higher risk of worse outcomes. A number of reports said that, again, cytokine blockers and other biologic therapies looked really good. A letter from Kevin Winthrop, on a survey he's done of, the ID community, where they identified over twenty five hundred patients, patients, three percent of whom were on immunomodulatory drugs, and in their cohort, twelve percent died, eighty two percent were hospitalized with COVID. They found that the patients who were taking, both, TNF inhibitors and JAK inhibitors, there were no deaths. So, I think that this begs the question, should we be revising our guidelines?

Our guidelines have said, you know, patients, should not change their therapies in this COVID era, that makes sense. Our guidelines have said that patients who are not severe at home can probably stay on their therapies, but once they're severe and going to the hospital, then everything should be stopped. And, you know, the only things that they said might could be continued would be hydroxychloroquine, that's out. Hydroxychloroquine really isn't going to affect the outcome. But then again, it really doesn't need to be stopped either.

And then tocilizumab where the data continue to be continues to be mostly positive but sometimes negative, it's still up in the air. So I think though the the data that we have that's accumulating says our patients should be continuing their therapy if they're infected, including if they're in the hospital. There's a lot to be said for patients being on TNF inhibitors and maybe they should also be on Anakinra where there's a number of consistent observational reports, I must say, and maybe the JAK inhibitors and maybe Tocilizumab. But again, still more research is needed. The good news is that there are lot of clinical trials that are about to mature and hit the publications, and hopefully they'll hit them fast, and we'll start seeing these in September where we can start making more definitive statements about treatment.

But so far, our patients are doing well, continuing therapies seems to be a smart move. That's it for the podcast this week. You can go to the website and check out these citations. Two announcements. Number one, last week, made a pitch for any second year fellows, third year fellows, ninth year fellows who'd like to join RheumNow and reporting on the ACR can send me an email at jackcush@roomnow.com.

Turns out that email was blocked and not working, so if you had a bounce back, please send it again. We're looking for some reporters to work on ACR twenty twenty. The virtual meeting is gonna be exciting. And lastly, we are about set to go with our viewer questions line. It's gonna be called, Backtalk.

You'll see it on the on the web page, you'll see it on the email. If you go to our podcast page, there'll be an icon for back talk. This is where you can send me a message, ask me a question. I'll bring up a few of them each week during this podcast. That's it.

Take good care of yourselves. See you soon.