RheumNow Podcast – In Times Of Trouble (4.24.20) Save

It's the 04/24/2020. This is the RheumNow podcast, and I'm doctor Jack Cush, executive editor of roomnow.com. The title of this podcast is in times of trouble. Let's begin with a quote from Paul Harvey, you know, the rest of the story guy. Stay in your seat come times of trouble.

It's only people who jump off the roller coaster who get hurt. Think about that. Let's begin with some news from the world of rheumatology. A nice study looked at the incidence of incident diabetes in a large cohort of RA patients. This is claims data, from two different data sets, one a Medicare, one a commercial data set.

Over seventy thousand rheumatoid arthritis patients who were taking a variety of biologics, and they looked at their risk of developing incident diabetes mellitus. What they found was that you had compared to abatacept, a twofold higher risk of developing diabetes if you're on adalimumab or if you're on infliximab. Let's think about the numbers here. Seventy thousand people, there were a total of about four hundred cases of new incident diabetes. So when I say a doubling, we're still talking about a very low number.

Nonetheless, what this does say, it looks like abatacept seems to be protective against developing diabetes, rather than the TNF inhibitors causing diabetes, which is clearly not the case. You know, the incidence of diabetes in our patients is been off reported. It's been reported in other inflammatory conditions like rheumatoid, like ankylosing spondylitis. It's been reported with osteoarthritis, is that the age and the obesity factor. It's been reported in people who are hyperuricemic and have gout, but then we know that diabetes is a it runs in a crowd of people of diseases that are sort of comorbidities with gout.

We do have studies showing that hydroxychloroquine lowers the risk of diabetes, but abatacept is the only biologic that I've seen, or DMARR that I've seen, that actually lowers the risk. Why? It's clearly not just related to inflammation. So it'll be interesting to see if this pans out in other studies. Kevin Winthrop did a study of, over a year ago, with his investigators looking at what happens when you give the live virus vaccine prior to the use of tofacitinib.

I believe they had a 100 patients entering that trial, and now they're looking at what happened downstream. Was this two years later or twenty seven months later? And what they showed was that Zostavax seemed to work as far as the immunogenicity that happened, but what they found was five patients within the next twenty seven months who developed herpes zoster, occurring at either two hundred and eighteen, two hundred and eighty, seven hundred forty eight, seven hundred forty one, and five hundred days post vaccination, suggesting that maybe the live virus, shingles vaccine, Zostavax, is not all that protective. And we know that to be true from the original data with Zostavax. It was about fifty percent effective and efficacy would wane as the patient got older.

We had a lot of problems using live virus vaccine. The good news is that Shingrix is like ninety percent effective, over ninety percent effective, over ninety percent effective in preventing postherpetic neuralgia, and it doesn't have an age waning that you saw with Zostavax. So, this is sort of interesting data that now says, oops, we probably shouldn't use that Zostavax, and should be using the Shingrix going forward. An interesting study came out about the use of rituximab in patients with, either GPA or MPA. So these are elderly patients who are treated with either Cytoxan or, rituximab, and it showed that overall patients who were treated, with those drugs had less overall organ damage and less overall hospitalizations, especially so for rituximab.

But what I liked about the study that was interesting was that the greatest risk of developing damage and or fatal infections in these people who were starting out treatment was in the first three months. That's when all the damage was occurred, that was the tenuous part, and actually it was when they were also on a higher dose of steroids. So, first three months is the dangerous part, especially so if you have them on steroids. We don't have enough studies in, scleroderma and systemic sclerosis. Dinesh Kano reported, his experience with riosequat, a guanyly cyclase inhibitor, it's anti fibrotic, it's anti proliferative, it's anti inflammatory, it might could work in systemic sclerosis except in this study, while it showed numeric improvement in modified Rodnan Skin scores minus 2.1 versus minus 0.7 compared to placebo, and Raynaud's, being improved forty one percent versus twenty six percent, and FVC 2.7 versus 7.6, these are numeric improvements, but they were not statistically significant.

This is such a difficult disease, we need more trials to be started, we need better outcome measures. I applaud, Dinesh and others for actually looking at these single variable outcomes, in this particular drug. It may have a role in the future. It's been studied in, digital ulcers, it's been studied in lung outcomes, it's just not faring all that well. So let's get to the coronavirus and where we are.

The current death rate as of today is over fifty thousand deaths in The United States, fifty thousand three seventy three. I wrote a tweet saying, this is scary as hell. What I was referring to was a really interesting tweet by Eric Topol that showed two studies that looked at the growth the growth rate for deaths in multiple countries, and mainly was looking at the doubling rate. How many days was it taking for the death rate to double? And United States has the highest death rate and also has the fastest doubling rate, somewhere between two point seven and three days for the death rate to double in The United States.

This is scary. This is why we need to know a lot and be involved even as rheumatologists. More news on COVID. A recent, MGMA survey showed that a high number of your practices out there are being severely affected, so much so that half of you have had to furlough your employees during this pandemic, and as much as a quarter or twenty two percent have actually had layoffs during this pandemic. Studies in, and these are surveys of all kinds of practices, including specialty practices, but what they saw as far as revenue was there was overall a 55 to 60% decrease in revenue during this period beginning in early March.

Yesterday, New York State came out with a survey. This is a survey of the use of antibody testing for COVID, 19, and they did this in multiple parts of the state. They surveyed, and they have samples of, I think over 3,000 samples, and they showed an overall rate of antibody positivity of thirteen point nine percent or fourteen percent. Again, positivity means you've been exposed. You could have exposed two years ago, you could have been exposed last week.

And they didn't say whether they're doing IgG or IgM, but they're just saying antibody positivity. So again, it means exposure, it doesn't necessarily mean infection. Presumably, obviously, a lot of these people were not symptomatic because the numbers are far less as far as symptomatic. And again, when you apply this to the population in New York State, where at this point they have a third of the deaths that are seen in The United States at fifteen point five fifteen thousand five hundred, that means the death rate from COVID in New York State is estimated to be zero point five percent, or roughly one in every two hundred people infected or proven infections will die from the condition. This is about tenfold higher than what you see with influenza.

There was a WHO brief this week that dispelled the belief that's still out there, that you can't use nonsteroidals with the COVID nineteen infection. Again, this was started by the French Ministry of Health, which put out an idiotic statement that everyone has basically claimed to be idiotic. And this particular scientific paper that looks at the evidence says there's no direct evidence of harm with the use of nonsteroidals with COVID-nineteen, SARS, or MERS infections. And again, whether it be regard to health utilization, quality of life, all outcomes, there's no data, and again, you can use nonsteroidals should they be appropriate for your patients. Now, let's talk about not another, a few other studies or drugs that are important to us.

One would be hydroxychloroquine. We know that hydroxychloroquine has been in the news. And the problem with a lot of the studies that we're gonna be hearing now and in the next few months is that these are gonna be preliminary reports. Often they will not have been completed studies, they will be interim analyses. They may not have even undergone review.

So this particular study from the VA study in Houston, is, one that has not yet been reviewed, but has been put up as a pre proof, and it's a study of three hundred and sixty eight COVID positive males, they dropped out seventeen females, so they didn't have enough data, but the three sixty eight males who were COVID positive and they looked at whether they were treated with hydroxychloroquine. So ninety seven were treated with hydroxychloroquine, one hundred and thirteen with hydroxychloroquine and azithromycin, and one hundred and fifty eight were controls, no hydroxychloroquine. They showed higher deaths in the hydroxychloroquine treated populations, twenty seven point eight, twenty eight percent and twenty two percent for the monotherapy or the combination therapy and only eleven percent for the control. Was no difference in ventilator use suggesting that there's no data. And now there's a stream of, again, uncontrolled reports, all suggesting that either there's toxicity with hydroxychloroquine or there's no particular benefit or there may be bad outcomes.

I think we're glad about that because we don't want our hydroxychloroquine to go in short supply over a presumed benefit in a condition for which it's not known to be beneficial. And there are a number of guidelines that have come out that have outright said, we don't know if there's any evidence that hydroxychloroquine is in fact beneficial, and I'll talk about guidelines in a second. There's another interesting study that was, NYU is taking the lead on, and that includes their, effort along with the Montreal Heart Institute, It's called the COLE CORONA study. I found some quotes from Mike Pillinger at NYU talking about the use of colchicine in maybe the early phases of COVID infection, and they're looking to treat six thousand patients. I assume that they're going to enroll people early.

They want patients with early disease and mild disease to see if maybe it may be important in basically managing what is probably an inflammasome driven process that may lead to the progression of disease. So congratulations to Pillinger and his colleagues at NYU for doing the cold corona study, we'll look for that result. GI has come out with, expert consensus guidelines, and I'll just read to you their statement, which applies to you and your patients in rheumatology. Their statement says, despite the potential for increased exposure to SARS CoV-two, the limited available data and expert opinion suggest that patients with IBD do not appear to have a baseline increased risk of COVID-nineteen infection. I think I would say the same is true for our patients with rheumatic disease, but we need more data.

There was an interesting report in the Journal of Experimental Medicine about the potential role of NETosis in the rapid progression of, COVID-nineteen. And this particularly comes out of a network of investigators, nine different institutes, including the whole Cold Spring Harbor labs, where they're going to get together and see whether measures of NETosis are particularly upregulated in patients with COVID-nineteen infections. So they have a protocol, they're enrolling patients, and they're doing this because there's a lot of association between NETosis or neutrophil extracellular traps formation, with conditions like ARDS and pulmonary inflammation, lung damage, and even thrombotic events. You know, again, I think that a lot of what we see in the cytokine storm looks to me like macrophage activation syndrome, but cross react that with what looks like bad lupus or catastrophic anti phospholipid syndrome with the thrombotic events and occasional bleeding that you're seeing, that kind of typifies the worst cases of CoV infection. So, we'll look for the work of these investigators, and their study.

The NIH published this week their consensus guidelines, they have a committee of over 34 physicians and a bunch of pharmacists, even pediatric rheumatologists on the committee. They came out with their guidelines on how to manage mild, moderate, severe and critical disease, and they make, really, I think what are two bold statements. Number one, there currently is no therapy proven to be safe and effective for the treatment of the coronavirus infection. None proven and effective. Hence, they cannot recommend treatment with anything, anything you've heard about, they're not recommending it outside of a clinical trial.

They're strongly recommending patients who might be treated with remdesivir, or tocilizumab, or, baricitinib, or whatever, be treated inside of a clinical trial. Now, obviously, you don't have to be in a clinical trial and you could use those agents, but recognize the expert consensus, of US experts say there's currently no evidence. They do go out and say that there's also no evidence favoring the either the use of hydroxychloroquine for either the treatment of the active infection or to prophylax against active infection with the coronavirus. That came out this week, and you can compare that to previous reports that we have up there for the ACR guidelines, and the NICE guidelines on how to treat patients. We had one last paper I thought was real interesting about the potential role of B cells in the COVID-nineteen infection.

This is a report from Italy that reports on two patients with, globulinemia, A and I think it was six patients with a common variable immunodeficiency. The A gamma globulinemic patients have no B lymphocytes and no immunoglobulin, whereas the patients with CVID have B lymphocytes, but they are dysfunctional. Turns out that both these populations had low measurable, amounts of immunoglobulin, but there were differences in the outcome. The agammaglobulinemic patients had milder courses and much more favorable outcomes, whereas the CVID patients had pretty bad outcomes, and in fact had, aggressive disease, hospitalizable ICU disease, suggesting maybe there's a role for B cells in the management of this particular condition. I put this up there because many of you have asked the question about what do I do about my, rituximab?

I would say, rituximab is more of a agammaglobulinemic kind of end result than a CVID end result. And so, would tell you, maybe you shouldn't start it, but I wouldn't discontinue it or forestall it when you know, especially it is in fact working in your, patients. I'll end with, an observation that mirrors, doctor. Cavanaugh wrote a blog on this that he's noticed a lot of good things with the coronavirus, era. I wrote down that humanity is really shining through these days.

I am really touched by the number of my patients who go out of their way to say, how are you doctor Cush, how's your family, take care of yourself, you know, we need you, that sort of thing. Again, excuse me, the altruism is really impressive, and in times of trouble people do bond together, do become quite humane and loving. And I'll end with another quote about in times of trouble, this one from John Denver says, perhaps love is like a resting place, a shelter from the storm. It exists to give you comfort, it is there to keep you warm, and in those times of trouble when you're most alone, the memory of love will bring you home. We need a lot of love right now, we need this in times of trouble.

This week on RoomNow and Tuesday night rheumatology, we had a great presentation by Alvin Wells called Moving Forward with Telemedicine, you can find that in podcast and video form on our website or on your podcast channels. Lastly, a call today and yesterday. I'd like to know what you think has been the effects of the COVID nineteen pandemic on you, your family, your practice. Tell me the upside. Tell me the downside.

Send me an email at JackCush@RheumNow.com. I wanna collect all of our experiences and report back to you some of the good things, some of the bad things. And if you got some pictures that you think are interesting, something that you resorted to that you think is humorous or useful, send pictures. We'll post those as well. That's it for this week on the podcast.

Tune in. Take care of yourselves. God bless.