RheumNow Podcast – Cardiovascular Risk in Psoriatic Disease (9.25.20) Save

It's the 09/25/2020. This is the RheumNow podcast. Hi. I'm doctor Jack Cush, executive editor of rheumnow.com. This week, machine learning, meta analyses, studies of transcriptomes.

Well, gee, just might as well turn the whole damn thing off and do something more enjoyable, but I'll try to make it enjoyable. Actually, I have a lot of interesting news this week. Maybe the best is that next year, rooms are gonna get paid more. What? You know, in 2020, the year everyone wants to forget, know, incomes are going be way down, you know, 30 to 50% for most people in practice.

But CMS has come up with a new payment schedule for next year due to a lot of your lobbying efforts. The, announcement from CMS and Medicaid Services is that endocrinologists and rheumatologists lead the way with 1716% higher reimbursement levels. Now, you're going to have to read the article that I posted to get the details if this really floats your boat. Me, I'm paid the same no matter what, which means I'm not paid very much at all. But I think it's a good thing.

Obviously, cognitive disciplines don't usually get big increases and things like radiology and ophthalmology are going to take minus increases next year. That's kind of good news. Maybe more good news, the EMA, CHMP, the, Committee on Medicinal Products for Human Use has recommended baricitinib for approval for the use of atopic dermatitis. And that's an atopic dermatitis patients who are candidates for systemic therapy, ones who have been refractory to other therapies. Is that really important?

Well, I think it is because, you certainly know about the data on the JAK inhibitors, including Tofa, Oopa, Bari, and I guess all the ones that will follow really incredible sort of news on a lot of skin disorders. And atopic dermatitis is on the list. This is maybe, notable because it's the first possible indication for a skin only disease other than psoriasis that we're going to see and I think it's going to be a lot more in the future. Maybe so much so that can you imagine dermatologists being the leading prescribers of JAK inhibitors in 2021 or 2022, it could happen. Talk to your dermatology colleagues, they'd like to know what you think about these products.

A cluster analysis of nearly two hundred patients with antiphospholipid syndrome looked to see what was most associated with mortality and the worst prognoses. They divided patients up into having, venous thrombosis and arterial thrombosis and having cardiovascular risk factors. And in their analysis, they showed that if you had, not surprisingly, arterial thrombosis and cardiovascular risk factors, were at higher risk for mortal outcomes, and the poorest of outcomes. This is sort of what we see. I think that most of us see a lot of patients who have venous thrombotic events, and they kind of do well, especially if you're treating them.

And we don't see many with arterial thrombosis, but when we do, the outcomes aren't so good. So it may be something to keep in mind when managing such patients. Analysts of Internal Medicine made a big splash with an old news, news from Jeff Curtis and others about the risk of steroids, risk of steroids causing serious infections. We know that steroids cause serious infections, especially at ten milligrams, maybe even between five and ten, but what was seen in this study published in Annals was that it was a significant risk, it was dose dependent, but yes, even small doses, less than five, were associated with an increased risk of serious infections in RA patients who were taking DMARDs. This was taken, from claims data from Medicare populations and, commercial insurance with Optum.

I think, again, it underscores the fact that steroids are chronically dangerous. There is this argument made by some that everybody should be on a little bit of prednisone, whether it's for lupus, whether it's for RA, that you kind of do a little bit better in the long run, less hills and valleys, less flares and whatnot, easier to manage. But then is there a downside? Is there a downside? You know, I don't wanna speak for Michelle Petrie, but I was with her in a lecture, this last year where she was making a case that lupus can be managed, chronically managed, without steroids.

I've always been of the thinking that patients should be on low steroids, as I'm rethinking this. I think we should probably get away from steroids and try to use more effective therapies. We have enough of them, you know. So machine learning, this is gonna be in our literature. The idea is you take big data, you throw it into the mixer, and out comes things you never expected.

Now, when it tells us stuff that we don't really care about, then machine learning and big data and artificial intelligence are not serving us well. But when that can be used to help us make these sometimes equivocal decisions, I think that's important. Well, this first exercise comes from the osteoarthritis initiative, where they were actually doing MRIs of patients entering the study prior to having osteoarthritic changes, and then three years down the line, after doing several MRIs, they showed that, the MRI could predict those who are going to progress and develop osteoarthritic changes, in in the knee, really based on a cartilage texture mapping. And the algorithm that they developed with artificial intelligence had a test accuracy of seventy eight percent in predicting those who would develop OA progression in the next three years. And they're predicting it from the first MRI that they did.

It's kinda interesting. The idea is with better tools, you make earlier diagnoses, you have earlier interventions, and you change the outcome. This is a good example where machine learning could be helpful in developing better treatment protocols. Relapsing polychondritis, you know, I've seen a bunch over my career, most of them don't have relapsing polychondritis. Let me start by saying if you're diagnosing relapsing polychondritis, please look up the criteria, make sure that you meet the criteria.

It's not someone with a red ear and fibromyalgia. I mean, are serious patients with serious consequences. In this particular study of two twenty nine patients relapsing polychondritis, they looked to see what kind of onset might predict what kind of outcome. Well, the poor prognosis patients were those who didn't have an ear or auricular only out, onset, but were those who had a respiratory, stridor, tracheal issues, onset, or those with systemic sort of onsets, CNS, eye, even musculoskeletal, that the combination of respiratory or respiratory with miscellaneous onsets were the ones who had the poorest prognosis. Rituximab, good drug being used for a lot of different things.

There is this phenomenon of late onset neutropenia. In this particular study of seven hundred and thirty eight patients treated at a single center chronically with rituximab, they had a total of one hundred and seven late onset neutropenia, that's an ANC less than one thousand, that occurred in seventy one patients, meaning a few of them got it more than once. That's an overall risk of six point six percent. The incidence was seven point two per 100 patient years. That's important enough to take note of if you're using rituximab, you should be following, like, neutrophil counts, the ANCs.

It was higher in lupus patients, it was higher in patients who had also previously received cytotoxin or receiving, cytotoxin contemporaneously. Forty percent had symptoms, but actually sixty percent did not, of the consequences of neutropenia. You know, other studies have been published in this area showing that while it happens, the clinical consequences don't seem to be that great. In this particular study, thirty one percent of patients had fever. Sepsis was seen in eight point five percent of patients who had late onset neutropenia, and that they re challenged the patient after their neutrophils came back up, they gave them again rituximab, that's a special kind of stupid, And twenty per twenty one percent had again late onset neutropenia again.

Kinda way Forrest Gump would say it, again. So, again did I say again three times in one sentence? You need to look for this. I think it's, it is an important issue if you're using Rituximab. The European Association for the Study of Diabetes, they had their recent meeting, this week, it was a virtual meeting, a particular presentation of interest to rheumatologists.

Their study of 1,600,000 participants found that rheumatoid arthritis, the diagnosis of rheumatoid arthritis was associated with twenty three percent higher risk of developing type two diabetes. We know about HLA DR4, and the onset of type one diabetes, and that HLA DR4 or the H shared haplotype also with the risk of RA, but a twenty three percent, chance of developing diabetes. Doesn't say how or why it happened, but it is important. You know, comorbidity is what kills our patients. We know about comorbidity, we talk to our patients about it.

We as rheumatologists don't do a whole lot on comorbidity management. Are you doing A1Cs on your patients? Are you managing blood pressure when you see it? Are you checking lipids in patients who have drugs that don't cause hyperlipidemia, like the IL-six inhibitors or even the JAK inhibitors? So, the idea is you do need to be involved in chronic disease management and looking for comorbidities, and I think maybe it should be part of the protocol when managing RA to do an A1C once a year.

Eustekinumab, a lot, I got a few interesting reports now about psoriasis. And, this particular report comes from this last week of JAMA Dermatology. Meta analysis, meta analyses, you know, it's a they're they're it's what you do when you got nothing else to do doing meta analysis, you know, original head to head trials, double blind placebo controlled trials, hard to do. Meta analysis, anybody can do, but you know, when you don't have the answer, sometimes it's all you got and it's what you gotta go go with. This particular study looked at the risk of cardiovascular events in patients starting Eustekinomet.

A while back, like twenty twelve, eleven, thirteen, you know, the twelve twenty three inhibitors were developed, you know, there was a drug called Breukinumab, where the there was the scuttlebutt was too many MACE events, major adverse cardiovascular events, strokes, heart attacks, etc. The drug wasn't developed for that reason and a bunch of others, but there were other twelve twenty three's and that's what ustekinumab hits the market. It's currently on the market, it has no cardiovascular warning in its product package insert or product label. This particular study set out to look at the issue again, looking for early cardiovascular events, almost ten thousand patients starting ustekinumab, they had a hundred and seventy nine who experienced a severe cardiovascular event, defined as either coronary artery syndrome, unstable angina, or stroke. When they looked at those patients, according to whether they had cardiovascular risk factors, high risk and low risk, low risk patients did not have any problems with cardiovascular events when they took ustekinumab.

But those who were high risk and got ustekinumab had a fourfold higher risk of a cardiovascular event. Now, it's not the same definition of of MACE as was used in those earlier studies, but it is noteworthy and makes me wonder whether or there should be a warning or should be further study on this issue. We do know that, number one, psoriasis patients, and this is a study of psoriasis patients, by the way, not psoriatic arthritis. Psoriasis patients are at higher risk for cardiovascular events, just like RA. Number two, this study didn't look compare those on to those on other biologics, because if they did, they probably would have seen the same risk rate.

And that's what's been seen in a number of meta analyses that precedes this study. They compared cardiovascular events in ustekinumab versus other biologics like IL-seventeen or TNF inhibitors, for instance. So, again, it's something to be, on the lookout for, I don't think it's an absolute contraindication at this point, but it's worth noting. Worth noting is also another report that comes from one of the dermatology journals, actually, this particular study looked at two zero nine biologic naive psoriasis patients who are about to begin, a biologic. And they did a cardiovascular assessment of them looking at coronary CT scores, and specifically we're looking at what they call high risk coronary plaques.

LRNCs or lipid rich necrotic core plaques, because these have a high risk of leading to cardiovascular events. So in this particular study, the, LNRC, the high risk, lipid rich core plaques were correlated with the Framingham Risks, scores, and also with disease activity scores for psoriasis. When they compared those who went on biologics, those that didn't go on biologics, those that didn't go on biologics had no change, or maybe a positive change in their, LRNC or their plaque scores. But those that went on biologics had a lowering, a significant lowering of these plaque scores, suggesting a benefit to biologic therapy in high risk patients, and that would be psoriasis patients. Also in psoriasis, Nature Communications this week had a nice report about restricted T cell clones in psoriatic arthritis patients.

And in this particular study, they did, they got blood, they got synovial fluid from about 12 patients, and they looked at, they did flow cytometry, they did transcriptome analyses, they looked at T cell subsets, they looked at chemokines. And in this particular study, they showed that there was a threefold expansion of memory CD8 T cells, okay, in the joints of PSA patients compared to blood. Moreover, single cell RNA sequencing of the T cell receptor suggests that there was clonal expansion of certain CD8 T cells, suggesting maybe, a single antigen could be driving the process. They also showed that these patients had, an increased expression, or increased CXCR three, the chemokine receptor. This chemokine receptor, as you know, is, when when signaling through CXCR CXCR three, you develop chemo traction for memory T cells.

So the the finding of this chemokine and its ligands suggest that, those, that chemokine is drawing in these specific T cell clones, and that may be involved in the, those patients who develop psoriatic arthritis. And we know that occurs in one third of all psoriasis patients. I think it's novel research, it could lend further evidence as to really, a better understanding of the pathogenesis and maybe even the approach to therapy. So, I'm going end with two reports on COVID. First, report from MMWR that appeared this week that young adults are taking over as to who's most affected with COVID.

As you know, on, this was a disease of the elderly and those were the ones who were getting it, those are the ones who were dying from it. However, in the time period from June to August, there was a shift, not from the elderly, but now to young adults aged 20 to 29, making up the single largest group of those affected with this virus. That includes those who test positive by nasal PCR, ER diagnoses of COVID, and those who are, diagnosed and hospitalized with COVID-nineteen. So, again, twenty percent of all confirmed cases were in that young adult group. Wait, this is the group that we're sending back to college.

This is the group we're making play college football in front of large crowds. This is the group that we're saying, hey, no big deal, go ahead and have a party and don't have a COVID party, that's, that's, that's crazy. But moreover, what they are showing was that, where they showed these spikes and these increases where there were regional outbreaks of COVID nineteen, that the increase in rates seen in this twenty to thirty nine year old age group, twenty to twenty nine year old age group, preceded a spike in the 60 age group by eight point seven days, suggesting that these young adults are not just getting, getting the disease, but they're also spreading the disease. Again, this speaks very strongly to vigilance in wearing masks, social distancing, washing your hands. The, COVID epidemic will continue on for at least another six months.

Another report, let me see, I have one more report here. Where is my other report? Well, I don't have another report. Well, do. It's actually, yes, as of September 20, the number of COVID, deaths in The United States was a hundred and ninety eight thousand seven hundred and fifty four.

During the week, it went over two hundred thousand. As of today, Friday, it's over two hundred and two thousand, making for almost four thousand new cases a week. In the last seven days, two hundred and eighty one thousand new cases of COVID. The trends over the last few months, last two months have been about forty thousand, as little as thirty, a little more than forty thousand cases per day, and somewhere between six hundred and eleven hundred deaths per day in The United States. This is still a big problem.

There is one more report, Dinesh Kana and colleagues reported, we have it in today, today's room now, Rheumilcumab. Rheumilcumab, this is a, a new monoclonal antibody that, targets IL-four and IL-thirteen. The idea here is that they gave this to, early systemic cirrhosis patients, ninety seven of them in fact, and they either gave them placebo or the, the new monoclonal antibody RMK, ramilcoumab, and they gave it because of effect, of its effects on T cells and also on fibrosis, and they did show a significant difference in modified Rodman Skin scores, I think it was over six months, it could have been a year, I think it was six months, but it was significant p0.29, favoring the antibody over placebo. It's a win, it's a early phase two study, early phase twos don't often count very well because they often get disproved in phase three, but this is exciting because we need scleroderma drugs that work, we need scleroderma drugs that work on skin, the scleroderma, as opposed to lung outcomes. So it'll be interesting to see where this goes in the future.

That's it for this week. Go to the website to check out these citations and more. Go to the website, click on the back talk link and give me your back talk, tell me your case, ask me your question, we'll cover it in future editions of the Room Now podcast. And lastly, look out for our coverage of ACR twenty twenty, the virtual meeting. You give us two hours, we'll cover the meeting for you.

We'll talk next week. Bye.