Location, Location, Location (7.26.2024) Save

07/26/2024. This is the RheumNow podcast, and I'm doctor Jack Cush, executive editor with roomnow.com. This week, we're gonna talk about location, location, location, the importance of geography. We're going to talk about lupus, some things that we may not think about as being important in lupus. And then I think we'll end up with some interesting data about chest CTs and coronary calcium scores.

So I want to begin with this tweet I put out this week. It's a TriNetX retrospective. So TriNetX, I think, is a large database of EHR information. And as you'll see more and more of these TriNetX studies where they do propensity matching comparing this to that. There are a lot of problems with the propensity matching and problems with some of the methodology.

Some of these studies are really good, some of them not so good. I think you need the, the epidemiologists that in your life, you know, we've got a few, don't we? Maybe we shouldn't. But to explain to you why this may or may not be valid data, well, I found this report about the protective effects of metformin in lupus. So there's a retrospective study that looked at nine thousand two hundred patients with lupus on metformin, not why, and compared that to almost seventy nine thousand patients not on metformin.

And they found that after propensity matching, that if you were a lupus patient and not on metformin, you had a significantly higher risk of lupus nephritis, CKD, and MACE, major adverse cardiovascular events, with anywhere from a twenty to seventy percent increase. And we've talked about the importance of metformin as co therapy, and that often a lot of the benefits of metformin may not be related to control of diabetes or control of hyperglycemia. So I think this could be real, that's why I posted it. But I want to put in the proviso that if you're really into this kind of stuff, you're really going to need to pull the paper and really go over the fine details to find out if this really is important or not. Another study, a smaller study of the effects of krill oil therapy in lupus.

This is a twenty four week study, where patients with lupus, seventy eight patients with lupus, were given, four grams a day of krill oil, or a placebo. And they followed them for twenty four weeks, and then patients were given the opportunity to switch over from placebo to krill oil, and follow for forty eight weeks. Anyway, they found that this lupus cohort had a few things that are relevant. Number one, the average, we measure sort of your, use omega-three, fish oils by something called the omega-three index. It's like DHA and EPA and a few other things.

And the number is, in the general population, is low. The optimal number is above eight percent for what's called a o three I omega three index. Turns out the average population in The United States, not lupus, just average people like you and me, well, we're above average, but still our, omega-three index is usually around four. And turns out that in this cohort of 78 lupus patients, their baseline, O3I was three point, I'm sorry, four point three percent. After taking, placebo, no change in their O3I.

But after taking the krill oil, after four weeks, it went up to 7.2. And then after being on it for twenty four weeks, it went up to 8.05. And eight is sort of the right number. Eight is the number that reduces risk of cardiovascular events in a general population or high risk populations. But this was a short twenty four week study, just a few people, there were dropouts in the study, it was an imperfect study, but it did show that it did work as far as increasing the, omega-three index.

And what was the benefit of that? None. For all the patients that were treated with krill oil, there was no real benefit, but they did a subset analysis, nine patients had a SLETE I2K score, meaning disease activity greater than nine, and those patients actually did show a significant improvement in their SLETE I2K scores when they lowered their omega, three index. So, is that just, you know, normalizing high levels and, you know, migration to the mean, or is that really an association there? I think we should see some more studies on this in lupus.

A study from Philadelphia looked at one hundred and fifty four patients with discoid lupus erythematosus. This was reported in JAMA Dermatology. And in this study, they looked at the outcomes of DLE activity using the CLASSES score, and they correlated that with a number of different things, including, geospatially disadvantaged individuals, as measured by something called, it's a geographic dis where you live within Philadelphia, and it's called, the Area Deprivation Index, or the ADI. So if you had an ADI of greater than five, they said that you were geospatially disadvantaged. And that, you know, there's a lot of things that go into that, but that would include education, and and financial, matters, etcetera.

And so it has to do with geographic density of where you live. But those who had an ADI, an area deprivation index, greater than five, again, geospatially disadvantaged, hadn't heard that until this week, those folks actually had a fourfold higher risk of moderate to severe disease activity related to their DLE. Well, this is not the only report we had on location. I think it was the journal Pain that showed geographic differences throughout The United States, and with regard to the risk of having arthritis related pain, or arthritis related outcomes. And they did show that, and they tried to show this on a state level, but also on the county level.

They did show that a higher level of pain and severe pain and arthritis outcomes was seen in the Deep South and Appalachia. Severe arthritis pain was more prevalent in the Southwest, Pacific Northwest, Georgia, Florida, and Maine. Really? So again, another report where geography and where you live may impact the outcome, especially as far as a rheumatologist is concerned. An NHANES study this week, from a few years ago, like twenty years ago, showed that in the NHANES population study, that twenty eight percent of the population reported erectile dysfunction, have to assume that's the men, and nineteen percent reported arthritis.

But if you had arthritis, you had a fourfold higher risk of erectile dysfunction. And that was mainly seen in osteoarthritis patients where it was eleven percent risk, and rheumatoid arthritis, where there was a three percent increased risk, and those were significant. The question is, you know, we don't talk about erectile dysfunction in my arthritis clinic, and we probably should. If you think about these numbers of all your OA patients, how many of them are taking drugs for erectile dysfunction? This would say about eleven percent, I think that's about right.

How many with RA have are on drugs for erectile dysfunction? This would say three percent. And I think that's about right. In fact, it might be a little bit low if I look at my RA and OA patients. The point of this is awareness.

You know, there were reports in the past about erectile dysfunction being a prevalent issue amongst gout patients. There can be a lot of reasons for erectile dysfunction, including disability and inflammation and whatever, body image issues, age, etc. But again, it wouldn't hurt to talk about this. And wouldn't hurt to have a conversation about sex and intercourse and things that are important to patients, because then you can, if you can't deal with it, then there's people who can, and your patients would appreciate that. A study of almost 5,500 patients with adult Still's disease looked at hospitalizations, And this particular cohort of five thousand four hundred and ninety five Still's patients who were hospitalized, they looked at a few things, but one thing they found was that those patients who developed MAS or HLH had a higher mortality rate than those who did not.

So, the incidence of HLH, was six point two percent amongst these Still's hospitalizations. By the way, Still's disease doesn't kill anybody. You shouldn't die from Still's disease. But you may die from complications of steroid therapy or other therapy, and you may die from MAS or HLH. So, number of six point two percent, which I think is about right, is important.

And what they found was mortality rates were nine percent in STILS patients who had HLH versus only one point five percent in those who did not. So independent predictors of death in STILS patients who were hospitalized with STILS was number one, DIC, six fold higher risk, liver failure, seven fold higher risk, infection, three point seven fold higher risk, respiratory failure, six point nine, and thrombotic microangiopathy, a fourteen fold higher risk. Now, Still's is rare. Hospitalizations with Still's is rare. And death from Still's is even more rare.

But these findings do approximate that reported by Bella Metto when she looked at this in, I think it was an NHS survey, of hospitalizations, and found that those were the predictors of bad outcomes in hospitalized Still's patients. I can tell you, I know Still's very well. DIC does occur, albeit rare. Liver failure is really bad, infection is not uncommon, respiratory failure, you know, we're talking about that. Thrombotic microangiopathy, always a bit for me a head scratcher, but it has shown up, and it is in the literature.

A study from The UK looked at how good are we who take care of IMiD patients, immune mediated, inflammatory diseases. And this UK study that looked at fourteen thousand RA, thirteen thousand IBD, three thousand eight hundred SPA, seven hundred lupus patients, overall, these thirty two thousand patients, only fifty seven percent of them were vaccinated against pneumococcus in one form or another. This number was lower if the patient was 45, thirty two percent. Was lower in IBD patients, forty two percent. But what they did show in this UK study was that vaccinating against pneumococcus had no association with FLAIR of those diseases, RA, IBD, SPA, and SLE.

So there's no good reason why your patients shouldn't be vaccinated. I did report on this association between myelodysplasia and rheumatic disease in weeks past. There's another report that just showed up this this past week about a very large cohort of patients with myeloid neoplasms, including eight sixty one with myelodysplasia, six forty with AML and a whole bunch of others. And they found that, amongst these patients with myeloid neoplasm like disorders, rheumatic disease was present in almost eight percent. The literature would suggest a risk of about eight to thirty percent in patients with myeloid neoplasms and myelodysplasia, etc.

The number was less in those with AML, four and a half percent versus nine and a half percent. The most common autoimmune diseases that were reported here were RA and forty two percent, other connective tissue disease eighteen percent, and PMR and fourteen percent, vasculitis and axSpA was less. So the point being that it's not uncommon to have this association between rheumatic disease or, myeloid, cancerous disorders. The question is, which comes first? In this study, I think it was that the myeloid neoplasm, or myelodysplasia, was the first event, and then autoimmune was often the second.

But they can be the reverse as well. So, I found this study really interesting. A German laboratory study of 72,000 laboratory tests, and they're looking for, how often they found abnormal tests for myositis autoantibodies. And basically, they found it in two zero nine patients, two thirty eight tests. And the question was, for those, you know, amongst as many thousands and thousands of laboratory tests, the ones who had a positive test, what was the etiology?

This was a head scratcher for me. You would think that they all had myositis of one form or another. Turns out only eighteen percent, or thirty seven patients, had idiopathic inflammatory myopathy. More importantly, other inflammatory rheumatic diseases, autoimmune and other rheumatic diseases, not myositis, accounted for forty three percent of those positive results, and in forty percent, actually thirty nine percent, they had no rheumatic diagnosis. How good are these myositis autoantibodies?

I thought they had, when I've looked at statistics on them before, I didn't look it up for this report, but I thought they had reasonable sensitivity and specificity. This would say, sensitivity, yes, but specificity, probably not. So just because it's positive, whether it's an anti JO-one or NXP, doesn't mean that they are automatically going to have a myositis, subset of some sort. I want to remind you that we did post up there a JAMA patient education handout on, PMR. It's a fairly good handout.

It's a one pager. And I think that you'll should download that and hand it out to your patients. A few more reports, two actually. One, a study looked at, a number of, this is actually a study from RUSH, I want to say. Doing that right?

I think these are RUSH patients, where they're screening patients in their clinic by either doing the MDHAC or the Rapid three. And they found that thirty six percent of RA patients and forty percent of OA patients screen positive for either anxiety, depression, or fibromyalgia using the MDHAC or the Rapid. All three were found in up to eight percent of patients. RAPID three was also elevated and abnormal in those who screened positive. And again, you, these are basically questionnaires.

There are other things, I think we talked about PHQ-nine as a specific depression scale that you can do as an outpatient. But, we've talked before about these being confounders in patient care, in those who don't respond, and in poor outcomes. It is important. So this is a big pitch for doing either the RAPID3 or the MDHAC, which has that information on the survey forms. By the way, it's also on the RheumNow clinic follow-up visit form as well.

We had a speaker at last year's RheumNow Live. By the way, this year's RheumNow Live is going to be December, it's going to be February 2025. We're sending out the invitations right now to our faculty. I think you're going to love this program. We really love it.

Last year, we had a great speaker from, the Brigham, Brittany Weber, who runs the Arthritis Cardiology Clinic, at the Brigham, and she had a recent presentation, at the Society of Cardiovascular Computed Tomography. They had their recent 2024 meeting, and she presented data on 2,800 lupus, I'm sorry, lupus RA PSO patients who did not have, any evidence or prior history of atherosclerotic cardiovascular disease. And these patients, that were studied all had a computer tomography of the chest, and they found that, only half of them had a normal or a zero coronary alci-, and these were, by the way, all identified by artificial intelligence. Forty seven percent had a zero score on their CAC. But having an elevated coronary artery calcium score was associated with a significantly higher risk of future mortality and or MACE events.

So scores of one to 100 was seen in thirty percent of patients, 100 to three 100 in ten percent, and greater than three hundred in thirteen percent. They found overall that the coronary artery calcium scores was greatest in psoriasis and psoriatic arthritis patients. So each of these elevations so as the higher you go up on the score, there is a higher increased risk of all cause mortality, about a forty percent increased risk, and about a fifty percent increased risk in MACE. So, and if you were really high at three hundred or more, the, it was a two point five fold higher rate of mortality in MACE. So, car, cardiologists like these scores.

It's sort of like a staging procedure, who should get more intensive evaluations with stress tests, nuclear or otherwise, or actual angiography. They're not totally predictive, but it may be helpful. And I think I would encourage my patients with chronic inflammatory disease, chronic autoimmune disease, we know to have a higher risk of cardiac outcomes, why not do that if it's offered? You're now finding another good reason to refer to cardiology to get a more complete cardiac workup. Anyway, you can find these citations and more on the website.

I hope you enjoyed this pod this week's podcast. We'll talk to you next week. And again, look forward to RheumNow Live twenty twenty five, February eighth and ninth. Be there. Bye.