ANA+ Consult (10.18.2024) Save

It's the 10/18/2024, and this is the RheumNow podcast. Hey, everyone. Hope you're having a good week. This week, we're gonna talk about chatbots, GWAS, ANAs, d two t p s a. It's a lot of letters and nonsense.

Chatbots. You know, AI has taken over. I don't know if you're using it. I use it a lot, actually. I think it's a great tool, and I think if you're not using it, you're missing out.

The question is, is it, you know, society going to hell in a handbasket, or is it change that makes you uncomfortable? There was a nice report this week, that tested the ability of artificial intelligence chatbot from Bing, to make up information and answer questions about 10 not 10, but 50 of the most common drugs that are out there. So it provided 500 answers, and these AI generated answers, were all really very good. I mean, if you look at the actual accuracy of what was printed, it was over 90%. The problem with it was, however, one, it was not very readable, meaning it wasn't for the common man.

Usually, that's meant to be about an eighth grade reading level. This was sort of written to complement the people who wrote it. So it was much higher than that. And then there were occasionally inaccuracies that the authors of this paper took the, you know, extra leap of saying these were potentially life threatening and serious complications to patient medication safety information. Again, a little bit of a stretch.

By and large, AI was pretty darn good. What you need to know about AI is that we're really in the first or early generations of AI. It's getting better year by year, and its utility in practice is going up. I think you should be looking into it. The FDA did approve a new drug this this, past week, although it was a biosimilar, a biosimilar for Stellar.

I think that makes the fourth ustekinumab biosimilar to hit the market. This one's called Emuldosa. Emuldosa. Emuldosa. Gotta say it three times fast.

And it's ustekinumab in four letters that mean nothing. Again, it goes for all the indications of ustekinumab. That would be psoriasis, psoriatic arthritis, Crohn's, ulcerative colitis. The originator sales for the J and J Janssen made product Stellara in 2023 was almost $11,000,000,000. Not surprising that there's now four, four biosimilars for ustekinumab.

Will that change things? It certainly has, I think, for the TNF inhibitors, especially for adalimumab. Although, the number one maker or seller of adalimumab right now still is the originator, Humira. The question is, will the overall cost of adalimumab and ustakitamab go down? By and large, it should.

And will more people be treated because of the lower course? Cost, I think it will be. Data starting to accumulate to that effect. A report this week on, looked at cardiovascular health. It's data from the NHANES study, and shows that the, calculation of a cardiovascular health score.

This means blood pressure monitoring, lipid monitoring, control of glucose, things like that that become cardiovascular risk factors. And if you get a score, and if you score well on this, for every 10 increase in the CVH score, you had an overall significantly lowered risk of mortality. So as your cardiovascular health scores went up, meaning good things, your cardiovascular mortality went down, and it went down by thirty eight twenty eight percent for every 10 increase in this analysis of almost 6,000 studies 6,000 patients. Most of the patients in the study were degenerative and osteoarthritis, Degenerative disease and osteoarthritis, which is where all the benefit was seen. They didn't show statistical significance for inflammatory arthritis, but I think that was a sample size issue.

Because certainly, we know that when you have healthier lifestyles with inflammatory disease, patients do better as far as cardiovascular outcomes. Sticking on the cardiovascular outcome angle, why not look at European Heart Journal? I know you read it all. I do. This is a report from a group that's interested in RA and cardiovascular outcomes, and they specifically looked at cardiometabolic factors in RA patients who are pregnant.

Overall, they found cardiovascular risk factors going up in RAs who became pregnant. You would think that would be relatively young RAs, right? 20 to 45. But in the last fifteen years, the incidence of these things that we would call what? Hypertension, diabetes, gestational diabetes, obesity, and dyslipidemia, that's all gone up significantly in the last five years.

Moreover, the RA patients that were included in the study tend to be a little bit older than the matched population, 31 years versus 28 years. And with age come some of these cardiovascular risk factors. Overall, though, again, women who were pregnant included in this analysis had a higher risk of cardiometabolic risk factors and consequently more adverse pregnancy outcomes, preeclampsia, cardiomyopathy, arrhythmias, acute kidney injury, venous thromboembolism, and hospitalizations. So again, we think of our RA patients who get pregnant as being, you know, they should be generally healthy, but, you know, they bring a lot of RA to the table, and that means a lot of comorbidities. This needs to be considered really when you're counseling these patients.

A large GWAS study of two point six million people looked at genes associated with gout. This GWAS study, I think the number was, like, three quarters of the data came from 23andMe, sample submission. From 2,600,000, they think they had a hundred and twenty thousand patients with prevalent gout. They detected, 377 loci, 410 independent genes. About a 150 of those were previously unreported, that were associated with gout.

This included genes associated with inflammation, epigenetic remodeling, cell osmolarity, I don't get that. NLRP three, the inflammasome, I get that. And, clonal hematopoiesis, an increasing factor in disease risk for many of the autoimmune and rheumatic, inflammatory diseases. But the bottom line on this, the takeaway that you'll see in the press was, you know, gout is not so much a nutritional disease as most people think. It's very much a genetic disease.

And I don't know that that surprises you, but that's what is in in the news this week on gout. Based on this large GWAS study and a large number of genes associated with inflammation and LRP3 and CHIP, we do see the evidence that gout is very much genetically based. Another study that came out this week, which I would say is a kind of a no brainer and a duh, but I reported on anyway for reasons that it's boring. It's about biosimilars. I'm hard pressed to find biosimilar data that's interesting, exciting, new, novel, gives you a oh, wow kinda, moment, and that's not one of these.

This is a study of the bio originators and biosimilars, the retro study with two years of follow-up, showed that when you compare the patients who were taking either the originator or the biosimilar of either infliximab or etanercept, that serious infection rates were the same. Now is that exciting? No. It's quite boring. But then again, I've been preaching for a while, boring is good.

Boring is what we want in the outcomes of our patients. Live for boring. Lifestyle, exercise, diet, how you take your medicines, how you get your follow ups, that should all be really boring because that's the key to success. This data, which is boring, is another added factor to success. So they looked at infliximab.

Alright. Well, first let's look at etanercept. The rates of SIE, serious infection events, with etanercept were significantly lower than with infliximab, like eleven point eight per 100 patient years. Actually, I think this is 1,000 patient years. And it was the same with the originator, versus the, biosimilar.

It was eleven point eight versus eight point four, not statistically significant between them. That's with etanercept. Infliximab SIE rates were almost three times higher, thirty three versus twenty nine, the originator, Remicade versus the biosimilars, you know, Inflectra and the other versions of infliximab biosimilars, twenty nine per one thousand patient years. Not significant. Again, it's it's duh.

I would expect that, but it does give you confidence when your patients are voluntarily or involuntarily switched to either enetanecept or infliximab biosimilar that the outcomes are gonna be the same as if they stuck with the original drug. I believe that strongly. Another meta analysis this week looked at the risk of ILD. I was always perplexed by data that said, RA patients that go on leflunomide have an increased risk of ILD. Really?

RA patients that go on TNF inhibitors have an increased risk of ILD. I don't think so. And what about RA patients that go on the risk of any new medicine, including methotrexate, increased risk of ILD. I think that's guilt by association. There's confounding going on here.

So this particular study, a meta analysis of 40 patients, 40 studies, almost a half million patients, almost four thousand cases of incident ILD basically showed, one, no increased risk of ILD when starting a new DMARD. No increased risk of ILD when starting either tofacitinib or a TNF inhibitor. Great data from the oral surveillance study, which showed an odds ratio with either of them about one or zero point nine four. More importantly, they showed that methotrexate use did not in any way increase the risk of ILD, but in fact significantly lowered the ILD risk to the odds ratio of zero point four nine with confidence that it was a zero point three two to zero point seven six, a fifty percent lower risk when you compare patients that went on methotrexate versus those that did not. I think, again, this is boring but exciting, brand new, helping you to practice data.

What is a lot of your practice? A lot of your practice is the ANA positive consult. Oh my goodness. I firmly believe that, ANA positive arthralgias that come to me are not all gonna be normal people. I believe about five, maybe as much as seven, eight percent of them will eventually become an autoimmune inflammatory or lupus like disease.

But that means ninety five percent of them are not. So here's a study, a two year study of two zero seven asymptomatic ANA positive people. ANA positive, asymptomatic. They don't even have arthralgias. How many of them progressed to a systemic autoimmune rheumatic disease?

What would be your guess? I told you my experience is that it's I just said, ANA positive arthralgias, five percent. In this study of two zero seven asymptomatic ANA positives, I didn't go into how high the titer was, eleven percent progressed to a diagnosable systemic autoimmune or rheumatic inflammatory disease. That means eighty nine percent did not. Of the ones that did progress, almost half of them were lupus, twenty two percent Sjogren's, thirteen percent scleroderma, and four four percent RA.

So, again, this is, I think, comforting to know what the fate of your ANA positive consult is going to be. There was a report this week from, I think, in JRoom on difficult to treat RA testing two different criteria for not difficult to treat RA, difficult to treat PSA. Difficult to treat RA criteria were established by EULAR. There are two criteria that have been established by Paroda and Kumbhecar, and they compared them and they have a sensitivity of about thirty five percent, a specificity of about eighty five percent. They both perform equally well.

In both of these studies, somewhere between fifteen and twenty percent of patients from a cohort of PSA patients qualified as having difficult to treat PSA. It's an important number to know, because these are the people that you're really gonna have to work at. These are the people that you're gonna have to decide. Is this a difficult to treat patient because of ongoing inflammatory activity? Some of them are.

Most of them are noninflammatory activity, which means that they need attention to fibromyalgia, other comorbidities, depression, pain due to mechanical causes, etcetera. So I think this is important. You'll be seeing difficult to treat, reports and studies in the future. I think that's gonna be, really important for future research in this area. Speaking of psoriasis and psoriatic arthritis, an analysis of psoriasis patients, a sub analysis of a ducravacitinib study.

It was a phase two study of almost two fifty patients with psoriasis, where they were treated with ducravacitinib for twelve weeks. They found that, when looking at biomarkers, that they mainly came from the IL-twenty three, IL-seventeen pathways, and that using ducravacitinib was associated with significant reductions in IL 17 a, IL 17 c, beta defensin, PI three. And all of these correlated with changes in the skin activity score, the PASI score. Again, lending some credence to the rationale behind to cravacitinib use. We did talk about this a little bit last week, did we not, about why maybe ustekinumab might be an ideal target when you start looking at outcomes in this manner.

A study of GI abnormalities in scleroderma, prospective scleroderma cohorts found that GI tract disease was very common, almost fifty percent. Negatively, scleroderma patients will have GI involvement of various types, but and it will negatively impact quality of life, physical function, and their employment. But interestingly, no effect on mortality. Good to know. Zoster vaccination, yes, our patients should be getting zoster vaccination, when they're immunocompromised, OnJac inhibitors or over the age of 65.

This is a VA study that looked at the use of the Shingrix vaccine, the recombinant zoster vaccine, approved in 2007. Originally approved for adults over age 50, modified in 2021, and that was in 2017. In 2021, it was modified to include, adults who are also immunocompromised, should be vaccinated with Shingrix or the recombinant zoster vaccinee. In this veteran study, ninety thousand veterans, receiving immunosuppressives. Only, I think it was twenty three thousand of them actually received the zoster vaccine.

So if you looked at the people over the vets 50 who were immunocompromised, only thirty six percent received recombinant zoster vaccine. That was at 2017. When the guidelines changed, the number went up from thirty six percent to fifty percent were being vaccinated by 2023. So it did go up. It's still only fifty percent of the people who were in fact eligible.

What about the vets who are 50? Again, at the original indication, only three percent. But then again, it wasn't indicated. But after 2020, it's only risen to thirteen percent in younger people. The bottom line is we're not doing a good job of vaccine against zoster with this inactive, very safe vaccine.

Those who are unlikely to receive the recombinant zoster vaccine were males, African Americans, nonwhites, nonurban livers. Interestingly and thankfully, RZV vaccination was higher in those receiving targeted synthetic JAK inhibitors, biologic DMARDs, or combinations of drugs that either involve biologic or DMARDs or targeted synthetic DMARDs. So that's encouraging, but we can do a better job. Two more reports this week were about the unconventional treatment of people with back pain. Both of these were published on MedPage today.

The first one was from the British Journal of Sports Medicine. This is about the use of a run walk program to treat people with chronic low back pain. They looked at adults who were 45 with chronic low back pain, and they compared in this British study, those who receive a structured program versus no program, those who are on the wait list for the program. And what was the, intervention? Again, it was a formal education with, digital, and phone follow-up, I believe.

And they showed in this twelve week runwalk program that the intervention had a significant reduction in pain intensity by, it looks like a median of 15 points. And that was highly significant at p point zero zero three compared to those who had no intervention. So this is just a run walk program. Right? No drugs, nothing else.

Similarly, another study published this week about I think this is from JAMA, looked at two sixteen patients with chronic sciatica due to herniated discs, and they were randomized to either receive either no acupuncture sorry, sham acupuncture or 10 sessions of acupuncture over a ten week period. Everybody's blinded. The assessor, the statisticians, the patients, even I think those who were given the acupuncture sham or real treatments. Well, actually, they couldn't have been blinded, right? So the bottom line was the results were significant and very significant for acupuncture.

I noticed this when I look at all the treatment guidelines for osteoarthritis of the knee, for instance, and hip, that many of the things we use, don't work very well. But a lot of these alternative measures like acupuncture, like chiropractic, like, in this case, a run walk program are highly effective. As we talked about last week, mindfulness therapy, highly effective. We need to use more of this. That's it for this week's podcast.

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