VITAL Info On Autoimmune Disease (2.9.2024) Save

It's 02/09/2024. This is the RheumNow podcast. Hi. I'm doctor Jack Cush, executive editor of roomnow.com. This week, the podcast is brought to us by Led Zeppelin, Linda Ronstadt, and the British band Ace.

What? Led Zeppelin, stairway to heaven, we're talking about uric acid levels. You're no good talking about telemedicine. And how long? Well, you'll have to tune in to find out what that's about.

How long is sung by ACE. So, let's start with steroids. You know, we use a lot of advanced therapies, expensive therapies. You know, they are significantly changing the lives of our patients. We often escalate to such therapies with the hope of better disease control, and even better, the option of simplifying therapy.

There was once a spondylitis study that showed the data I'm gonna show you now, but this is kind of disheartening. And the point is that, RA patients who are put on either targeted synthetics or biologic DMARDs, you know, and do well, you would think that they would be able to discontinue their steroids, the drug we shouldn't be on, but we use as a bridge therapy or temporizing therapy. In this study of two twenty eight RA patients, sixty eight percent were on very low dose glucocorticoids. Thirty two percent therefore were on no steroids at all. They looked at these people after three years of taking advanced therapies, and of the sixty eight percent, almost half of them are still on glucocorticoids, thirty two percent.

Twenty three had stopped their their steroids, twenty five percent never took steroids, and twenty percent are on and off. So, if you consider the twenty percent who are on and off, and the thirty two who are still on, more than half of patients have been on steroids, even though they're getting advanced, expensive, successful therapies. Now, this study did not link steroid use with, actual disease activity measurements, or a measure of drug success. So, you can assume maybe that it's allowable that some of those people didn't respond well enough. But isn't it the point that you're going to use these advanced therapies and get people off of steroids?

We don't do that because I think it's just sort of something we overlook, and patients are happy to take them. It's something we need to think about. Great data on early arthritis comes from the Leiden Early Arthritis Clinic. In this study, they looked at the contribution of, ACMA positivity, to disease activity, and obesity. So they had how many people?

Six hundred and forty nine RA patients. They showed that, being obese in that clinic increased your DAS score, significantly by point three two. That if you were ACMA positive and obese, increase your DAS score significantly by point four three. Being ACMA positive increased swollen joint count 60%, tender joint counts 55%, and there was a mean CRP of 3.7, and that would be higher than people who were ACPA negative. Again, are significant contributors to disease activity.

Interesting study looked at whether or not telemedicine, and remote evaluations was the same as, face to face on-site evaluations. It's a small study, seventy eight patients, and they had RA, and they were eighty three percent CCP positive. And they looked at what happened when they did an evaluation within two weeks of the face to face visit. And they compared disease measures, mainly RAPID-three. So by RAPID-three, twenty seven percent were in remission, by telemedicine, versus the DAS ERP remission of seventy one percent in the face to face visit, and the DAS ESR remission of thirty three percent, showing a significant discordance.

Now, they're not using the same measures, and they don't always behave the same. But basically, remission is remission, and they're making the case that the kappa statistics showed moderate to low agreement between the measures done in the clinic and measures done on as an outpatient. Now, of course, you can't do dash twenty eight and dash or CRP or ESR as an outpatient visit because it requires tender joint count, swollen joint count, and simultaneously done CRP or sed rate, but they should have compared rapid three levels at the face to face visit. I like this report about the risk of fracture with CCP because it makes me think, if there is a risk of fracture with CCP, why would that be? In this particular study of eleven forty eight patients who had acute pseudo gout or CPPD disease, they were matched one to three with comparators, and they were all old, over 70 years of age.

Yes, patients, with CPPD received more steroids and had more osteoporosis and osteoporosis therapy, but we're not talking big numbers here, we're talking like steroids in eighteen percent of CPPD, and I don't know, eight percent of the of the other ones, and osteoporosis therapies were, I don't wanna say ten versus seven percent. But the point here was that that if you had previously acute pseudogout, your risk of fracture, subsequent fracture, was eighty percent higher, almost twofold higher risk. The risk was highest for the wrist, and that was a three point six fold higher risk. But arm and hip, you know, and all bones, they looked at, I think, four areas, those are all also increasing. The question is, mechanistically, how does this happen?

You could blame it on first off, they're all older patients, right? So they're kind of primed maybe for more fractures, but the rate of osteoporosis therapy was a minority, maybe they were undertreated, maybe getting steroids even intermittently was a risk factor here, But, I don't historically think of a fracture risk in patients who have acute pseudogout or acute gout attacks, and maybe we should be thinking about that and counseling patients, on fall risk and fracture risk. We have seen, you know, associations between our inflammatory disorders and cancers. We haven't really seen that very well, and it's hard to prove in kids. This particular study looked at the Danish registries, you know, they have lots of very reliable registries, patients, mothers who had maternal autoimmune disease, and then had children, they looked at the risk of those children developing cancers, and it was a significant twenty five percent increased risk, an odds ratio of one point two five, with a higher rate of acute lymphoblastic leukemia, fifty two percent higher, Burkess lymphoma, two point six fold higher, and CNS tumors, forty five percent higher.

And when they just looked at just the women who had RA, they saw the same increased risk of childhood cancers. So there's something to the story, and I'm the only thing I can say that's good about this data is that the numbers are low for actual risk. So, when they say a higher risk, you know, they're comparing low numbers in two different cohorts, but still, it is significantly elevated. The Korean database also looked at a risk of cancer amongst their patients with ankylosing spondylitis, and they compared, almost eighteen hundred patients with AS, in a one to four comparison with, healthy controls. They found that the AS patients, percent developed cancer, and there was no overall increase in cancer in AS patients with a adjusted hazard ratio of 1.1.

But there were a few cancers, when you looked them individually, that were higher in AS patients, and that included upper GI cancers hazard ratio 1.51, that was significant, and hematologic malignancies, a hazard ratio 2.4. You know, maybe what's going on here is that a lot of these kids are being treated with nonsteroidals. We know nonsteroidals do have, we talked about this a few podcasts ago, do have, the potential of lowering cancer risk, but why not these particular cancers? And again, you other data suggest that NSAIDs do not lower, hematologic or GI cancers. So, colon cancer, yes, right?

Head and neck tumors and breasts and a few others. But so is this an NSAID effect, or are AS patients from Korea really at a higher risk? The question sometimes comes up. I have a gout patient who's having an attack. Should I start, urate lowering therapy with either fevoxacet, allopurinol, whatever, or should I restart it to someone who was had stopped it?

And this particular meta analysis of six study, six randomized controlled trials, four forty five patients showed no significant differences, in any measure of what went on with their gout, especially with regard to the flare. So time to resolve the flare, risk of further flares, active gout beyond thirty days, again, no difference. Again, they did receive urate lowering therapy often with, prophylaxis. So another interesting report was in JAMA this week about the risk of gout. This is based on a UK, The UK PRD or PRD link, I can't remember the name of this other of the dataset, but, over three thousand gout patients, compared to a same, number in a control group, and they looked at flare rates based on baseline uric acid levels.

So, for those who had a uric acid level of six milligrams per liter or less, the rate was 10.6 per 1,000 patient years, or one per 100 patient years, a very low risk. But as you go up, you know, in the sixes, it goes up to forty. In the sevens, it goes up to eighty two. In the eights, it goes up, and that's eight to eight point nine. It goes up to a hundred and one.

In the nines, it goes to one twenty five, and in the over 10, it goes up to one thirty two. So that's like now one in ten risk of developing a gout flare. Hospitalization rates were also astronomically high In patients with uric acid levels greater than nine or greater than 10, the hospitalization rate was either thirty four fold or forty five whole higher. Again, I think this is important information that you can use in counseling the many people who you see, who are reluctant to take therapy and prophylactic therapy or urate lowering therapy. They'd rather roll the dice and have their third, fourth, fifth, you know, gout attack in the year and manage it how they like to manage it, which is often wrong and goofy, ill advised, and a lot a little bit too late.

These data, you know, speak to actual risks that they will have the next year, if they don't do something about their gout. And I think particularly scary is the hospitalization rates. Again, if you're over nine, thirty four fold higher. If you're over 10, it's 45 fold higher. That's scary.

Many of you in 2021 were, I think, quite excited by Karen Costenbatter's presentation at ACR, where she presented the results of the VITAL study, showing you that supplementation with vitamin D and omega three fatty acids, could be associated with a lowering of the risk of autoimmune disease. And now I'm gonna present the follow-up to that. So let's go back to the VITAL study first. It was a study that was designed to look at if you gave two thousand units of vitamin D a day, or if you took, I can't remember the dose, omega-3s, and they followed a large number of patients, twenty thousand plus patients, for five point three years. The study was done to see if the supplements would lower the risk of cardiovascular events or cancer, and it proved to be not the case.

And this was published in New England Journal. Doctor. Kostenbatter's report in 2021 said, guess what? There was a significant lowering, a seventeen percent lowering of the risk, that was I I I think that's the number, With let's see. I'm gonna have to read this.

I I I I'm sorry. I have to get the facts straight here. Yeah, let's the idea was vitamin D significantly lowered the risk, and omega-three fatty acids almost lowered the risk. So what happened was, at the end of the study, they stopped their vitamin D and their their fish oil therapy, and they followed around eighty five percent of the patients for another two years. And now we saw a flip, meaning that if you had stopped vitamin D, you are no longer protected from incident autoimmune disease, where the hazard ratio was basically one.

But if you, stop the omega-three fatty acids, it was now six, significant, and that was a seventeen percent lowering that was significant. The point here is that if you want to have some benefit from vitamin D, you need to continue it and can't take it intermittently, or you can't stop it and assume there's a benefit long term. And that maybe there's a long term effect of omega three fatty acids. If they have to go off of it, maybe they can get away with that. That's one interpretation.

I look at this data and I'm saying, I'm not sure I believe it. You know, many of you know, I know I'm a I'm a curmudgeon about vitamin d data. It's associated with everything and and cures nothing. So when I find that vitamin D can prevent autoimmune disease, that's interesting. Vitamin D has significant immune effects, above and beyond what it does to bone, and we certainly know that fish oil therapy is anti inflammatory.

But can you make the leap that routine pedestrian use of these supplements will lower the risk of autoimmune disease? Let's make an autoimmune disease out to be something really simple, which I don't think it is. So you can judge the data for yourself. It's actually published in Arthritis and Rheumatology. Two more reports.

I like this one about the, and this was I think in Arthritis Care and Research, about the association of inflammatory arthritis with scleroderma and systemic sclerosis. In their study, I want to say there's over a thousand patients that they followed with systemic sclerosis, thirty three percent had evidence of inflammatory arthritis. When they looked at the associations, between having inflammatory arthritis with scleroderma, you are at higher risk, significantly higher risk for the following: diffuse scleroderma, thirty three percent higher joint contractors or tendon friction rub, seventy percent higher myositis, a doubling, two eleven percent higher sickness symptoms, fifty seven percent higher and having inflammatory arthritis was negatively associated with pulmonary arterial hypertension. But that makes sense, doesn't it? In that PAH is associated more with limited disease CREST and not with diffuse disease, and inflammatory arthritis is associated with diffuse disease.

What was not important here was U1RNP antibodies or rheumatoid factor, but CCP was seen more in the inflammatory arthritis patients, albeit at a very low rate, seven point five percent, versus those who didn't have it, inflammatory arthritis, where it was only seen in one point five percent. So, inflammatory arthritis, the question is, if you treat it aggressively, does it change the outcomes for systemic sclerosis? You'll tell me. Our last report is about a topic I like to talk about, difficult to treat RA. This is another cohort study, we talked about it last week, a Greek study, showing the twenty percent, incidence of difficult to treat RA in a large CAR RA cohort.

That was, in my opinion, higher than what I've seen in many other studies where it was about ten or eleven percent. But here's another study where they had a total of almost 1,500 patients, and they found sixteen or seventeen percent that met the EULAR definition for difficult to treat RA, d two t RA. But when they came up with another definition of polyrefractory RA, it was a much smaller number. It was only forty out of the fifteen hundred, that's two point seven percent. And to be a polyrefractory, that meant that you had to have failed four lines of biologic therapy, TNF, IL-six, abatacept, B cells, so that that made you a different subset.

Turns out that if you are a poly refractory person, you are more likely to have higher DASs, higher CRPs, and have a history of smoking twenty percent versus four percent. They also went and did ultrasound on a subset of the D2 TRA patients, about a hundred of their two hundred plus patients, and they identified them as having either persistent inflammatory disease or non inflammatory disease based on ultrasound evidence of synovitis. And you know what, was about split, 57 had persistent inflammatory, RA, and forty three percent had non inflammatory RA, And the non inflammatory RAs are are pain and fibromyalgia patients. The inflammatory RAs have higher inflammatory indices. And hence, this identification means that of all the patients who have D2TRA, at least half of them may benefit from more aggressive, systemic therapies, but that half of them won't, and you need to decide either by ultrasound or by exam, or by clinical parameters that they are in this non inflammatory group, and, you know, you need to talk to them about what is bothering them and figure out if if fibromyalgia is in play.

That's it for this week on the podcast. Hope you enjoyed it. Go to the website to check out these citations and more. Next week, we will do some Ask Cush Anything recordings. Take care.

Bye.