Linger On The Fingers (9.6.2024) Save

It's 09/06/2024. This is the RheumNow podcast. Hi, I'm Doctor. Jack Cush, executive editor with roomnow.com. This week on the podcast, I got a few topics and presentations that are all about the fingers, You know, color of fingers, things that happen to fingers, and fingers are really important to us rheumatologists.

Think that's what's great about rheumatology because while your patient evaluations may begin with a handshake, I know that my patient assessments begin with reaching for their hand and holding their hand and examining their hand. Sometimes I'm I'm taking in their hand while I'm talking to their their face, and I'm feeling temperature, color, the smoothness of the skin or not. And there's a a lot can be told. I mean, the way to the diagnosis is often through the hands. So I like that it begins with the hands, and I like that I'm highlighting fingers in this podcast.

Of course, it all ends with what we do and what we prescribe, and we're gonna cover that cover that today as well. I don't know if you noticed, some of these reports that have appeared in roughly the last few years about the associations between GERD and H. Pylori and the etiology of rheumatoid arthritis. I put those up this week as tweets back to back, I think it appears today on social media, and it's curious. So one comes from nature and it's a sort of an explanation paper about how, the gram negative bacteria H.

Pylori may actually either exacerbate rheumatoid arthritis, which it's been reported to do, or may even be involved in a pathogenesis. And the idea here is that infection of gastric epithelial cells, will lead to an upregulated expression of PAD4, an enzyme very important in rheumatoid arthritis pathogenesis and what's going on in the synovium. And this increased PAD four activity, can lead to increased citrullinization, which will lead to ACPA, which may have a role obviously in the pathogenesis of the disease. So is this real? Is this something that we should pay attention to?

Should we be treating everyone for H. Pylori? I know I look for it from time to time. So another study I found from, I think a year back 2023, a study of almost 5,000 patients who are undergoing, and these are not arthritis patients, these are people undergoing upper endoscopy. And of the five thousand, about two thousand three hundred had an H.

Pylori infection, and about less than half of those have what's called a long lasting H. Pylori infection, twenty two percent. Of those people, they had they they noticed overall a six percent incidence of atherosclerotic cardiovascular disease and a four point three percent incidence of rheumatoid arthritis. Okay? None of this sounds too surprising.

These people are average age of around 50 years of age, but it turns out that having this long lasting H. Pylori infection increased the odds of having cardiovascular disease with an hazard ratio of one point five seven, fifty seven percent increase, and increased the risk of developing RA or having associated RA with a 2.6 fold increased risk. So hazard ratio 2.63. If you had RA and you had a long lasting H. Pylori infection, you had an eightfold higher odds of cardiovascular disease.

Obviously, this association between RA inflammation, cardiovascular disease is not surprising you. What's surprising here is what's the deal with H. Pylori and GERD? Is that part of a mucosal hypothesis upon which maybe rheumatoid inflammation may start? I think this is interesting.

I think we have to pay attention to this. A quick report this week about, better management of problematic Behcet's and how to prevent uveitis. There's an open label head to head trial adalimumab versus cyclosporine. It just basically showed adalimumab was better than cyclosporine preventing relapses in patients who already had severe Behcet's. Do I want to spend a lot of time on this?

No. The point I want to make is I'm not an expert on uveitis prevention or uveitis management in Behcet's. I may even not be an expert at Behcet's. How do you manage these cases? Well, staying up on the literature is one thing, me, I pick up the phone, I call Youssef Yazzyki or I call, you know, the rheumatologists who are great at eye disease and ask for advice because they know this kind of data.

I think we encounter these fringe difficult cases all the time, and I don't think it's a problem for you to reach out to me or anyone else you want to help to get some input on these difficult cases because sometimes you just can't do it alone. RA and MACE, a well known association, this particular report of a cohort of over 4,000 patients followed for looks like maybe six years or so. They had three hundred sixty two cardiovascular events, major adverse cardiovascular events called MACE. Turns out there was a good association between rheumatoid arthritis and info activity and inflammation markers and MACE risk, but only in people who were not taking biologic DMARDs. Guess what?

When you look at those who are taking biologic DMARDs, the risk association went away, which says that more effective treatment can help to abolish that risk. Again, sometimes the question at hand is, why should I use an expensive biologic? Well, this could be one reason, but I don't think it's the only way you get to disease control and, the abrogation of of the sed rate and CRP that seems to be high. I think it might get you there if in combination, but whatever it takes to get there, inflammation, and inflammatory markers need to be nullified. A claims analysis of a fairly large cohort of GI patients with IBD, and or RA found that the overall risk of an invasive fungal infection, IFI, was about zero point five percent.

That would be about five per one thousand. Turns out that the actual risk, think, was, oh, I didn't write it down here, I wanna say it was three point three per one thousand patient years for IBD and about the same two point eight or maybe a little bit higher, maybe it was four for RA. I've often said that these in fungal infections, opportunistic infections, rare infections, it's a one in one thousand risk. And, this is the risk of people who are taking a TNF inhibitor. So that's really what I the point I wanna make is that TNF inhibitors, you know, the risk of serious infections is what?

Two to nine per one hundred in a, you know, in a year. But rare infections like the fungal infections are roughly one in one thousand, a few in one thousand events, but you got to think about them when they're on these drugs because they're so rare, they often go undiagnosed. Histoplasmosis was in this cohort was the most common. The IBD risk was three point three. The RA risk was two point eight per one hundred patient no.

Per one thousand patient years. Okay? Dactylitis is seen in fifty percent of patients with psoriatic arthritis. This particular report says it's associated with a more severe phenotype and more severe disease, and it may be the initial presenting feature of the disease. I added the editorial comment that while dactylitis is common, we don't really yet have a drug that really works great for dactylitis.

Actually, all the drugs we would use for PSA and SPA are all pretty good. TNF inhibitors, IL-seventeen inhibitors, 23s, even aprimolast, they all work pretty well in dactylitis, but none stands out. Eustekinumab is in that group, but none stand out as the clear cut winner. I would like to see a clear cut winner because in some patients, that's the main thing I have to manage. Speaking of fingers, I I found on the website Radiopaea, that's spelled the the British way, radiopaeia.com or .org.

It's a it's a radiology website. It gives you great radiology examples with small case reports. And I came across one of acrosteolysis in a patient with scleroderma and renal failure. Patient had bilateral hand pain. They did an X-ray, and you can see the resorption of the distal tufts of the distal phalanx in a few fingers.

They called it vanishing fingers, and there are other causes of acrosteolysis besides scleroderma, psoriatic arthritis, hypertrophic osteoarthropathy of the chronic kind, several skeletal dysplasias, frostbite, parathyroidism, hyperparathyroidism, And there are a bunch of rare, rare, rare genetic disorders that can cause this. But, again, I think often this acroceliosis is is something you're gonna get in a radiology report from the radiologist, and now you have to think of the differential diagnosis. There was a nice report in Lancet rheumatology this week about Raynaud's phenomenon and how how and when it occurs. And the point that was the standout point of this particular report was that it it obviously is most common with very cold temperatures. But guess what?

It also happens with very warm temperatures. So I give you a bunch of temperature ranges and frequency rates and and the bottom line is that the hotter it gets during the summertime, the more you get reports of rain hours presumably because of the hotter it is, the more air conditioning the patient is exposed to. So this was based on q three month assessments of over twenty two hundred Raynaud's patients. They were mostly women, mostly white, etcetera. But this is a report in Lancet rheumatology.

Another nice report came from JAMA Network Open, I think it was, about scleroderma findings in patients with skin of color. You know? So what happens when you have scleroderma and you're if you're African American, Hispanic, Asian, whatever, not white skin. White skin, obviously, all the skin lesions of scleroderma show up really, really well. Well, in this particular review, with a fairly good sized cohort, Raynaud's was common in both, in all, skin color groups.

But in the people with skin of color, there were fewer of the hallmark findings that we rely on, and that would include telangiectasia's calcinosis and digital swelling. Patients with skin of color were more likely to have more severe pulmonary disease, more atypical skin findings, and increased mortalities suggesting that patients with skin of color, and autoimmune disease can be a challenge. And thank goodness you're experienced and expert in managing and diagnosing these patients. Further, reports on lupus this week, there are a number of them. A retrospective observational study in frontiers look at ninety six patients with lupus who had maintenance therapy with either hydroxychloroquine or belimumab and the takeaway point on this was that flare rates when you're on either belimumab or hydroxychloroquine were roughly the same the flare rate on hydroxychloroquine eighteen percent, a little over eight percent with belimumab that no significant difference in flare rates or in damage done or in sleet eye or prednisone or adverse events and the point by the authors was that blimumab makes a good maintenance option when you can't use hydroxychloroquine.

I think the point is that I'm going to use hydroxychloroquine in everyone as much as I can and then maybe I fall back on toblumep because obviously hydroxychloroquine works very very well. Speaking of hydroxychloroquine, there was another, another report. Actually, this one was from JAMA Network Open. The other one, you're gonna have to look up the the citation. This is about the, a French population study that showed that sustained use of hydroxychloroquine was associated with significant reductions in future cardiovascular outcomes.

We know that. Everybody with lupus should be on chronic vitamin h or p, hydroxychloroquine or Plaquenil, and it's because of the many, many benefits, one of which is reduced cardio future cardiovascular risk, you know, also reduced insulin resistance, better diabetes control, antithrombotic effects, and go on and on, better pregnancy outcomes, etcetera. Anyway, this French population study of fifty two thousand lupus patients mean age 44, mostly eighty something percent women, followed nine years that there were nineteen eighty one cardiovascular outcomes, myocardial infarction stroke, thromboembolic events, and they match that basically one to fifteen, it looks like with match controls without lupus, and basically the hydroxychloroquine exposure. So so the match controls must have been on the lupus patients, not hydroxychloroquine, that the composite cardiovascular endpoint was thirty seven percent lower, odds ratio of zero point six three. Also, and then the composite was MI, CVA and thromboembolic events and the reductions on those were again about thirty forty percent each that when all that was significant.

So again, I put this up because I think it is a major point in rheumatology that about the less than obvious benefits of chronic hydroxychloroquine use. The other interesting study this week that I missed actually from a few months ago, I think it was published in June or July from Karen Costenbatter who, was, looking at the nurses health study, as you know, a prospective study of over 200,000 nurses followed for a bazillion years. And in that cohort, there were two twelve patients with incident lupus. They found a significant association between the intake of ultra processed foods and the developing lupus. So basically a greater than fifty percent increased risk in incident SLE and a doubling of the risk for positive double stranded DNA titers.

In this cohort study, they showed that sugar drinks and artificially sweetened drinks was also associated with a higher risk of lupus, about a forty five percent higher risk. Again, this goes down the path that we've been talking about lately about those, you know, ubiquitous factors that are probably unhealthy lifestyles or unhealthy exposures that do add to the development of autoimmune disease, especially in some susceptible people. What the susceptibility here was, I don't think it was being a nurse by the way, was, something beyond the diet. So lastly, a really cool study in New England Journal from yesterday, was a letter to the editor about achieving CAR T cell like effects with a new bispecific monoclonal antibody called teclistamab. Teclistamab, the trade name is TeCvali, t e c v a y l I.

A It's drug that's FDA approved for use in multiple myeloma. They so a single case report, but I think the fact that was in New England Journal because, the claims that were made here make it worth bringing to your attention. The patient was a 23 year old, in Berlin who had very severe, lupus that was refractory to multiple therapies. And while they probably would have liked to have given CAR T cell therapy, they chose this one. It's a bispecific agent that binds to c d three and also to BCMA, a B cell maturation antigen, which is another way of targeting B cells, and they notice rapid and complete CAR T cell like effects, you know, all the autoantibodies going away, all the b cells dropping, all the skin and joint and systemic symptoms, boom, gone.

Patient was in total remission at week sixteen. So why is this different than CAR T cell? Well, number one, it's a lot cheaper. Number two, there's no need for preconditioning. Number three, we don't know that it's gonna last as long as CAR T cell.

You know, doctor Schetz got some incredible data that says that, you know, few few years out after CAR T cell, those patients are not yet taking any therapy and their lupus is in remission. They only give you sixteen week endpoints. The drug is given as a subcutaneous injection, three injections in the first week and another injection on week two and week five, something like that, sort of an odd regimen. But they adhere to the myeloma regimen and I think you'll I'd like to see, you know, clinical trials, in this in the future. I think it's kinda cool.

So our last report is about from Doctor. Smolin, it appears I think in rheumatology, pardon me if it was ARD, but I think it was in rheumatology and it's about a sub analysis of the ACCELERATE study, which as you know was published a number of years ago, a head to head trial of cerdulizumab versus adalimumab in RA patients. As you know, the drugs were equal in their effects. In this sub analysis, it's a the EXCLIRE-eight was a two year study. In this sub analysis, Doctor.

Smolin had the idea and his investigators as well, had the idea that cerdulizumab doesn't have an Fc portion and that adalimumab does have an Fc portion. What about patients with really high titer rheumatoid factor? Might you get binding of rheumatoid factor to Fc receptors on the adalimumab thereby making its effects different than that of cerdulizumab which doesn't have an Fc receptor? So that's exactly what happened in this sub analysis. Four hundred and fifty three patients, treated with cerdulizumab versus four fifty four with adalimumab.

They compared those in quartiles, the fourth quartile being high high titer rheumatoid factor greater than 204 international units per ml, and the first three tertiles were rheumatoid factor positive but in lower amounts. What they found was that adalimumab concentrations were lower in patients with the highest titer of rheumatoid factor, but cerdulatinib patients had no change in their drug levels even in the high titer rheumatoid factor group. So this was not just drug concentration, there were clinical benefits both to dash 28 CRP levels, dash 28 CRP low disease activity state and C. Dye low disease activity state, meaning you got better responses with cerdulizumab in the high titer rheumatoid factor group and you had somewhat less responses. Now the overall study as you know, not looking at rheumatoid factor, ACPA, anything else showed no difference in the response between adalimumab or cerdulizumab.

But if you look at the rheumatoid factor, maybe there's something there. And there have been other reports that mirror this kind of research in small cohort analyses. The other thing about this particular sub analysis of the EXHILARATE study shows that it didn't matter if you had high titer ACPA or not. Right? Only rheumatoid factor is gonna bind to FC.

So anyhoo, this was kind of a cool thing and we'd I think I'd like to see more studies and maybe if this were true and consistent, it might color whether I would use cerdulizumab versus adalimumab in the future. I want to remind you today is the September 6, today begins the, Advanced Rheumatology and Therapeutic Symposium run by Orin Traum and Alvin Wells. So if you're in Chicago, the JW Marriott's got a two or three day meeting that is a powerhouse meeting that I think you really should attend. If you look at the faculty on this, Doctor. Schett's gonna be there.

The organizers of this is Truman Wells and, Michael Putman and, Alexa Mira and whatnot. The faculty is John Botson, Eric Campbell, Anisha Dua, Philip Meese, Amanda Mixon, Jeff Peterson. Again, a lot of great faculty for this meeting. If you're in Chicago, check it out. It's at the JW Marriott.

That's it for this week on the podcast. Go to the website to check out these citations and more. We'll be talking to you next week on the podcast. Take care.