Blue Collar Arthritis (10.25.2024) Save

It's the 10/25/2024. This is the RheumNow podcast. Hi. I'm doctor Jack Cush, executive editor of rheumnow.com. This week, we have a lot of interesting information.

We're gonna end with a case from the, call in audience, ask Cush anything. But let's get into our report for this week. I found a study of, nail fold capillaroscopy in patients with Behcet's. I didn't know, I'm not surprised, Behcet's being a microvascular disease, I didn't know that there would be much in the way of nail fold changes. I kind of equate nail fold changes in those patients who have sort of periungual hyperemia and desquamation, the sort of ratty changes you see in patients with lupus and dermatomyositis.

But this is a study of sixty five patients with Behcet's syndrome who underwent nail fold video capillaroscopy by a group that knows what they're doing. And they found that depending on how they measured it, that about forty five percent of patients had vascular abnormalities on on nail fold studies. They found a lot of the same things that you would find in dermatomyositis and lupus, enlarged, tortuous, giant, blood vessels, microhemorrhages. They had, like, five or six different abnormalities, none of which sounded truly specific but, sounded like what we do see in other disorders, other autoimmune disorders. And they said that if you had two or more of these neuro I'm sorry, these now full video caproscopy abnormalities, you had a significantly increased risk of a vascular event.

And there were really only two, either venous thromboembolic events or superficial thrombophlebitis. There was no association with nail fold changes and either Raynaud's or ANA positivity or other features of Vichette's. So good to know who might be at risk for those, you know, those dangerous things, VTE, and whatnot, but maybe I'll start doing this. It's again, it's not something I I have been doing, previously. Saw an interesting study this week about, the relapse rates in patients with idiopathic inflammatory myositis.

Study, a single center study, one hundred and five patients saw that sixty two percent had a evidence of relapse over time. And, the question is what was predictive? ANA positivity was somewhat predictive, but not as strong as a positive muscle biopsy with histologic findings compatible with, dermatomyositis. And protective was the use of immunosuppressive before the relapse. Well, you know, if it's protective, you didn't get a relapse, but again, it seemed to reduce the rate by fifty percent.

And again, a positive biopsy increased the odds of relapse by sixty nine percent. These are, I think, worth noting. Another vasculitis study, came out this week, which I don't know if you would have guessed the results, but let me ask you, patients with giant cell arteritis, we all use high dose corticosteroids. Have you ever used pulse steroids? Have you ever attempted to use pulse steroids?

What do you think would be the difference between high dose oral and pulse IV methylprednisolone, a gram times three days or whatever the regimen you like? Again, this is a study of 419 patients, a retrospective analysis, which in itself therefore has an inherent bias. Like, why were they doing pulse steroids and whatnot? And the question is, was one superior or they non inferior? Of the patients that they did do, that were in this study, over ninety five percent of them had visual symptoms at the onset.

A quarter of them were treated, twenty six percent with IV methylprednisolone, and it was not superior to oral high dose corticosteroids with regard to either survival or what subsequently happened to their visual acuity. So again, no good reason to use it. Wait, there's more. Those who got treated with IV pulse steroids had more diabetes, more diabetes one year after the diagnosis of GCA. So that's the reason I've never used it, and I don't think I would use it based on this report.

Again, I'm looking for a good reason to do things. I like the data, on preclinical RA, clinically suspect arthralgias at risk RA, I started talking about this, a few years ago with the Prairie study. And you may remember the Prairie study. I'm gonna talk about it again because now we have a two year follow-up to that study. The PRAIRI study was a single cohort open label treatment with one gram of rituximab given to, or placebo to patients who, had clinically suspect arthralgia.

So and it was seventy eight patients. So half got rituximab, just one thousand IV, one time infusion, and then they followed them. Again, at one year, it was somewhat beneficial. The real benefit was for about, you know, twelve months where the lines separated as to who's going to get our RA or not. A lot of people thought this was maybe a delay in RA onset.

Some people said it was a negative trial, arguable, but then again, it was suboptimal treatment with rituximab. Well, the question is what happened to those people two years later? And two years later, there's no difference between the groups and there certainly is, it was no benefit either as far as the development of RA or as far as quality of life measures, patient reported outcomes. So, the PRAIRE study inhibiting B cells in at risk individuals, there's not a lot of movement for that. And even though I think there was some partial benefit here, I don't know if this is ever gonna be repeated again.

But it adds to our body of knowledge that on the many things that don't seem to work or don't seem to have a sustained effect in treating patients who may be at risk. There was a report this week which got a lot of press. I don't know that I'm wild about it. It basically said that when you looked at patients, this was a retrospective study in patients in Sweden, and they looked at patients who were started on JAK inhibitors versus those on TNF inhibitors. And the bottom line is while the patients did equally well, maybe there was an edge in pain relief in patients who were treated with JAKs, but it's a modest benefit.

And when it comes to that residual pain kind of stuff that happens when you control disease, achieve an ACR20 or you achieve a DAS remission, the patient's doing very well, but yet they still have pain. The question is, is inflammatory activity, noninflammatory activity? Is it health defined, difficult to treat RA? Again, these are things we've discussed in podcast past. So I don't think that's a major addition to our knowledge base on this, but it did get a lot of press this past week.

An outcome study looked at, what happens in, lupus in pregnancy and adverse pregnancy outcomes. This is a large meta analysis, adverse pregnancy outcomes, and they the bottom line on this was it tended to be higher in patients who had nephritis, chronic hypertension, lupus activity before and at conception, and patients with the antiphospholipid syndrome. These are the high risk patients when it comes to pregnancy. I don't think there's any surprise there, but there's big data, big numbers of meta analysis that support this. I like this other study that came out of, I wanna say this out of China.

This was a biomarker study in lupus patients who are receiving, low dose, IL-two treatment. And again, the preliminary reports on that was that it was effective. The real question in this is maybe, since they were doing a lot of clinical assessments and also a lot of biologic assessments trying to look for maybe a biomarker, They wanted to see in the sub study of three forty two patients who received low dose IL-two or placebo. They found in that study, forty percent of the patients that received the IL-two treatment were responders. The biomarker sub study showed predictors of responders were, an SRI-four response was predicted by rash, lupus rash, proteinuria, urinary RBCs, and urinary casts, and the percentage change in c d four positive T cells and c three levels.

When you combine those into some kind of combined score, you could have predicted an SRI four response with an AUC of ninety three percent. That's really quite good. What they did show in this study is that renal markers did not correlate with clinical response as measured by any measure, including, the LL DAS measure. So it is possible. Again, this is the big issue with me and biologic therapy.

We got lots of biologic therapies, they're all unique in what they do and how they work and whatnot and whatnot. But, honestly, why would I use it over anything new if I'm not gonna be able to predict the response? So my word to manufacturers is give me a biomarker that gives me more than the expected response, than a $50.50 coin flip, or if it's an ACR, if it's an RA study, a sixty forty twenty ACR twentyfiftyseventy response. You have to do better than that. And again, having a biomarker, I mean, it's highly targeted biologic therapies.

We have to get there. That's really the future. An interesting study from New York and Virginia Pasquale's group looking at, mitochondrial DNA. Mitochondrial DNA has been promulgated as a player in the pathogenesis of lupus. In her studies, what they did was they looked at, opsonized RBCs that contained, mitochondria and was taken up by macrophages.

And they showed that those macrophages were then potent at producing, interferon, and the interferon gamma and alpha, I believe, was actually then important in activating the inflammasome to produce more IL-one beta. So, again, a lot of mechanisms where alpha interferon obviously takes over and stimulates, many, many different cell types to promote lupus activity. In this study, it's also gamma interferon, coming from macrophages that were stimulated by mitochondrial DNA. And that's sort of connecting the loop there. I think an important advance in our understanding of the pathogenesis of lupus.

Looking for information about biosimilars this week, I saw a report on The US health care expenditures grew from $4,100,000,000,000 in 2020. Two years later, it's up $4,500,000,000,000. That's a 17% increase in just two years. Yeah. We're out of control in our spending, but they did say that, in The United States, we did see over $400,000,000,000 in 2022 by the use of generic drugs and biosimilar drugs.

You can imagine biosimilars are making up a big chunk of that being that they're a lot more expensive than most of the gen the generics that are out there. So I I like that data. There is more use of biosimilars that will save the economy here and in really all countries where it's being used. Another interesting piece on biosimilars came from a study about persistence and adherence to drugs in patients with psoriatic arthritis. The point being on the six hundred and eighty five PSA patient, they looked at six hundred and eighty five patients were started on either a biologic or targeted synthetic between, 2018, 2019.

They showed that persistence wasn't good. It was only forty nine percent in a year. In a year, we said that that PSA patients for some reason don't stay on drugs, And that's really kind of disheartening and why there's a lot of cycling early on when these patients were sick enough to get either a JAK inhibitor or a biologic, they offer on are on many within a five year period. Interestingly, they did show that when patients were started on adalimumab, persistence rates and adherence rates were the same, whether it was the originator, adalimumab or the biosimilar of adalimumab. And in the case of etanercept, let me get this right, the, originator had actually lower adherence than did the biosimilar, which had higher adherence.

Data in favor of the use of biosimilars is what I'm getting around to. Scleroderma, we worry about, systemic sclerosis and its overlap with other conditions is also worrisome. A study of a hundred and forty one patients with overlap associated with scleroderma found the most common autoantibodies that were seen were row 52 antibodies, and then that you would expect anticentromere and anti SCL seventies. SCL 70 in the subgroup was associated with more ILD and more renal crisis. Centromeric antibodies was protective against the development of ILD.

And then lastly, as you might expect, having either renal crisis or pulmonary hypertension, which was pulmonary hypertension not being associated here with anything. But renal crisis and pulmonary hypertension was associated with increased mortality in these patients. I saw a patient this week with a ganglion, looked up a lot of things about it. How do they respond? What happens and whatnot?

Again, ganglion cysts, tend to occur over the extensor surfaces of joints. They'll ICM over wrists, more commonly than any other place. They are thin walled. They contain a mucinous viscous, it's almost gel like substance. Again, they're found, adjacent to joint capsules, but they do not communicate with joint capsules.

They tend to arise with repetitive strain or overuse syndromes, trauma, or in the setting of inflammatory arthritis. While you can aspirate them and that may work, studies have shown that actually peri cyst inject injections with corticosteroids don't change the outcomes. I've injected a few of these. I'm not sure I can convince myself that I did a lot of good, although I do have a magical needle and magical skills in this regard because I am a rheumatologist. But nonetheless, the data doesn't look so good for steroid injection of, ganglion cysts.

I did put up put up this week, a full read, review of ILD and autoimmune disease, and the point that's taken from this, it was in the American Journal of Managed Care. I like the the data that was presented, but I like that, these people, that you think who are with autoimmune disease, who are at risk for ILD or have any signs of it that your imaging should be high res CT, and that is also how they may need to be monitored. If they do develop ILD, monitoring is largely done with PFTs, and this paper did strongly recommend a multidisciplinary approach, that would include the use of immunosuppressants and antifibrotics. I think we're good at, one, we may not be good at antifibrotics, and we may not be good at co managing these with pulmonary. I think it's probably something we should be considering.

Some PSA and spondy kind of data, I learned from Georg Chet about 10 ago about, his work showing that people who do manual labor jobs have a higher risk of developing PSA. A cohort study from this week, five sixty four patients that blue collar workers were much more likely to be, in evidence at baseline compared to white collar workers, eighty four percent versus twenty percent twenty eight percent, suggesting again that blue collar and manual labor may be a risk factor for developing disease. However, occupation, blue collar versus white collar, had no influence on disease activity as measured by dash 28 CRP and as measured, a year later. So I think that's important to note, meaning that if they are a blue collar worker and they have PSA, should they stop their job? I don't think there's a lot of great data to suggest that.

That's certainly not suggested by this mostly retrospective analysis. A Turkish, retrospective analysis of only 30 patients with either PSA or SPA looked at what happens if they went on secukinumab, but they had a prior exposure, a prior malignancy, and then they were exposed to secukinumab. So this is a cohort study of patients collected between over six year period. They followed them for almost three years. Retention rate on secukinumab was high, ninety percent at twelve months, eighty one percent at twenty four months.

Only one of the thirty eight patients had a local tumor recurrence, and that was a bladder cancer recurrence. The feeling being in this small cohort analysis that it is going to be safe to use a biologic with a prior malignancy. And wanna reiterate, again, ACR guidelines on on RA, which has studied this much better, says that if you have a solid tumor like bladder cancer, it shouldn't influence whether you take a biologic or not. Here's someone I would say the same holds true, in my thinking for the spondyloarthropathies. Lastly, study of pregnancy in, almost four hundred patients with ankylosing spondylitis.

I think the patients were started in the study at and 2,000 and they studied up until 2015, like almost ten years. At the, pregnancy rate, in the beginning of the study was three point eight per one hundred thousand. It rose significantly to eight cases per a hundred thousand by after this ten year period. And that's after, a lot of these biologics are being, have been approved. So the question is, are we and again, they didn't really talk much about biologics.

That wasn't the point. I just wonder if these patients are better controlled because of the biologic era that maybe they're more apt to get pregnant. Anyway, they found that pregnancy was, a little more likely if the patient was older, white had higher incomes. They compared AS patients who are pregnant to like, I don't know, nine million people who didn't have AS, I'm not sure I like that comparison. It should have been a little bit better, matched, if you will.

Nonetheless, the AS patients had more pregnancies, C sections, more gestational diabetes, and then they had a few more of the rare events, placenta previa, neonatal, small for gestational age, intrauterine fatalities. There was no difference when it came to eclampsia, preeclampsia, nor malformations. And, I wanna reinforce that these other events like the fatalities and whatnot, there are very few events, but it was higher in percentage wise in the AS patients than those who did not have AS. So in our last, bit here, I want you to listen to, doctor Shams who's got a a case of Still's disease and elevated LFTs. Doctor.

Shams.

Hello, I am Doctor. Shams, rheumatologist from Lahore, Pakistan. I want to ask about a patient of adult onset Still's disease who has deranged LFTs at presentation. We have started this patient on steroids and I want to know about recommendation or guidance regarding start of methotrexate, atosolizumab in this case in which LFTs are deranged due to the active disease. How long should we wait for this patient to have normalized liver function test before starting methotrexate, atosolizumab, or we can start these medications while the LFTs are more than two to three times the upper limit of the normal.

Thank you.

Okay. Thank you, doctor Shams. So again, to reiterate, Still's disease, didn't say what age. Patient has elevated LFTs, didn't say how high. He did say at the end when the LFTs are two to three times the upper limit of normal, that would be, you know, 40 times three up to a 120 AST ALT, we're assume I'm assuming.

Again, the numbers, about two thirds of patients will have elevated LFTs with the diagnosis of Still's disease. That's true in both kids and adults. And that can complicate when they're elevated, you know, a little bit doesn't complicate therapy, but when they're a hundred, two hundred, 300, makes you nervous. Right? Are you gonna use a nonsteroidal?

Are you going to use prednisolone over prednisone thinking that prednisone is safer? And I don't do that, but a lot of people do. Are you gonna use methotrexate or other drugs including, as he mentioned, tocilizumab as the other drug he wanted to use, which may also have LFTs? For me, this is a simple story. Elevated LFTs do not prevent me from using any therapy in Still's disease, meaning I'll use methotrexate and steroids and tocilizumab and a JAK inhibitor if I need to, and, because you need to control swiftly, right away, in high doses, control inflammation as aggressively as possible, and you'll see those LFTs come down.

The best way, of course, is with high dose steroids, right? If you were and and but I would not worry about using high dose steroids or tocilizumab as he asked specifically on this. If you were 10 times elevated and you're seeing LFTs of two to 400, you may wanna wait a week or two, use the high dose steroids, go ahead and use the IL-one or IL-six inhibitor because very, very high dose very, very high levels of LFTs could be the earliest signs of macrophage activation syndrome, in which case high dose steroids and an IL-one or IL-six inhibitor would be indicated and you would hold off on methotrexate. So again, really high, you know, more than several 100 going closer to, you know, again, three hundred, four hundred thousand, I worry about macrophage activation syndrome. But again, I would not hold off very long because you got to control the inflammation and it is generalized inflammation that's driving those LFTs and this, inflammatory noninfectious hepatitis that is part and parcel of the Still's disease presentation.

Hope you found this useful. Make sure you check out roomnow.live. That's the website where you can register for RheumNow live, February eighth and ninth in Dallas, Texas. We already got, I don't know, sixty, seventy people registered. You can do it from home online or you can come to Dallas.

We're gonna have a really good time. I'm gonna drop a hint on you. We're gonna have a great reception on Saturday night followed by the gong show and karaoke. Yeah. You gotta see it to believe it.

See you in Dallas.