Dr. Quotes (11.8.2024) Save

It's 11/08/2024. This is the RheumNow podcast. Hi, I'm Doctor. Jack Cush, executive editor of roomnow.com. The early polling on this podcast said it wasn't going to be a good one.

I think they may be right. Let's get into it. The first two are basic science reports from journals I don't think many of us read often. The first one is from the journal Science, and it's an interesting article about changes in the synovium in patients who have either early RA or who are at risk for RA. And the findings were that, in samples taken of synovium in these rheumatoid or rheumatoid wannabe patients, that early signatures of the cells that were predominating there showed a myeloid signature with a lot of CD40 expressing CD206 and CD163 positive cells.

Those are macrophage cells. Macrophages are usually CD206, CD163. They're not usually CD40 positive. And that's sort of the interesting change here, is that in the people who were progressing, from at risk to developing disease, they had a heightened and new expression of CD40 in these macrophage clusters. And that could have been the earliest finding in the conversion from at risk disease to actual disease.

This is important. CD40 is involved in co stimulatory signaling, like CD28, CD86, what we attack when we use abatacep, except CD40 expression is important in RA, in lupus, it drives B cell responses, T cell responses, stromal tissue development. This finding, I think, is an important one, and could be attacked therapeutically. Interesting. Another interesting one comes from Thomas Donner and Peter Ellipsky in Nature Reviews of Rheumatology, where, for me, they sort of answered the question, and their review article is about memory B cells and how they function in lupus.

And basically they say that memory B cells in lupus are quite dysfunctional. On one hand, they're allergic to usual B cell receptor signaling, and on the other hand, they respond well to Toll like receptor signaling and gamma interferon type one interferon signaling. It is this hyporesponsiveness to the B cell receptor, in these memory B cells that might explain why previous attempts at non depleting B cell targeted therapies didn't work in lupus. Whereas the more recent therapies, including CTLA-four, I'm sorry, including CAR T cells, effective, and that they are depleting and whatnot. So, that's sort of, I think, another pathogenic insight that makes sense out of some of our observations in the past.

A study of patients, over one hundred and thirty five thousand patients treated with, antineoplastic drugs compared, what happened to those who received checkpoint inhibitors to those who did not. And those that were on checkpoint inhibitors had a twofold increased risk of psoriasis. Now we do know that psoriasis and psoriatic arthritis, inflammatory arthritis, PMR, a number of things can occur. But you know, in the grand scheme of the autoimmune phenomenon that occur with checkpoint inhibitor therapy, these immune related adverse events, you know, hypothesitis and GI things happen much more commonly. And down the list is actually our diseases, the rheumatologic diseases, and these autoimmune diseases.

Again, one of the ones that came to the top of our list was psoriasis, and I haven't seen those. I have seen psoriatic arthritis, and the question is how we treat them. That wasn't the point of this claims based analysis from Taiwan. Came across a report this week about Cusak syndrome. I've heard of Cusack syndrome, I've never seen Cusack syndrome.

And so that led me to say, what is that all about? I know it's kind of in the realm of rheumatology, because it is an autoimmune vasculitis. It's a small vessel vasculitis, with occlusive disease that preferentially affects the, the brain, the retina, and the inner ear. And that's the triad behind Sous Sax Syndrome. Often difficult to diagnose, difficult to treat.

But in this particular report in Lancet Rheumatology, they looked at a collection of studies, and to make some comment about treatment. And they said that first line therapy seems to work in most, and that is glucocorticoid therapy, starting out at high doses. But what they did show was that the use of immunosuppressive therapies on top of glucocorticoids did not seem to hold any additional advantage. I'm still waiting for my first Soussac syndrome, but now that I know this, I know that I'm gonna have to find other alternatives beyond steroids. EULAR this week published a, what I thought was a guideline paper, it wasn't, it was kind of a review of the literature on what the effect of lifestyle improvements are on rheumatoid arthritis outcome.

So they had a UR task force. They evaluated, lifestyle changes that could be dietary, nutritional, animal, vitamins, all kinds of things. And the bottom line in this was that the data was pretty underwhelming, especially when it came to, dietary manipulation and dietary components. Specifically, that there's very little high level evidence. There's moderate evidence of minor, significant effects from things, you know, omega-3s and glucosamine and chondroitin and even vitamin D.

But while they may be significant, they're not clinically meaningful, meaning really minor effects. You know, throwing another damp, wet towel over our enthusiasm to be aggressive with dietary management or supplement management in RA. Speaking of supplements, a UK study of almost 900 patients found that fifty five percent do take daily supplements to manage their disease at a cost of 10 to £200 a month. You're going to have to consult your financial pages to do the conversion on what that costs. But it's obviously a lot of money.

Most common were the use of vitamin D, C, B complex, multivitamins, omega-three and six. Eighty two percent were taking prescription medicines, over the counter medicines, for pain medicine, pain management. Thirteen percent were also on sleep aids. They noted that of all the patients who were taking NSAIDs, half of them were also taking over the counter supplement medications. So, again, there's a lot of use of these drugs, not a lot of evidence of their benefit, and often you're not aware of what they're taking.

So this is a question that you probably need to ask. A full readreview in JAMA covered ILD. It's written by a pulmonologist who tells us overall, ILD is a mixture of things. A third of the cases are what they call idiopathic pulmonary fibrosis. Fifteen percent are due to hypersensitivity pneumonitis, and twenty five percent of cases are from connective tissue diseases, the things that we see.

They noted that not everybody has a cough. Less than a third of patients will have a cough at presentation, and that the main diagnostic test is chest, CTs with a 91% sensitivity and about a seventy percent specificity. The thing to watch is the FVC. Even a five percent decrease in FVC over twelve months is associated with a doubling of the mortality rate. Think about that.

Only a five percent decrease in FVC, a doubling of the mortality rate. Oh my goodness, that's not good. Again, they throw in there that the treatment options are nintedinib and perfenidone, in addition to tocilizumab, mycophenolate, and rituximab. And, you know, I think we've all used tocilizumab, mycophenolate, rituximab. How many of you have used nintedinib or profanidone?

Not many of us rheumatologists. And the data is there. I mean, they're FDA approved drugs. They've been shown to flatten the curve on progression in these patients, and that's felt to be a win in these patients. I think we need more experience with these anti fibrotic therapies in patients with ILD.

A study of scleroderma patients, two eleven patients, showed that overall, both men and women, and younger women, have lower BMDs than the population. Fifty two percent of the patients had osteopenia, and sixteen percent had osteoporosis. That low BMD was associated, mainly in women with finger ulcers, diffuse skin involvement, older age, and of course, being postmenopausal. A study of readmissions in RA found that half the patients, were, and this is one hundred and thirty three thousand patients in the nation, a nationwide hospitalization database, half the patients were designated as frail, using a survey tool to measure frailty. And it turns out RA patients who are frail had significantly more, almost double the rate of readmissions, fifty seven percent versus thirty one percent.

Frailty patients also with RA also had higher mortality rates, almost four percent versus zero point four percent. That's right, a tenfold increase, albeit the rate is low. Frailty is a horrible thing, and one we should be paying attention to. There were two articles this week. Actually, I'll get around to these articles about back pain.

First, I want to say the ACIP, the Committee on Vaccination, came up with new recommendations to say that, everyone over the age of 50 should be receiving a pneumococcal conjugate vaccine, a PCV vaccine, whether that's PCV fifteen, PCV twenty, that's Prevnar twenty, or the new one, PCV twenty one, that came out in June 2024. These are indicated in adults 50, but they're also indicated in young people who have underlying conditions and who are predisposed. So again, they say if you're 19 to 64, and you have an underlying condition, you probably should be receiving the newly approved PCV-twenty one. That's a 21 conjugate, pneumococcal vaccine. A study from Nicola Dalbeth's group, looked at what happens when you give colchicine to, gout patients who are starting allopurinol or urate lowering therapy.

This is an RCT trial, a fairly well done six month RCT trial. And of course, you give colchicine to people starting allopurinol so that you can prevent the flare rates that will be induced by mobilizing uric acid with urate lowering therapy. And that has been shown to be effective. The question is: Does the combination of colchicine and allopurinol lower, or better control the disease, and they measured better control disease as the number of patients who achieve gout remission. Turns out that whether you receive gout, prophylaxis with colchicine, it did not lower the remission rates after a period of time.

So that I found to be a bit surprising. A cross sectional study of one hundred and seventy six, psoriatic arthritis patients meeting CASPAR criteria showed that, they could come up with a biomarker that would correlate well with disease activity, as measured by the CDAPSA score popularized by Joseph Smallin. The elements of this biomarker include serum serum amyloid A, IL-eight, CXCL-ten, that's a gamma interferon inducing IP-ten, it's a chemokine, M CSF, SGF beta, SDF1A. The area under the curve on this is over point eight, and that was superior to the comparator biomarker, which you all use, and that is CRP, had an area on the curve of 0.72. Almost a full 10% better, if you will.

Now, is that going to be available? Is that a research tool? People need to take these kind of research and, and extend them to real life practice, or at least repeat them, right? A study, by Anthony Chan and coworkers in The UK looked at their sixteen year experience, almost a thousand low back pain referrals. Amongst those patients, thirty seven percent were diagnosed with axial spondyloarthritis.

And what they noted in this time period, sixteen years, almost a thousand patients, almost three sixty six AS patients, that the increase, there was an increased number of women with a diagnosis of axSpA. They showed that the time to diagnosis decreased from nine point eight years in 2008 to one year. That's a significant drop of almost nine years by 2023. The greatest delay in their system, as the National Health Service, was from the onset of low back pain to GP referral, was still three point two years on average. What they said in this paper was that this was a systematic organizational change that had to go through many iterations over the sixteen year period to get to this degree of success.

So you have to work at this, if in fact you want to show earlier referrals and better outcomes in patients with axSpA. A three year study from Scandinavian Journal of Rheumatology looked at a cohort, 24 patients with early axSpA, who had symptoms of less than five years. So they did a time zero baseline assessment, by MRI of the SI joints and spine, and then they did it, repeated that at three years. And what they showed was, over a three year period, SI joints progressed, not surprising, showing the development of bone marrow edema, SI sclerosis, and SI erosions. In the LS spine, they showed that fat lesions decreased over time, while erosions tended to increase.

But I think the real important point of this study, one that I found surprising, was that the presence of facet joint inflammation at time point zero, at baseline, predicted future development of lumbosacral spine bony fusion and sclerosis. So that this was a forerunner to future bridging some desmophytes, if you will, in the lumbar spine. And I think that's a new, a new finding, and useful information. So, lastly, I got a few more, three more reports here. Eleven year study of over 2,000 RA patients, over 3,000 treatment courses with biologics, or JAKs, found that amongst the two thousand one hundred, about ten percent, two seventy five new cases of CKD in patients on biologics or JAK inhibitors with RA.

Turns out that if you use abatacept as their referent, TNF inhibitors had a lower rate of CKD, about a thirty three percent lower rate compared to abatacept. But again, compared to abatacep, JAK inhibitors had a doubling of the rate, it has a ratio of 2.16. Again, I tend to think of TNF inhibitors, abatacep, JAK inhibitors as generally not causing CKD, or renal dysfunction. So you have to wonder, one, is this something I should be looking at? Or two, does this eleven year study reflect how these drugs are being used?

Maybe you're using TNF inhibitors first early in the disease. Maybe you're using JAK inhibitors last or late in the disease, when there are maybe other cofactors involved. I guess the point is that the longer you follow your patients with RA, the more you should be paying attention to those creatinine and renal function indices. Two final reports, JAMA reported this past week about the value of virtual yoga instruction on chronic low back pain outcomes. This is a twenty four week randomized trial of chronic low back pain patients who were, one hundred and forty of them who were randomized to either an active program of virtual yoga being taught, I think it was like every two weeks.

They looked at week 24 and week, week 12 and week 24 outcomes, versus those that were on a wait list and not receiving yoga instruction. The yoga group had significant reductions in, mean pain intensity, and also in the use of analgesic therapy. Going into the study, these chronic low back pains had a baseline pain score of 5.7 out of 10. If you got yoga, your mean pain drop was 1.5 at twelve weeks, and 2.3. That's pretty good.

That's like a 15 to almost 40% drop with just yoga. They stayed on their background therapies. Again, we've talked before about mindfulness therapy, and other things that you're generally not doing in your patients with low back pain. Add yoga to the list, okay? Another report this week, this is from JAMA Dermatology, showed, that COVID-nineteen patients may be at higher risk for rheumatic disease and autoimmune disease.

You know, this has been bantied about ever since we had COVID. Does COVID cause exacerbation of rheumatic disease? I'm not sure that we've seen that. Does COVID or COVID vaccination cause these rheumatic conditions to arise? And we've kind of scratched on that a little bit with some positive and negative data.

And the reason we don't have a clear picture is because often the cohort sizes are small, and the follow-up is short. So how are we going to know? Well, this is a report from Korea, and six point nine million people in the study. I want to say that three point one million had, the Delta variant of COVID. These are unvaccinated individuals.

And they were compared to three point seven people, three point seven million people, controls, who did not have COVID, and also unvaccinated. And they looked at when you followed them for, oh my goodness, it was a long time. I want to say three to five years. That's certain there was a number of autoimmune diseases that were significantly increased, and I'll just rattle them off here. 11 increase in alopecia areata, twenty four percent in alopecia totalis, eleven percent for vitiligo, forty five percent increase, and these are significant increases for Behcet's, thirty five percent for Crohn's, fifteen percent for ulcerative colitis, nine percent for RA, fourteen percent for lupus, thirteen percent for Sjogren's, eleven percent for ankylosing spondylitis, and sixty two percent for bullous pemphigoid.

What they did show in patients who had more severe COVID, hospitalization, etc, that the rates were higher in many instances. In some instances, things that were not significant before, sarcoid and psoriasis, now became highly significant. So can COVID and I think I like the mechanism whereby the spike proteins stimulate the inflammasome, and you get a spike of innate immunity that then in maybe predisposed hosts, boom, is the start of an unwanted cascade. By the way, it's not unusual that we have an infection that leads to chronic autoimmune disease. Right?

That's part of our past, is it not? I want to remind you about RheumNow Live coming up in February eight and nine. Now's the time to register at roomnow.live. You're going to love the meeting. And I'll end with a famous quote from a famous doctor.

The quote is, Nothing is going to change unless someone does something soon. The famous doctor is a non rheumatologist, Doctor. Seuss. Have a good week. Tune in next week.

ACR coverage, it's going to be plentiful.