Happy Diwali (11.1.2024) Save

It's 11/11/2024. This is the RheumNow podcast. Hi. I'm doctor Jack Cush, executive editor of rheumnow.com. A lot to cover this week.

We're gonna talk about holidays, hand surgery, and diabetes drugs for arthritis patients. I saw a report this week on one of my favorite subjects and that is after you fail the TNF inhibitor, do you keep going or do you switch? Do you change within the class or do you swap classes to another MOA? We've talked about that before. I'm a big believer of one and done with TNF inhibitors with, RA and another report surfaced this week about the same practice in psoriatic arthritis patients.

And, yes, it turns out that it is better to, instead of cycle to swap to another MOA, to get better responses. And in this case, it was so going to another TNF inhibitor that you would switch to an IL seventeen inhibitor, and that seems to work. Again, my rule of thumb is if you were number one, a primary nonresponder, you should definitely be changing to your MOA drugs. Right? But that if you failed secondarily, I mean, they respond initially and then they lost response, or maybe if you've had a toxicity, you could stay within the class.

But again, the safer move, the no brainer move is to change because you've got lots of choices, whether it's, in the world of psoriatic arthritis or rheumatoid arthritis or spondylitis, etcetera. A few years ago, I was invited to be an advisor to the company that was making the collagenase injections for Dupuytren's contracture. And their hope was, well, rheumatologists see Dupuytren's contracture, they can do this procedure just as well as the hand surgeons. Well, this became the topic of a New England Journal report this past week where they specifically looked at surgery versus collagenase injections. And this was a study of, almost 600 patients, randomized to either the collagenase injection group.

And again, that you find the nodule, you inject the nodule directly, you're supposed to slam it with a Bible, which could make a bloody mess, and may have to repeat the procedure. So, in this study that, there was really no significant difference, this is a non inferiority trial, and it was, basically not significant, meaning that one treatment, collagenase injections, was not inferior to limited fasciectomy. Maybe the collagenase did a little bit better, but the collagenase also had more need for reintervention compared to the limited fasciectomy, fifteen percent versus three or four percent. So, again, what do you advise your patients? One, don't let a rheumatologist do this.

Two, send them to a hand surgeon who has experience with this. I tend to go with their expertise. Some are married to the surgery, some are willing to do the new technology, which is the less invasive collagenase injections. A recent study looked at predictors in patients with, MDA five autoantibody dermatomyositis. A study of one hundred and sixty eight patients found that the predictors of all cause mortality.

Now that's a bad subset of dermatomyositis patients, mainly because they get that rapidly progressive lung disease, which much more so than you see in many of the other variants, including the antisynthetase syndrome. So they found the predictors of six month, all cause mortality was number one, IL-six levels greater than 13 picograms, per ml, lymphopenia less than 500, being older and a high LDH. Sounds reasonable. I've been seeing some of these MDA five, dermatos, saw them actually twenty years ago, didn't know what to call them, didn't have the blood test, but, more recently have seen them and I do worry about this subset so much so that I am now in favor of doing myositis associated autoantibody testing, not just for the antisynthetase, j o one, etcetera, but also for this this recent set of m d a five and n x p two, etcetera. I think it's worth noting this kind of data.

The STAR study was a recent study that sought to look, to assess something I wouldn't have done, which is which is the better way of getting off a prednisone, which is something, of course, we're not very good at doing. And in this study, they looked at patients who are on, I think, five milligrams or more of prednisone, and they either did a prednisone taper or the alternative group were switched to hydro hydrocortisone twenty a day, and then they tapered that to like ten and five and then off. And they looked at the success of discontinuing the steroids and then how well tolerated it was. And it turns out that one was not better than other. I mean and I've never switched my patients to hydrocortisone with the hope of tapering them.

But at twelve months, discontinuing glucocorticoids was fifty five percent in the hydrocortisone group and forty seven percent in the prednisone tapering group, not significantly different. But then again, not all that is successful. Right? I mean, if you really wanna get off prednisone, you're gonna have to work at it. It's a lot of education.

And getting half the patients off of steroids meant to me means you failed. So this is something we have to struggle with. And my best advice is, two things. One, prednisone being prescribed to inflammatory arthritis comes with an expiration date. I'm only giving it to you for this number of weeks or months.

And that's to be clearly explained to the patient. You gotta live by that, promise. Second, you don't prescribe steroids unless you tell them you're gonna get fat, ugly, acne, stretch marks, you know, fractures, infection, bizarre infection, serious infections, heart attacks. You know, just basically lay it all on them and they're gonna be like, well, dude, why are giving me that medicine? And and then then now they're motivated to get off it.

Again, something I do. With some success, although it's not a 100%. Again, we have to work at this. A recent report looked at proteinuria associations with patients with proliferative, lupus nephritis, two forty nine patients. They had longstanding lupus and the average degree of proteinuria in this cohort was over two grams.

And what they showed was that the patients who had low levels of proteinuria were more likely to achieve steroid withdrawal, guess, or I'm sorry, or of renal recovery, not renal recovery. So that was achieved in seventy one percent of patients who had basically seventy nine percent of patients who had one gram or less. About 10 points lower in people with one to three grams and a lot lower in patients with greater than three grams who had the worst outcomes. So lower levels of proteinuria, again, more common, very common with proliferative disease, better prognosis, bottom line. The question that I often wonder about is what happens to patients who get referred for psoriatic arthritis.

They got a lot of experience, and a lot of data about patients with arthralgia, who may be considered as having future RA for whatever reasons, serology, family history, whatever. This is a study of, almost 1,400 patients who referred to rheumatologists. Of the fourteen hundred, they looked at patients who met criteria for inclusions, that was about ten percent. And then the ones who actually develop PSA, within one year, and that was only thirty five out of the fourteen hundred. The predictors of patients with psoriasis who were going to progress to psoriatic arthritis, and that is about a twenty to thirty percent progression rate, included those who had one, a family history of psoriasis, two, ultrasound synovitis or enthesopathy on ultrasound, and thirdly, lower tender joint counts.

So if you have really severe polyarticular problems, it could be a whole bunch of things including not, inflammatory psoriatic arthritis. I thought this was interesting. Another study, looked at the correlations between, the extent of skin disease, psoriatic arthritis psoriasis as measured by the psoriasis area severity index or the PASI score and the clinical variables of psoriatic arthritis. And what they found was that PASI score didn't correlate very well with usual PSA clinical variables and outcomes. I found that surprising.

But then again, this was only a seventy six patient study. They had well established psoriasis, almost two sixteen months, etcetera. Those who had PSA ultimately was half that amount in disease duration. But they found that the most significant correlation was between Posse and enthesitis. And I like that and I agree with that and I've seen that before.

But I gotta say this study doesn't say what the literature says. And that the more severe the cutaneous psoriasis involvement, the more likely you're gonna get psoriatic arthritis and the more severe it can be. I remember this because when I was a fellow, I had this argument with the chief of dermatology who made this assertion, and I found a paper or two that that argued against it. But ever since then, that was 1985 or '86, I've seen a whole bunch of studies that really confirm that the severity of psoriasis increases the risk and maybe also the severity of getting psoriatic arthritis. I do like this point that poxy does correlate with enthesitis, and enthesitis is a psoriatic arthritis severity marker, is it not?

The journal chest this week looked at airway disease in a cohort of one hundred and eighty eight RA patients who did not have interstitial lung disease baseline respiratory problems. And they found that when they looked for airway disease by a number of different measures, they got different kinds of measures. So by airway obstruction on PFTs, twenty one percent of RA patients were abnormal, more so in older males who were smokers. Chest x-ray abnormalities were more plentiful, sixty one percent, most of those being bronchial, thickening or bronchiectasis, fifty five and twelve percent. And that was more so in patients who were seropositive.

But that the thing that correlated best would ultimately with respiratory symptoms was quantitative CT scanning. So, and their point was that maybe, and this was a a pulmonary journal, right, the chest, probably talking to pulmonologists. But maybe the advice for rheumatologists is that maybe you should be a little quicker to do quantitative CT scans in patients who have, respiratory symptoms or who you suspect. Again, you might suspect that in patients who are seropositive or symptomatic. Yeah.

You should do PFTs and a chest X-ray. Look for other causes of their pulmonary problems including TB, etcetera, but maybe ordering more quantitative CTs because that might give you more prostate prognostic information. JIA, a nice report in arthritis and rheumatology this week about the twenty year changes in in DMARD use in juvenile idiopathic arthritis. And I think this parallels, the twenty year changes in RA as well. That basically in these last two decades, there's a rising use of the newer, biologic and targeted synthetics coupled with a decline in conventional, DMARDs.

Conventional DMARDs, methotrexate, hydroxychloroquine, sulfasalazine, ninety percent in 2001, but by 2022, this had dropped to forty three percent in this large cohort of JIA patients. That was very significant. In the same era, biologic DMARDs increased from ten percent to over fifty percent, very significant. Most common biologic being used that grew in this time period was from 2007, adalimumab grew from about seven percent to about twenty percent by 2022. Etanercept use declined significantly from twenty eight percent to four percent and I'm not sure really why that is.

Maybe because etanercept prescriptions were were maybe first to be used and now other drugs coming along the way, I believe that being second to, etanercept and then other biologics. And then in the same era when etanercept is dropping, you're seeing more use of ustekinumab, secukinumab, and abetacept that account for about seventeen percent of all new prescriptions by 2022. What happened with the JAK inhibitors and the only good data in here about tofacitinib that that went down, rose from two point nine percent at approval to five point two percent in 2021, but by 2022 that had dropped or also been cut in half and that's due to the safety warnings, etcetera. So, again, I think that the this is what you're using at least as counted by these authors in this study. I found an interesting study this week about myelitis and rheumatic disease.

I've seen good cases of myelitis in my practice over forty years, probably half dozen. In their study, forty one patients, most of them were women, the most common cause was lupus, forty one percent, Sjogren's, surprising to me, twenty four percent, undifferentiated disease fifteen, overlap disease twelve, and a few with, antiphospholipid syndrome. The interesting thing about this report was when they looked at those, half of them had antibodies to aquaporin-four, which is associated with the neuromyelitis optica spectrum, NMOSD, neuromyelitis optica spectrum disorder. And that some of them, also seven percent had this other myelin oligodendrocyte glycoprotein autoantibodies and that's the MOGAD, that's myelin oligodendrocyte glycoprotein associated disease. These are syndromes well known to the neurologists.

This article appeared in neurology, neuroimmunology and neuroinflammation, and they are trying to remind us that if you see myelitis, maybe you should be doing the aquaporin-four autoantibody test. When that's present, ninety percent of them had extensive spinal cord lesions. Or maybe you should do it the less common, but nonetheless found, myelin oligodendrocyte glycoprotein autoantibody. I've never done those, never considered those, now I will. Our last two reports have to do with rheumatic disease and diabetes, what happens when you use the diabetes drug.

The first is a report, about the use of the sodium glucose cotransporter two inhibitors or the SGL two inhibitors, in lupus patients. And this was claims data analysis where they compared two thousand plus lupus patients with type two diabetes who started on the SGLT two inhibitors and another two thousand who started on the dipeptidyl peptidase four inhibitors, DPP DPP four I drugs, and they compared outcomes. And so obviously, these drugs, these diabetes drugs were being used for secondary prevention of diabetes complications. And in this lupus cohort, that was in fact found, meaning, a fifty percent significant, fifty percent reduction in acute kidney injury, a forty percent reduction in chronic kidney disease, a sixty percent reduction in end stage renal disease, and a twenty eight percent reduction in heart failure, and a ten percent reduction in emergency room visits. What they did not find in this claims data analysis was a reduction in all cause mortality, MI, stroke, or hospitalizations, or lupus nephritis.

So the good news is lupus patients who need to go on a diabetes drug, the SGLT2 inhibitors are great options and fare better than the DPP4I drugs. I think that's important to note and I think that we'll see more of this research going forward. So much so you might see these drugs being used in patients who don't even have diabetes, right? Because all these outcomes, chronic kidney disease, acute end stage renal disease, heart failure, heart outcomes, etcetera, are as meaningful to lupus patients as they are to diabetics. This week, New England Journal had an interesting report about the Wegovy drug, semiglucide, the GLP-one inhibitor and its effects on knee OA pain.

So this appeared in yesterday's New England Journal article. It was a study of four hundred obese patients with diabetes who had, I believe it was severe OA of the knee or moderate to severe OA of the knee. These patients were 56 years at entry as far as age of BMI of 40. A mean Womack pain score on a zero to 100 scale of 70. Eighty percent of these patients were women.

The outcomes at like week sixty eight was a 13% reduction in body weight, 13.7% with Wegovy versus three percent with placebo, and that resulted in a reduction in Womack pain score of minus 42 points versus minus 27 points with placebo. That means that again, they started out with 71 points. They went from 71 out of a 100 in pain down to 30 out of a 100 in pain. And that was much better than the placebo. In an accompanying editorial, David Felsen from, Boston pointed out that we know this.

We know that substantial weight loss results in a dramatic reduction in pain. What we don't know is that these GLP one drugs, are they exerting an effect beyond what they do with weight control? Are there other anti inflammatory immunologic effects? And the only way you're gonna know that is by testing GLP-one receptor agonist, in patients who, aren't obese. And to see what it does as far as their pain even though they may have moderate to severe knee OA on x-ray.

That's the study I wanna see. Again, these drugs, whether it's the SGLT2 and the GLP-1s are gonna be big players in the field of rheumatology going forward. And I think we're gonna see a lot of combined therapies, with those drugs being used with our drugs and looking at combined outcomes, your arthritis outcomes, the weight outcomes, the hard endpoint outcomes. And that's really, I think the point I wanna make on this. One thing to talk about pain, it's one thing to talk about a reduction in C.

Dye or swollen joint count or death score, it's another thing to talk about the things that really matter, hospitalizations, death, the need for major surgery. Those are the hard outcomes that I wanna see with these really big important studies going forward because this is gonna dramatically increase the cost of care if we start using GLP-one drugs or even the SGLT2 drugs in our patients who are already getting expensive care, right? And the disease itself is expensive. But if the outcomes are dramatic, well then it makes sense, does it not? Let's consider that.

I wanna remind you, RheumNow Live twenty twenty five is coming up. We already have a 100 patient a 100 patients. A 100 of you who are registered for this, or that's about twenty percent of what's going to actually show up. Now's the time to register at roomnow.live. I wanna end by, saying happy Diwali to all of our Indian colleagues.

Diwali is the Hindu festival of lights. It's a five day celebration where there's a lot of festivities, fireworks, feasts, and prayer. And I know Diwali well because when I was chief resident in New York, my job as chief resident was to make sure everyone was happy. I had to make sure that the Orthodox Jews got their holidays. I had to make sure the Christians got their holiday.

I had to make sure that our Indian physicians got Diwali, and there were a few others thrown in there. I learned to like all these holidays because I felt it was another chance for me to ask for the day off as well. And when I didn't get it, I could at least rejoice in the happy smiles of those who returned from their Diwali holiday or from Rosh Hashanah or from Easter or whatever. Anyway, happy Diwali. We'll see you next week.