Ro, Ro, Ro52 (9.12.2025) Save

It's 09/12/2025, and welcome to the RheumNow podcast. Hi. I'm Jack Cush, executive editor of rheumnow.com. This week on the podcast, diet. Wait.

Vegan diet. Should you recommend it? What about menopause? I'm gonna tell you about menopause having an influence on connective tissue disease in a way that you probably hadn't thought of. And lastly, row 52 makes a big appearance this week on RheumNow.

First, let's begin with diet and its effects on rheumatoid arthritis. You know, the research hasn't been very good. I don't know really I don't really have anything good to say about, you know, a clear cut dietary benefit to RA other than an anti inflammatory diet, a Mediterranean diet may have some benefit, but that's not been, I think, well established in my mind. You know, losing weight obviously is good for any arthritis. A meta analysis of seven studies looked at the effects of a vegan diet in RA patients.

These studies were done between '79 and 2023, and overall showed no improvement in disease activity, no improvement in physical function, but did have a small but significant effect on pain. When they looked at other factors, other outcomes like fatigue, there was insufficient data. The bad news is that even though it's a meta analysis, there's low certainty to the evidence that's been provided. So still not enough, information or evidence that you can be positive about diet, although you should talk positively about diet. It's the one thing that patients can do to control their conditions.

Sleep apnea is something I think we in rheumatology, sleep disorders in general, I think we in rheumatology pay no attention to, and we should. I think it's a gigantic influence on the way our patients feel. If you have anything wrong with you and you sleep badly, it's gonna make whatever's wrong with you a whole lot worse. Sleep apnea is a big contributor. It's expected to rise from its current rate of thirty four percent in 2020 to forty six percent by 2050.

By 2050, it'll affect seventy six million Americans with sleep apnea. By 2050, there's going to be overall more males with sleep apnea than females, but the rate of growth between 2020 and 2050 is going to be higher in females. So forty six million by 2050 will be males, and thirty million will be females. So again, pay attention to the women, pay attention to sleep, ask about sleep, coach on sleep. I don't know why more rheumatologists aren't doing at home sleep studies from their office.

Making this a part of your business plan. It's something you can do, something you can identify. They can get an at home study, it can be a big part of your income, and you can have positive referrals to people who can actually manage this problem. That's just my advice. Methotrexate was again in the news this week.

We've had a few weeks in a row of methotrexate in the news. We love methotrexate. Methotrexate in an Australian study was shown to significantly lower systolic blood pressures, not diastolic blood pressures, thereby suggesting maybe yet another mechanism where methotrexate may lower cardiovascular risk. Good news always on methotrexate. Hydroxychloroquine and retinopathy, always good news until someone wants to rain on our parade.

A recent international multi center study of four zero nine patients who, had hydroxychloroquine retinopathy looked at the ability of artificial intelligence to make a diagnosis. So from four zero nine, one hundred and seventy one had evidence of of retinopathy due to hydroxychloroquine. All these people were tested by OCT scanning. When they applied, you know, the the machine learning, they were able to predict retinopathy in one hundred percent of cases when they were diagnosed, and ninety eight percent before they were diagnosed. And they did so a mean of two twenty one days before the diagnosis.

This is yet another example when AI comes into play on your EMRs and is put into action with the right algorithms, this is going to be incredibly useful in identifying patients at risk for multiple things, in this case, people on hydroxychloroquine and their risk of future retinopathy. It's coming to a clinic near you. A cross sectional study of three twenty dermatomyositis patients, this is an analysis I think from JAMA Dermatology, A hundred and ninety eight or almost two hundred of these people had classic dermatomyositis, and a hundred and twenty two had CADM, clinically amyopathic dermatomyositis. Those, you know, that's CADM has often been associated with the MDA-five antibody, right? But also other autoantibody profiles.

So in this three twenty, they collected data on a large cohort of patients, they looked for patients who had serologic testing with panels, and in the many panels that they saw, up to 16 panels, you know, patients were usually screened with on average one to two panels looking for myositis. And when they compared the outcomes, looking at serologies, either ANA, myositis specific antibodies, that's usually the antisynthetase and others, and myositis associated antibodies, that's MDA five and NXP two, etcetera, they showed that ANA positivity was different between classic dermatomyositis and CADM. ANA was positive in sixty three percent of classic patients and less than half, forty nine percent, with the amyop amyopathic brand of myositis, dermatomyositis. The other ones, the MSAs, the MAA's, were not really differentiating between those with classic dermatomyositis and CADM. So MSAs were positive in forty seven and forty percent between the two, and that was not significant.

MAA's, twenty nine percent and twenty six percent, that would mean classic dermatomyositis and CADM, not significant. And when you looked at double negatives for MSA and MAA, found in forty percent and forty eight percent, not significant. So here, you're looking at the relative efficiency of serologic testing found in fifty to sixty percent of patients you'll find in ANA. If you're looking at MSA antibodies, about forty plus percent. If you're looking at myositis associated antibodies, less than thirty percent.

And nearly half the patients are going to be double negative for MSA and MAA. Again, I do both these panels now. One point I didn't do them because I don't know if they had enough predictive value or prognostic value, and I've been convinced that they do. I've been convinced that I may look at them differently, and I'm especially swayed by, again, TIF-one gamma, MDA-five, NXP-two, the myocytes associated antibodies as being important in having discussions with the patients, cancer, explaining calcinosis and other things that we've talked about here. An interesting study this week comes from Italy.

It's the Spring SIR Registry looking at systemic sclerosis patients, the spring SIR registry. In this study, they had, I think over two thousand patients overall. They looked at the patients that were in menopause at the time of analysis, that was seventy five percent of patients. When they looked at overall their patients, fifty percent had the onset of systemic sclerosis in the premenopausal period, one year before menopause. Fourteen point four percent had the onset of systemic sclerosis.

Well, I guess it would be the rest would be fourteen percent had early menopause, onset of menopause was before age 45, and then they went to get on systemic sclerosis. What does what does menopause mean here? The postmenopausal onset sclerodermas had more crest, more centromeric positive centromeric antibody positivity, more ILD, and more GI symptoms. Okay, what about those who had premenopausal onset of systemic sclerosis? They had more diffuse disease and more peripheral vasculopathy, which I really wouldn't think of as being a, you know, are they talking about digital ulcers there?

Well, the ones who had the early onset of menopause, they were at higher risk for digital ulcers. So it turns out that menopause probably plays some role in manifestations and disease expression in systemic sclerosis. Can we say the same for other autoimmune diseases? Certainly we could for lupus, but what about RA? We often talk about older onset RA after age 60, not after menopause, which would be like after 50 for most people.

Interesting, distinction here or separation and clinical characterization. A study of treatment in Takayasu's comes along and I think is instructive. This is one hundred and eleven patients with Takayasu's arteritis who were either treated with mycophenolate seventy four patients, sorry, mycophenolate plus methotrexate seventy four patients, versus treatment with cyclophosphamide and azathioprine thirty seven patients. Response rates at six months and one year were roughly fifty eight and fifty five percent in the methotrexate mycophenolate treated patients. This was superior to cyclophosphamide and azathioprine, which at both time time points had about a thirty two percent response.

So you're getting, you know, thirty two percent versus greater than fifty five percent using drugs that you're more familiar with and maybe happier to use, methotrexate and mycophenolate. This is the first study to show this, and maybe it would be helpful to have another larger cohort confirm these results. But I like these kind of data. We have a lot, as you know, this this month we have a campaign on interstitial lung disease. We had a very successful Tuesday night rheumatology that you should look at.

We have a video and a podcast on that. Now I got a number of reports on ILD. A nine year study of row fifty two and its association with ILD looked at a thousand plus patients, fifteen percent of whom were row fifty two positive. When you looked at what kind of disease were you seeing in these thousand patients, interstitial pneumonia with autoimmune features for about half, CTD related ILD thirteen percent, idiopathic pulmonary fibrosis ten percent, hypersensitivity pneumonitis six percent, and idiopathic ILD twenty four percent. In this study, antibodies against row 52 and being row 52 positive was associated with younger disease and younger onset, more autoimmune disease, the presence of myositis specific antibodies, greater ILD progression, higher rates of death, higher rates of lung transplant.

Row 52 is a bad player in the ILD world, and I'm sure many of you knew that, but some of you may not have known that. That's important. If you're looking at autoantibodies that you should be looking at in patients who have ILD, this is one that you probably wanna play with and look at. I'll show you more on this in another abstract coming up. I like the a review article on biomarkers in ILD.

I think it's a good read from that article. I gave you a few quick one liners in tweets. Thirty percent of patients who have systemic sclerosis and ILD won't progress. Won't progress. That's important.

You know, there are factors that we've identified that are helpful in identifying those who will progress, but not all of them are going to progress. Patients who are triple negative are not going to progress. That is ninety plus percent will not progress. Triple negatives is what? Anti centromeric antibody, anti RNA polymerase III antibody, and anti topoisomerase antibody.

If you're triple negative, you've low risk of lung progression. Males and diffuse disease having diffuse disease were more predictive predictive than these antibodies. So I think this is an important article telling you maybe what you should and should not be worried about. Another study of systemic sclerosis patients looked at pulmonary arterial hypertension. That was found in almost thirteen percent of patients, seventy seven out of six zero seven.

And in the study, being on immunosuppressants didn't change the odds of getting PAH overall, and including when it was given early. But one drug did stand out, and that was the early use of mycophenolate, which substantially and significantly lowered the risk of future pulmonary artery hypertension by seventy eight percent, eighty eight percent, and that was significant p less than point o five. I don't know what this means, but hydroxychloroquine significantly improves survival. MDA five, we antibody we've talked about, it's associated with rapidly progressive lung disease, a higher risk of mortality, strange skin disease, and clinically amyopathic dermatomyositis. This particular study looked at twenty six MDA five positive DM patients, average age 56.

They had Gottron's papules eighty one percent, ILD seventy three percent, periungal erythema sixty nine percent, heliotropic rash sixty one percent, V neck shawl like rash forty two percent, arthritis and weakness about forty percent, mechanics hands thirty five percent, and Raynaud's nineteen percent. Seven of the patients with rapidly progressive seven of the nineteen patients with rapidly progressive ILD died. So again, twenty six percent twenty six patients here. The ones that had ILD was seventy three percent. The ones who had rapidly progressive ILD was a little less than half, seven out of nineteen.

Okay? But I'm sorry. Nineteen out of twenty six, but seven of those died. This is a bad news marker, is it not? So in the big news, I think, this week were two important articles.

One was the publication of the EULAR, European Respiratory Society, ERS, guidelines for CTD related interstitial lung disease. That was published in two, in ARD, and another pulmonary journal at the same time, last Friday. We wrote about them this week. They came up with 50 disease specific recommendations, and you might wanna look at that report on RheumNow. It's a little fast to read.

These articles are pretty long. Again, they have lots and lots of PICO questions, lots and lots of answers and recommendations that stem from that. The big high points for me, that are departure maybe from the ACR guidelines, is that all patients should be screened, with a few caveats. So all patients with systemic sclerosis, MCTD, and maybe, myositis should be screened with high res CT. You don't screen patients with inclusion body myositis.

We're talking about idiopathic inflammatory myositis. A little different for RA and Sjogren's, that you should only screen them if they have high risk factors for ILD. What are the high risk factors for ILD? That's a good question. Being older, tobacco history, rheumatoid factor, CCP, high sed rate and CRP, being male and having high disease activity.

Anyone or combination of those major is a risk factor for an RA patient, and maybe a Sjogren's patient to progress. They had another recommendation for risk and that was in patients with, idiopathic inflammatory myositis. The risk factors for them to progress was gonna be having the antisynthetase syndrome, having CADM, clinically amyopathic dermatomyositis, mechanics hands arthritis, and having the antisynthetase antibodies MDA five, or as we said earlier, row 52 antibodies. These are people you should worry about, you should definitely be screening for, and being aggressive when you identify it. Not in this guideline, but, you know, we've talked about it before, many of these connective tissue disease related ILDs are deadly, and we're looking to halt the process, level out their FVC decline.

But you know patients with myositis have a potential to turn around. Being aggressive with them might actually lead to an expectation of improvement. So keep that in mind when seeing these patients. They suggested that, basically everybody get mycophenolate here, and then in patients with scleroderma associated ILD, the drugs are mycophenolate, tocilizumab is a unique standout here, rituximab another unique standout, and then also cyclophosphamide as an option. They say that patients with ILD related to myositis RA, Sjogren's MCTD, and lupus shall all be on immunosuppressants, and that includes mycophenolate, azathioprine, etcetera, if only to treat the underlying disease, but may even have a benefit in control of, ILD associated, and that's usually in combination with other drugs.

They made a case for Nintedna being used in any situation of progressive pulmonary fibrosis and in scleroderma ILD or any CTD ILDs that have a lot of fibrosis. They make a case for Perfanidone, a drug we're not usually familiar with, in patients with RA ILD and a UIP pattern. Difficult patients get combination therapies. So look at those guidelines. I think you'll find them instructive.

One last report, and that is the SMART study. We talked about that at last year's ACR meeting. This was a unique study coming from India. It was an investigator initiated study from six centers in India, an open label single blind study of new onset active RA with, more than four tender, more than two swollen joints, disease duration of a little more than two years, two fifty three patients randomized to receive first time methotrexate either as a single weekly dose of oral methotrexate or a split dose of oral methotrexate. Everyone started out on 15, everybody quickly escalated to 25, split dose was given as fifteen milligrams, and then twelve hours later, or the next day, as ten milligrams.

Everybody's on folic acid, and they're looking to see if there's a difference. The primary endpoint was at week twenty four, which was a big mistake, because at week twenty four there was no difference between those two groups, and I would have been shocked by that, but if you look closer, you'll see at week sixteen, people who had not yet responded could be, could have their therapy augmented by adding a second DMARD, leflunomide, sulfasalazine, etcetera. So if you made week sixteen the primary endpoint, oh boy, yes, there was a big significant difference. Split dose did much better than single dose. Much better than single dose, highly significant.

And also, patients on split dose were less likely to receive a secondary DMARD at week sixteen for non response. It is also the split dose group that had numerically higher, not significantly higher, but numerically higher, more cases of transaminitis or GI intolerance. And you would expect that because by using split dose oral, you're doing the same thing as if you gave parenteral I'm sub q methotrexate. You're making it much more 90% or more bioavailable, and you know at doses above fifteen, fifteen milligrams and above, bioavailability of methotrexate is highly variable. But you can obviate all that by once you get to fifteen or higher doses, go to split dose.

And this is what I've been doing for years. Mike Weinblatt pointed this out to me over ten years ago, and this is the standard of care that everyone should be doing on anyone over the dose of fifteen milligrams that's using oral methotrexate. Fifteen milligrams, it's now three pills bid on Thursday once a week, or three pills Thursday night and three pills Friday morning. Again, everybody needs to be on background folic acid. Really good study.

These authors should be commended. They they got a lot of buzz at ACR for their hard work, and, and they certainly deserved it. Again, this week, this month is Room to Breathe, our campaign on interstitial lung disease, especially as pertains our autoimmune diseases, the connective tissue diseases that can result in ILD, scleroderma, RA, lupus, MCTD, myositis, Sjogren's, there are more, but those make up the bulk of them. A lot of great things already this week. Next week we're going to have a Tuesday night rheumatology.

We had tremendous number of people looking at our first Tuesday night rheumatology this past week, where we talked about therapy, future therapy for CTD related ILD next week. It's Controversies in ILD Care, and the panel is going to be, led by Doctor Jeff Sparks, Janet Pope, and Elena Yorns from Mayo. It's gonna be a lively group and a great discussion. Be there on Tuesday night. Take care.

We'll talk next week.