ILD Begins (8.29.2025) Save

It's 08/29/2025. This is the RheumNow podcast. Hi, I'm Doctor. Cush, executive editor of roomnow.com. This week on the podcast, vaccines are in the news again.

Good news, bad news. Antibiotics, they're probably okay in kids. Our safest drug may not be our safest drug at all, especially when you're pregnant. And we've got news on methotrexate. Maybe we're a little too, I don't know, fastidious, detail oriented when it comes to the lab tests.

Let's start with a discussion of cancer and rheumatoid arthritis. Colorectal cancer is a common cancer in society and certainly in the RA population. You know, the overall risk of cancer in RA is not elevated. The SIR is one. That's not really true because some cancers are up and some cancers are down.

The up ones are, you know, lung cancer, skin lymphoma. The ones that are down are colorectal cancer and maybe, head and neck and breasts and a few others. So here's a study from a large Korean insurance claim study looking at forty thousand RA patients, comparing them one to five with non RA controls, looking at the risk of cancer. And this data reaffirms the fact that cancer risk is lower, significantly lower in RA compared to the population and other non RA individuals. The interesting thing about this data, and of course the overall risk, by hazard ratio was zero point eight nine, eleven percent lower risk, and that was significant.

It was actually more significant if you consider if you consider seropositivity or not. It was lower, even less of an association with seronegative RA, but when you looked at seropositive association, seropositive RA, it was numerically lower but not significantly lower. So all that number comes from seronegative RA patients having a lower risk of colon cancer, and most of the colon cancer itself was from rectal cancer more so than colon cancer being found in other parts of the colon, and was also driven by women more so than men, each women having a 20 lower drop, rectal cancer having a thirty seven percent lower risk in RA patients. Interesting data gives us a little bit more granularity as to who's affected here and what types of cancer we're talking about. An article appeared in, I think it was ANR this recently and written about on Medscape.

This was a large cohort analysis from a major, US health care system looking at EMR data, patients with knee OA who were being seen for the first time. Over and the question is how often are they referred to physical therapy? Overall, twenty six percent were referred. But if you looked at, early referral, meaning when you see them, you should probably refer them. This speaks to attention to detail, conformance with guidelines by the ACR and Arthritis Foundation and Orthopedic Foundations.

Turns out physical therapy is under prescribed. And I put this up because it's quantitative evidence of what I know to be true that we don't in rheumatology use physical therapy as much as we should and certainly in patients with chronic knee pain. Again, this goes against all the guidelines that show it's clear cut utility. And and what was the number? The overall number was one in six people were getting referred, after the first visit.

That's about sixteen percent overall. The MUC5 mutation, we know to be associated with ILD specifically, RA associated ILD. Is it associated with ILD and other disorders? A study of two thousand three hundred systemic sclerosis patients with ILD, looked at those who with systemic sclerosis patients who had ILD and those who did not. And then they did the MUC5B promoter variant analyses.

This was a multinational done in throughout Europe and The United States. What was good about this is they had a very large number of patients. Overall, it was, three thousand five hundred scleroderma patients without, ILD, fifteen thousand non scleroderma controls, and two thousand three hundred scleroderma ILD. So again, strong numbers here. No association with, SSC, systemic sclerosis ILD.

Why is that important? Well, we know that the MUC5b, promoter variant that's linked to RA, we can put that into a story as to how they're getting and why they may be getting ILD. We can't use that same line of evidence certainly in systemic sclerosis. So maybe the mechanism by which connective tissue disease, systemic autoimmune disease, can get ILD may be different across the board, and in this case, it's less likely to be related to MUC5B promoter variants in systemic sclerosis. An announcement from the FDA this week that they, took a chikungunya virus vaccine called XCHIC, I x c h I q, off the market.

They've been investigating this in the last several months. They've received twenty more than twenty serious adverse events that resulted in twenty one hospitalizations and three deaths. And at least one of those fatalities is directly related to or thought to be causally related to the vaccine. So that was pulled off the market. Again, not a lot of chicken gun you going on in The United States.

We do see some people who travel, and this is why it's important. The recommendation here is people who may be at risk, should get this, if they're elderly. Well, this leaves only one of the two chikungunya vaccines on the market. There is another one, that's out there. Let's see.

That one is called that's a virus particle vaccine. The other one is a live virus. The X chick that was taken off the market was a live virus vaccine. Again, who should get these vaccines? The one that's available now would be travelers going to high risk areas where there's outbreaks for high risk and, elderly who you worry about them coming down with chikungunya, which can be a serious illness.

Another bit of vaccine research was in the news this week looking at recombinant zoster vaccine use in patients with lupus. This is a fairly, large retrospective analysis of both patients with Medicare and the diagnosed lupus and commercial claims with lupus who receive the appropriate two doses of recombinant zoster vaccine, and they were followed for about one and a half years. They compared the readout here was zoster effectiveness, or I'm sorry, vaccine effectiveness comparing the lupus patients getting a vaccine to non lupus patients, one to four, with the non lupus patients or actually the well, it's the non lupus patients. The vaccine effectiveness was good. It was seventy percent in Medicare and fifty four percent in commercial.

Why the difference? Well, those seem like they would be different. They're not statistically different, so that may be a red herring. These numbers for vaccine effectiveness are lower than what was reported with the, ZOE 50 and ZOE 70 trials that got this drug that we call Shingrix, FDA approved. So again, the more important part of this, because of the, way the viruses may that maybe it might cause flares.

Previous research has shown it did not cause flares in RA. In this group, there was no increase in flares when you looked at the lupus patients who actually received the vaccine and those that did not. The FDA approved its third biosimilar, version of the IL-six inhibitor tocilizumab. So there's three now on the market. That third approval came in January 2025.

It's a Celltrion product, tocilizumab, a n o h, or Avtosma. They and in research, it was called CT, p forty seven. Again, a report this week showing, that you can switch from the reference material, the innovator, Actemra or tocilizumab made by Genentech to this biosimilar, and again, good outcomes, no untoward effects in year long study of four forty four lupus patients. The other thing about this particular, version of tocilizumab, it is available in sub q and IV forms, and that's an advantage. A meta analysis of a fairly large cohort of, psoriasis patients shows that they had a significantly higher risk, two to two and a half fold higher risk of the metabolic syndrome compared to the general population, compared to RA patients, compared to spondyloarthritis.

We know psoriasis patients are at higher risk for cardiovascular disease and obesity and depression and a number of other comorbidities that are really problematic in this population. The data on metabolic syndrome, which, as you know, is having three of, you know, the following that would include obesity, insulin resistance, dyslipidemia, and hypertension, the association has not been as well established. I think this fairly, cinches that association here. The other thing that's important here is that the, association between psoriasis and metabolic syndrome was also, seen in psoriatic arthritis, important to both us and dermatologists. You know, primary CNS angiitis, think I I've had one of these in my career.

I think I've considered the diagnosis a few times. It is an uncommon vasculitis that usually affects the brain but can affect the leptomeninges or the spinal cord. And the symptomatology is thought to be bilateral in most. This report this week reports on unilateral primary angiitis of the CNS, specifically forty eight patients, basically showing you the presentations. And a diagnosis in most of these was made by imaging, specifically vessel wall imaging, perfusion study spectroscopy.

And then if when you can have brain biopsy histology showing, small to medium size lymphocytic vasculitis. So again, a rare condition. I like it when we, throw out information about rare conditions because who knows when it's going to show up. That's why it's rare. Another study on Still's disease and lung disease coming from the autoimmune disease network.

It's a worldwide study, and this was a study of, I want to say it's ninety patients with Still's disease with, and they were young, mean age 36, thirteen percent were from, the systemic JIA world. The others were adults with Still's. And they reported on lung findings. The most common lung finding with Still's was pleuritis in seventy two percent. And that kind of goes along with all large cohort analysis.

Parenchymal lung disease usually manifesting as pneumonitis was less common. In this cohort, they looked at thirty four percent and other cohorts is about twenty percent. ARDS, a lot of case reports on that, but in this cohort, nine point five percent, pulmonary hypertension at two point three percent. And I think that these are important things to consider, when you're considering a diagnosis of Still's disease, you can have these pulmonary complications. The parenchymal involvement was associated or correlated with sore throat pericarditis, high systemic inflammatory activity, but not associated with receiving IL-one or IL-six inhibitors.

And that's kind of a big thing these days, right, both in the pediatric world, the adult world, that there's a small subset of people get a chronic lung disease of different pathologies. And is it related to the use of IL-one inhibitors or IL-six inhibitors? Is it a dress like syndrome or allergic reaction? Again, that seems to be speculative at this point. There are more reports not showing association than there are, at least in my opinion, based on what I've been reporting here.

A few more reports. Methotrexate, you know, we love it, we use it, we know how to use it and how to use it safely, and part of that is monitoring of laboratory tests. A recent report, from four thousand seven hundred patients who were on DMARD, not just methotrexate but DMARDs, who received 59,000 laboratory tests. In this cohort, they did an analysis of abnormal, labs and very abnormal labs, specifically looking at five labs, ALT, EGFR, hemoglobin, white count, and platelet count. And the bottom line is that despite all the labs we're doing, very abnormal labs, and for instance, a very abnormal lab, I think, was a platelet of less than 90 or 100.

A very abnormal lab was an ALT greater than 300, so that would be like five times normal. Very abnormal labs, at two years were ranged from point two percent to six percent, not that much. Most of these very abnormal labs for which usually you were acting on and making changes about usually appeared in the first six months. And when they did appear, they occurred after a dose increase. And when they did appear, they were related to factors that were already in play, that you already knew about.

This analysis brings up the question, are we overlapping our patients on DMARDs? I'll use methotrexate as the example. Do we need to relook at what the ACR and the UR have come up with as far as monitoring guidelines? I think that the point that the authors made in this particular paper was that we might need to be a little bit more individualized in our monitoring plan. There are low risk patients and there are high risk patients.

And maybe the high risk patients deserve Q3 months on a DMARC, but maybe low risk does not. Again, we need more study, but we need I think some, societal, analysis of this. Speaking of methotrexate, there was a nice report. I think it was from Annals Internal Medicine this week. One of these two, either the lab monitoring or the methotrexate was from Annals.

But two hundred RA patients, who were on methotrexate for an average duration of forty six months, almost four years, looked at methotrexate intolerance as defined by a survey. And methotrexate intolerance was seen in thirty five percent of patients. That probably conforms to what you would expect. It depends on how hard you ask and how detailed you are. It can go up as high as fifty percent.

This study is thirty five percent. Nausea was the predominant problematic symptom at eighty five percent. GI discomfort, from, around fifty percent. These were most prevalent. So it basically says that methotrexate intolerance is a bit of a problem that we try to tell our patients to power through.

The people who are more likely to experience this were women, patients who have more severe disease, and patients taking a methotrexate dose of higher than fifteen milligrams per week. So again, that's a very dose related phenomenon. And and again, the intolerance was more likely seen when the dash CRP was greater than 3.2. So will that change how you, monitor your patients or what you do with methotrexate? I think you should be asking, certainly about how they're tolerating it.

I'll remind you here, this is a pearl not in this week's reports or on social media or on the website, but the two big side effects of methotrexate that I always talk about that I learned from a methotrexate, Maven who, did folate research and treated pediatric oncology patients with, methotrexate. The two big side effects, oral ulcers and the methotrexate blahs, CNS effects. The CNS effects, the blahs, you treat with dextromethorphan. And that can be Robitussin DM or that can be Mucinex DM. You give it with the methotrexate and then the next morning.

I like to give methotrexate in split dose, so I'll give it with the two split doses. Take the first one at night, the next one in the morning, and take one Mucinex DM tablet with each one. That treats about seventy percent and cures seventy percent of methotrexate blas. But blasts can be lots of different neurologic findings. And the reason for it is well worked out.

It's breakdowns of homocysteine, methotrexate does, into excitogenic amines like homocystic acid taken up by NMDA receptors in the brain. And you get these symptoms. It can be from blindness to impotence to headache to most of it's methotrexate blast. I feel really bad for about thirty six hours after methotrexate. So you give the dextromethorphan only with the methotrexate, it's a short lived phenomenon.

What about oral ulcers? Oral ulcers, you can treat with vitamin A eight thousand units a day, and that will also cure about seventy percent of cases. But you got to give the vitamin A every day, and that's very, very safe at eight or ten thousand units a day. And there's animal models to explain why that happens, but that's a pearl. Last two reports about, antibiotics, first about antibiotics not being linked to the higher risk of autoimmune disease in children.

So this is another analysis. This has been written about many times with a split in the data, some saying there is an association, others saying there isn't, that when, children are exposed to antibiotics, either in utero or while breastfeeding, later on have higher risk of autoimmune disease or JIA. This Korean National Insurance database, identified mothers who received antibiotics during their pregnancy or while breastfeeding. Again, they retrospectively looked at these people and then went out to seven years and did not find an association with autoimmune disease. So if that's been something that's been worrying you, it has not been worrying me, and I do treat kids, I think that this is good data, useful data.

Now, a little bit more concerning is acetaminophen. Acetaminophen is probably our safest drug, is it not? Acetaminophen is probably the most prescribed drug for pain and is the most prescribed drug for pain during pregnancy. However, there have been a number of reports and we've reported on this previously, and this is yet another meta analysis that looks at whether prenatal acetaminophen is linked to a higher rate of autism and ADHD. This is a problem.

More than half the women who are pregnant are taking acetaminophen or paracetamol worldwide. And what happened here, this was a Mount Sinai, meta analysis of 46 studies. In these 46 studies, 27 of the studies reported a positive association with significant links to these neurologic disorders. Nine showed no association and no significant link, and four showed a negative association or maybe somewhat protective effect. Again, lot of these studies were high quality studies, especially the ones showing this positive association between autism and ADHD.

We do know that acetaminophen crosses the placenta. The mechanism, however, by which that may cause these neurologic, issues is really unclear. So maybe think twice about using acetaminophen. I think I will at this point. I'm very liberal about the use of nonsteroidals.

I think nonsteroidals are quite safe after you complete organogenesis, is anytime really after eight or ten weeks. You can safely use a nonsteroidal at normal doses to manage pain. And you need to stop it, you know, in the last eight weeks so they don't have premature closure of the ductus arteriosus. You stop all anti inflammatories, aspirin, NSAIDs, etcetera, right, in that period because you don't wanna, cause that final complication in the home stretch of pregnancy. So between week ten and, like, week thirty two, you can certainly use nonsteroidals.

Push comes to shove, could you could even use acetaminophen, there is this data out there now that maybe we have to be concerned about. That's it for this week on the podcast. Starting in a few days, the month of September is, interstitial lung disease month. And in September, RheumNow is going to be doing a campaign on interstitial lung disease. You're gonna see a lot of content from the world's best experts on ILD from both the rheumatology world and the pulmonology world.

You're gonna like the content we're doing. We're doing a therapeutic update, a series of 12 videos that are going to do deep dives into treatment of ILD and guidelines of ILD. Because in the last year, we have guidelines on ILD and its management from the American Thoracic Society, from ULAR and from ACR. We're gonna discuss those. We're gonna discuss some of the problems that some people are finding with those.

We're gonna have Tuesday night rheumatologists every Tuesday starting on the September 9. We're gonna do panel discussions on issues important to ILD. We're gonna have one great journal club that I think you're going to enjoy. We're gonna be doing surveys on ILD and what you think about ILD. So it should be an ILD month to remember.

Be there. Be square. Take care of yourself.