September to Remember (9.5.2025) Save

09/05/2025. This is the RheumNow podcast. Hi, I'm doctor Jack Cush, executive editor of roomnow.com. This week on the podcast, Unemployment. The best way to diagnose Sjogren's?

What? With ultrasound? And that's right. September is ILD month, lung fibrosis month. We'll be talking a lot about that.

Let's begin with a talk on lupus and unemployment. This is a six year study from the Dutch where they looked at a large cohort of two 21 lupus patients. I think about half of them were employed at the time that they started the study or baseline. I looked at them six years later. Over time, unemployment rose.

The ultimate number was fifty four percent. You have to understand that there were a lot of people who became unemployed, and then there was about sixteen percent who became employed during this period, but it was high. Factors associated with being employed included supervisor support, decision authority, working hours and skilled discretion. Unemployment, when it happened, in two thirds of the cases, was due to lupus activity, lupus symptoms. And other things associated with being unemployed with lupus was being older, less educated, disease duration, longer being worse, and organ damage.

Again, is something we don't often talk about, probably should talk about it, it's very important to our patients, you know, to keep them under control so that they can continue to work. That's a big benefit because what you're doing there is you're telling them you're okay. Do the things that we're talking about here in the plan, you'll be okay, and you can get married, have babies, go to work. These are the things that people want. We got to pay attention to it.

A study from Clinical and Experimental Rheumatology, a retrospective study, one center, six hundred plus systemic sclerosis patients looked at pulmonary artery, I'm sorry, pulmonary hypertension, pulmonary arterial hypertension. It was found in twelve point seven percent of patients, or seventy seven out of six zero seven. Overall, our therapies didn't matter much in preventing PAH from happening. That includes all the immunosuppressants, all the steroids, etc. But what did reduce the odds significantly was early aggressive use of Mycophenolate.

It was protective. It looks like it dropped the rate by eighty eight percent and that was significant at p point zero four eight. And then interestingly hydroxychloroquine improves survival significantly, which why is a systemic sclerosis patient on hydroxychloroquine? And we know hydroxychloroquine has multiple effects in lupus and in rheumatoid, where, yeah, mortality numbers can be better. So maybe the same effects, the anticoagulant effect, the anti diabetogenic effect, the vascular effects.

Interesting. A prospective study of one hundred and seventy one Sjogren's patients, actually they were patients with suspected Sjogren's, and ultimately one hundred and thirty of them were diagnosed and everyone got the big workup, and it turns out, what was most accurate in making the diagnosis? Labial gland biopsy. This was the best with an AUC of 0.9. Next was the presence of SSA or anti Rho antibodies AUC of 0.79.

Using the Olmarac score to make a diagnosis, almost the same, about 0.78. And the paper really went into using multiple things to improve the diagnostic accuracy in diagnosing Sjogren's. They looked at both parotid and submandibular gland ultrasound. It had to be grade three, and that sort of predicted a positive biopsy of 0.77. But diagnosis, it was inferior to everything I've mentioned before.

So it's good in combination with other factors, but by itself it had, you know, it went along with biopsy and correlated with salivary flow, but the correlation coefficients were about 0.5. Not bad, not great. So I think this is like everything else with ultrasound. It's operator dependent, it's depending on how good you are at doing it, and, I don't know of many people who are, but I would encourage you to continue to do this research. It is something you can pull out of, pull into your clinic and do on the spot point of care service.

What's not to like about that? Johnson and Johnson this week halted a clinical trial. It was called the DAISY trial. This was a proof of concept phase 2A trial of combination biologic therapy in difficult to treat RA patients. The combination biologics was a TNF inhibitor plus nipocalimab.

Nipocalimab is their neonatal Fc receptor antibody that was shown to be effective in Sjogren's at last ACR and it's in multiple trials. So they halted this combination trial, but nipocalimab is in other trials, we'll be looking to see what happens with that going forward. I found an interesting study this week on the risk of latent tuberculosis infection or LTBI. This was a review from a single center with a lot of patients, twelve thousand rheumatic disease patients. I'm sorry, it wasn't a single center, it was a meta analysis of 18 studies, 12,000 patients.

And LTBI was found in twenty two percent of these reports. It was significantly associated with current smoking, fifty percent increased risk. Galimumab, a threefold increased risk. That's like the two hundred and ninety percent increased risk. Chloroquine use, twenty seven percent increased risk.

Age greater than 40, an eighty four percent increase, odds ratio one point eight four. Prior TB, odds ratio three point two six. So the big factors in predicting risk of LTBI in rheumatic disease patients was the TNF inhibitor golimumab in a prior TB history. What didn't increase the risk was seropositivity, adalimumab, etanercept, BCG status, prednisone smoking, and diabetes. Now in other studies, these have often been linked to, risk of TB and late especially latent TB.

I'm gonna guess in this study or in these studies, adalimumab and etanercept were being used probably early in the course and maybe used according to guidelines with testing, either by IGRAs or by, tuberculin skin testing. And golimumab may have been sort of a tertiary, or later drug, and maybe that's why that may we do know that, you know, of all the biologics, it's TNF TNF TNF inhibitors that increase the risk. The other MOA biologics targeting T cells, B cells, IL-six, JAK, TIC, these are not major risk factors for, to biologically get or be susceptible to opportunistic, especially mycobacterial infections. So anyway, I found this to be instructive and is a reminder that you need to adhere to guidelines, and when you're dealing with a patient who's got, you know, refractory disease and you're using drugs like the fifth TNF inhibitor, fourth TNF inhibitor, or Chloroquine, which we don't often use, then maybe you're dealing with a higher risk patient just by those factors alone. I want to remind you that, again, September is the month that we're doing an interstitial lung disease campaign on RheumNow.

You've seen a lot of content on that. It is Pulmonary Fibrosis Awareness Month according to the Pulmonary Fibrosis Foundation. They remind us that, pulmonary fibrosis and ILD affects two hundred and fifty thousand Americans, and they're going to lead the charge on this. JAMA, this last week, has a patient education piece on interstitial lung disease. It's a good download that you can hand out to patients.

I encourage you to get there. A number of reports this week on ILD, so CTD, connective tissue disease related ILD, is a big market right now. Drugs are being developed, we have new drugs that are on the market, there are more to follow. In 2024, it's valued at a 5,800,000,000 industry and is projected to go up in the next ten years to 9,300,000,000, almost double. This increase being driven by a growing risk of autoimmune disease may be greater awareness, greater use of biologics, and more trials that are looking to develop anti fibrotic agents to treat, ILD.

So I like this report because it's got a good blanket description of the problem, especially RA and ILD. It's a Korean retrospective study where they found one hundred and fifty one patients with RA and ILD, and they, in their analysis, showed that what significantly influenced the prognosis and outcomes of these people was the duration of the ILD and a UIP pattern, which is the usual pattern you see with RA, usual interstitial pneumonitis, UIP. Sixty three percent of their population were non smokers, they had a DAS of 4.9, UIP was seen at sixty percent. At four years ILD progressed in almost sixty percent of individuals and the mortality in an RA patient with ILD was high at twenty one percent with just four years of follow-up. That's pretty ugly.

That's why we're devoting a month to this in education and a lot of different things. An interesting report on the combination use of abatacid plus methotrexate was shown to significantly lower the risk of getting ILD in RA patients. So this was an amalgamation of 10 phase three trials. These are registration trials, you know, the AVERT study and all the A studies that, abatacep, is usually labeled as patients on methotrexate who had active disease were either treated with abatacep or placebo, and they looked at, 3,700 patients, 10,000 patient years, and they showed that, the ones that were on abatacept had lower rates of hospitalization, lower, development of ILD by ninety percent. Now, this is not a perfect study, those studies were not designed to look at ILD, patients could have been enrolled in all those Avatacep studies if they had ILD.

A few of the studies said you couldn't be enrolled if you had significant lung disease. But anyway, by these analyses it looked like maybe there's a benefit of Avatacep in preventing ILD. That needs to be repeated. Another report, I think this is a kind of an important report that we retweeted from Arthritis and Rheumatism that lung cancer, is higher in RA patients who have ILD. This is a retrospective match cohort study from the VA that shows a fifty percent increased risk of lung cancer, and altogether if you look at prevalent RA ILD, the cancer risk had a hazard ratio of three point two five, a threefold increased risk compared to non RA controls.

So again, this is something we have to worry about and maybe why we should be treating ILD as rheumatologists. Another report on cancer associated myositis looked at the use of myositis specific antibodies, the MSAs, the antisynthetase antibodies, and now myositis associated antibodies. This is a meta analysis of five studies and four thousand five hundred patients either with dermatomyositis or polymyositis, and they showed that the cancer risk was higher in dermatomyositis, fivefold higher risk, four point six, was the SIR, meaning and compared to normal controls, it's fivefold higher. And polymyositis was higher, 1.75 SIR, but it's certainly less than dermatomyositis. So cancer risk was associated with certain biomarkers, and that included KL6, TIF1 gamma, NXP2, and HMGCR, the autoantibodies associated with, statin use, and and other associations.

So think about it. Again, think that there's too much of this, personally, think there's too much of a reflex. Polymyositis, dermatomyositis, oh my god, work them up for cancer. I don't do that. If they have either, I'm doing age appropriate health maintenance.

If they have factors that might otherwise make me think of cancer, including TIFF-one gamma NXP-two HMGCR, yeah, I might do a more specific evaluation for cancer. And I'm more likely to do it if they're older, over 50, if they're male, and if they have dermatomyositis, as opposed to polymyositis and younger. But you gotta make up your own decision about these issues. A nice report about again, about GLP one receptor agonist now being associated with a lower risk of uveitis compared to controls. So they looked at two hundred and fifty thousand plus patients on GLP-1s or not, and if you were on a GL-one, RA, you had half the risk of developing uveitis than if you weren't on it.

So this protective effect was better than that seen with metformin and insulin, but actually lower than using SGLT2 inhibitors. So I wanna point you to a few interesting things that are on the website, this past week and for you to find. One would be, an interesting blog written by Richard Conway on combination therapy for RA and ILD, and his point was, you know, he's advocating for triple therapy or quadruple therapy, but not what you're thinking. His quadruple therapy is number one. These patients should be on a background of CSD MART.

There's some evidence that patients who are treated with CSD MART, you name it, doesn't matter, actually are going to do better in the long run. Number two in his triple, and part of number one, if you will, in his triple approach or quadruple approach is control the disease, control RA. Number three, he goes right to anti fibrotic. This includes the use of Nintedinib, there's some other new ones coming up maybe next year, and even maybe the use of Perfentadone. And then as his fourth drug, mycophenolate or other immunosuppressants, which would include azathioprine and maybe others, but he likes mycophenolate, others, in this area like mycophenolate the best.

That's the quadruple therapy for him, and it's a throwdown for you to consider. Another great blog, both video blog and soon to be podcast by Doctor. Scott Matson from the University of Kansas, He talks about, rheumatoid arthritis ILD and its complication and the decisions you've got to make in management. It's a really nice eleven minute video listen, and ten minute read. I want to point you to the therapeutic update that you'll see on every email this month and also on the website top right corner, it's called therapeutic update.

It's called and the theme here, we're going to have a dozen videos that are going to address ILD treatment and ILD guidelines. And we're off to a blazing start with great videos from Cindy Johnson, who led the ACR guidelines effort, Janet Pope, Elena Yorns from Mayo, John Giles, Alisa Hines, Brian England, and Elizabeth Volkmann Volkmann, and others to follow. You might wanna look at that. And we'll end this week's podcast by a reminder that next Tuesday, September 9, we have another Tuesday night rheumatology. Before that, Monday you're going to get a survey, 10 questions that will inform, and this week we're talking about, on Tuesday night rheumatology, we're talking about treatment of ILD and future treatment of ILD.

I'm going to moderate, I'm going to be joined by Sindhu Johnson, Anna Maria Hoffman Vold, who was the author of the recently presented at Barcelona EULAR guidelines on ILD, and Scott Matson, has a very good video and I think you're going enjoy him. He's a pulmonologist with a lot of insight and a strong interest in ILD and RAILD. Don't want to miss where we're going, and where we should be right now. That's coming up Tuesday. Sign up for it or watch it afterwards.

Have a great week, take care.