Associations in Rheumatology (10.3.2025) Save

It's the 10/03/2025. This is the RheumNow podcast. Hi, I'm Jack Cush with roomnow.com. This week, a lesson in music. Who sang the following songs?

These are hits from the nineteen sixties. Were you born in 1960 or after? Oh my goodness. Along Comes Mary, Cherish, Never My Love, and Windy. Yeah, those were staples in the sixties from the band known as the association.

And that's what we're talking about today, associations. Associations with RA, PSA, Urticaria, Methotrexate, Back Pain and more on this podcast. First, gout, very famous febuxostat study mandated by the FDA called the CARES trial, which was good and led to the FDA approval of febuxostat, but a post hoc analysis of remission in gout comes from the CARES trial, and again they were all treated with either placebo or the urate lowering drug febuxostat. They showed that remission in this trial increased from thirty seven sixty three percent over a six year period. By six years, fifty nine percent achieved remission at least one time, and those who achieved remission in gout, it was associated with age, race, high disease severity, comorbidities, and febuxostat.

A lot of factors in play. The fact is that true remission is seldom achieved. In fact, in gout we do not even achieve target thirty-sixty percent of the time, and that's amongst us rheumatologists. Gout remains a challenge, especially remission. I found an interesting study on flare definition in PSA.

It's a of a meta analysis of many studies, 12 studies, showed that the incidence of flares range from seven to ten percent at six months, and as high as twenty two to twenty three percent at twelve months. If you look at who's reporting a flare, the patient or the doctor, patients reported flares more frequently than the doctor, seven percent ten percent versus seven percent. So there's a lot of swerving all over the road here, and the big problem is there is no consensus on what constitutes a flare in PSA. And you need that if you want to be able to treat flares and have trials designed to manage flares. I know what you're going to say, I know a flare when I see it, or you're talking about pornography, I think you're talking about RA and PSA flares.

But the fact is, in RA, Austrian group defined what is a flare in RA with increase, I think it was 4.5 in S di, the constitutive flare, and that kind of goes along with an increase of two swollen joints, two tender joints. But again, there is no formal flare definition in PSA, and there should be, because we've got a lot of PSA trials, we've got a lot of effective treatments for PSA, why isn't someone measuring this? Speaking of PSA, some of our leaders are very interested in this topic of is there axial PSA? For instance, there's data that IL-twenty three inhibitors don't work in axial disease, axial spondyloarthritis, but maybe some that says it might work in axial PSA. How common is that problem?

You know, always say that if you do the breakup of subsets of PSA, less than twenty percent have axial PSA that looks like ankylosing spondylitis. Well, in this particular study, a cohort of five eighty one patients with PSA mean age of about 45, they did MRIs and they found MRI evidence of SI joint involvement in thirty one percent. So we call those MRI axe PSA patients. It's actually different than radiographic axe PSA. The ones that had MRI evidence of the SI joint with PSA, the MRI axe PSAs, bone marrow edema, bone marrow erosions about seventy percent of the time, fat lesions fifty eight percent of the time, and that cohort of five eighty one, about forty five percent had x rays.

The number of people that actually met x-ray evidence by modified New York criteria for AS was only twenty nine percent. If you used MRI as a tool to find SI involvement, it was ten percent more prevalent at thirty eight percent. SI MRI was predicted by being male, B27 positive, having a high CRP and having a history of inflammatory low back pain. Things that you would expect. So there is this subset of AxPSA, there are clinical trials going on right now in this subset, we'll be hearing more about that going forward.

Another study of two forty six patients with spondyloarthritis and one third had non radiographic eighty two people, and two thirds had radiographic ACSPA, what you might used to call AS, one hundred and sixty four patients. This is from the Scandinavian Journal of Rheumatology, these patients had well established disease with a symptom duration of twenty six years. These patients with axSpA had more comorbidities. They had higher Charlson Comorbidity Indices, CCI scores, and it was driven by uveitis in axSpA, twenty eight percent versus one percent in non axSpA. IBD, much more prevalent, PSO, much more prevalent, cardiovascular disease, and FM was actually more prevalent.

That's comparing AXPA to general population. But when you compare the radiographic AXPA and the non radiographic axSpA, these comorbidities were not different. Isn't that interesting? You would have expected it for the AS like variant, but it looks like the non radiographic axSpA also seems to bring the same degree of co morbidity to the table, and that leads to poor outcomes. Let's switch gears and talk about methotrexate and fibrosis.

How many have you had? You know, I think it's gotten so rare with our use of methotrexate in RA, that we really don't think about it very much, we do the same monitoring. We do know that PSA patients are at higher risk, are they not? So this study is of thirteen hundred plus PSA patients, and they looked at the incidence of liver fibrosis. Of the thirteen fourteen patients with PSA, twenty eight percent were on methotrexate.

They compared methotrexate to non methotrexate, and they found a few interesting facts. Baseline, before ever getting methotrexate, three percent had evidence of liver fibrosis. That over time, a median follow-up of five and a half years, eleven percent or twelve percent developed liver fibrosis. And it turns out that the predictor of future liver fibrosis in these PSA patients wasn't methotrexate, and wasn't cumulative dose of methotrexate. In fact, the factors that drove risk for liver fibrosis were metabolic factors, especially high BMI and diabetes.

I think there's a lesson there. Chronic low back pain, you know, it's a miserable condition, these people have hard lives, but you know it's not just because of their back pain. In the 2019 National Health Survey of eighty seven zero individuals, twenty percent had chronic low back pain. And it turns out, these chronic low back pain patients, as opposed to acute or episodic, they had much more comorbidities and multimorbidities was seen in sixty two percent. So six out of ten chronic low back pain patients had two or more conditions that were not arthritis related.

These patients with multi morbidity had more activity limitation, they had more depression, and they had more cardiovascular disease and cardiovascular events. So chronic back pain comes with a price, a higher risk of multi morbidity and the things that run along with that. That's kind of ugly. Again, this is the last podcast for the month that was ILD month. We had a lot of reports on ILD.

This week we had a discussion in our Tuesday night rheumatology webinar, where we discussed monitoring diagnosis and screening. And the question came up, how often are patients referred for the incidental finding of interstitial lung disease. And it turns out that interstitial lung abnormalities, what's called ILA in pulmonary world, is found in seven percent of the general population. And the vast majority of these are found on CT scans or MRIs done for other reasons, and then they're found to have lung inflammation or lung fibrosis. The vast majority of these people are asymptomatic, and the question is, what do you do with them?

Some of them will progress to ILD or idiopathic pulmonary fibrosis. Some of them are at increased risk of future lung cancer. And the bottom line is that an incidental finding, I'm not talking about you have a SARD, a systemic autoimmune rheumatic disease with lung symptoms, and you do screening. That's not incidental finding. I'm saying it's done for another reason, and ILD comes back.

And the question is, what do you do? And the advice from the pulmonologist is that you screen them, you monitor them, and you ask about risk factors. You ask about whether they may have a systemic autoimmune rheumatic disease or connective tissue disease. You look for risk factors like smoking, exposures, seropositivity, autoantibodies, age, males and other risk factors. This is an interesting subset that is a bit of a head scratcher even for our pulmonary colleagues.

If you're a rheumatologist and you find one of these, I think I'd refer them to the pulmonologist for monitoring and screening. An interesting retrospective study of one hundred and forty patients with UIP pneumonia looked at the frequency of myositis antibody testing. And what they found was myositis specific antibodies in eleven percent of individuals. These individuals were, not surprising, were more likely to have autoimmune disease, positive tests for ANA rheumatoid factor. The ones that were going to be MSA negative, you could predict with 100% specificity, but only thirty two percent sensitivity, but those that are negative for rheumatoid, low titer or negative for ANA, no hypergammaglobulinemia, and no Raynaud's, they're not going to have MSA antibodies and then are not likely to have associated myositis.

We have talked a lot this month about RA ILD, we found a few reports on RA patients and pneumonia, and clearly population studies show consistently RA patients are at higher risk for pneumonia, and we know that RA ILD patients are at really high risk of pneumonia and serious infectious events and dying from that pneumonia. This is just a general population study of forty one thousand RA patients, matched one to five with over 200,000 age and sex matched controls. In the RA patients who had four years of follow-up, they had a seventy three percent higher risk of pneumonia. They had a two twenty six percent higher risk, or a two plus fold risk of hospitalization from that pneumonia. The risk of pneumonia was higher with seropositives than seronegatives, and then interestingly, it was also higher when the individuals had a biologic DMARD or a DMARD, but not targeted synthetics.

Synthetics. So my take on that, my interpretation of that is, that these are people with really active disease, and activity drives risk of serious infectious events. So the activity was such that they got on DMARDs, and they got on biologic DMARDs. Now, is it not higher? Again, the adjusted hazard ratio with biologics DMARDs was like 1.73, same for DMARDs, but targeted synthetics, JAK inhibitors, was only 0.93.

Either they're more effective and quicker at getting disease control, or there's a selection bias in these findings. I find these findings interesting, nonetheless. Talking about associations, chronic urticaria obviously has a strange differential diagnosis. I would assume that not, well here's a caveat, most of you don't probably know that Still's disease, which is supposed to be the classic skin finding, is the salmon pink rash over the extensor surfaces that comes and goes. So an evanescent salmon pink rash.

What you don't know is that thirty-forty percent of Still's patients, whether it's kids or adults, are going to have urticaria, that can be episodic or could be chronic. And the point of this particular paper we posted this week is that chronic urticaria and other things that you might consider should lead you to consider auto inflammatory diagnoses, yes, Still's disease, but also Schnitzler syndrome, the Cryopyrin Associated Periodic Syndromes, CAPS, which is, as you know, Mucklewell syndrome, Nomycinca, and Familial Cold Auto inflammatory syndrome. And there's a other condition called neutrophilic urticarial dermatosis, that's an auto inflammatory condition. But urticaria, think auto inflammatory. Two last reports, an interesting blog we posted this week from the University of Colorado, Kristen Demarell, talked about lung involvement in pre clinical RRA.

As you know, the University of Colorado there in Denver has a great research effort, Kevin Dean and Kristen and others, that have done a lot of work on pre clinical RA, and she points out in this paper that's worth reading, that there is a number of reports out there about RA ILD being diagnosed either before the RA, or contemporaneous with the diagnosis of ILD, and that as much as ten to fifteen percent, the ILD happens before joint inflammation is apparent. Mike Hoers and his group there at Denver also had this great paper where they did bronchoalveolar lavage on patients who were CCP positive, and they found a high incidence of inflammatory lung disease. This is the center that has led this mucosal hypothesis for what is the onset of RA, and Kristen's point here is that, which comes first, the chicken or the egg, is it the lung or the joint in the pathogenesis of RA, and there's a lot of evidence that says the lung should be implicated. You might want to look at this particular report, I thought it was highly insightful and really well written. The last report comes from MedPage Today about the use of activity trackers, and that includes like your Apple Watch, your Fitbit, look at mine, come from China, $31 from Xiaomi.

These are very good tracking a lot of things, including activity. In their study of 53 individuals, who were either using an Apple Watch, a Fitbit or an Oura Ring, they had data on either 47 or something like that, where they showed that you could predict a flare of RA activity based on analytics derived from the activity tracker and heart rate variation. Heart rate variation follows a circadian rhythm that is disrupted weeks before people are going to have their flare of RA. So, I found this really interesting, and you know, I don't think that most of us yet know how to incorporate activity trackers into our care, but in the future it's going to be a part of it. I like to look at it from the standpoint of sleep and number of steps, it is also useful in detecting heart rate abnormalities, but it could be useful if I can, in the future, give you a formula for this times that, and let AI tell you that this patient, based on their activity tracker, could be at risk for flare in the next few weeks.

There you'd want to do some instruction, would you not, on how to recognize a flare and then manage a flare. Easily done in the future. That's it for this week on the podcast. That's the end of our great month on ILD. We want to thank Boehringer Ingelheim for sponsoring all the great education on ILD this past month.

Now we're going to look forward to ACR, which is in three and a half weeks, and RheumNow Live. RheumNow Live registration is open. Go to roomnow.live. Our meeting is going to be on February 2026 at the Westin Hotel in Dallas. The agenda is there.

We'll be talking about this going forward. It's going to be a fabulous meeting, I know because Artie Cavanaugh and I just finished putting it together, you're going to like it, we'll talk more about the specific lectures and speakers in future editions here on the podcast. Go to the website to check the show notes to get the citations for this week's podcast. We'll talk next week. Take care.