Dot The I, Cross The T (10.11.2024) Save

It's the 10/11/2024. This is a RheumNow podcast. Hi, I'm Doctor. Jack Cush, executive editor of roomnow.com. This week, if there's a theme to these many reports I'm going to review, it might be, where can we look for help when we need help?

And often we're not that good at identifying when we need help or, in fact, seeking it. I mean, we tend to think we've got all the answers. Know, we're the guys that make the diagnoses and we're the gals that write the prescriptions and maybe, we don't need so much help. But, you know, if you look at the outcomes, a lot of what we do can be made better by some of the things I'm going to review today. So, I'm gonna begin with rheumatoid arthritis.

I always liked the early arthritis, cohort studies. I've got two, one from the Leiden Early Arthritis Clinic, a study from 2011, 2017. And they found in a cohort of four thirty one patients that the outcomes over the long haul were different, based on whether you made a diagnosis within twelve weeks of symptoms to diagnosis. So, symptom onset, making a diagnosis within twelve weeks. How often is that getting done?

Well, have an early arthritis clinic there, that facilitates it. But when that diagnosis is done earlier, they found a significant treatment cost benefit in both seropositive and seronegatives. Much larger in seronegative individuals, where maybe the diagnosis is harder. But again, if it was, if the diagnosis was made after twelve weeks, and the patients were seronegative, the costs were threefold higher, or 316% higher in seronegatives. It was also higher in seropositive patients, but only about twenty percent higher.

But still, A, the point here is early diagnosis, better outcomes. But it's not just better outcomes as far as, you know, joint counts, erosions, you know, things that you worry about. It is the overall cost of care. And that can be, I think, something that we need to think about. Again, I think that in countries where you have early arthritis clinics, you're ahead of the game.

In The United States where there are almost no early arthritis clinics, you're definitely not ahead of the game. Because the only way you're going make an early diagnosis of RA in your clinic is if your new patient consultation wait time is less than two weeks. Otherwise, you're never going to meet that benchmark of making a diagnosis within twelve weeks of symptom onset. Another study from Canada, the CATCH cohort, their two thousand plus early RA patients, they found a higher incidence of hypertension. Now, we don't often talk about hypertension in RA, but what I found interesting was that in doing a one time or a baseline cut, a quarter of the patients had hypertension.

It was about ten percent higher in patients who were older. And those who had, and if they were older, they had cardiovascular risk factors. But even those who at baseline didn't have hypertension and they had RA, if you follow them over a median of five years, again, a quarter of them, twenty four percent, developed hypertension. RA is a vascular disorder. Hypertension is a bad comorbidity.

There are clinics where blood pressures aren't taken. I think that's a mistake. I think you should be doing vital signs on your patients, especially weight. Especially BMI calculation. But I think blood pressure makes a lot of sense.

I don't know if you saw this report in JAMA this past week. It's the LAMP study. It's about mindfulness based education of patients who have chronic pain. And they had three time points in this. I think it was like a short twelve weeks, six months, and then one year time point.

And they had three groups of patients. I believe these were Veterans Affairs patients with chronic pain. And you were either randomized to receive group, mindfulness training through telehealth. And then, and then, so it was training, but then also ongoing group, mindfulness classes. And then there were sort of self initiated mindfulness, training, where the patients did it on their own.

And that was compared to, usual care, not getting mindfulness training. And it turns out that at all three time points, those who had the mindfulness training had significant reductions in overall pain, pain intensity, patient global status, physical function, fatigue, sleep disturbance, depression, and the frequency of PTSD. You know, pain, we're going to discuss later, is something I don't think we do a good job of. We hope that if we make a right diagnosis, and we institute the right anti inflammatory, immunosuppressive therapy, the pain is controlled. Not often the case, though.

I find that, and it appears a real problem with mindfulness. I wish I could do more of it. I don't know who to send them to. It's not like there's a mindfulness clinic right next door. In fact, I did have a mindfulness clinic right next door for about twelve years of my practice.

And that was easy. We sent them over, and patients bet Half the patients liked it, the other half were resistant to it. So I don't know if they ever gave it a fair chance to know that it would do them well. It serves you and your clinic well to find out where the referral goes. This is far, by far and away, one of the best ways of managing chronic pain, managing fibromyalgia, managing a number of things that we really don't know how to well manage.

I found a very interesting study from University of Pennsylvania, Victoria Wirth, Wirth's clinic, where they did a, this is an ACR open, a study of almost 700 adults with either chronic lupus erythematosus skin disease or dermatomyositis. In their survey of their patients, a third of them were taking herbal supplements. What? Again, we often don't know about this. But the more important point here was, one, it was more frequent in younger patients, and also in Latinos and Hispanic patients.

Amongst the patients with dermatomyositis, thirty one percent of either the disease onset or flares were associated with supplement, recent supplement use. That was compared to ten percent with chronic LE, CLE patients. The most common natural product or supplement product with, it seemed to be, an immunostimulant, was elderberry. Again, I was not aware of this. One, we should be asking our patients about herbal supplements and over the counter products.

But realize that they may be relying on these, and it could be to their detriment, especially if they have autoimmunity, especially if they have dermatomyositis. Is there a cancer risk with systemic sclerosis? I think I actually reported this a few two months ago, maybe? Well, I found another report, this time in rheumatology. This is from a data set of almost 10,000,000 individuals.

They found nearly sixteen hundred patients with systemic sclerosis, two hundred of, two zero six of them developed a cancer. The most common cancers were skin and mucosal cancers, four point five percent, lung cancer, two percent breast cancer, two percent. And overall, cancer risk was higher, in systemic sclerosis patients. But, big but, after the diagnosis of scleroderma, not before. After diagnosis of scleroderma, the hazard ratio is one point four, hence a forty percent increased risk, but it was not significant before diagnosis.

Again, goes along with the concept of needing a chronic inflammatory process to result in a malignant transformation. That, I think, we've talked about in the past, or I think everyone kind of accepts that. In general rheumatology, they did an interesting study this week that looked at the importance of CPPD crystals, and whether or not they're intracellular or extracellular in predicting what's going on. So, theoretically, you can tap a joint, someone with gout or someone with pseudo pseudo gout, and you might find crystals, that are free floating and maybe not inside of cells. What does that mean?

Well, in the case of CPPD, calcium pyrophosphate disease, crystal associated disease, what they found was in a study of one hundred and thirty four patients overall, one hundred and eight of them had intracellular crystals, twenty six had extracellular crystals, and it turns out intracellular crystals had greater specificity. So overall, I think they found either having acute or chronic calcium pyrophosphate crystal disease, ninety seven percent were intra, had intracellular crystals, versus, a much lower number, about half that with extracellular crystals. So again, arthritis, acute or chronic, was more likely to be associated with intracellular crystals, and I kind of would have expected that, but I've never seen this research ever reported. I don't know if you've seen, I I am not a big fan of these big, long studies where a drug company says, you know, the ten year outcomes of, you know, dopelimumab and how safe it is, and, you know, I'm not a big fan of that. But, I must say that Gerd Burmester, has been working with AbbVie for many years on these very large cohort analysis of patients taking adalimumab, and showing the incidence of the, mainly the c, the severe, or not the severe, the serious adverse events.

And I like those reports because it lets us know that they really are quite uncommon, if not very rare. Well, Doctor. Burmester and colleagues have reported again, this time on the safety of opadacitinib in a large cohort of greater than 15,000 patient years, patients with RA, PSA, AS, and atopic dermatitis. When they reported on the rates of the SAE, they reported them in terms of per 100 patient years. So compared to a comparative drug, UPA was, had a higher rate of zoster, skin cancer, CPK, all higher than the comparator.

Usually that was adalimumab in those head to head trials. But the rates were about, and I'm now going to switch from 100 patient years to 1,000 patient years, because that's sort of the standard, that I like to consider, especially for rare events. Zoster, sixteen to thirty six per one thousand. That's on par with other JAK inhibitors and zoster frequency. It is much higher than TNF inhibitors, at least two to three, if not five times higher.

Non melanoma skin cancer, it's eight per one hundred or eighty per one thousand patient years. And that's one of the more common skin cancers. One of the more common cancers, right? Period. CPK, we occasionally see, but the numbers are either forty five to seventy nine per 1,000 patient years.

So it still is quite uncommon. Death rate was very, very low. You know, again, eighty per 1,000 patient years. SIE, less than four per 1,000 patient years. MACE, four or less per 1,000 patient years.

And VTE, either ten to forty per 1,000 patient years. Turns out cancer, and and or malignancies overall were lowest in patients with AS and atopic dermatitis. So I like having those numbers because then I can have, I I like to say the really rare stuff, aside from SIE. SIE, we know the rates are, you know, three to five, two to five per one hundred patient years. Right?

And that's a most one of the most common serious adverse events. But when you start talking about TB, opportunistic infection, death, you know, MACI events, you know, these are often about one in one thousand, patient years, or maybe they're higher, right? But still, we're talking about one thousand as the denominator. So hope you find that helpful. Kareem's, Korean, insurance claims database analysis looked at the risk of recurrent cardiovascular events in patients with spondyl radiographic axial spondyloarthritis.

We do know that most inflammatory forms of arthritis, RA, PSA, etcetera, do have an increased risk of cardiovascular events. And most of those studies have also shown that using effective anti inflammatory therapy, like a TNF inhibitor, mitigates that risk. But what about recurrent events? Well, that's what they looked at in four hundred and thirteen patients with axSpA. And, so only seventy five of them, that's about less than twenty percent, were exposed to a TNF inhibitor.

The overall rate was thirty two per one thousand patient years, but it was significantly lower if they were treated with a TNF inhibitor, nineteen per one thousand patient years. So as has been shown with other inflammatory authorities, it does lower event rate, and it does lower the rate of recurrent cardiovascular events, which would obviously be much more concerning, much more deadly, if it were in fact to happen. I found a nice, genomic study of ANCA associated vasculitis, thirty four patients who had ANCA vasculitis and glomerulonephritis, and they did both, I think, blood sampling, but also renal biopsy sampling. And they looked at, genomic profiling, either using spatial transcriptomics or single, cell RNA seq analysis. And basically they found in patients with glomerulonephritis, that a strong preponderance of Th1 and Th17 cells, that were basically CD4, CD8 cytokine producing cells.

And on that basis, they were making the suggestion that maybe the most effective therapy in ANCA associated vasculitis with glomerulonephritis might be ustekinumab, the IL-twelve twenty three inhibitor. And in fact, they did treat four patients who had relapsing uncontrolled glomerulonephritis due to ANCA vasculitis. They treated with ustekinumab, usual doses, and then a low dose of cyclophosphamide and steroids. They had very favorable responses, improved renal function, GFR, and improved Birmingham Vasculitis Activity Scores. Know, ustekinumab has been thrown about as a potential agent for vasculitis management.

I haven't heard about it in glomerulonephritis. I found this to be an interesting analysis. Another report this week from France and Maxine Dugaldos' group, seven thirty one patients from two different cohort studies in axSpA. One was called the rapid axSpA study, and the other one was the C optimized study. These are studies, clinical intervention trials, but they had an MRI analysis.

And basically what they found in this study was that forty five percent did not have SI inflammation and hence were then classified as non radiographic axial SpA. But that sixty percent had evidence of SI inflammation via the central readers. Now they took the seven hundred and thirty one patients, as MRI scans, and they subjected them to, AI. And they found that they were good in reading these and not great. This is important because I don't know how good you are at reading MRIs, especially and specifically for sacroiliitis and scoring them even.

But that can be done by AI, and that can be done anywhere by AI. And this is going to be the future. So what what was the absolute agreement? Assuming that the physician reading by experts in this case was correct. The absolute agreement was 74%.

Sensitivity of of of AI in redefining inflammatory sacroiliitis was 70%. Specificity, 81%. Positive predictive value 84%, negative predictive value 64%. So these are not great, but these are pretty good. Couple this with the fact that AI is going to get better.

We're still almost in the in the infancy of using AI for this sort of purpose. This is only going to improve, in the next five years. When given the option of having AI read my radiographs, read my chest CTs for ILD, read my, pelvic MRIs. Yeah. I want to see those results.

I want to look at it myself. Again, the whole thing about AI and the future of AI is that it will give you data that is useful if you're knowledgeable. Right? If it gives you data that makes no sense, well, that could be an AI hallucination, and you don't you don't have to accept it. But when it does make sense, or when it adds to your knowledge, why not?

I think this is the future. Rheumatology this week had a, a large analysis over two different time points, looking at analgesic prescribing in, a large cohort of patients with inflammatory arthritis, RA, PSA, axSpA. They looked at patients in 2004, and then again in 2020. And while they did show that analgesic prescribing, this is non narcotic, narcotic, NSAIDs, was eighty two per one hundred patient years. Pretty much everybody got it.

Over eighty percent of people got it. In 2004, it was now down to sixty four per 100 patient years in 2020. Two thousand and four NSAIDs were most prescribed. Fifty six out of that eighty four was NSAIDs. In 2020, opioids most prescribed.

That's thirty nine out of the sixty five. So opioids are still in play, even in 2020. Gabapentinoid prescription went up from one in twenty two thousand and four to ten per 100 patient years in 2020. NSAID use still remains prevalent amongst males with axSpA. But how are you treating pain is what I wanna know.

I think most of us are not treating it. I gather this from being an attending and talking to fellows and other attendings about their management in clinic, where you kind of compare notes. Most people aren't prescribing nonsteroidals anymore. Most people aren't prescribing tramadol, or acetaminophen or even narcotics. And of course, if you don't want to prescribe them because you read a paper that says they don't work, well, you're you're satisfied.

But is the patient satisfied? What's the effort you're going to make to manage the patient? It could be mindfulness training. It could be physical therapy. It could be getting a structural evaluation by either radiography, radiology or, a consultant, like a, either an orthopedist, or maybe even a colleague rheumatologist for a second opinion on how to best manage this person's pain.

Again, I still think that this is one of the bothersome points in rheumatology management. My last report, I liked this week. It had to do with screening patients to prevent, multi morbidity in patients with rheumatic disease. So this was about 1,100 patients, it looks like, with either RAPSA or SPA. And when they, and this is sort of an EHR or a claims analysis, and they found that two eighty six of them were screened, right?

Or exposed to a screening procedure, which then might lead to the endpoint of prescribing drugs that would prevent multi morbidity, right? Either lipid lowering drugs, antihypertensive, diabetic drugs, etc. So, if you were in fact screened, you had a sixty percent greater chance of meeting the composite endpoint of receiving a prevention drug. Odds ratio 1.6, and that was significant. This after they did propensity matching, it was still significant.

Fifty five percent were given these drugs if they were screened, versus forty four percent if they weren't screened, and that's a odds ratio of one point five, and that was significant. Again, overall, this was the utilization of vaccines, cholesterol lowering drugs, anti osteoporosis drugs, etcetera. You know, I know you're busy as a rheumatologist taking care of highly complex disease, and when I ask you, you know, who should be managing, or identifying comorbidity and doing something about it, the most common answer rheumatologists will give is, Well, I often pick it up, but I like to refer that stuff to primary care. The problem, of course, being your patient thinks you're the most brilliant doctor they've got, and that their primary care doctor doesn't misunderstand them the way you do. So they rely on you for everything, because you talk about, you know, how the Buffalo Bills did last week, you know, what the weather is tomorrow, and, you know, advice on whether you should buy this SUV or that SUV.

They're going take your advice on things like weight loss and prevention of these other comorbidities that are highly prevalent in patients with inflammatory arthritis. Oh, even better. I didn't, I've missed this point, that patients who were screened ended up having fewer emergency room visits, and fewer hospitalizations, like seven percent versus fifteen percent, cut in half. Odds ratio 0.42, so it's a fifty eight percent reduction. Also, a significant reduction in severe infections, zero point seven versus three point nine percent, all from screening.

Dot the I, cross the T. That's the way to go in rheumatology. RheumNow Live is coming up. See you in Dallas, February 2025. It's gonna be a great meeting.

Check out the website, rheumnow.live. Take care of yourselves. We'll talk next week.