Participation Is Up! (1.31.2025) Save

It's 01/31/2025. This is the Room Now podcast. Hi, I'm Doctor. Jack Cush, executive editor of roomnow.com. Pleased to be with you.

Room Now live is coming up next week, next weekend, seven days away, February eighth and ninth in Dallas and online. It's probably too late for you to make arrangements to be in Dallas, although I highly recommend it. Listen to the end of the podcast and I'll tell you why, but you can still attend virtually. Go to roomnow.live to register. Today's news: we're going to start with a study about the risk of cancer in lupus.

I'm sure you know that pretty much all the inflammatory diseases are a breeding ground for cancer. It's disrupted immune responses that, you know, there's like that cartoon of normal immune dysfunction, cancer, and happy smiley face, and then a frown when you get to the end. Basically, it's a continuum, and the point being that chronic inflammation adds cancer risk, and that's been shown for lupus. But in this Korean study of 10,000 lupus patients, ninety plus percent of whom were female, they looked at the influence of immunosuppressive therapy on future cancer risk. And overall amongst the ten thousand there were only three sixty eight cancers in the cohort, which is still a higher than population risk, right?

And the incidence there is fifty nine per ten thousand patient years. It sounds really low to me. And the most common was thyroid, breast, gastric, colon and cervical cancer. Certainly all that being colored by this predominantly female population. But when they looked at the role of immunosuppressives comparing those on and not on immunosuppressives there was no additional risk.

And I think that's always a concern, that's always a confusion. Is it the drugs that we're using to control inflammation that cause cancer or is it the inflammation and disease itself? I like the latter nine times out of ten. I mean, there are some drugs like cyclophosphamide, chlorambucil, etc. Multiple chemotherapies make for a higher risk of cancer due to drugs.

But I think that this is a clarity kind of presentation. I like the clarity in this particular study. It's a study of clinically suspect arthralgia patients, and it was an evaluation of the literature. So they looked at 39 imaging studies done in patients with CSA or preclinical RRA, whatever you want to call it. And they wanted to see what the value of imaging was at this stage of the disease.

Of course, they have that label because they don't have synovitis, they just have arthralgia. What if you do imaging and you find synovitis? You find synovial fluid, you find bone marrow edema, or you find tenosynovitis on Doppler ultrasound. I've said here before, and I still believe, that Doppler ultrasound findings of tenosynovitis is highly predictive of future progression to disease. Well, in these almost 40 studies they showed that the predictive value of either ultrasound or MRI there were 12 MRI studies, 26, ultrasound, there was a few others that I'm not going to count, was variable and not as great as you want, largely due to a low sensitivity.

And when they looked at those modalities they found a low sensitivity for ultrasound thirty seven percent, MRI forty five percent, but high specificity ultrasound ninety percent, MRI eighty four percent. So, which would you do? I like ultrasound because it's easy and if you're experienced at it and finding tenosynovitis or synovitis should make you worry a little bit more. I think this is a sobering evaluation, albeit a meta analysis that says that these are not the be all end all, and maybe these tools should be reserved for large cohort studies. The NIH did a really interesting analysis.

I pulled this up because I was writing the chapter in Harrison's on the evaluation of the musculoskeletal complaint and found the data that there are approximately one hundred and twenty seven million people in The United States with musculoskeletal disease or arthritis. But in this study that was published, and this is interesting if you're a researcher and dependent on NIH funding, they looked at the burden of disease in the population in The United States and NIH funding for those diseases. So they looked at 60 different diseases, and overall studies showed a very good correlation of NIH funding with the burden of disease in our population, except for musculoskeletal disease where it was woefully deficient. So they again they matched up the population prevalence of these disorders and how much they and then matched up how much of the was it in twenty twenty three nine eighty billion dollars almost a trillion dollars being spent on research and whether it matched up. Did not for osteoarthritis.

Lowest in funding was neck arthritis. This was really surprising. So one hundred percent would be appropriately funded. Neck pain was zero point eight three percent. What?

Low back pain fourteen percent of what it should be. Osteoarthritis thirty five percent what it should be and RA about sixty six percent of what it should be. So again, low back pain itself is about $500,000,000 less than it should be based on the prevalence of the problem in The United States. To rectify this problem, the NIH would have to increase its funding 120 fold for neck pain, seven fold for low back pain, and three fold for osteoarthritis. This is important to all of us in practice, and especially at academic centers and those who are getting NIH funding.

We need to pitch for greater funding and for the advocacy necessary to get that funding. An NHANES study looked at two thousand two hundred RA patients and looked at the impact of dietary modification. This is not a surprising report, but it strengthens what we said before. The association is with diet and all cause mortality, and they looked at two different measures: the healthy eating index and the low and the dietary inflammatory index. Healthy eating index, when that's high, that's like, you know, a Mediterranean diet, a healthy diet, ones that have been shown to improve all outcomes The dietary inflammatory index one, that is high.

That's not good. That's an inflammatory diet, and we know that that's not good. Anti inflammatory diets, Mediterranean diets are good. So, they found a high healthy eating index and a low dietary inflammatory index, where we had an overall reduced mortality. So, these were the best possible diets.

Really healthy and low inflammatory diets reduced mortality by thirty percent. And I think that's a number that you can quote. That if you eat healthy, meaning and let's let's you know, know, fish, vegetables, fruits on the healthy eating index, and avoiding, you know, Burger King and french fries and waffles with lots of maple syrup and butter, you know, that's what I wanted for breakfast today, but I didn't have. But nonetheless, because I'm going for that, excuse me, low dietary inflammatory index, that's where you don't want to be. But advocating for the healthy diet, the low inflammation diet, you can tell your patients you can lower your risk of death by thirty percent.

That's equivalent to what you would get if you were on a GLP-one agonist. That's powerful data. More powerful data comes from the German database that looked at, 16,000 patients in their database of rheumatic disease patients, and what they showed, they were looking at work participation. That's the new word participation in work. It's not enough to go and do a good job at work, you just have to participate and you get paid.

And that's a measure of success by at least this study. A little worrisome, but again employment is the issue here, and absenteeism, non unemployment, and disability were the the main factors. They showed that since 2010, for about a ten year period, all these parameters went up in rheumatic disease patients. So, and this is the national database of German collaborative arthritis centers looking at people 65. During this time period, RA employment went up from 54 to 68%, PSA from 58 to 72%, a 14 improvement.

Scleroderma forty seven to sixty six, almost a 20 improvement. Lupus forty eight to 60, and axSpA sixty five to 73. Absenteeism also decreased significantly for RA, axSpA, PSA, lupus, scleroderma and ANCA associated vasculitis. So, we're doing something right, are we not? However, yet is always a but.

Our patients have not reached population employment rates, population absenteeism rates, and disability rates. So, we still have a ways to go. Better control of the disease makes for happier patients. A sub analysis of the STOP Gout study that was published last year: Jim O'Dell and a bunch of others were on that study. They looked at a sub analysis of patients in that gout study, where patients were either receiving febuxostat or allopurinol as urate lowering therapy.

They looked at patients who had chronic kidney disease, and they showed that the good news was that in CKD patients using either urate lowering therapy you were able to achieve your urate goal and that the protocol was driven by achieving your goal of six or less, or five or less if you had TOFI. It was achieved in eighty percent in the trial. That's really good. It should be a hundred percent, but it's still really good because even studies where people say they practice treat the target in gout, only like thirty forty percent of rheumatologists get to the target goal. Nonetheless, they found achieving the goal and even though they looked at gout flare rates in the second six months, because they're high in the first six months when you start your rate learning therapy, they still had, you know, thirty to forty percent.

And they actually had less, gout flares with allopurinol than febuxostat, thirty two percent versus forty five percent, significant favoring allopurinol. And there were some cases of acute kidney disease, but they didn't go into it very much. We do know that both these drugs can be used in patients with CKD. Most of those AKI's were allopurinol hypersensitivity. What you need to know about this study was that the mean dose achieved in the trial was about four hundred milligrams for allopurinol, and about sixty milligrams for febuxostat, meaning that I think some of the febuxostat was a little under dosed, but they again it was protocol driven, right?

So this does tell you, like we talked last week, that you can use these urate lowering drugs in patients with renal insufficiency, with really low risk, and I think that's important. The other important thing is, you know, get to your target and escalate your dose, and be on effective doses. We should be on higher doses we treat patients with gout that are problematic means that we should not be using, you know, three hundred-four hundred milligrams of gout a day. We should be using as high as possible. Another study from Oren Traum, Brian Lamerey, looked at a real world experience of starting methotrexate in patients on peglodecase.

Now, what's different about this study: we do know that giving methotrexate with peglodecase lowers the risk of toxicity and flares and whatnot. But in this study they had 11 uncontrolled gout patients on peglodecase already, and they started the methotrexate secondarily, right? So they were not doing well on pegilodecase, and would methotrexate make them better? Only one of the eleven patients, or nine percent, benefited from adding methotrexate. The take home point here is if you're going to be using methotrexate with peglodecase, it's got to be there from the start, with the initiation of peglodecase.

And there are other drugs that you can use, and you're using methotrexate so as to reduce the amount of anti peglodecase antibodies. You could use azathioprine. You could use mycophenolate. You could even use febuxostat, although I would not recommend that because you're monitoring the uric acid levels as a measure of whether you're getting into trouble or not. So, anyway, think about this when you're starting peglodecase.

Last bit on gout: febuxostat, made by Takeda, marketed as Uloric, has been discontinued in The United States. That doesn't mean that febuxostat is not available. It means that it's now on generics and there are generics that are available. And that's important. Takeda made the decision, and this was discovered on the FDA drug shortages list just recently, they made the decision based on the generic availability dropping sales, continued concerns about cardiovascular safety when you for febuxostat it's written about a lot really since the beginning of the febuxostat trials, the FACT trial, the APEX trial, the CONFIRMS trial which was done to figure out whether there's an increased cardiovascular risk with phobixis that it wasn't.

And then the CARES trial which said oh maybe it is. This is always banthied about. I don't to me this is like the cancer risk with the drugs we use for RA, and is the cancer from RA or from lupus or from the drugs we use? It's always from the disease, and in this case it's the same thing in my opinion. These drugs don't cause heart attacks and bad cardiovascular outcomes.

It's the gout, Does it not? I mean, gout is a horrible comorbidity machine, and I must say, of of the there's I can think of three patients who I wanted to put on peglodecase, Two of them died before I could get them on peglodecase from cardiovascular events, and one of them, didn't die, but while waiting had an MI and was hospitalized, and then didn't want to do it because heart cardiovascular side effects were in the list of side effects. This is really complicated, but not for you and I, because we understand the relationships here. You can still get febuxostat at your local pharmacy. It's going to be generic.

There was a Chinese study this week that was published 135 patients who had infectious sacroiliitis. Pyogenic sacroiliitis was most of those cases about seventy percent. The twenty one percent were TB sacroiliitis and thirteen percent were Brucella sacroiliitis. This is their experience, a collective experience between 02/2020, and they looked at everything that they did. The important points here is to make this diagnosis you need to do a CT guided biopsy of the SI joint.

Eighty seven percent of patients who had that done had a positive result yielding the pathogen that changed the course of therapy. Very important. The other interesting report, obviously these people, not all of them have back pain, but most of them have back pain, that fifty one percent of these patients met ASAS criteria for axial spondyloarthritis. So you should be worried about this, right? Back pain was lower in patients with pyogenic sacroiliitis only nineteen percent than with tuberculous and brucella that where it was forty or sixty five percent.

The MRI findings in these people was bone marrow erosions and bone marrow edema. Sed rates were high, but not always high. They were generally about 50 points 50 millimeters or so, and it was higher in pyogenic and tuberculous sacroiliacs than it was in brucella where it was only about thirty three as a mean. But the point that you really got to remember two points I guess really is do the CT guided biopsy SI joint with suspicion and and I think you should think of suspicion when it's unilateral when it's although these cases were often bilateral, and when there's other systemic features including fever. And the other point is that these people might look like axial spondyloarthritis and you need to be wary of that.

Another cohort study of, patients with JIA and uveitis, eighty one patients who were on adalimumab and they randomized them to drug withdrawal. So, half of them who were doing well with their adalimumab as far as their joints and as far as their eyes, They either kept them on adalimumab or they did switch them to placebo. In follow-up, fourteen percent of the adalimumab continued patients had a flare of either joints or their eyes, whereas almost seventy percent sixty eight percent on placebo, flared. So, if you withdraw therapy after a year, you have an eight fold higher risk of treatment failure. So I guess the bottom line is, maybe only one third of patients who have stable JIA uveitis on enalumumab can safely discontinue without flaring their eye or their joint problems.

What? I found this patient also this is a study that I found really interesting. It's from the Swedish national registries, and they looked at forty thousand 18 year old Swedish males, who I guess at the time, in that time in their life, they undergo comprehensive examination. And I guess it maybe might be for future service, military service, whatever. And that happened in 1969, 1970, and they followed these people until age 60.

And they wanted to see what their lifestyle practices were as far as future disease outcomes. They were looking at cardiovascular, respiratory and musculoskeletal disease, And they found that a few things that you would probably expect: that if they had a higher BMI, it increased the risk of musculoskeletal disease, cardiovascular disease and respiratory disease somewhere between twelve and twenty two percent. If you had as a young adult male, okay, higher muscle strength and good cardiovascular fitness, that too was associated with an increased risk of no, not cardiovascular respiratory, that was lower. But musculoskeletal diseases were higher overall at an eight percent risk, but it was largely osteoarthritis, a twenty three percent increased risk, back pain eighteen percent and shoulder disease twenty seven percent. So, and of course as you would expect smoking was not good when it came to all of these musculoskeletal, cardiovascular and respiratory disease.

What they were really talking about here is the potential for damage and you know being more fit might come with a risk of damage, and better instruction and guidance by clinicians might avoid that going forward. I've got two Ask Cush Anything questions. One was an email question from Mariah Mansour in Delaware. She asked, because I often teach about how to use methotrexate better, She asks: How many, how much vitamin A do you give for patients who have nausea with methotrexate? And how much dextromethorphan do you give for the lethargy associated with methotrexate?

So vitamin A usually comes as eight thousand units. I know you think that someone who has nausea or ulcers you increase the folate that's going to help. It doesn't, okay? But you're treating yourself if you think it does. Vitamin A does, and I learned this from again a great pediatric oncologist Bart Kamen.

He showed me the experiments where they if they took methotrexate and they poured it down the mouth of a rat they got a hemorrhagic enterocolitis. If you pretreated the rat with vitamin A they didn't get it. I'm using vitamin A. Vitamin A comes eight thousand units, and you take one pill a day to prevent the mucositis and maybe the nausea associated with methotrexate, because sometimes the nausea might be an upper GI effect as opposed to a central effect on the brain, and it does work there too. But some nausea and queasiness is a central effect, and the brain stuff the lethargy, the methotrexate blas, the blurry vision, sexual dysfunction, even nausea, the queasiness, is treated by dextromethorphan.

Dextromethorphan blocks NMDA receptors in the brain. NMDA receptors get taken up by excitogenic amines, breakdown products of methotrexate homocystic acid affect the brain by binding to NMDA receptors. You can block that with dextromethorphan, Robitussin DM, but that's syrupy, goopy and yucky. I use Mucinex DM which has thirty milligrams or sixty milligrams of DM. Thirty milligrams is enough.

And you take it only with the methotrexate. Vitamin A every day for the mucositis. Mucinex DM for the CNS effects only with the methotrexate. So you take it with the methotrexate, I give methotrexate at night, you'll take one Mucinex DM, take another one in the morning, and another one the next day. You need at least two doses to get the effect, and three in some patients.

Again, I think it's the best way to, to do this. Let me see, I have another one here from, New Jersey. Ken, my goodness. Ken from New Jersey, I'll look this up, asked me the question about Oh, here we go. It's Ken Wasser.

Let's listen to what he has to say.

This is Kenneth Wasser, RheumAtalus in New Jersey. The St. Barnabas system is offering low dose radiation for recalcitrant osteoarthritis. Curious about your take on this modality. Thanks.

Well, I can sum that up pretty quick. That's a special kind of stupid, is it not? Radiation therapy for osteoarthritis. There is a long literature about radiation therapy in arthritis in general, especially inflammatory arthritis, where it was felt to potentially be anti inflammatory and immunomodulatory. You only hear about this none of us rheumatologists are writing about this.

Any rheumatologist that actually has done any research on this shows no benefit, and it's a placebo effect or regression to the mean. That was proven in a 2022 Lancet article with long term follow-up. It doesn't work, it shouldn't work, it's a money grab. Shame on the people who are advocating this. If you're one of them, let's arm wrestle about it at the next meeting, because I think it's goofy.

Again, just look at the history of what's going on in osteoarthritis and treatment. Nothing works! The NIH is underfunding it! They need at least a threefold increase in their funding to catch up with the population based need, and there certainly is not any funding. Sorry about that.

I went a little overboard. Talking about overboard, RheumNow Live, you've got to come to this meeting, because it's going to be a great meeting. Look at the program. It's stellar. We have but but the hidden gem I talked about last week, the keynote speaker, Doctor.

Charity Dean, she's going to just amaze you. But after that we've got a reception. Yeah, that's nice, you know, a few drinks, you know, some mac and cheese and roast beef and whatever, but after that we're doing karaoke. That's right, rheumatologists do karaoke. This happens I know much of you that go out after ACR and EULAR, or during the meeting, and you're out all night singing and showing up late for the the great debate the next morning.

So we're gonna do it at this meeting, and we're gonna have fun, but it's not just karaoke. We're what's Cush gonna sing? It's probably going to be Warren Zivon's Werewolves of London or Garth Brooks' Friends in Low Play Low Places. You know, blame it all on my roots. I showed up in boots.

Anyway but the better part is it's gong show karaoke, meaning we're going to have the audience members on stage as the judges, three of them. And if they don't like the presentation they're gonna gong them off stage just like they did in Chuck Barris's gong show in the 70s and the 80s. Look it up if you're if you weren't born in 1970 or weren't alive in 1970 or 1980. Gong Show karaoke, it's gonna be a ton of fun. We'll see you at RheumNow live.

Take care.