Reefer Madness (12.12.2025) Save

It's 12:12 twenty This is the RoomNow podcast, and I'm Jack Cush with RoomNow. This week on the podcast, Biomarkers in scleroderma NGCA. Great videos on osteoporosis and seronegative RA by our APP colleagues and reefer madness in rheumatology. What has it come to? This week Roche announced that its new B cell targeted drug obedentuzumab was approved in in The EU by the European Commission for its use in the treatment of lupus nephritis.

Its indication is it's being used with mycophenolate mofetil in treatment of adults with class three or four, GN plus or minus concomitant class five disease. So, again, this comes about six weeks after it was approved by the FDA in The United States. So that's good news for those of us who manage lupus nephritis, another, and this time more effective drug than, rituximab. Dutch International Scleroderma trial this week looked at, their results in there. I guess it was a stem cell therapy trial of 21 patients.

It was against an active control. And in that study they did some biomarker study and they found, I think, some interesting data about biomarkers that could be used, and approximate that which is seen with what's happening in the skin as measured by the modified Rodnan Skin score. So they did a number of these, COMP, which is cartilage oligomeric matrix protein, and collagen type four alpha one, CO four a one. And they did a few others, Tenesin and a few others, but only those two, COMP and COL four a one, significantly correlated with the skin score at baseline. But only COMP was correlated with changes in modified rotten and skin score.

Again, the search for biomarkers goes on, any kind of positive data in scleroderma is always going to be welcome. An interesting study from Taiwan looked at what we know to be true in RA, but here they did it in PSA. This is two thousand four hundred PSA patients, a retrospective study. They had to be on one or more DMARDs, and they compared PSA patients were either treated with biologic DMARDs in almost twelve hundred versus almost twelve hundred with conventional DMARDs. And compared to conventional DMARDs, biologic DMAR treatment in PSA was associated with a significantly lower risk of MACE these are significant at a thirty five percent reduction All cause mortality fifty six percent reduction.

Cardiovascular mortality a forty six percent reduction. But the price was biologic DMARTs compared to conventional DMARTs had a higher rate of forty five percent, significantly higher rate of hospitalisable infections and admissions to the hospital for infections. So, again, it's always the plusminus and the management of inflammation as it relates to cardiovascular risk and infection risk. New England Journal this week published a study with a phase three trial showing that the Novartis drug, enalumab, the dual targeting was at BAF and APRIL drug that B cell depletes. It was tested in ITP, idiopathic thrombocytopenic purpura, and was shown to be effective, significantly effective in more than fifty percent of patients.

So that's a nice thing. I don't know about you, but when I treated ITP in the past, my go to drug was CD20 rituximab therapy. But it's not approved, there's only observational trials showing its efficacy. Now we have this, and I assume this might go to an FDA indication. Another study this week looked at the association between sleep and RA.

I wouldn't have thought that sleep I mean, we know that sleep's a part of fibromyalgia and like diseases, and certainly a part of pain. An NHANES population survey study of 28,000 individuals found that, nearly fourteen percent had self identified sleep disorders. And that in that same population about four point three percent had RA, and that there was a significant association, that if you had a sleep disorder, you had about a an odds ratio of getting RA of one point seven six, and that was significant. So basically a seventy six percent increased risk of RA. Isn't that interesting?

I don't know why that would be. Maybe the pain shows up before evidence of RA and the diagnosis of RA shows up, and then the pain interferes with sleep. But again, sleep is a big part of our business and we have to be good at sleep if we're going to be good at what we do. A recent Cochrane review also did a study of RA, 14 studies, three thousand three hundred and sixty nine RA patients, and looked at nurse led clinics, and compared them to rheumatologist led clinics. And they showed that nurse led clinics were highly effective in managing RA patients, generally doing better than usual care, and equating to rheumatologists in their outcomes as far as disease activity, and as far as patient measured self outcomes, self efficacy, pain, quality of life.

So, this month when we're talking about advanced practice providers and whether you should have them, and work with them, and how you utilize them, this is another bit of evidence that they are effective in managing RA. I found this study about gout and trends in gout from China being interesting, and I think it might equate well with The United States, but this was a cross sectional cohort study of over ten thousand gout patients between almost a twenty year period, 2000 and '3 to 2022. And during that period, the age of onset of gout went down. That they're seeing younger patients, especially in the 19 age group, six percent, and in the twenty to twenty nine year old age group, that was almost ten percent. Turns out that younger onset gout was associated with gout severity markers, tophi flares, kidney stones, and they also had a higher incidence of metabolic derangements like hypertension, diabetes, but they did have less dyslipidemia.

I think this is an interesting change, and in China I don't think that they've had the obesity epidemic that we've had in The United States and other Western countries that would account for a rise in gout. I don't know if anyone's reported this trend towards younger onset of gout. I'd be interested in knowing if you see that. There was a great paper in Nature this week by Tahina Niochi from Boston, saying it's time that we consider OA more than a wear and tear disease, that there's good preclinical and clinical data that suggests that OA is a systemic whole body disease, and that this should be driving new research and new treatment approaches in RA. Doctor.

Nioji is going to be at RheumNow Live in February in Dallas, is going to talk about disease modification in osteoarthritis. I thought it was interesting I saw this report in Nature, and then there was another report, I think it was in PLOS, about a phase one trial of an IL-six vaccine, immunotherapy vaccine, called PPVO-six, and it was a phase one trial of 24 patients. They had inflammatory neoA, so it was inflammatory. And they did show that the drug in several doses was safety, that it was able to effectively neutralize IL-six levels and also decrease CRP values, and show clinical outcomes as determined by the KOOS scores. That's an orthopedic score for knee OA outcomes.

So, this is encouraging that, and I assume they're going to go forward with this IL-six therapy being given systemically in patients with OA. Now, they do it just in inflammatory OA? You know, the story there isn't very good. You know, first off, the story that biologics, they don't work. You know, DMARDs, they don't work.

You know, nothing really seems to work in OA, and even if you self select or you narrow your selection to just inflammatory disease, still hasn't panned out in the well done trials. So, advances are sorely needed in osteoarthritis, and I think that's why I'm going to tell you about cannabis next after this report. So there was a simple analysis done in GCA patients, one hundred and nineteen GCA patients versus one hundred and thirty one non GCA patients, just looking at the CBC sed rate and CRP. And so, while the sed rate and CRP were elevated in GCA patients, obviously, the CBC components can be used to come up with other surrogate measures of inflammation: the neutrophil to lymphocyte ratio, the platelet to lymphocyte ratio, the monocyte to lymphocyte ratio. And in their study they found that all of these measures, especially the NLR and PLR, were significantly associated with both sed rate and CRP, but unlike the sed rate and CRP that did not predict mortality over time, the neutrophil lymphocyte ratio and the platelet lymphocyte ratio and also the monocyte lymphocyte ratio all significantly correlated with future mortality rates.

And it all comes from the CBC. Now, unfortunately your CBC doesn't print out that MLR, PLR, NLR. I can tell you I've studied the NLR, the neutrophil lymphocyte ratio, and if it's more than four point zero, you've got a very inflammatory disease. So think about looking at that. A number of interesting articles we wrote this week: I wrote a compilation piece about medical cannabis for pain management, mainly because in osteoarthritis and in pain we've been told what?

Darvon's off the market, propoxyphene is off the market, gabapentin is dangerous and doesn't work, Acetaminophen doesn't work. Nonsteroidals don't work, and nonsteroidals are dangerous, supposedly. I I grew up with nonsteroidals in the eighties and nineties. That's all we use. I still use a fair amount of nonsteroidals, but with caution.

And then, you know, tramadol is being chastised. How am I supposed to treat pain? I'm am I not in the pain business? How am I supposed to treat osteoarthritis? Let them go, let them be miserable until they are out of their mind with pain and damage, and then get them surgery like I did, like twelve, thirteen years ago, and my knees replaced.

I went from having, you know, pain that was activity limiting. Now I don't have any pain. My life's just great. I run around, do everything I want. My knees are never a problem.

But you have to go through twenty, thirty, forty years of pain to get to surgery in most cases. Anyway, there were a lot of reports in the last week or two about cannabis and its use, in The United States, and it's in Canada, and its use in pain. Twenty seven percent of US and Canadian adults have used cannabis for medical purposes. Right now in The United States 40 out of 50 states have approved cannabis for medical use, in 24 states you can use it recreationally. Briefer madness.

So four reports: one from JAMA Internal Medicine Montefiore Hospital did an eighteen month retrospective cohort study of two hundred plus patients who were on chronic opioids, and looked at the ones who took adjunctive cannabis as well. These people had substantial pain, 10 scale, about 6.8, and they had, you know, they were not the best patients. Half of them had depression, many had insomnia, anxiety, PTSD, and after eighteen months they showed that those who took cannabis, that and this is like in New York State where they had data before the approved cannabis program and date after. After the approved medical cannabis program, and people that were taking cannabis, daily opioid doses dropped by 22%. And that was significant.

Medscape did a review article, that came out of the fifty eighth Congress of the Argentina Rheumatology Society showing that, it's being used in medical conditions with most of the average to poor evidence coming in osteoarthritis and fibromyalgia. And they say that these should be used as sort of second line studies, and they point out the efficacy, they point out that the evidence in favor of their use is weak, and that we need more studies. And they review some of the side effects. Annals of Internal Medicine had an interesting study, just recently with, a Canadian study out of Ontario, where they looked at what happened in Ontario before and after cannabis was approved. I think it was approved in 2018.

And they showed that prior to cannabis stores becoming available in Ontario, cannabis use was rising before it was approved. And then when the stores became available cannabis use plateaued and maybe went down a level, but that was only in certain areas where it was available, those called the exposed areas and those that were unexposed. And then interestingly, when they looked at cannabis associated ER visits, after cannabis became available, associated ER visits plateaued or went up, where in the exposed areas where there were the dispensaries, and when there weren't in the unexposed areas they went down. So the point is that there is an association between cannabis related harm and the geographic distribution of centers, when these drugs become available. The last article came from JAMA that pointed out that while most cannabis is being used for chronic pain, insomnia, anxiety, there is no FDA indication for that.

There is no FDA indication for pain, insomnia, or anxiety. And also the evidence for their efficacy is, they say, insufficient. Right now, medical cannabis is FDA approved for HIV and AIDS induced anorexia, where it's been shown to increase body weight. Chemotherapy induced nausea and vomiting, where it's been shown to be modestly better than placebo or active comparators. And then in certain pediatric seizure disorders, oral oral cannabidiol has been shown to decrease, the frequency of seizures.

But they do say, you know, this is a warning paper that says that you shouldn't use these drugs in, or avoid them in, or extreme caution in, people who have substance abuse disorders, mental illness, cardiovascular disease, pregnancy or breastfeeding, or 25. And that's for neurodevelopmental concerns. Also, no real research in that group. They say that you should be screening people, who are on cannabis for the cannabis use disorder and hyperemesis syndrome, that there are drug interactions with cannabis, that there are liver enzyme elevations cannabis and CBD products, and that you should be using the lowest potency preparation first, and use those not as non inhaled routes and lower doses before you start going to the higher potency. Higher potency is clearly associated with more side effects.

And that you should be avoiding cannabis and CBD products when there's concurrent use with other central nervous system, the depressants. What else? Again, two great videos this week that I think you should look at. Derek Muller, a physician assistant, did a great piece on I Can't Believe It's Not Seronegative RA where he talks about the differential diagnosis of seronegative RA and why it's important to reconsider the diagnosis. I thought it was a really well done video, it's been seen I think by almost 500 people at this point.

And then Elizabeth Kirchner from the Cleveland Clinic talked about metabolic bone pearls and her experience in basically managing osteoporosis. She talks about how to calculate fracks, how to have a team of individuals that do follow ups on people who have fractures to then make sure that they get osteoporosis assessments. How to assess for vertebral fractures efficiently. A really well done video by Betsy, and I thank her for that. You know, there's another interesting study came out this week, Almost 80,000 practices in The United States compared practices who don't have nurse practitioners to those who do.

And the ones with nurse practitioners were more likely to be in lower income, and lower educational communities in rural communities. And so they predominant they predominated in areas of highest need, but also areas of lowest supply. So they're fulfilling a tremendous need, in health care and health care delivery. You know, the nurse practitioner program actually started at the University of Colorado in 1965, and since that time there's over two sorry, over 461,000 licensed nurse nurse practitioners nationwide. That's up, about 80,000 since 2023.

These 461,000 have provided over a billion patient visits every single year. A billion! Must be doing something right. If you want to know about the value of a nurse practitioner or physician assistant, you should take a look at this past week's Tuesday night rheumatology webinar. TNR, we had Cases and Guidelines was the title.

We discussed three cases, I moderated a session with three advanced practice providers: Audrey Gibson, a physician assistant Ben Smith, a physician assistant and Emma Babbage, a nurse practitioner from Tasmania. You should listen to this session. If you don't work with a nurse practitioner or physician assistant, you should watch what they do when present when they present these cases and how they manage them. I was not surprised because I've worked with many, but they said things that I didn't think of. They brought up questions to each other that I thought were incredibly insightful.

It's a great learning session. It's available as both a podcast and a video that you can look at. That's it for this week on the podcast. You can, register for RheumNow Live February in Dallas, Texas 2026. Go to roomnow.live to register.

We have, I think, only a few more days left of early bird registration, which is like at half price, especially if you're a nurse practitioner, physician assistant, or rheumatology fellow. The program looks great. When you go to roomnow.live, check out the video that Artie Cavanaugh and I did previewing the sessions that we're going to be looking forward to at RoomNow Live on February. That's it for the podcast. Take care of yourselves.

Tune in next week.