Panacea of Prednisone & Cannabis (5.16.2025) Save

It's 05/16/2025. Hi. I'm Jack Cush with the Me, Myself and I podcast, What? Yeah, you know what podcast. This week on the podcast, good news with cannabis use, good news steroids are going down, and good news, less opioid deaths.

It's a podcast of good news. Welcome to the RheumNow podcast. But first

Great rheumatologists go to great rheumatology meetings. Now for the first time ever, RheumNow live on demand is available. We'll have more coming up after today's podcast.

We're gonna begin with a report, regulatory reports, and I have two of them. The CDC this week announced, in its analysis of overdose deaths in The US that in 2024 overdose deaths dropped by twenty seven percent, In 2023, it was one hundred and ten thousand, and in 2024, it was only eighty thousand. There are numerous reasons for that. One of the biggest drops was in fentanyl overdoses, and education and and some legislative changes. And these are very welcome changes, yet the problem remains.

Overdose is still the leading cause of death in Americans age 18 to 44. So more work still to be done. Another announcement this week from the FDA recommending caution and maybe holding off using the chikungunya virus vaccine. As you know, we've talked about the chikungunya virus, prevalent in, it's a mosquito borne illness, prevalent in The Caribbean and temperate, climates. There is a like a year ago we announced a new vaccine, actually there are two new vaccines.

One's called Ixchik. It sounds like the name of a town just past the reservation, you know. That was approved in 11/23, but they're now saying hold off on using it, because they've had, some serious post marketing safety reports, namely seventeen serious adverse events, mostly neurologic and cardiac, including two deaths. These all occurred in mainly elderly people with chronic conditions. A third of them occurred in The United States.

So, there isn't widespread use of this vaccine yet, only about 80,000 doses since its approval, but nonetheless, that needs further investigation. J and J announced this week the results of a phase three ICONIC total trial. That's their study of Ichotrokinra. We always struggle with the new names. Ichotrokinra.

This is a drug under investigation. It's an oral IL-twenty three inhibitor. It's being studied in psoriasis, and this study that was presented, I guess, at, actually just a press release, talks about the results of a three eleven patient trial looking to see if the oral IL-twenty three inhibitor would have effect on difficult to manage scalp psoriasis and genital psoriasis, and overall success was seen in fifty seven percent, skin clearance in sixty six percent of the scalp lesions, and genital psoriasis improved by seventy seven percent. These are all substantial improvements in a difficult to treat subset of patients with psoriasis. That's with icotrokinra from the iconic Total Phase three trial.

I posted up this week a report and a suggestion that maybe this is an important paper to look at. The number two most downloaded paper from the Journal of Clinical Medicine in 2024 was titled IgA Vasculitis and it's a nice review of HSP, as you know it has a bimodal distribution in kids and then in adults, but they say that steroids are first line treatment, especially in adults who have severe IgA vasculitis. But they note that there are many other studies, and most of them are uncontrolled, so the reliability of these are I don't know, but there are other treatment options beyond steroids that includes colchicine, dapsone, hydroxychloroquine, methotrexate, leflinamide, calcineurin inhibitors and mycophenolate, even rituximab, even IVIG the list goes on and on. I think what we're really saying here is that nothing really works, or that these people are difficult to treat. Maybe it's why this kind of paper is worth reviewing.

Another report on vasculitis was a meta analysis of patients with ANCA associated vasculitis who also happen to have interstitial lung disease. So, this is a bad complication in any of our disorders, whether it's RA, lupus, myositis. Anyway, this meta analysis, eight studies, six fifty four patients show that there's a significant mortality risk associated with this development. It's especially so and significant the more, age or the older the patient. If they were ever a smoker, sixty one percent increased risk.

If they have UIP pattern ILD, two fold increased risk of death, history of acute exacerbations, and a background of microscopic polyangiitis, a fourfold higher risk of death associated with ANCA associated vasculitis and the development of ILD. Not good. I found a very odd publication from the Baylor University Medical Center, which I was associated with for a long time. I still think it's a great center. They have their own Baylor proceedings journal, and there's a report in there that's an analysis of the national inpatient sample it's a retrospective study of RA patients.

And they looked at the ones these are patients who would therefore have been RA patients who would have been hospitalized and they compared those, on cannabis to those not on cannabis. What? Now, how that was discerned from the NIS, data set, I don't know, but in their report, patients, RA patients on cannabis had a significantly lower mortality fifty percent lower odds ratio of zero point five zero, that was significant. A significant reduction in depression by fifty three percent, chronic pain by fifty five percent, anxiety by forty five percent, but this cohort also tended to use more opioids, a ten percent increase, and more nicotine. So, while, you know, the lifestyle, maybe, and the psychology that goes along with cannabis use in RA patients may have certain benefits, It is also the lifestyle of cannabis use with more opioids and more nicotine that may be problematic in some.

So, I think I want to see data like this, not that this is great data. It's from a large sample, and it's from a third party sample, so it wasn't built to do this. As you can imagine, advocates of cannabis are widely touting this kind of research, normal and others, but we need more data to know about the safety and potential benefits of the current trend for widespread use of cannabis for no reason or medical reasons. Between 02/2021, a Swedish study shows in a cohort of nearly four thousand lupus patients there was a significant increase in hydroxychloroquine use, but a modest decrease. So over five years, over I guess that's fifteen years, glucocorticoids dropped from, sixty eight percent to fifty four percent to forty six percent as chronic therapy.

That's pretty good. Hydroxychloroquine however increased by twenty nine percent during the same period. So in lupus these are very welcome changes, are they not? So as you know, this week and this month we are doing a lot of lupus news. Some of the highlights also include an article about trends in lupus and drug use.

So methylprednisolone followed by low dose steroids is basically the recommended regimen. It is currently recommended by the ACR lupus nephritis guidelines. Risk factors for FLAIR when you're starting to withdraw glucocorticoids in, lupus patients include high disease activity, active serologies, younger age, shorter remission duration, faster tapering, and shorter duration of hydroxychloroquine or cessation of hydroxychloroquine. All that's very, I think, common sense, is it not? Don't be stopping steroids when basically patients are very active, very young, very uncontrolled, or you're stopping hydroxychloroquine or lowering hydroxychloroquine.

It doesn't make any sense. A single center study, I like this because it talks about cytoplasmic staining on ANAs. This is a single center study of 2,741 ANA tests. Sixty five percent were ANA negative, thirty one percent were ANA positive to the nucleosome antigens, they had nuclear antigen staining, but only two percent had exclusive cytoplasmic staining, so an ANA negative with cytoplasmic staining, or ANA positive but only cytoplasmic staining, I'm not sure how it's worded. And it was, I don't know, ten, fifteen percent that had nuclear staining and cytoplasmic staining.

When they looked at just the cytoplasmic staining, were either due to reticular dense fine speckle patterns, reticular or dense fine speckles. Two different patterns. The reticular pattern was more often associated with other diseases, especially primary biliary cholangitis, which had antibodies against the M2 antigen. And then the dense fine speckle was mostly associated with lupus. So cytoplasmic staining can be a part of lupus, but when you see it you should be thinking other, diagnoses or variants of lupus like SCLE and other things.

I think this is a nice, report. The big report of the week was probably the publication of the ACR twenty twenty four guidelines for the treatment and management and evaluation of patients with lupus nephritis, you know, this was a big hit at the ACR twenty twenty four meeting, and I just want to give you the highlights of this in a few points. They basically say that if you have newly diagnosed or you're instituting treatment for a flare of lupus nephritis, they should get intravenous glucocorticoids, pulse steroids, followed by an oral glucocorticoid regimen that basically is weaned down, right? And that everyone with lupus nephritis should be on triple therapy. If they have class three and four disease, with or without five, they should get one of three options.

The top option is actually all of them get mycophenolate no, actually a few of them get mycophenolate. Mycophenolate plus blimumab is a top option. And the triple therapy is therefore steroids plus mycophenolate plus blimumab. They consider steroids one of the triples, okay? The second option is steroids plus mycophenolate and a calcineurin inhibitor.

Third would be this oral cyclophosphamide, I'm sorry, low dose cyclophosphamide, the urolupus nephritis regimen plus belimumab. Okay? So, and then, if they're on cyclophosphamide at the outset, then you wean in mycophenolate after you stop the cyclophosphamide regimen for four or six months. If they have class five nephritis only, then it's triple regimen with steroids plus mycophenolate plus a calcium neuroinhibitor. A few key points: the guideline it says kidney biopsy kidney biopsy kidney biopsy.

If you don't get it, you're guessing. If they have extra renal manifestations, they recommend a triple regimen therapy again that contains belimumab, and they prefer that over a calcineur inhibitor for extra renal manifestations. They conditionally recommend a target dosing of mycophenolate to be two to three grams per day, And if they're non responsive or refractory, then you're really out on a plank there, right? You need to if you're on dual therapy go up to triple therapy, if you're on triple therapy you consider alternative therapy like CD20 monoclonal antibody rituximab, but that'll be changed in the future if we get obentuzumab. What else?

We have a nice report this week from Cassie Sims, Catherine Sims from Duke University, where, she was at the pregnancy and lupus meeting in Vienna this week covering it for RheumNow, and wrote a few good articles. I like her article where she compares the recently published EULAR 2025 guidelines versus the ACR 2020 guidelines on the safety of lupus medicines during pregnancy. And a few points, you know, drugs that weren't considered in 2020, are now sort of recommended in severe cases. That includes anifrolumab, Benlysta, or belimumab, but not voclosporin because there's still not enough data on voclosporin. They strongly, again the EULAR recent guidelines strongly recommend against the use of leflunomide and methotrexate, and especially against the clear cut teratogen, which is mycophenolate.

They do say that you can use azathioprine. Both of the guidelines say azathioprine is okay. Both of them say that cyclosporine and steroids are okay, both of them strongly recommend hydroxychloroquine. So, think, and even rituximab could be used, according to the new UR guidelines. So, So, useful publication, one you might want to reference if confronted with how to manage a lupus patient who has active disease and needs treatment.

I wrote a blog this week on, hydroxychloroquine for everyone, and I was really saying hydroxychloroquine for RA, everyone should get it. And I wrote a blog because twenty five years ago I used to say hydroxychloroquine is the most useless medicine in rheumatology for RA, meaning it was modest. It was modest, and the I've changed my thinking, and I've changed my thinking really because of a plethora of reports on the efficacy and safety of this drug, especially in lupus, where it's been shown to lead to less lupus flares, better disease control, improved survival, less pregnancy loss, it has anti thrombotic effects, which has greater mortality and cardiovascular outcomes, it has anti diabetic effects and it significantly lowers plasma lipids. And the fact is, while we know all of this for lupus, and it has now become a standard of therapy, everybody with lupus should be on hydroxychloroquine, You can say the same thing for RA, where it's been shown for all those things: remission, flares, cardiovascular events, less thrombotic events, less incidence of diabetes in RA patients on hydroxychloroquine. There's no reason that we shouldn't be using hydroxychloroquine in everyone with RA.

Why? Because it's effective and incredibly safe and it's cheap. That it has the same benefits as has been seen in lupus, and it really should be used in chronic inflammatory disease states like RA because it prevents a lot of the comorbidities that accompany these diseases. And lastly, RA is incredibly hard to control. I'm looking for an edge that I can get better control of my RA patients and a higher percentage of my RA patients.

It's my moneyball approach to RA, and this is one of the things I strongly advocate for, which is everybody should be on hydroxychloroquine. We have two cases from Ask Cush Anything, Doctor. Ali Jawad. Sorry, Doctor. Jawad, I didn't get where you were from.

He asked a question about nausea with methotrexate, that you take methotrexate and the patients report a few hours later, and for the next, you know, half day or day they have nausea. And the answer to this is pretty simple: number one: lower the dose or stop methotrexate. But I don't usually have to do that. The big mistake most people make is say: well, I'm gonna split the dose and let them take half in the morning and half at night, and split dose oral is the same as once weekly I'm You're delivering more medicine. You're getting better efficacy, but you also get more toxicity.

So don't split dose oral, don't go I'm lower the dose, or add vitamin A or dextromethorphan. Vitamin A, eight thousand units a day, every day, significantly lowers the risk of oral ulcers, some nausea, and other GI complications like diarrhea. On the other hand, nausea could be more of a central effect rather than a GI effect, and that can be mediated through NMDA receptors in the brain, and can be blocked by giving dextromethorphan. I like using Mucinex DM as a pill, and you just take it with methotrexate once a week. So I have my patients take methotrexate at night, I usually have them take it with the DM, Mucinex DM at night, and then the next day they take another pill twelve hours later.

Sometimes they need a third pill, but these work in like seventy percent of cases, these two manipulations. Again, you can try vitamin A, if that doesn't work you can try the dextromethorphan. They're cheap, they're easy and they work. Check my website to find out why that is. Another great complicated case from Marissa Meissner from the Geisinger Medical Center, thank you Marissa for this case, a 44 year old male who started with arthritis at age 39 with pain swelling warmth redness in the MCP's PIP's and wrist.

She the patient also had knee and shoulder pain at one point, responded best to steroids, responded some to non steroidals, and again the problem has been all the treatments she's given have not quite worked. And the main pains and problems have been in the hands, best responding to prednisone ten to fifteen milligrams a day. So, what do you do with this? Again, what she did was she did x rays, and x-ray showed mostly OA findings without clear evidence of chondrocalcinosis or pseudogout. She did a dual energy CT scan that also showed chronic slack wrist changes, but also changes that did suggest CPPD arthropathy, including traumatic, damage to the scapholunate ligament.

So the patient has been studied further by hepatology and found to have a gene mutation for C2A2Y. This is one of the gene mutations associated with hemochromatosis, but workup did not show an iron overload state. So, is this hemochromatosis? Is this just a heterozygous gene mutation? Maybe with a hint of hemochromatosis, which could lend credence to the diagnosis of CPPD?

The patient has been treated and failed treatment with adalimumab, sulfasalazine, methotrexate, etanercept, colchicine all changed and stopped for lack of efficacy. Anakinra is the only drug that has had some effect, but not complete. Anakinra plus steroids. So, what's the diagnosis? What's the treatment?

Again, this is a tough case. I don't think it's RA because of the lack of response to RA therapies. The patient is seronegative for CCP and rheumatoid factor, and you don't get a picture of articular erosions or synovitis here. It seems to fit with CPPD, and is a hard to treat case, and in those cases my mainstays are steroids, colchicine, methotrexate and anakinra. If anakinra works, but not completely, it's because anakinra has a half life of six hours.

And maybe you would do better on a longer acting IL-one inhibitor, canakinamab, but getting that approved would be a little bit difficult, but you could probably do it by writing a long letter and providing some references. The gene mutation at C2A2Y suggests a possibility of hemochromatosis. There are also associations of this gene defect in patients with beta thalassemia, and when looking this up and finding this, I was a little surprised to see that beta thalassemia is associated with RA, autoimmune arthritis, inflammatory arthritis, etc, and it looks a lot like RA. So, I don't know if this patient has something that looks like sickle disease, but a hemoglobin electrophoresis may prove useful. Obviously, if the hemoglobin electrophoresis is abnormal, I would get the hematologist involved.

If not, I would involve the to further evaluate hemochromatosis, and I would still treat this person as if they had calcium pyrophosphate deposition disease. Really difficult case. If any of you have a great suggestion, email me and I'll pass it on to Geisinger Medical Center. That's it for this week on the podcast. Tune in next week.

Room Now Live twenty twenty five has wrapped up, but you can still register for all the great content. Just go to Room Now. Live. Room Now. Live is available to you on demand.

You'll have comprehensive access to all the 2025 RoomNow live meeting content. This includes expert led lectures, multidisciplinary panel discussions, and focused step talks on rheumatology's hottest topics. Plus there's our world class instructors including Drs. Jack Cush, Michele Petrie, Jeff Curtis, Desiree Vanderheide, and Alexis Hoggi. All sessions end with a thirty minute question and answer panel with the faculty.

Register now. Head over to roomnow.live and start streaming today.