An Epidural Letdown (4.4.2025) Save

It's 04/04/2025. This is the RheumNow podcast. Hi, I'm doctor Jack Cush, executive editor of roomnow.com. And before we get into this week's podcast, I have a correction. I made a mistake.

Shame on me. Two weeks ago in our podcast and online on X, or as we know it, Twitter, I incorrectly described the study. It was my report from the American Academy of Dermatology on the phase three ICONIC lead study. It was really a report about J and J's oral IL-twenty three inhibitor called icotrokinra, and in that report I said it was superior to ducravacitinib, that was wrong. It was actually studied against in this phase three trial against placebo and shown to be highly significant, 65 versus 8% in total skin clearance, PASI ninety, fifty versus 4%.

Again, it's the oral twenty three inhibitor versus placebo, not ducravacitinib. And also the primary endpoint was week 16, I reported week 15. It was an off week, you know. And don't worry, there's going to be a lot of reports in the future about dukravacitinib both in psoriasis it's already approved for, but more coming up on it in psoriatic arthritis. But I wanted to make that correction because that was incorrect.

This week we've got a lot of interesting stuff. I want to begin with a matched cohort study of RA patients, almost eighty thousand RA patients. And in this very large data set, they were trying to make the point that, that there are a lot of avoidable hospitalizations amongst RA patients. So when they looked at these RA patients versus controls without RA, RA patients had a twelve percent increase risk of avoidable hospitalizations, which they describe as ambulatory care sensitive conditions. These are things that should be well managed as outpatients, and should, if they're well managed as outpatients, not end up in the hospital.

This includes seizure disorders, chronic lower respiratory disease, asthma, diabetes, CHF, pulmonary edema, angina, right, as examples. They said the predictors were, for these avoidable hospitalizations were age, steroids, having these comorbidities. And, it really is a call for, ambulatory care access and better primary care management can reduce the risk of these disorders. Avoidable hospitalizations, which bring significant morbidity, mortality, and cost to health care. A Korean nationwide cohort study of almost 900,000,000, 900,000 people with newly diagnosed osteoarthritis looked at the safety of nonsteroidals.

You know, don't use as much nonsteroidals today as we did during my fellowship, but still they're out there, and this study did underscore the things that you know about, the risk of nonsteroidals in OA, you know, cardiac, GI mainly, hematologic, etc. But talking about nephrotoxicity, they weren't quite all the same. And I thought that was a little interesting, and just to give you a little perspective or comparative risk assessment, if you will, that the lowest risk, which was not higher than its comparator arm, was meloxicam with an adjusted hazard ratio of 1.22 and the confidence intervals overlap one, saying it wasn't any higher. However, it was higher with other nonsteroidals: loxoprofen, xelicoxib, and naproxen, each of those having hazard ratios being almost four, two point four, and 4.7. And those were significantly elevated.

So, there are differential risks. I wouldn't have guessed honestly that meloxicam has a lower nephrotoxicity index. I often wonder whether this is related to duration of use, but more importantly the dose that's being used. But I thought it was important to at least throw this up for you to consider. The EMA and The US are on a fast pace for approval of biosimilars.

In 2024, the EMA approved 28 new biosimilars, mainly for cancer, more so than musculoskeletal or immune related disorders. But it was for cancer, osteoporosis, macular degeneration, and immune disorders like psoriasis, ulcerative colitis, crohn's disease, etc. In The United States during 2024, we had 18 new approved biosimilars. Again, this is a big deal, and, it's going to change the way we treat treat patients. Right now, there's 70, biosimilars approved in The United States with, you know, more for oncologic indications than for rheumatic, but we're pretty close, actually.

And that makes the next bit of news even a little more interesting. As you know, that, biosimilars have been around now since, I think for about fifteen years, and there was a recent FDA review of of the legislation that led to that. And you know that biosimilars get onto the market with an abbreviated course for development. You don't have to do as many studies, you don't have do it in all the indications, you have to do one bioequivalent study as far as the primary endpoint clinical outcome. Interestingly, this week the EMA has proposed a new pathway for biosimilars, suggesting that we don't need to do the clinical trial anymore.

Usually it's a large clinical trial showing that the PASI 90 score was the same with both the reference product and the new biosimilar, or that the ACR 20 was the same, etc. They're saying as long as you show structural and functional comparability along with the pharmacokinetic data and the drug interaction data, relative to a reference product, that that should be good enough to get a biosimilar approved. That's a game changer. Now that's up for discussion in Europe, and that's not been discussed nor proposed by the FDA here in The US. But it'll be interesting to see where that goes.

A review article out of a Taiwan dermatology journal says that, something that you probably know, but maybe you don't, and that is adding methotrexate to a TNF inhibitor increases the efficacy of one over two drugs over one drug, and that's for the treatment of psoriasis. Adding methotrexate TNF increases the efficacy. But there's limited data, but some data saying that adding methotrexate to an IL-seventeen inhibitor or an IL-twenty three inhibitor may have positive benefits more positive benefits psoriasis. However, conversely, in psoriatic arthritis not so much. Adding methotrexate adds no efficacy Methotrexate to TNF inhibitor adds no efficacy compared to the biologic monotherapy alone.

You know, and that's kind of the frustration of managing psoriatic arthritis. A nice review article from the NIH Division of Complementary Medicine on music therapy and its benefits in patient management. I found it interesting. I really never considered music therapy. I thought my music therapy was some guy named Led Zeppelin, and, that was good enough.

Led Zeppelin, Jackson Brown, Warren Zivon, Lindner on Stadt. Yeah. I kind of listen to all the same stuff. I'm sure you do too. Music therapy is not quite simply performing music or listening to music.

It's actually being seen by a professional music therapist, not Jackson Brown or, you know, whoever you listen to, and that there is a specialty for this. And that interventions in music therapy have been shown to be beneficial in managing anxiety, depression, pain, chronic pain, dementia, MS and Parkinson's. I found it interesting because I've never considered it, and I think we should be knowledgeable about these non pharmacologic interventions and find out how they will work in our patients. Because as you know by now, your best medicines don't always work, do they? And maybe, an intervention like music therapy is something to consider.

A study in Alberta, Canada looked at travel burden for the management of rheumatoid arthritis patients. They found in, and this is in Western Canada, there's more rural space, that on average the median time for a patient in that jurisdiction takes thirteen minutes to get to their general practitioner and thirty four minutes to get to their rheumatologist. However, there are significant differences between urban areas and rural areas, and if you look at rural areas it can be four times as long to get to the GP and eight to nine times as long to get to the rheumatologist. And this is a little disheartening. However, they did show the surprising result was that despite these differences in travel time travel delay if you will travel duration had no effect on the utilization of health care, meaning patients are motivated to get your health care, to get your expertise.

Again, these sort of numbers should be another endorsement for remote patient care, telemedicine, etc. Two things on steroids: a review in rheumatology about diagnosing PMR, where they pointed out that about half the cases of PMR out there are given steroids before they ever get to a rheumatologist who makes the diagnosis. That seems about right, given my experience in this arena. But then they looked at the what's the influence of steroids and steroid use prior to getting to the rheumatologist, and it dramatically reduces the sensitivity of how we make the diagnosis using parameters that you all know how to use. And I won't go into the numbers here, but if you get them before they're on steroids and you employ usual methods, you know, it's a sensitivity specificity it's well over eighty percent.

But if the patient's on steroids, that drops quite a bit. And this is analysis based on case report forms of sixty patients, prior to steroids and another cohort that were also with PMR or suspected PMR who got steroids. And again they found that, again getting a patient prior to being on steroids was made an easier diagnosis, but I think that's important, to know that, when you see patients on steroids, obviously a medical history is probably going to be the most important thing that you do, is it not? So, another interesting steroid, I kept seeing a lot of reports this week about a new, dissociated steroid compound. I don't know what that means, but it's a different steroid compound, it's supposed to be safer, it's called vamorolone.

Vamorolone, it's a promising alternative to traditional steroids that you use, prednisone or prednisolone, in the management of inflammatory diseases. This particular report that we put up this week showed its use in an animal model of a mouse model of inflammation, showing that it was equally effective at its anti inflammatory potential, but that it had less steroid side effects. And you know we've seen reports of new steroid compounds being developed that might could possibly be better than the ones we're using, and they never quite pan out. And when you look up this drug vamorolone, it's actually FDA approved for the use of Duchene's dystrophy, right, in both kids and adults. It's incredibly expensive.

You know, you use it at the higher dose, it could be $70,000 a year. But it's a new steroid, and hence it's it's it's you know going to have a higher price. It's got a restricted indication. And the question is whether we might see a steroid like this in our inflammatory diseases. When you look at the reviews on this drug, this was only approved I think in 2023, that it shows that it does have less glucocorticoid toxicity, and it does seem to be as effective.

But the question is how will this perform in our patients, especially if we're going use this at higher doses? So that remains to be seen, but I thought you should know there is another one on the horizon that's under development. Three more reports, one on Still's disease first line biologics are the preferred therapy in patients with new onset or flares of Still's disease, and we're talking about mainly systemic disease fever, rash, serositis, crazy labs, etc. This is a German multi center retrospective study that looked at patients enrolled, like over 200 patients enrolled over I think a fifteen year period, and it had eighty six patients for evaluation. Half of them received either IL-one or IL-six inhibitor, tocilizumab for IL-six.

Anakinra was a dominant IL-one inhibitor with some canakinumab, but mostly anakinra. Eighty nine percent of patients received an IL-one inhibitor, eleven percent received atosolizumab, and half received conventional DMARDs, which was steroids and methotrexate. And patients were assessed at week twelve and 70 two. These people, when they went on this, were not on pre existing therapy or glucocorticoids, and the primary endpoint was sustained event free remission, which meant normalization of CRP with no evidence of rash, arthritis, or fever, or complications. And it was a slam dunk for the biologics.

Fifty percent of people at week fifty two with, this was adult Still's disease, alright, not kids, fifty percent had this primary endpoint of sustained event free remission, compared to only twelve percent with DMARDs. You were If you used IL-one or IL-six inhibitor, to treat these patients as you should, there was a seven fold greater odds of achieving that endpoint. You know, this is evidence in support of the EULAR press guidelines on managing Still's disease in both kids and adults, and the ACR guidelines on managing Still's disease. Both of those guideline sets, done at different times by different groups, have in there that the treatment is an IL-one or IL-six inhibitor at the onset, plus or minus steroids, right? While you write the prescription you can give them steroids and then give the drug the next day, that evening, whatever, but that is the way to go, and that's why I published this.

I found this other interesting publication, from BMJ, it's a consensus guideline on the management of chronic spinal pain. This is chronic spinal pain of more than three months duration, so it's not acute back pain, acute spinal pain. But more than three months duration, that is not associated with cancer and not associated with inflammation or inflammatory arthropathy. This still is a tremendous number of people in the general population. So the prevalence of chronic low back pain of greater than three months duration is four percent in adults between 24 and 39, and twenty percent, if you go up to age 59.

In 2016 in The United States we spent $134,000,000,000 in the management of low back and neck pain. So this is a big problem. This guideline panel multi disciplinary, multinational, had patients on there, basically throws a, you know, damper on all the things that you do. So they say relative to sham procedures, you know, things that you commonly do like epidural steroids etc. Not proven to work.

So they are confident in their guidelines, and stating that with moderate certainty that in treating chronic axial pain, epidural injections with an anesthetic with or without steroids don't work, and that joint targeted steroid injections also don't work. That means facet injections. And that for the same can goes for radicular spinal pain, that epidural injection of anesthetic with without steroids and dorsal root ganglion injections or radiofrequency procedures had no effect on pain. This is a that's a big industry. I just had a relative that just got referred for one of these procedures this week.

But this is comparing, you know, studies where there was a sham arm, right? Which basically says most of people are going to get better with time and movement, right? Whether that's going to change your therapy, I'd like to know. The big report this week in New England Journal on Thursday was the Select GCA study, a phase three trial featuring upadacitinib in patients with GCA. Two zero nine patients were enrolled in this trial, seventy percent had new onset GCA, and they were randomized to receive either fifteen milligrams of upa versus seven point five of upa versus placebo with a pre specified twenty six week steroid taper in all patients.

The primary endpoint was sustained remission at week fifty two, and that was forty six percent with fifteen milligrams versus twenty nine percent with the placebo arm. That was significant. The seven point five milligram group was not significant compared to placebo. It was only forty one percent, not that different than forty six, but it did not achieve significance. Based on this data I would assume this is going to go to the FDA for a decision for a new indication for upadacitinib.

That's it for this week on the podcast. I want to remind you, you will see announcements for you can sign up to receive on demand access to RheumNow live content with something like 22 lectures and 10 TED talks and a lot of content, you know, five panel discussions etc. We had a bunch of people that signed up after the meeting to do that. You can do that as well. If you have got a case you'd like me to discuss here on this podcast, please go to the website lower left hand corner, click on ask Cush anything, record your case or question, and we'll discuss that here in the future.

I want to give you a heads up, in the month of May we're going to do a campaign on lupus. We're working on that right now with a lot of great lupus content. It's really exciting. It's coming up in May, which is lupus month as you know. That's it for this week.

We'll talk to you next. Take care.