Fallen Angels (1.17.2025) Save

It's 01/17/2025. This is the Room Now podcast. Hi, I'm doctor Jack Cush, executive editor of roomnow.com. I want to invite you to roomnow.live. That's where you go to register.

Our meeting's coming up in three weeks. It's gonna be a fabulous meeting. I'm talking at it. Artie Cavanaugh's talking at it. We'll be hosting the meeting along with Janet Pope.

Our speakers are unparalleled. The program looks fabulous. We hope that you'll be there. Register now if you want to get a hotel room. I think there's only a few left for Friday night and Saturday night.

That's the one thing I need to let you know. Okay, let's get into the podcast this week. This week I want to start off with a discussion of lupus and infection. A report came out this week, a fairly large cohort retrospective study, one hundred and nineteen to one hundred and twenty patients with lupus. Only twelve males compared to one hundred and seven females, and they looked at the incidence of infections.

And who do you think had more infections? Men or women? I don't know why they wanted to look at this, and my reflex answer was going to be women, but it turns out the right answer, of course, is men. Because if you compare men and women with lupus, men have more severe disease. It takes more for a man to get lupus than a woman, and hence they are pre wired to have maybe more severe disease.

And that's shown up many, many, many studies. Therefore, it's not surprising that men having a greater risk of more severe disease are at greater risk of infection. In fact, it's a six fold higher risk. The highest and most common infection was pneumonia, and that was much higher in men. Women actually did have a much higher, frequency of urinary and urogenital infections, if you will.

But I think it's important to note that again that's an infection in males might be something, to worry about. A company called Setpoint Medical who's been working on, the neuroimmune modulation of rheumatoid arthritis through an implantable vagal nerve stimulator, has applied the FDA for pre market approval of their product. As you know, this was presented many years ago as an early phase two by Marc Genovese. Looked good in I think like thirteen, nineteen patients. A lot of complications because of the surgery, near the vagus nerve, blah blah blah.

A subsequent study was sort of equivocal. Now, at ACR, they presented the results of the RESET RA study. It was a February patient, twelve week outcome of, again, placebo versus the vagal nerve stimulator. ACR twenty response was thirty five percent with vagal nerve stimulation versus placebo twenty four percent and that was significant. But is it clinically meaningful?

That's really the concern. The good news is low complication rate, serious adverse events, only one point seven percent. This is a non pharmacologic way of down regulating inflammation, down regulating pro inflammatory cytokines by vagal nerve stimulation. I think we had a report at either last ACR or EULAR that said patients population studies showing patients with vagotomy had less incidence of RA. So there's something here, is there not?

But will it be clinically, useful? Is the I think we need to see, some larger studies and get some more opinions about this. The VA study did an interesting study of, vets who have been exposed to, smoke. And when they looked at this, and this is like, you know, nine thousand ninety seven hundred of vets with incidence RA amongst whom five hundred and thirty one had ILD, they showed that pollution overall increases the risk of RA and RA ILD. We probably know that, but that fire smoke was mainly associated with the risk of RA ILD with a twofold higher risk.

But that was not seen in incident RA. So incident RA was not a consequence of exposure to fire smoke. Other things like nitric oxide, ozone, etc. Was associated, and this is popular general pollution sort of things, was associated with an increased risk of RA with about a sixteen to twenty five percent increased risk, but that was for seronegative RA. So is fire smoke one of those pollutants that wouldn't cause an increase of RA?

Yeah, it looks like. And and especially for, RAILD. Again, speaking of, RoomNow Live, we have a fabulous lecture by Karen Costenbatter talking about environmental rheumatology and why we need to pay attention to this, because these are big time risk factors for the development of autoimmune disease and inflammatory disease. A network meta analysis, and I'm not sure I like network meta analyses, because they seem to manipulate the data in favor of someone that's doing the study, but how else are you going to get comparison of the use of small molecule inhibitors? That includes, you know, all the JAK inhibitors, the TIC inhibitor do cravacitinib, aprimolast as well, and they showed nine RCTs in three thousand seven hundred patients who took these drugs, looking at ACR fiftyseventy, PASI seventy five HAC outcomes with sixteen weeks outcomes.

Overall, OOPA did better than most of these, and did better than compared especially compared to adalimumab. UPA was better than adalimumab at PASI 75 responses, ducravacitinib was better than aprimelast at HAC responses. But in general, the small molecule inhibitors work in patients with PSA. The FDA this past week approved the GLP-one receptor agonist Victoza as the first GLP-one drug for use in diabetes. I think that's an important milestone, because the GLP-1s, as we discussed last week, are a big deal in many areas, including rheumatology, nephrology, cardiology, and endocrinology.

And having a cheaper alternative here, Right now the drugs are expensive. You can get compounded drug either semaglutide or Mounjaro equivalent. You can get that compounded and save a lot of money, But now having a generic, what will that do to the cost? Hopefully lower it sufficiently. An analysis this week, reported on, the overdose death rates in The United States compared to other countries, and we still are way out front.

In 2023, there were over one hundred thousand overdose deaths in The United States for the third year in a row. That's over fifty percent increase since 2019. The rate was three twenty four events per million individuals. This rate in The United States is generally being attributed to the widespread availability of both legal and illegal fentanyl, the bigger problem of poly substance abuse in The United States, counterfeit pills, and variance in state policies on harm reduction. If you haven't read Malcolm Gladwell's book on The Return of Blink, Not The Return of Blink.

It's, oh, my fur my goodness. His his first book, about marketing. It's about change. Anyway, his new book looks at, especially this issue of substance abuse abusing, compares, overdose death rates in states where they require triplicate prescriptions and don't. And just the use of triplicate prescriptions dramatically reduces reduces the rates of these overdoses.

Tipping Point is The Return of Tipping Point is the name of the book by Malcolm Gladwell. Interesting read, nonetheless. I want to talk about lifestyle interventions. A comparative study looked at two sixty four patients with arthritis, and included inflammatory arthritis, OA and FM patients, followed for two years or more, and they looked at the, what happens when you did a lifestyle intervention which could include nutrition, exercise, relaxation, and sleep. And in all these studies, significant reductions in important outcomes to patients, including weight, BMI, and patient reported outcomes, especially pain, stiffness and fatigue.

And I don't think we spend enough time on lifestyle interventions. I think rheumatologists are very good about weight. And now with GLP-1s you'll maybe be getting into that significantly. I think all too often we recommend diet and exercise without being specific about what that means. And then, you know, we're really good about talking about smoking, but this needs to be a part of the narrative that we talk to with our patients, because it is as effective and as adjunctive as anything else you'll use in the management of your patients.

A study out of Leeds looked at what happens in RA patients, who are at risk for RA, should say. So they had they were ACPA positive and they had arthralgia, and they compared these to other patients showed there was a low diversity of the gut microbiome, and that what they did see in the patients who proceeded to develop RA was a change in the accumulation of especially Prevotella capri and the whole Prevotella ACA class, and that that was maybe an important factor in why patients may progress from being at risk with autoimmunity, and then what and then maybe as a result of an environmental exposure have that next key, that next switch that makes them go to inflammatory arthritis. Interesting research out of Leeds. I'm going to end with three studies that I thought were important studies. One from Lancet, dazucibart, which is a monoclonal antibody against beta interferon, thought to be important in active dermatomyositis, is shown to be effective.

So this is a controlled trial with seventy five patients with dermatomyositis, randomized to either one of several doses and they had different phases of getting different doses, and then or placebo. Ninety three percent of patients were female, they had skin predominant disease, some had that did not had muscle predominant disease. And the main outcome here was using the classy A outcome measure for skin outcomes, showing very significant reductions in the classy A scores in those in all patients, but even greater in the skin only dermatomyositis patients. So, this is another interesting you know, are trials going on right now of JAK inhibitors in dermatomyositis, and we might see that in the future. This is good, we need clinical trials in dermatomyositis, and I think hopefully this will go forward as well.

Another interesting study: That's the generic name for a drug commonly known as Promacta. Promacta is used in the hematology world as a treatment, an FDA approved treatment, for ITP not controlled by usual measures: steroids, DMARDs, IVIG, etc. This particular study, I think it was out of Japan, was an open label experience of fifty two patients who had connective tissue disease related ITP. More than half the patients had lupus, twenty eight, fourteen had Sjogren's, five had MCTD or two had UCTD sounds good they were confused. But the idea here was that they gave these patients the regimen of Promacta.

All these patients were treated with steroids, all of them received either DMARDs or biologics or IVIG. I didn't see where they received rituximab. So my story on ITP patients or autoimmune associated ITP, my go to drug has always been B cell depletion with rituximab, and that's always worked very well every time I recommended it. But these patients were refractory to all the usual therapies they may or may not have gotten rituximab, I couldn't tell. But with a median of six months follow-up, the success rates on these refractory patients was really high more than ninety percent.

At six months it was ninety five percent. Platelet counts which started out going into these studies, eighty percent of patients were ANA positive. The platelet count was 13,000, and ranged from 1,000 to 30,000. Again, patients had an increase in their platelet counts above 50,000 within two weeks of receiving this drug. And I like this report to have a good friend who's dealing with this, and didn't respond to rituximab, didn't respond to IVIG, and was getting steroid related side effects, and hated steroids.

And he went on Promacta, and oh my goodness, it worked really well. So, when they could measure disease activity, lupus patients and scleroderma patients had significant improvement in disease activity, and those in whom they measured steroid doses, there were significant reductions in steroid doses. So, think about that: Promacta or the generic name, Eltrombopag. Sounds like a bad toy from my childhood. Eltrombopag, or an instrument I should have learned how to play.

The last study is baricitinib in early polymyalgia rheumatica. This is the bachelor study where, a small pilot study where patients thirty nine, half of whom one patient dropped out before treatment, and the week twelve efficacy comparing placebo to baricitinib, four milligrams per day, was seventy eight percent for baricitinib and thirteen percent for placebo. I mean, that's a gigantically significant response. There were more, musculoskeletal side effects, adverse effects in baricitinib, and I'm not sure why that was compared to placebo, but there were no deaths, no major adverse events or major adverse cardiovascular event. So it's a small pilot showing again the efficacy of a JAK inhibitor in patients with PMR, and we talked about previously this is, going on with other drugs and other trials right now.

I want to end, I think the most popular report this week on the website was the twenty twenty four memorial salute to our rheumatology fellows and brethren who have passed away. These are the people we know, these are the people who've done the hard work of doing, fabulous research, fabulous mentorship, you know, endearing care of their patients. I just can't say enough about these patients, and these these rheumatologists. Look at the list. I'm sure you'll see names.

I've done this now maybe last four or five years, and I must say the exercise of sitting down and trying to find the rheumatologist who passed away in The United States and around the world in the last year is, a little bit depressing, very sobering, a bit shocking, and cause for great, introspection. So, great academics and leaders who have taught many and have changed the face of rheumatology include, Paul Plotz from the NIH, Harry Bluestein from San Diego, from, UAB, J. Claude Bennett and Jean Ball, From Vermont, Sheldon Cooper. From the NIH, Joe Croft. Everybody loved Joseph Croft.

Arthur Graysell from New York City, and from Stanford, Halsted Holman, and good friend Betsy Melons, who did such groundbreaking work in pediatric rheumatology on JIA and systemic JIA. She became my friend and colleague, and she'll be sorely missed. In this list are a bunch of rheumatologists who died way too young. Salman Anwar from Ontario, Canada Stephen Back from St. Louis and Carolyn Chang from Hawaii.

Sad, sad, sad. And there were many other names that I'll point you to, and friends of mine. Doctor. Erdal Dieri, one of our fellows at UT Southwestern who was a mainstay in the Dakotas in taking care of patients in an underserved area. Jeffrey Junt down in Temple Texas who was covering a wide area of referrals and taking care of all those patients in Texas for many many years.

And the shocking news that Norm Illawite from Long Island, who became a good friend he's a pediatric rheumatologist, died at age 70. Everybody that knew Norm loved Norm because he was a big guy with a big personality, a big smile, He was fun, he was smart, he was committed. These are big losses for the world of rheumatology. When I published it I got a nice note from a friend and colleague Alan Gebowski, who pointed me to the quote from Sir Isaac Newton, who said, if I had if I have seen further if I have seen further, it is by standing on the shoulders of giants. And Gibeaux said that these men and women were giants for us.

Hopefully, they've left us a little bit of their stature so we can teach the next generation in their names. We'll see you next week at RheumNow.