RheumNow Podcast – Rheum Lives Matter (8.28.20) Save

It's the 08/28/2020. This is the Room Now podcast. Hey. I'm doctor Jack Cush, executive editor of roomnow.com. This week, of mice and men in cartilage and why room lives matter, some sort of haiku opening.

We'll get around to room lives matter at the end but there's a few reports this week about the efficacy of JAK inhibitors in patients who are having skin problems. There's a four patient case series of refractory JDM, Juvenile Dermatomyositis patients, who were treated with baricitinib, either four to eight milligrams, fairly high dose of baricitinib, and they looked at outcomes at four, six, eight, ten weeks whatever. But by week four, these refractory cases who pretty much failed the kitchen sink for their refractory skin disease has significant improvement in all global scores in their skin scores, but they and some weakness changes and very little change actually in muscle enzymes or calcinosis. But when it comes to treating the skin, which is often a big deal in JDM and dermatomyositis, JAK inhibitors seem to work well. We've reported this before, this time with baricitinib before, there's been reports with tofacitinib, I'm sure it's going to be a class effect.

There's also a nice report from, Gayard Schett's group on the use of, tofacitinib in patients with refractory plantopustular, palmoplantar psoriasis in a psoriatic arthritis patient who wasn't responding to other things. Again, I think we're going to see, a flourishing of indications for JAK inhibitors in the few year future and I think it's going to be a nice addition for both the dermatologists and the rheumatologists. You know who's been really helpful lately? That's Creaky Joints. Those sneaky people at Creaky Joints had an advanced bulletin I didn't know anything about, but I think it's a great thing and that is non radiographic axial SpA has got its own ICD 10 code.

Imagine that. We gotta learn from the patients how to code. Well, as you know, this has been one of the big issues with, the indications for non radiographic axial SpA. We've seen some reports recently of new drugs showing efficacy in that area secukinumab and other drugs getting FDA approval in this area both cerdulizumab and ixekizumab. Non radiographic axial SpA, they're out there, but and now it's approved, but you don't have a code.

Well, now you do. The, as of October 20, the code is going to be M46.8. M46.8. Bingo. Good news.

Now I like cool technology things. I know Paul Sufka has taught me a lot about this, but there's an interesting report and it's in some kind of geeky journal. I don't even know what this is, but it's about the use of saliva to detect uric acid levels. And you know, this is sort of a big area of development. It's called point of care diagnostics, point of care analytics, and the idea that you can use a number of different flexible, flexible polymers that can be embedded with all kinds of things and then be connected via Bluetooth and other mentors other measures to be biosensors for bodily functions.

In this particular analysis, by uric acid, was built in as a biosensor using PET, a polymer, that was coated with uric uricase, and that was helpful in detecting uric acid, showed great sensitivity, showed it was able to correct to detect uric acid at very low levels and showed a wide range with linear characteristics, is what they wanted. I think it's kinda cool. The idea is you could have one of these, flexible polymers that can be implanted on your tooth and you can have a real time monitoring of your uric acid levels. Why not your CRP levels? Why not your your your what's the fibromyalgia biomarker?

It's gotta come to me in about fifty years, I think. Alright. So, I like this report coming out of Japan where they discuss the, added advantages of metformin. And and really the bottom line is, should metformin be embraced by rheumatologists as co therapy? You know it's been shown, in animal models to have benefits, it's been shown in humans, in a population based study of those on metformin, low doses and high doses, taking twenty five over two thousand five hundred milligrams a day actually was two thousand five hundred and fifty, lowers the risk of incident RA in women, not men, but surprisingly nonetheless.

Again, it has effects on mTOR, it's got effects on IL-seventeen mRNA. This Japanese group reported that it basically suppresses osteoclastogenesis, and it also suppresses the upregulation of a number of different pro inflammatory cytokines, proteases, and other growth factor genes. Like not surprising that we see when metformin is on board in patients with autoimmune diseases, better things happen. And that could include the spondyloarthropathies, rheumatoid arthritis, lupus, RA and even gout. So again I I'm I'm not saying that that's happening right now I'm just saying a lot of the data when you piecemeal it together is really quite encouraging for metformin and someone should do a great study on that.

Maybe it's a good NIH study that needs to be done. So, you know President Trump, he's up for reelection and he took hydroxychloroquine. He also said, this week that he also took azithromycin, I think many of us knew that. Well, this comes in the face of Lancet Rheumatology, doing a compilation report about the effects of hydroxychloroquine, basically showing that, in RA patients, it seems to have really no cardiac risk. But when given in COVID, it may increase cardiovascular mortality and that may be a problem, especially in with long longer term use or higher higher doses.

And that what they showed was that the risk of cardiovascular mortality was also augmented by the use of azithromycin. My read on the studies with hydroxychloroquine is yes, it does not work in COVID nineteen. And that all the reports are basically neutral showing no effect or negative. And where it has shown a negative effect is when it was used a, in high doses and b, selectively in people who were sick. The sickest patients got the most, you know, risky drugs or not even risky, the hopeful drugs.

And early on, you know, through March and April and May, hydroxychloroquine was a hopeful drug. So if you were admitted to the hospital or really sick, you were going on hydroxychloroquine. Well, if you were really sick, you know, you were really sick because you had comorbidities. And a lot of the people who died with hydroxychloroquine had cardiovascular comorbidities. So I don't think it's a it's been a disaster as far as death, but because it's been given to people who are at a higher risk of death.

So, it's a selective reporting bias I believe. I think we'll see when more studies come out that again it really has shown to have no use. An interesting study comes, from the epidemiology in, RA study from Sweden. This actually looks at the risk for incident RA, and the influence of respiratory disease. In this particular study they looked at sixteen hundred incident RA cases and matched that one to two with controls and they showed that the, association of having respiratory disease either acute or chronic was associated with an increased risk of rheumatoid arthritis unrelated to seropositivity with rheumatoid factor or CCP.

This was mainly seen in nonsmokers. So all the things that you would think of, you know, as far as risk factors for RA, smoking and and, seropositivity and respiratory disease, you know, when you start to combine them, it's really the respiratory disease that has its own, independent association with RA. So this was independent associated independently associated with chronic upper respiratory infections, a forty percent increase in adjusted odds ratio of one point four, acute lower respiratory disease of two point four odds ratio, and chronic lower, a sixty percent increase with an adjusted odds ratio of one point six. It was shown that patients who were double positive for ACPA and RF did have a higher rate than those who didn't. So, again, lung disease, and this goes back to, some of the work about preclinical RA, and Mike Hoeller's work about showing that patients who are first degree relatives and are preclinical RA patients have a high amount of intrinsic lung inflammation, and that may be a risk factor for developing RA.

It's very interesting work. Other interesting work comes this week out of Stanford where the bottom line is, oh my goodness, maybe they can grow cartilage and that cartilage might be useful in replacing your bad cartilage. Well, of course, this is all mice research where in Stanford they were able to show that they could grow new functional cartilage in mice osteoarthritic knees using skeletal stem cells that were generated during microfractures microfracture surgery. Turns out that if they these stem cells were put in cultures, they often became fibroblastic like. But if they were, you know, juiced up with BMP two and VEGFR one that they had a skewing of these stem cells towards developing true articular cartilage.

Again, this is very early work. It's kind of what people have been hoping on on on for years. All those of you who are waiting not to have knee replacement because someone's gonna invent new cartilage that they can paint on your ugly cartilage, well, you'll be dead by the time this is available. Sorry for the bad news. But your offspring will actually benefit from this kind of research.

Congrats to the folks at Stanford for doing the hard work. Mayo continues to do the hard work as they always do. Mayo Clinic case control study of, two twelve autoimmune patients, half of whom had CNS inflammatory disease, the other half did not, basically showed that TNF inhibition in those that were given TNF inhibitors was associated with an increased risk, a threefold increased risk of inflammatory CNS disease. What we're talking about here is MS like disease, demyelinating disease, but it's a much more broader, definition of inflammatory disease that includes MS and demyelinating disease. You know, I had a poster a few years ago with Sergio Schwarzman where we did a, an analysis of MedWatch data and you'd be shocked at the amount of, of CNS inflammatory disease associated with biologics across the board.

It's not just TNF inhibitors. Here they had a lot of TNF inhibitor use. I'm sure if they had a much larger cohort like the FDA does, and looked at all biologics, you see a lot of CNS disease suggesting suggesting that it may be in the background, it may not be a drug specific effect, but I think it's a very confused situation. The question is whether your patients who have CNS inflammatory disease should receive TNF inhibitors or not, or should they receive other biologics right now I would say go for it until more clear evidence is is on board but, it has gotten better since it was first introduced, actually by me in a hotline I think I wrote with I wanna say I wrote it with, Eric Madison and, maybe Arty, but, it was a interesting hotline about, TNF inhibitors causing, MS like disease mainly seen in seronegative patients, lot of whom had psoriatic arthritis. So again, this is out there, I think this is helping a little bit, but not enough.

What helps fibromyalgia? Well, most of us prescribe exercise, and I think, some of us are indiscriminate about the exercise. Some are like me and have very specific ideas about exercise. Well, forget about my ideas, let's look at a systematic review of 50 trials that showed when compared to usual care, those who were prescribed exercise had a moderate benefit with regard to their fatigue. Overall, a small benefit on sleep, and there were other forms of exercise including meditative exercise programs that did also improve sleep quality, but not a big benefit from, exercise.

Again, my exercise recommendations are don't come back and tell me about walking, jumping, joining a gym, lifting weights, I don't want to hear it because that always makes everybody with fibromyalgia worse. Fibromyalgia is exaggerated pain and spasm, let's do the exact opposite. So you need yoga, Tai Chi, Pilates, pool, build that into your regimen and I think you have much better effect. But that's my opinion which was not covered by this particular, report. So we talked before about class switching of biologics, do you keep switching TNF inhibitors or do you swap out and go to another MOA?

You know, the old Ed Keystone post methotrexate response with TNF inhibitor is sixtyfortytwenty, but if you go to a second TNF inhibitor, guess what, it goes down to fiftythirtyfifteen, it goes down with successive uses irrespective of why you failed the first TNF inhibitor. Well, now it's been shown in spondyloarthritis. In this particular study that, that there was a basically a drop, with, from fifty one percent to the second TNF inhibitor to, forty one percent, a ten percent drop when looking at one of the ASDAS criteria. The bottom line is now shown as spondyloarthritis that TNF switching basically gets you a detrimental response with subsequent TNF inhibitors. So compared to primary failures where you have the worst outcomes you didn't do so bad if you had a secondary failure or failure for toxicity, the same that has been shown for Rheumatoid Arthritis.

My last report actually is a very novel report from Haroun and others, in arthritis and rheumatology about hepatitis C antiviral drug, associated, arthritis and musculoskeletal symptom worsening. This is a really interesting report. It's, it's a report of a two fifty patient prospective cohort of patients receiving what they call DAT therapy, anti viral therapy, one of two drugs for Hepatitis C. These patients, a number of them actually, I think a quarter of them had pre existing musculoskeletal disease and guess what? The ones who had pre existing musculoskeletal problems, mostly fibromyalgia I must say, but, you know, half or quarter had inflammatory arthritis, three quarters of them actually had worsening of their musculoskeletal symptoms upon completion of their antiviral therapy when they were PCR negative for Hep C.

Of those who had no prior Musculoskeletal disorder and received that therapy, that twenty five percent or twenty percent developed new Musculoskeletal symptoms and about half of those were inflammatory arthritis. So, I think it's a novel new association, it's another new drug induced association and I think that, that's something the rheumatologist needs to know about. You also need to know about BackTalk, that's a new feature on the webpage and on the email where you can click on it, go there and record a question that will be covered in subsequent episodes of the RheumNow podcast. Love to hear from you on what you think. Give me a question about something we talked about or, you know, even a case, but don't give me a nineteen minute presentation and then the chloride levels were this and what now just give me like a two liner and let let me just riff on it if that's what you want.

Also if you're looking to join the RheumNow faculty, if you're a fellow or a recent graduate and would like to participate in the exercise send me an email at jack cushroomnow dot com, and we'll, talk to you. So, Room Lives Matter. Gee, it sounds a lot like Black Lives Matter. Room lives matter is sort of confusing. Black lives matter, you either get it and are bought into it and sympathetic to it and would like to help the situation.

Many of us and many of the people we know are upset by Black Lives Matter. They're upset that, well, doesn't every life matter? Why is it just Black Lives Matter? They think it's a little overboard, and and they're not on board with it. And, you know, we have there's a lot of impediments to improving race relations in The United States, and this is one of them.

I think this is all about generosity. Room lives matter. You know, I was gonna write about Black Lives Matter by telling a story about how, if a rheumatologist is asked to describe what it's like to have lupus or what it's like to have rheumatoid arthritis. You know, we can talk the talk. We can kind of delineate a lot of emotions and symptoms and what it may feel like because we've heard it thousands of times.

That doesn't mean we understand it. That doesn't mean we've ever lived it. It just means that we're really good at mimicking it and actually many of us even aren't that good at that. But, again, if you listen to it thousands and thousands of times, you're empathetic. You can, join the discussion.

You can be helpful in the discussion. I tried to use that as a, bridge between the whole Black Lives Matter idea as well. How I wrote about it in the blog, however, didn't come off quite so simple. I was trying to be, insightful and whatnot. I gave the blog to a number of people who I trust and and really want their opinion And I was told, do not print that, you're gonna get a lot of trouble, you're gonna incite a lot of people.

And that made me upset because I really wanted to, show some empathy to this problem. I wanted, others to start to think about this problem. And you may not want to and you may not want to hear me talk about it here, but it's too late. You've gotten seventeen, eighteen minutes into the podcast and you can turn it off now. I'm going end by basically saying it's all about attention and trust.

Attention is fairly easy. You can be generous and give your attention to someone who wants to be heard. Get their perspective. Listen and don't talk so much. I don't think people want to hear so much what I think.

I think I wanna hear what others think who feel like, I need to listen. And I will listen. Trust is the other part of this, which, you know, is really hard. Trust is in short supply. We don't dole out trust.

We dole out trust to our patients. You know, we'll give them our attention and our trust because we need that reciprocal relationship to make that work. I'm asking you to do the generous thing and provide attention and trust to this discussion. And and then figure out how you fit in, whether it's holding the door for someone, that's of a different color, whether it's hiring people of different colors, whether it's, you know, you know, joining a movement, marching, and hopefully not getting shot. I think we can all do our part.

You know, Cory Booker who ran for the presidential nomination got a little far, but, you know, Peter sort of didn't get there. You know, his whole, tagline for his candidacy was love. And it was a little bit too much for people to take. You know, this really is about love. If we all loved each other, this wouldn't be such a big issue.

But love is a bridge too far for many of us. So maybe we'll get to love, but let's start with attention and trust. I think, you'll be happy and others will be happy if we can share at least that. You take care of yourselves. We'll talk next week.

Bye.