Sjogrens Graduates (8.22.2025) Save

It's 08/22/2025. This is the RheumNow podcast. Hi. I'm doctor Jack Cush, executive editor of rheumnow.com. This week on the podcast, the FDA has made some new regulatory decisions.

We've got data on safety. Safety is always good news. And when does a syndrome graduate and become a disease?

What will the rheumatoid arthritis experts say about biologics and DMARDs and their evolution over the last twenty years? Join us for a deep dive live webinar on Tuesday, August 26, at 7PM Eastern. Doctor. Jack Cush will moderate Tuesday night rheumatology session where the experts unpack the results of a nationwide three part survey covering treatment milestones, changing practices, and what the future holds for RA therapy. Don't miss this opportunity to hear what your peers are saying and where the field is headed.

Register for this TNR on roomnow.com or catch it on the YouTube, Twitter, or LinkedIn live streams. We'll see you there. This program was sponsored by Bristol Myers Squibb.

But first, we're gonna talk about a new FDA approval. The FDA this past week approved a new drug for fibromyalgia, the first drug in fifteen years. It's called TOMIA. It's got a new name, but it's an old drug, cyclobenzaprine, now available as a sublingual tablet. So it's taken sublingually.

The dose is, I think, at six milligrams per dose. What do you need to know about this? It's a new approval. It's based on two large phase three trials, 1,400 patients. The dose is two point eight milligrams.

Supposed to take two or one, depending on the dose that you'd like. Peak concentration levels are four point three hours. But, again, cyclobenzaprine has a long half life of thirty six hours, so I guess there's always the potential that this drug could leave a hangover. The half life is longer in the elderly and is longer in people with liver disease. So let's talk about some safety issues, and and I I found a few this week that I thought were important.

You know, I don't how long are you doing your rituximab infusions in? You know, the old guideline was that it was a four hour infusion, sometimes longer. If they had problems, you had to slow it down. It was five or six hours. Well, I think more recently, many of you have gone to what's called a more rapid infusion.

A meta analysis of, the efficacy and the utility and the safety of that was done. Seven trials, five hundred and thirty eight patients with a variety of rheumatic or autoimmune diagnoses were given either the oncology dose or the rheumatology dose, a thousand milligrams times two, two weeks apart. And they specifically looked at the, outcomes of ninety to one hundred and twenty minute infusions. All of these were done with premedication, and they all had a very low risk, three to fifteen percent of grade one or two infusion reactions. Very few were, there was only six patients with grade three, and that's not even a serious infusion reaction.

So you can go fast. And, I think you can go faster on the second, third, fourth infusion than than than the first, but, this is how, I've been doing it in maybe the last five years. But I must say I don't have many people on rituximab this day, but I'm not associated with a clinic that has an infusion center, So that might be one good reason. Another safety study comes from, an analysis done by Joe Marola, a rheumatologist who also does dermatologies at UT Southwestern. He did a claims data analysis of eighty two thousand psoriatic arthritis patients and found about one percent of them or five forty two who are receiving what he called combination targeted, treatment or CTT, for more than three months.

That means you're getting targeted therapies, expensive therapies, newer therapies in combination. So this is not this could be called combination biologics, but it turns out that the most common targeted combination that was being used was a Primalast either in combination with a TNF inhibitor or Primalast in combination with an IL seventeen inhibitor. And in that combination, the rates of infections were not any higher than patients who were on, one drug alone. So, again, that's sort of good news. Combination was not associated with more serious infections.

The relative risk was point five three, for SIEs, that spanned over one, so it was not higher. And opportunistic were were also not any higher. And this was looking at, outcomes after three or six months of patient taking these combinations. You know, I guess one of the points of paper was maybe you should be using more of that. But then again, can you get too expensive therapies paid for?

We really don't have good trials or any trials, reliable data about the efficacy of combining a premilast with a biologic. We do know that there are biologic combination, biologic trials going on right now in psoriatic arthritis. So this is kinda observational data. I don't know if that's a, you know, a get out of jail free card that you can use this without impunity. Obviously, patients getting combination therapy are more likely to be more more severe and have more of a refractory kind of disease that's, that merits more aggressive therapy.

So we need more on that. Another safety issue is, with JAK inhibitors and Jack knee. We've talked about the occurrence of acne with JAK inhibitors coined JAK knee. The data, I must say my rheumatology colleagues say, I don't see known as JAK knee. And the truth is that most of the reports come from the dermatology studies where I guess they're tuned into dermatologic features and outcomes.

This particular study is the occurrence rate of JAK knee in over two thousand patients with inflammatory bowel disease who were getting JAK inhibitors. Two hundred and seventy two, so that's more than ten percent developed, this. The crude prevalence was sixteen percent with upadacitinib, four percent with tofacitinib, two percent with filgotinib, and it was somewhat dose dependent with upa and tofa. Again, patients who did get Jack knee tend to be, middle aged, thirty to fifty years of age with mild to moderate, disease severity, and it usually occurred in the first three months. There was a higher risk if you had a prior history of acne vulgaris.

Well, why isn't that just acne occurring in someone on a JAK inhibitor, which may actually help their acne? But nonetheless, if you had prior acne vulgaris, it gave you a fivefold increased risk of developing jack knee. So it's not just the derm patients. They're seeing it too in IBD cohorts. I put up a Cochrane analysis this week on the use of immunosuppressive therapy in idiopathic inflammatory myositis.

This was looked at about three or four years ago where basically the Cochrane analysis said, sorry, there's really no data to support their use, and it's not much different at this point. Again, they looked at a number of therapies including biologics, and they really found insufficient evidence to really come down in a very positive way on the use of immunosuppressors. And clearly, is an unmet need. We do need trials of immunosuppressors and immunomodulatory drugs. And for me, I you know, we we we we use methotrexate and we use azathioprine based on pretty weak data and no indication.

Alright? We don't have drugs that are indicated in, inflammatory myositis, and we certainly need trials, going forward in this area. I wanna see you you do know the rituximab trials failed, but there were some say there were problems in the design of the trial, and there's still some who advocate for that. I wanna see trials with leflinamide with actually, I'm sorry, take that back. IVIG has been FDA approved for use, in patients with myositis.

And those were well done trials, and there are trials going on with JAK inhibitors in inflammatory myositis as well. So we do need trials, and I don't think we need, trial emulations or TriNetX database looks at what happens when you look at 3,000 people from EMRs from across the country. That's really made up data, in my opinion, to answer what is a serious clinical question. Data this week on the use of cognitive behavioral therapy, we've talked about that before. It really is something we should be using to manage fibromyalgia, to manage pain.

This was a study looking specifically at cognitive behavioral therapy delivered via telehealth. A study of twenty three hundred patients with chronic musculoskeletal pain of many varieties, looking at a pain reduction of 30% or more was achieved significantly more with, this CBT compared to other forms of intervention. Basically, thirty two percent versus twenty one percent with usual care. I thoroughly endorse this, I just wish I knew how to do it. The fact that it can be done by telehealth means that you should search for someone who does CBT, either face to face in your town, locale, or find someone that does it via telehealth.

Most mental health professionals are doing a lot of telehealth since COVID, and they continue to do a lot of that. So maybe that's still a possibility for you and your patients. We found a report this week at the autoimmune autoimmune disease treatment market is currently valued about $7,000,000,000, in The United States, and that's gonna rise in the next, six to eight years by another 5,000,000,000, 12,600,000,000 by 2032. Again, you take care of a lot of very sick patients. The numbers of autoimmune patients in the population, a number of patients with autoimmune disease in the population has considerably increased over the last two decades.

I was looking at some reports this week about gout and whatnot, and I decided to put up a tweet on my gout stop card. You may wanna look at that on Twitter or find the the link in the show notes. You can download the gout stop card. It's got a front and a back to it, And it's a card that's a little bigger than a business card that you can print out at your local printer and hand these out to patients. You know, gout patients are notorious for a, mismanagement and b, never coming back.

And why not equip them with some of the facts that they need to know that they can have in their wallet when they get their next gout attack? And that's what the gout stop card. The front side is about, just in general information about gout. The backside is about management issues. It's a good download.

I thoroughly endorse it. You know, gout affects twelve point one million Americans currently. That's at the last NHANES assessment. Takayasu's, what do you use for treatment? A retrospective multicenter trial this week showed you the efficacy of both infliximab and adalimumab in patients with Takayasu's.

There was no control group of placebo or another active control that the two, patients with getting either of the TNF inhibitors did get better, and they were basically non inferior to each other. So you can endorse the use of TNF inhibitor in patients with Takayasu that need better disease control. A recent study, looked at the incidence of IBD. We looked at this before. How many patients would SPA spondyloarthritis have a cold IBD and how many patients with patients with IBD have a cold SPA?

This is a study of fifteen hundred IBD patients, either Crohn's or ulcerative colitis who were being treated with either biologics or JAK inhibitors. And they, found that almost seven percent of them had, musculoskeletal symptoms, and that a minority of those people, two percent of the overall number were later diagnosed with spondyloarthritis. You know, so we've shown that, you know, it's thought that IBD patients up to twenty percent can get arthritis of some sort. In this cohort study, it was only seven percent. We do know from, studies of SPA patients.

And if you look hard, camera studies, colonoscopy, fecal calprotectin levels, up to twenty percent of them, may have occult evidence of inflammatory bowel disease. So it goes both ways. IBD, you should look for or consider. SPA, you should look for and consider IBD. A really good review on sleep apnea is published this week in JAMA.

It reminds us that a billion people have obstructive sleep apnea, and it goes over in detail the management, the presentations, the management, the monitoring, the interventions that includes positive airway pressure, CPAP machines, oral appliances, positional therapy, weight loss important, and upper airway surgery. I can tell you weight loss that the issue there is, you know, for your obese patients who have sleep apnea, losing 20 pounds is not gonna help. The only only thing that really helps with sleep apnea is major weight loss, like 20% or more. And that's certainly, a greater possibility these days, with the use of some of the newer drugs, including the GLP one agonist. So, I was informed this week by, friends at the Sjogren's Foundation about this nomenclature change that there's been a shift from the term Sjogren's syndrome to Sjogren's disease.

And it's well founded. The concern has been going on for years both at the, Sjogren's foundation in The US and in international groups. An international group was started two years ago, in 2022. And then in 2023, they had a meeting in Rome where they went over the, terms by led by a steering committee and a larger committee after that to test the results in a Delphi method. They did a literature search.

Anyway, they did voting, and they basically overwhelmingly endorsed the change from Sjogren's syndrome to Sjogren's disease, that the appropriate acronym is, capital s, low lowercase j, and capital d for Sjogren's disease, SJD. That, you shouldn't be using the term secondary Sjogren's anymore, that you should be associated Sjogren's. That's the preferred term. So Sjogren's disease associated with whatever autoimmune disease, that the patient has. And that there is no need to refer to primary or secondary.

It's really not useful unless you're doing research or clinical trials where homogeneity of the population is paramount, in which case you could use the term either primary or associated instead of secondary Sjogren's disease. Write that in your diaries. This is the day that the syndrome graduated to the disease. You may know about Kawasaki's disease. You know, we it is a a kid disease, but we sometimes see it in adult rheumatology.

I was unaware, I don't know why it was more historic than this, but Kawasaki's disease was first described in 1967, which is relatively recent, right? And this recent article that we published or reported on talks about what happens to people who were diagnosed in that era. This is a study from Japan, where they could identify patients hospitalized for cardiovascular events once they had a prior pediatric or adolescent diagnosis of Kawasaki. So this is a long term follow-up of almost 800 hospitalizations in adults who had severe cardiovascular events years after their initial diagnosis of Kawasaki disease. It turns out that there was a clustering of subsequent later cardiovascular, severe cardiovascular complications.

One in young adults and later, a surge in the late thirties. The mean age of the overall cohort was 37. The cardiovascular events, twenty percent were acute coronary syndrome, thirteen percent were percutaneous coronary interventions, bypass graft in fourteen percent, and twenty fifty three percent with heart failure or arrhythmias. Fifty three percent heart failure or arrhythmias. This cohort, twenty five percent were smokers, higher in those who had acute coronary syndromes, And then at discharge, seventy one percent were on antiplatelet therapy, twenty five percent were on anticoagulation, but only thirty one percent were on statins.

I think I'm painting a picture here. Patients that were diagnosed with Kawasaki's disease in the sixties, seventies, and eighties are now in their adult years, and we should be expecting that there might well be cardiovascular complications. And having, I think, a keen eye for this will serve your patients very, very well. Lastly, a report on, oh, I actually did talk about the the this already. This was a Joe Morola's safety of combination targeted therapies, and I think that, that may bear mentioning a second time.

That's it for this week on the podcast. This week coming up on RheumNow. On Tuesday night, we have a Tuesday night rheumatology session. It's a webinar for you, the rheumatologist. This is a twenty year look back at what we've learned about DMARD and biologic therapy and how we can apply that going forward.

We've got a great TNR panel discussion. The panel is, Jeff Curtis, from UAB, Catherine Liao from, the Brigham, and Stan Cohen from UT Southwestern in Dallas, one of my mentors. Actually, all these folks are my mentors because they're so smart and they teach us. I'm gonna be moderating, and I'm gonna be throwing at them the answers that you provided in the last three weeks where we gave you a bunch of survey questions on this topic. It should be a very interesting discussion.

You might wanna tune in on Tuesday night or look for it on RheumNow or any of the other channels where we'll be live streaming that includes LinkedIn, Facebook, Twitter, X, and YouTube. That's Tuesday August at 7PM. Be there. It'll be fun.