Mixed Drinks, Mixed Results (10.30.2026) Save

It's 10/30/2026. That's right. The day before Halloween. This is the RheumNow podcast, a special edition since it's the day before Halloween, and I'm Jack Cush wearing a goofy Halloween cap. This week on the podcast, new guidelines for PMR.

Certainty about good and bad beverages in gout, mixed results in Sjogren's, non lupus drugs save lupus lives, and big hips sink ships in psoriatic arthritis. If you can decipher that, you'll know everything about rheumatology. At the top, Novartis announced, this past week that the European Commission has approved Cosentyx secukinumab for use in adults with polymyalgia rheumatica. That would be adults with PMR not responding to, or intolerant of glucocorticoids. This makes secukinumab the first IL-17A inhibitor approved in Europe for PMR.

That's good news. I think we're awaiting the same sort of action by the FDA sometime in the next few weeks in The US, but we shall see. A study of psoriasis and biologics, from Italy shows that, obesity does affect drug responses. We know that, but I like the numbers on this: five sixty two plaque psoriasis patients treated with biologics, a third of them thirty four percent were obese. Obesity was associated with primary failure.

Not secondary failure, not failure due to toxicity, only primary failure. The obese patients had primary failure seventeen percent versus those that were non obese primary failure six percent. That's a threefold increase in primary failure due to obesity. What they showed was for every five kilograms per meter square BMI there was a thirty seven percent increase in the failure rate. The lowest failure rate was seen with IL-seventeen inhibitors and IL-twenty three inhibitors, especially compared to TNF inhibitors.

About a fifty percent lower rate compared to TNF inhibitors. And again, obesity did not associate with secondary failures or toxicity failures. I found that to be a new wrinkle, a new bit of news to me. And you know the problem with therapies in psoriasis, psoriatic arthritis is we've got a lot of them, yes, but we also have what I think are somewhat disappointing, survival statistics on when you go on a biologic, a new therapy, a JAK inhibitor, whatever, people don't usually respond and stay on the drugs long enough. Is that because we have so many to choose from?

And we have a low threshold to change? This study from the British Society of Rheumatology, they have a psoriatic arthritis registry of eight fifteen patients and the good news was at twelve months with their index drug new drugs, you know, biologic target synthetics twenty four percent had minimal disease activity. Great! Twenty four percent had an ACR 50. Great!

But when you looked at the follow-up that they had, a median follow-up of thirty one months, only two thirds of patients were still on the index drug. It falls off pretty quick, and not surprisingly patients have to cycle. Discontinuations were higher with aprimolast PDE4 inhibitors, are also higher in people who had high baseline activity, and patients who had poor patient reported outcomes at baseline. So the worse they were, the more likely they were to not do well. Is that not the case for probably most of the disease we take care of?

JAMA had a nice uveitis review that I put up that you should just look at. About forty percent of uveitis is linked to systemic disease, B27 and axSpA, or spondyloarthritis, being the most common. But they remind you, you should, when you see uveitis, which peaks twenty to forty years of age, half to two thirds of its anterior uveitis. When you see it, you need to actively worry about infection TB, toxoplasmosis, herpes. Anterior uveitis gets treated with topical steroids.

Posterior and pan uveitis gets DMARDs first, and you know methotrexate effective in fifty percent, mycophenolate seventy one percent, adalimumab if they're refractory to conventional DMARTs. I put that up because there was an interesting report on brepocitinib. We've talked about the VALOR study and brepocitinib looking good in dermatomyositis. It's a TYK2JAK1 inhibitor. They have two studies: CLARITY one, CLARITY two.

Phase three trial showing brepocitinib is effective in non infectious uveitis, three seventy one patients, given either forty five milligrams of brepocitinib or placebo for forty eight weeks. They had a steroid taper and brepocitinib was highly effective, highly effective, when it came time to look at them at the end of forty eight weeks. So, that's good news. We need more drugs to be approved for uveitis. There was a systematic review of cardiovascular outcomes in patients with IMiDs eleven hundred thousand patients (one hundred and ninety) from five studies.

And they looked at patients who were treated with SGLT2 inhibitors that includes drugs like Jardiance and the like. In this group seventy percent were lupus patients, twenty five percent scleroderma. SGLT2 inhibitor use was associated with significantly lower all cause mortality and heart failure risk. You know, this shows up, you know. And so, again, these people were taking SGLT2 inhibitors for, usually non insulin dependent diabetes, but I compared a group of people that are not on these drugs with those diseases.

And again, there's a significant lowering, but no clear MI benefit. We do know that these drugs are FDA approved and have established use in diabetes, heart failure and CKD patients. The question is, with this kind of data, and other data that I think that will follow, will lupus and autoimmune disease be an indication for SGLT2 inhibitors. I mean, we're talking about that now when it comes to, for instance, psoriatic arthritis and getting GLP-1s, right? Great effects on psoriatic arthritis.

It's been effective in gout, rheumatoid, osteoarthritis, but the, you know, the controlled trials have been done now in psoriatic arthritis. That's probably going to lead to an FDA indication. So, your arsenal of drugs may extend outside of anti inflammatory, anti rheumatic and immunosuppressive. These drugs that will manage the cardiovascular consequences and the comorbidities that are deadly in our diseases are going to be important going forward. That's my opinion.

How good are we at comorbidities? You know, I started teaching about this back around 2000, and, you know, every rheumatologist I came in contact with said, yeah, comorbidity is a big problem. Not my job. It's somebody else's job. But, you know, twenty years later, many of you are very good at smoking.

Many of you are very good at lipids and diabetes, and identifying the problem, and starting treatment, and then maybe referring. Now you're getting better at obesity, knowing the hazards of obesity in all of our patients. So this is a study of two thousand two hundred inflammatory rheumatic disease patients and one hundred and forty rheumatologists. And herein lies the problem: Rheumatologists think that they're doing pretty darn good! You know, identifying and managing comorbidities and screening for comorbidities seventy two to ninety two percent.

That includes screening for hypertension, osteoporosis, and vaccines and cancer. When you ask the patients of those one hundred and forty rheumatologists, not so much: twelve to thirty three percent. There's always been this discordance about what you think you're doing and what they know you're doing. And that's a communication gap, is it not? The truth is that rooms do agree.

They have no structured process for comorbidity screening that's in place. And they point to time, responsibility, lack of reimbursement, not enough staff, as all being factors as to why you're not doing it. Well, you should be doing it, because your patients see you, they think you're the one who knows the most about them, they trust you more than anyone else. Many of your patients who you think are seeing primary care aren't seeing primary care. So you've got to start up.

You've got to identify the problems. You've got to mandate that they have a primary care, and you need to use a screening tool. You can download, load one from RheumNow. A study of scleroderma, was published this week, and it looked at a new way. It's called spatial frequency domain imaging.

It's a non invasive evaluation of skin, and they did it in twenty five systemic sclerosis patients and thirty normal controls, and they showed it was effective, and it had correlations with modified Rodnan Skin score, and also correlations with histologic fibrosis. But when you looked at the correlation coefficients, they weren't real... They were sort of on the weak to moderate side from the modified Rodden Skin score, and maybe moderate in histology and fibrosis. So, I like the idea of having a, you know, a non invasive automated way of assessing skin disease, because I don't know how many of you do modified Rodden Skin scores on every scleroderma patient. I do.

You know, you start in fingers, back of the hand, forearm, arms, chest, face, thighs, lower leg and feet. You know, she scored a zero to three and added up. You know, I just saw a guy this week who has... I've worried that he's going to have progressive disease, but the fact is he has sclerodactyly up to his elbows. No face, and very little on his feet.

But he's got rainouts, and I'm treating him as if he has limited disease or a crest. And he's getting methotrexate, and he's been stable. His modified Rodnan Skin score for the last five visits was 12, 14, 13, and 13. And I'm gonna do it in every visit. But wouldn't it be great if I had another measure that could be done before they see me out in the waiting room even?

Well, we're working our way towards that, are we not? CAR T cell is all the rage. You know, rheumatologists believe, based on the fabulous experiments of Georg Chet and Erlangen, that, you know, it could be the answer. That we could get to a reset of a deranged immune system, and patients will go into remission and won't need biologics or steroids or DMARDs. Well, we know that that's not quite true with long term follow-up of his original cohort, but there's still encouraging data.

So there was a survey this past week published, and it looked at German rheumatologists and asked their opinion on CAR T cell and T cell redirecting therapies. The cohort size was large, the response rates were good. This was a survey done in the last quarter, I think, of twenty twenty four, and rheumatologists were ninety five percent willing to refer their patients to specialized centers for depleting therapy, cellular therapy, CAR T cell therapy. But, the rheumatologists said maybe five percent or less of their patients are severe enough to be suitable for this cellular therapy alternative. They cite a number of barriers: high cost, limited experience, limited numbers of appropriate patients.

And when... So there's... I don't know how this is going to go. I mean, right now there's, I mean, I don't know, 50 to 100 trials in rheumatology looking at CAR T and like therapies. They're all struggling with enrollment.

And it's for these reasons: you may not have enough patients, you may not have enough faith. When they did a cert... In the survey they asked the rheumatologists some knowledge questions about depletion therapies, and on a possible score of zero to 10, they scored a 4.86. So your knowledge is good, not great. This is still a challenge.

The development of these drugs, recruitment of these drugs, and your buy in is still a challenge. You know, we had the announcement a few weeks ago that Novartis suspended its CAR T cell trials, I think it was eight or nine trials, based on a few deaths. B, BMS, had, prior to that announcement, held up its trial because they were doing some safety considerations. But there's been no new news about the restart of those CAR T cell studies. We'll find out at ACR, maybe, what's really going on.

Arteva this week Arteva is a company that's been developing something called AlloNK, an allogeneic NK cell depleting therapy, and they're doing it in RA in autoimmune disease, a phase two trial. They had two deaths. Different reasons and whatnot. It's a minority of the patients, but it basically killed the trial. So, they have suspended the development of ALLO NK, they halted a phase three trial of ALLO NK, and they're downsizing this particular type of development.

We're going to see some hurdles in, cellular depletion therapy development, because these trials are difficult to do. But that's the news from this week. You know, we subscribe to everything here at RheumNow. The Journal of Physiotherapy Research International reported this week that TENS transcutaneous electrical nerve stimulation does not work in NEO A. A sham controlled trial with ninety six patients with NEO A, all of them were treated with exercise, and half received TENS, and the other half got a sham TENS, and showed no difference in the outputs at one month.

And they use a formal score, the CUSE score, that's the orthopedic knee outcome score that is a reliable validated measure. Moreover, it didn't matter which group that you were in, the ones that got better didn't achieve the minimally clinically important the minimal clinically important difference, the MCID. So yeah, TENS doesn't seem to work here. A review article from a nutrition journal looked at the risk of hyperuricemia and gout with certain therapies. This is a meta analysis of 52 studies, and yeah, it showed that alcohol had basically a two fold increased risk of gout and a fifty percent increased risk of hyperuricemia.

The same could be found for sugar sweetened high fructose corn syrup sodas and beverages that increase gout thirty seven percent and increase uric acid elevations forty eight percent. The same was seen with, tea. Tea also, will increase the risk of gout twenty nine percent. Again, this is this is a, you know, putting all this data together from 52 studies. While tea may increase your gout risk, coffee will decrease your gout risk, and decrease it by forty six percent.

The Journal Advances in Rheumatology had a report this week from Panlar looking at the TB and latent tuberculosis burden in Latin America. They reviewed the Panlar registry that had five ninety imid patients taking a wealth of the drugs that you and I use. Half are on glucocorticoids, forty four percent are on biologic DMARDs, mostly TNF inhibitors, twenty nine percent JAK inhibitors, twenty seven percent were on conventional DMARDs. Five ninety of your patients, why were only four thirty of them screened for TB? Uh-oh, that's a problem, that's an oversight.

I know that... And by the way, I did a survey of rheumatologists back in 2012 that basically showed the same number. Now, if I just hit you over the head, new patient, gonna start on TNF inhibitor, yeah, you're gonna say I'm gonna screen for TB. But if you make it a complex case and you bury it amongst all the choices that you have to do in a busy first visit, it's often missed. So, in their study only four thirty or seventy three percent had TB screening.

But of that number, four thirty, there was fourteen percent who had evidence of latent tuberculosis. That's very high. Alright? And maybe even higher, and it's higher because they're probably on TNF inhibitors, and maybe other drugs, but the main drug that drives TB risk here is TNF inhibitors. Much more than JAKs, or IL-six, or abatacept.

I mean, a lot more. At twelve months they, did a repeat TB screening in only ninety nine of the four thirty, and they had five new LTBI cases, meaning... Well, why did they have to rescreen? Well, they should have rescreened. First off, you don't do annual testing.

That's a special kind of stupid. You only do retesting when risk changes, new exposures. Maybe you're... You needed to do it to start a new biologic. But they found five new, LTBI cases.

Of the five, there were only two that had active TB. So there's a lesson to be learned here. In The United States, if you're born in The United States, and in England, and Western Europe, and Scandinavia, and Australia, the risk of TB is very, very low. Incidence rates are about, you know, in the general population about one per one hundred thousand per year. In an RA population, it's going lower and lower every five years.

It's probably around five per one hundred ks. Put them on a TNF inhibitor, that risk doubles if you're born in these low risk areas. But if you're from Latin America, there the population risk is thirty to sixty. If you're on a TNF inhibitor, it can go up two to nine fold. So, if you're from a high risk endemic area, that's Southeast Asia, all of Russia, Africa, all being higher, higher, higher than Latin America.

And all of those are gigantically high compared to The United States, Canada, England, Germany, Austria, etcetera. But, again, do you need to do repeat testing? Not unless risk changes, or unless you're mandated to do so by an idiot guideline that your insurance company is adhering to. And then, again, the risk of getting TB is much lower, is it not? Okay?

It's really ident... Now we're really identifying latent TB. So, I hope you found that helpful. I liked it from a number standpoint. A lot of interesting articles this week, including an article by Eric Dine on IVIG and scleroderma.

Interesting, some evidence, but no good studies, right? Evidence... A good article by Brian Jaros looking at how to best treat Takayasus. You should look at that. Two articles I want to bring up because they're pretty popular.

One is a New England Journal article, on enalumab, the B cell depleting monoclonal antibody. Enalumab is an IgG1 monoclonal antibody that depletes as a dual mechanism for depletion of B cells. It targets BAF, and it works via ADCC. At ACR last year, they reported the Neptunus I and Neptunus II trials. A lot of buzz, lot of excitement, you know, definite improvement, met its primary endpoint, you know, finally we got a biologic that looks good.

Well, it showed up in New England Journal, all the data, and it still looks good. It still met its primary endpoint, which was the change in SDI over forty eight weeks. But if you look at the graphs, you know, the change in SDI over forty eight weeks happens at the end. It doesn't happen like right out of the gate when you compare it to placebo. So the Neptunis I had two arms: placebo versus enalumab, and this is a parenteral therapy given monthly, and the Neptunis two trial was a medium dose versus...

No, usual monthly enalumab versus every three month enalumab versus placebo. And they both worked at week forty eight. The p value in Neptunus one was 0.05 and the p value in Neptunus two was 0.04. So congratulations on all of that. But there are mixed results here.

When they looked at a bunch of secondary outcomes, something called the SSSD and the SPRE, and other measures that are important to patients, Unalumab was numerically better than placebo, but not significantly so. So when they looked at the SDI responders to be an SDI responder, you had to drop your SDI score composite score of many measures by five points or more. STI responders in the Neptunus one study was fifty seven percent versus forty eight percent. Looks good, but not significant. Neptunus study, the STI responses were sixty percent, sixty point five percent for the two enalumab doses, arms, versus fifty five percent in placebo.

Also not significant. So, you know, why did this not look great? And I think the answer is quite simply: a very these are two very large trials, altogether the number of patients was seven seventy nine patients that were enrolled in these studies and treated. The ESTI response is the primary endpoint it's a composite measure with a score that goes from zero to 123. The mean entry SDI score at baseline in both Neptunus one and two was around 12, plus or minus five or six, meaning they had mild disease for the most part.

How many of them had more than mild disease and that's an STI greater than 13? That doesn't sound like moderate disease to me, but about a third of patients. So I think that the main fault of this trial was that they enrolled relatively mild patients, and they asked them to, you know, do an Olympic kind of performance. Novartis has already started another phase three trial with more severe patients. That's called the THALASSA study that's currently enrolling.

We'll probably see that maybe 2028, 2029, I don't know, but that's... I will get that. The question is: with this data that they have, and this is two phase three trials, that's enough for the FDA to make a consideration. The FDA has had this data for a while. They're supposed to make a decision, a regulatory decision, on enalumab by the end of this year.

My guess is it might happen, the week of ACR, but I'm just guessing I have no inside track. The last report I think was really important because last year, twenty twenty three, September, we had a campaign on polymyalgia rheumatica. My campaign advisory committee, you know, four great people in in, PMR, you know, made one of their goals were were to have PMR on the program the next year at ACR, they did, to have new guidelines for PMR, and they have. But now this is the BSR guidelines. And this is updating guidelines that are a number...

I think... I want to say 2009 or 2015? 2015, I think. Anyway, these are worth reviewing. And you remember at EULAR this year, there were new EULAR guidelines on large vessel vasculitis, which included Takayasu's GCA, and they threw in PMR as well.

What the BSR, puts forward kind of aligns with that fairly well. Number one: start low. Starting with the prednisone twelve point five to fifteen, not fifteen to twenty five, that wherever you start you can increase it up to a max of twenty five, and that once you have a response you can begin tapering two to four weeks after symptom control. They did say outright doses starting doses below ten milligrams at ten milligrams a day or lower are incomplete and not even worth going... Going for.

Standard taper is one pill, two point five milligrams every two to four weeks, down to ten milligrams, then one milligram every four to eight weeks thereafter. I like the one of Richard Conway, which he makes monthly changes, kind of along the same line, and we've covered that here before. If steroid toxicity or risk is high, you can do a faster taper, which is one milligram every two to three weeks, aiming to stop within six months. That's often what happens in the clinical trials. The other thing that's new in these guidelines from the BSR is bone protection is mandatory.

These people are going be on steroids, they're going be on steroids for a long while. Don't wait for them to have a bad DEXA. Everyone gets protection by being on a bisphosphonate, calcium, vitamin D, unless it's a contraindication. Get a DEXA, follow them going forward. Third new thing is methotrexate is an impossible option.

I don't like this one at all. Then they point to a small 58 patient PMR mode study, which I have had problems with in the past. That's twenty five milligrams of methotrexate a week, trying to achieve GC free admission, and in a fifty two week study it showed that it worked. But that trial had problems. There are other methotrexate trials that have some problems.

And the UR guidelines said that you can use methotrexate for problematic steroid sparing with PMR and GCA, and when asked what's the data? They basically said the rest of the world doesn't have IL-six or JAK inhibition access, that they can use that. So they're going with the next best thing even when the data is not all that great. But this is a BSR guideline. Congratulations if that's what you want to listen to.

Faster tapers are legitimate and can be done within six months. In the MODE study, half the patients achieved GC free remission within six months and being off steroids. So, it is possible you can do fast tapers. Maybe you should do a fast taper and challenge the hell out of everyone. And then when you can't taper, well then you need steroid sparing.

And then you'll be using steroid sparing therapies faster. But the bottom line is, PMR patients are on steroids way longer than what you promised. Everyone promises one to two years, the average is four to five. IL-six blockades or other steroid sparing therapies is for refractory disease, not first line therapy. They think that patients...

These guidelines were kind of given to NICE and The UK population, especially to primary carers, and they said that you should consider rheumatology referral because rheumatologists will talk about the earlier possible use of methotrexate in newly diagnosed patients. They say that patients who are refractory and may need steroid sparing therapy should be referred to rheumatologists at all. And that you should consider methotrexate in patients who have relapsed or who are at higher toxicity risk. Read the article, get more insights into to whether your standards of care with PMR are up to snuff according to the BSR. Next week, we go to Florida, Orlando, Florida for ACR.

We'll be there. Come by the RheumNow booth. Come by. Get a rheumatology card, a pocket brain. You can hand this out to your mentors.

Get a RheumNow pen. You know, we give those out. We got plenty plenty for you. Come by. Get a picture.

Tell me what you like. Get a picture with me or my avatar that'll be at the... You won't want... You don't... You can't imagine what they did to this big fat head of mine, in the booth.

Go by and either take a picture with it or give me what they did. They gave me a temporary biopsy, they they put things up my nose, they gave me a Mexican mustache, it was not pretty. But we hope to see you at ACR, it's going to be fun, it's going to be a lot of great information. Follow us at roomnow.com. Take care, God bless.