ANA Pollution (2.06.2026) Save

It's the 02/06/2026, and this is the RheumNow podcast. Hi. I'm doctor Jack Cush, executive editor of rheumnow.com. This week on the podcast, a lot of regulatory stuff, a lot of bickering, long term outcomes with drugs like SGLT two inhibitors, methotrexate steroids, also air pollution, also what happens with GCA in a large Canadian cohort. I think you'll like this data.

Tomorrow is the beginning of RheumNow live. I hope you'll be there. You can still register. Rheumnow.live. Great rheumatologists like us go to great meetings like this.

Let's start with FDA announcements. They made some announcements on this breakthrough designation for three drugs and one test recently. The breakthrough designation is sort of a fast track. It makes it easier and hastens the development of a drug that seems to have promise, based on phase two and phase three trials. The drugs we're talking about here, the first one from Biogen, Biogen litifilumab, which as you know is a monoclonal antibody against dendritic cells in lupus.

And this has been tested and being developed specifically for cutaneous lupus erythematosus using a CLE class E endpoint like we talked about last week. Woo hoo. We'll see what happens. Novartis and its drug, enalumab, the BAF receptor blockade has looked good in Sjogren's trials. And Janssen has the FcRn receptor drug nipocalimab looking good in Sjogren's.

Again, all of these seems like there's positive data, and that's why they gave them this breakthrough designation. They're still a ways away from being FDA approved, however. That's the next report. There is also one test from Encarta, a pocket Lyme test. Not sure I want it in my pocket unless I'm living in Long Island or Connecticut, but nonetheless, point of care testing, that probably is the future, is it not?

FDA also has, and actually not the FDA, companies have been writing about what drugs look like they might get FDA approved in 2026. There's a few of them on the menu that are of concern or interest to, you, and this would start with ducravastatinib, so TYK2. As you know, a TYK2 inhibitor that is currently approved for use in psoriasis. But clinical trials, including phase three in psoriatic arthritis have looked good. Also, the oral IL-twenty three inhibitor, icotrokinra, these new drugs, icotrokinra, also called icotide, looked really good in psoriasis, not yet had any results in psoriatic arthritis.

First approval or decision by the FDA will be for its indication of psoriasis. And then another drug in the JAK tick class, brepocitinib, a TYK2JAK1 inhibitor, has looked good in dermatomyositis trials. So the projections are that they're going to have their PDUFA date, which is the decision date. Sometime in 2026 for these three drugs, you might want to look for those. That's encouraging.

Somewhat discouraging were reports avacopan and anifrolumab. We reported this week that the EMA in Europe has started a review avacopan, the oral C5 inhibitor, also called TABNIO's indication is for steroid sparing in both GPA and MPA. The drug was FDA approved in 2021 based on the pivotal ADVOCATE trial. Well, first report seemed like it was from the EMA, but turns out the FDA is also doing the same. So the EMA is going forward with its investigation with serious questions about how the data was handled in the phase three trial, specifically on a few patients, specifically about liver enzyme issues, which we know to be a problem.

It's in the package insert. Same thing with the FDA. The FDA has been in discussions with the maker or the current seller of the drug. The drug was developed by ChemoCentryx, which then sold the drug to Amgen. Amgen has even though the FDA has gone to Amgen and said, you might wanna take this down, Amgen said, no, let's talk it out.

Let's go over the data. And so this is currently under review by both the FDA and the EMA. The drug is still on the market. And it wouldn't change my use. I will watch what comes of this.

You know, if anything, I think this could end up with a change in labeling. When things are really bad or looking bad, hint, hint, and then they withdraw the drug from the market, and then they tell you why. That doesn't seem to be the story here with Avacopan, but let's wait and see. The FDA sent a complete response letter recently to AstraZeneca for their applications called a BLA, a biologic license application, that gets you a new indication for a drug that's already FDA approved, that drug being anifrolumab, also called safnello, the alpha interferon targeted monoclonal antibody currently approved for use in lupus as an IV administration agent. Well, they've done clinical trials and it was published last month, I think in ANR in January about the benefits, the good results, positive results of the TULIP SC sub Q trial showing that the responses were basically on par with what you would expect with IV anifrolimab.

Also recently in Europe, the EMA has approved sub q anifrolimab for use in lupus. But the FDA is not so fast. They're saying, well, here's the complete response letter saying halt. We're we're we have to discuss this. The again, the reasons behind the complete response letter for sub q anifrolimab were not detailed as yet, but this is currently under review by the FDA with AstraZeneca.

Right now, the only administration is the IV one, but that could change in the near future. Interesting report this week, a cost effectiveness analysis on fibromyalgia drugs. As you know, these are very hard to do. So what you do is a simulation using available data cost, direct cost, indirect cost, the experience with the drugs basically. So in this cost effectiveness analysis, they did what's a standard model.

And they were specifically looking at our drugs, pregabalin, duloxetine, and melnasopran, How are they cost effective by comparison with amitriptyline? And in several of the analyses, duloxetine, especially in high doses, look to be the preferred strategy. So they considered direct costs, which, you know, cost of drug and a few others, and then societal costs, which is a cost of everything, including hiring Uber to go to a clinic to get your drug or whatever. When societal costs were considered, duloxetine one hundred and twenty milligrams a day and pregabalin four fifty milligrams a day were cost effective relative to the cheap, cheap drug amitriptyline. But what does that tell you?

That's pretty good news for duloxetine and pregabalin, but you got to use high doses. One hundred and twenty duloxetine, four fifty pregabalin. Otherwise, at lower doses, amitriptyline was more effective and less costly than Pregabalin and duloxetine and milnaciprin, and also no treatment at all. So sometimes choosing your next drug after simple analgesia and sleep aids and exercise, maybe this kind of data can guide you. An article this week about the effects of SGL2 drugs inhibitors in gout comes from a journal Diabetes Care, where the group at the Mass General and Brigham looked at a large cohort over almost twenty seven thousand patients with gout and type two diabetes.

And what they found was that sadly, sixty seven percent were plagued with polypharmacy. Gout and diabetes, that's maybe expected, but certainly not desirable. The surprising part was that if they were on an SGLT2 inhibitor, allopurinol initiations were significantly lower when compared to the dipyridamole drugs, thirty eight percent lower. Also lower with the SGLT2 drugs was the use of high dose steroids, nonsteroidals, colchicine, and diuretics being about 20% less. And that was all significant.

So another good example where effective management of the comorbidity can actually make everything better, not just the comorbidity. So in this case, managing the diabetes effectively made the gout easier to manage and probably with better outcomes. Speaking of outcomes, I like this study, which looked at what happens with RA in the long term, according to what kind of onset they had. So in a cohort analysis, they looked at patients whose onset was either that of typical RA, chronic symmetric polyarthritis, I guess is what they meant by that, versus undifferentiated inflammatory arthritis, not quite the symmetric polyarthritis, UIA, or palindromic rheumatism, which I've asserted recently that that's another version of clinically suspect arthralgia, preclinical RA, just like undifferentiated inflammatory arthritis. I think these are all the same thing.

When it comes to progressing to RA, the people who presented as RA were more likely to progress faster and get there sooner, followed by undifferentiated inflammatory arthritis with palindromic being the slowest to progress to a diagnosis ORA. The palindromic patients or presentations were more likely to have a positive family history of rheumatoid disease and the ACPA positive. Those who qualified under the heading of undifferentiated inflammatory arthritis were more likely to be female with knee symptom presentations. And the overall best remission rates once they did get to RA were those that had the palindromic onset. I think this is I like this kind of information.

You might look at it and say, you're you're nuts. I mean, I just treat what I see. That's what we all do. But do you not want to prognosticate when you're presented with, a set of symptoms or an evolution or a trajectory with your patients? We do.

The question is, how often are we accurate? We need data like this, I think. Another good report on methotrexate intolerance. This is from Cairo. A fairly large cohort, three fifty five RA patients starting on methotrexate being on it for more than three months.

And what do they find over time? Fifty one percent were intolerant of methotrexate using methotrexate questionnaire for tolerability. Two thirds or sixty six percent were compliant, meaning one third were non compliant with methotrexate. Predictors of methotrexate intolerance included younger age, parenteral use, that makes sense, Combined leflinamide use, maybe it makes sense. No sense to me was longer disease duration having more intolerance, higher tender joint counts having more intolerance.

I don't quite understand it, but that's their data. And then they threw in just to really confuse me that people who took their methotrexate before meals versus after meals were more likely to complain of intolerance. And maybe that's the whole nausea thing induced by methotrexate that they thought might be potentiated if they took it before their meals as opposed to after. I'm being speculative here, so who knows? Speaking of what to do, there was a report this week on the ARCTIC trial, which was reported like eight or nine years ago.

It's a treat to target study where new onset RA is started on methotrexate with a bridging plan for prednisolone, starting out at fifteen milligrams a day with the new methotrexate, and then over seven weeks, the prednisolone is tapered to zero milligrams. This was two thirty seven new DMAR naive RA patient. Turns out in this study, I'll think about it here, two thirty seven new DMAR naive methotrexate, you're starting prednisone. In their hands where it was protocolized, prednisone discontinuation was successful in eighty four percent at seven weeks, eighty nine percent at three months, ninety five percent at twenty four months. Are you this successful?

Well, maybe they're successful because they're following a protocol. Maybe because the prescription for prednisone that they're writing comes with an expiration date of seven weeks. And a small number, five percent, were on prednisone at every visit for two years. Their point was that you can discontinue prednisone when you start a new patient who's very active. You just have to make it an important part of the protocol.

Long term outcomes in twenty two patients with Still's disease was reported by Tom Taguchi and colleagues in Japan. Seventy three percent completed the long term extension study with an observation of about three years. Only three of the twenty two, one in seven, had serious adverse events, and their efficacy was good. ACR seventy was seventy percent. That's a joint outcome.

Nobody really has a systemic disease outcome measure, and that's unfortunate. But they did say that ninety five percent were able to reduce glucocorticoid doses, and forty one percent were able to be off of steroids in that three year follow-up. So again, the prognosis, we don't know though when Still's is going to stop. And this is, by the way, I didn't say this, is treatment with atosolizumab and a three year follow-up. And the idea is that it can steroids spare, but we don't have any data about when you can stop the tocilizumab or when you can really stop the steroids.

But this is still, I think, encouraging. A nice report out of Ontario, a Canadian study of ANA positivity being due to air pollution. What? They had 3,500 patient serum samples collected between 2010 and 2013, and they correlated this PM 2.5 particulate matter number with serologies. So the PM 2.5 refers to particulate matter that's, you know, less than 2.5 microns.

You can't see it. It's less than the width of a thin hair. We're talking about vehicle exhaust, factory fumes, smoke. Again, really small particulate matter that could gain access to the lung, damage lung, take up residence there, stimulate the immune system, etcetera. Anyway, when they compared highest to lowest quartiles of PM 2.5 levels, they showed that there was a forty six percent higher risk in that highest group for an ANA of greater than one to six forty.

That there's a fifty four percent higher risk of an ANA of greater than twelve eighty. The point is pollution has systemic immune effects, can induce ANA positivity by itself. They didn't get into how many of those ANAs from that high PM 2.5 number resulted in disease. I guess that's gonna be their long term follow-up, we have to wait on that. An interesting study out of Florida looked at nurse practitioners.

We talked about NPs and PAs last month and this month, and we had a whole session about independence. And there are areas of this country that need APPs to practice independently. There are some APPs who feel that they should practice independently. In Florida, they passed a law that if an APP or nurse practitioner has greater than three thousand hours of clinical practice care, they qualify to be autonomous, practicing primary care. Except in this study of three twenty eight NPs that about half of them were working outside of primary care, Cosmetics, anti aging, IV hydration, goofy infusion therapies, hormonal therapies, psychiatry and addiction medicine, urgent care and ER care, inpatient medicine, cardiology, half were now outside their scope of practice.

Obviously, I think that's a problem. I think this drives the AMA crazy. This is why there really shouldn't be a battle between APPs and MDs, but it's over this kind of issue that there might be. That doesn't exist in any of the APPs I've ever worked with. Right?

They're working under my hire and supervision. And if I was to run like a remote care clinic in the sticks, in places in Texas where no one was practicing, I would be fine with the APPs that I've worked with and trained them practicing independently and doing rheumatology, knowing that they have me as a backup. But this is a hot button issue. Two more reports. Alto repaired in JAMA rheumatology this past month.

As you know, this is the long term four plus year outcome study to the Apipra study. Apipra was a one year study in at risk individuals who were randomized to receive, again, they had no synovitis, they just had aqua positivity. They were randomized to receive either abatacit for a year or placebo for a year. And at the end of that year, abatacit was highly protective against developing RA, only six percent on RA versus almost thirty percent on placebo. And then after one year of therapy, they all stayed on nothing and they followed for twelve more months.

So at twenty four months, it was still significant. And that's the end of the Epipra study, twenty seven percent versus thirty eight percent, ABBA versus placebo. But now Alto has another seventy, what's it, seventy one going into Alto long term extension on ABBA, seventy two on placebo. And going out to four years, it still is significant. Forty eight percent on ABBA developed RA versus fifty six percent on placebo.

The numbers are starting to cut the lines, which were separated over time, are starting to get closer together, almost to the point after four years that it's no longer seems to be significant. But that is a significant delay. Remember, they stopped therapy at the end of twelve months, and now they're following them out to forty eight months, and it's still fairly significant. Oh, and there is this one caveat, which no one can really explain very well, but I think it's still really interesting that the subset of patients that had what they call an extended RA auto antibody profile, the five serotypes, meaning you had five different auto antibodies that were associated with RA at baseline. That would identify a group of patients with really bad disease or bad risk of disease, would it not?

Turns out if you had the five serotypes, the lines never came together. Going out to four and five years, the lines stay apart, showing that abatacep has its greatest benefit in that five serotype subset. I think this is really interesting data. Where it goes, we have to wait and see. A giant cell arteritis outcome study from Canada was published this week.

I like this one hundred and twenty one GCA patients. And first point, how many of them achieve remission? Turns out it was about seventy percent whether they receive glucocorticoids alone or glucocorticoids plus tocilizumab. Obviously, tocilizumab would be used for steroid sparing therapy, but it was much lower if you use glucocorticoids, again, high doses with other immunosuppressive drugs like methotrexate, azathioprine, where it was only forty percent effective. So that's point number one.

Point number two is at one year, the vast majority of patients are still on steroids suggesting it's really hard to wean steroids. And even with the use of steroid sparing therapies, weaning is difficult. The other point, third point is that relapses were seen in forty eight percent across the board. Median time to relapse was after two eighty three days. So that looks like, again, what's that?

Nine months, which is probably around the time that you're really pushing hard on trying to wean off steroids and whatnot. They did say in their study that methotrexate showed very limited ability to be glucocorticoid sparing, and they weren't so high on that. They did show that patients who were treated with tocilizumab had the lowest amount of glucocorticoid exposure compared to the steroid only treated group, three thousand four hundred milligrams total versus almost four thousand seven hundred milligrams. But even with tocilizumab discontinuation, which I think in Canada is mandated after a year, that twenty five percent relapsed. So that's half the relapse rate of what was seen overall, which was forty eight percent.

So there was some benefit to tocilizumab. Anyway, the authors said that tocilizumab at one year may be inadequate for long term control, that they would like to see more steroid sparing options, patient centered management, allowance and for extended therapy. So anyway, that's it for this week on the podcast. I don't know if you've seen, but you should tell your dermatology colleagues that I do a podcast called Derm on RheumNow. It's done monthly.

The January edition is up. It's just basically the same things I cover here, just focusing only on topics, reports, decisions that are germane to dermatologists, as we tend to co manage a lot of patients with psoriatic disease, cutaneous lupus vasculitis, hidradenitis. We use the same drugs. That's why I think it's a useful podcast for them. I certainly enjoy doing it.

Put the word out. I'd appreciate it. We'll see you at RheumNow live. Take care.