Vitamin D and Lupus Outcomes (11.21.2025) Save

It's the 11/21/2025. This is the RheumNow podcast. Hi, I'm doctor Jack Cush, executive editor of roomnow.com. This week on the podcast, we'll talk about preventing disease with colchicine and romecizumab. How about monitoring disease by ferritin or IL one receptor antagonist?

And we all know what we all know what to do when the ANA shows up. Right? Well, we're gonna actually talk about vitamin D. You love it. I'm bothered by it.

Let's see what the data shows. First, a study of lupus nephritis. A hundred and thirty six patients looking at the natural history of steroid use in this cohort. They followed these patients for one hundred and twenty one months. The mean time to wean steroids to seven point five milligrams a day was nine months, to five milligrams a day was twelve months, and to get off steroids was twenty nine months.

So not too bad weaning, but obviously not good enough if the goal was getting off. The predictors of a shorter time to discontinuation was having a sustained complete response or a slew die of four or less, having membranous lupus nephritis, and being on hydroxychloroquine. If you were on steroids for a long period of time, guess what? You had more renal flares and more organ damage. That goes without saying, does it not?

Why else would you be on steroids? But you know, in this era where we're talking about trying to minimize steroids and get to very low or no steroids, you know, this data is important, telling you it's still a challenge, it's still in your court, and it still is either your responsibility or your fault or maybe your accolades if you're good at this. I was raised in a very lupus heavy environment at a county hospital, where I found that getting totally off steroids was not a good idea, but getting down to five milligrams or less was probably a good idea. There are others who believe this, but I think some of our leaders right now, including Michele Petrie and others, are really advocating for getting off steroids whenever you can. A good idea.

A recent study caught my eye about prevention of osteoarthritis, either hip, knee, or hand, OA, and in this target emulation trial they looked at 12,145 patients older, mostly female, mostly 80 years of age, and they showed that when you looked at women on Romecizumab, the sclerostatin inhibitor, or versus Teriparatide, PTH targeting, that you had a significantly lower risk of developing mainly OA in general, but specifically knee OA, where there was about a twenty to twenty one percent lower risk. Hip and hand OA was also lower, but not to statistical significance. There was still, and the confidence interval still overlapped one a little bit there. So there was this trend with Romecizumab, and I put this up there because there has been data out there about, you know, for a long time, about bisphosphonate use may lower the risk of osteoarthritis. Conflicting evidence, certainly not conclusive.

I did trials early on where we looked at bisphosphonates trying to retard x-ray erosions in rheumatoid arthritis. And there's always been this idea that better bone metabolism drugs, if you will, might lead to better bone outcomes in general. The mechanisms as to how Romexizumab would be better than teriparatide or paraparatide, I am not too certain of. But I find this interesting, and I think there's another call to use these more aggressive therapies in managing osteoporosis. A recent Cochrane meta analysis weighed in on something that we have talked about in the past, does colchicine lower cardiovascular risk?

Does it lower the risk of MI? This was a Cochrane review of what's the number of patients here? It was large. It was 12 studies, twenty two thousand nine hundred patients compared to eleven thousand of the twenty two thousand, half of them, eleven thousand were on colchicine. They found overall good evidence that colchicine lowers the risk of MI by twenty six percent, and stroke by thirty three percent, those being significant.

Overall, colchicine did not give an increased risk of serious adverse events, but we know colchicine does increase the rate of GI events by in over fifty-sixty percent of patients who take the drug. I do think chronic colchicine use, which I don't use much of I must say, is good at retarding exotic homes, and this is why the cardiologists are in favor of colchicine for a lot of indications in, the cardiology world. A MarcusScan claims data study looked at, the infection rates with adalimumab either in hidradenitis suppurativa or psoriasis. And what do you need to know here? You need to know that serious infectious events in the pre biologic era was nine per one hundred in RA.

When you're doing great in clinical trials and drug development, you're at like one to two per one hundred patient years. When you're doing bad, you're closer to nine. Most of the drugs in TNF inhibitors, for instance in RA, were in the three to six range, right? But what happens to other disorders? And it turns out, as I said last week, that other disorders are either as dirty as RA, and that includes inflammatory bowel disease, right?

Or much cleaner than RA and IBD, and that's psoriasis with psoriatic arthritis falling in between. So in this study, they looked at adalimumab, a popular TNF inhibitor, and rates of infection with hidradenitis suppurativa, which I say is dirtier, it looks more like RA and IBD, and there the rate was, or actually just gave us a hazard ratio. It was a fifty three percent significant increase in hospitalizable or serious infectious events, and this was especially true for sepsis and, genitourinary infections. So it's much higher when comparing, infection rates in Hidradenitis suppurativa versus psoriasis, which we know has a relatively low rate. And that tells you again a lot about expectations when using biologics are not the same across the board, they may, differ according to the host and the host disease.

I like the study on Still's disease because it's Still's disease, and they looked at ferritin and how useful is ferritin. You guys love ferritin, you're like all gaga about ferritin, no I'm not. Hyperferon anemia, like ten thousand ferritin and more, is more likely to be due to some other disease than it is to be due to Still's or macrophage activation syndrome, well it certainly happens there. But high ferritins in Still's disease, ferritin being acute phase reactant, is far inferior to CRP and Sedrite, those being elevated in over ninety percent of patients with active inflammatory systemic Stills, kids or adults. Ferritin, fifty percent or less.

In this study, a retrospective review of one hundred and thirteen adult Still's patients, mean age 45, mean ferritin levels at baseline were 4,600, ranging from 1,100 up to 14,000. They looked at the ability of some intervention to avoid advanced therapy need, and here they counted advanced therapies as the use of IVIG, IL-one or IL-six inhibitors. This was a study a few years ago before IL-one and IL-six became the standard of care. In this cohort of one hundred and thirteen patients, thirteen percent required advanced therapy IV, IG, IL-one or IL-six inhibitors. These were not predicted by ferritin levels.

If ferritin levels were continually high, sustained high, it would tell you who's got the worst disease, is going to need the more aggressive therapy. Ferritin was not a reliable biomarker in Still's disease. Ferritin is a very good biomarker for impending MAS, or MAS that's ongoing and active and needs to be treated. But you could order it, just I don't order much of it, to be honest with you. And it tells you in this study it's not a great biomarker.

What could be a good biomarker? In large vessel vasculitis, which I think in many ways is an auto inflammatory, certainly a innate immune system, involves the inflammasome, is the use of IL-1Ra. This is a relatively small study of twenty one patients who are treatment naive with large vessel vasculitis, thirteen with GCA, eight with Takayasu's arteritis. IL-1Ra was two to three fold higher with Takayasu's and GCA than in those without, where in normals the IL-1Ra levels, and this is a receptor antagonist which is counter regulatory to IL-one, right, was 170 picograms, but in Takayasu's in GCA, it was three eighty five and four sixty five. Also elevated in large vessel vasculitis is IL-six, but really variable and so was IL-one beta and gamma interferon.

IL-one beta and gamma interferon were increased in GCA, IL-seventeen was increased in Takayasu's, but it looked like IL-1Ra was maybe the better measure and did correlate well with CRP. It should be evaluated in future studies. I like this Japanese study, the answer cohort study was basically a thousand patients being enrolled on biologics, they looked at, different outcomes of biologics. Here is a subset study of, patients in the ANSWER study, three thousand six hundred RA patients that were started on a biologic DMART or JAK. From this cohort, they found one hundred and eighteen RA patients who were pregnant.

And they looked at how good were their clinicians at maintaining a treat to target strategy during pregnancy and using biologics. Overall, the one hundred and eighteen pregnancies, ninety three percent full term deliveries. That's really good, that's really high. Eighty five percent were in remission or in low disease activity throughout pregnancy, and many of those were due to the continuation of the biologic DMART or JAK. That was about over thirty five percent continued therapy during pregnancy.

But compared to those who didn't continue, the ones who did continue had significantly lower DAS28 CRPs versus those who stopped, and that was highly significant. Again, this data speaks strongly to the point that control the inflammation and you'll have the best outcome with the baby, and it's not risky to use these biologics. Data is really really strong for TNF inhibitors. I think it's good for all the drugs, but you should certainly refer to the package insert, talk to the medical affairs people with the drug that you're considering on continuing. An interesting study this week looked at postmenopausal women who were exposed to, estrogen hormone therapy, and they showed a modest risk of developing an autoimmune disease.

A thirty three percent, increase by hazard ratio, that was significant. This was a new autoimmune disorder arising five to ten years after the use of hormonal therapy. This is, one of them, TriNetX large database EMR studies of almost nine hundred thousand people on hormonal therapy versus two point six million not on hormonal therapy. The risk of developing autoimmune disease if you are not on hormonal therapy was five point three percent. If you were, I'm sorry, if you were not on it, it was six point seven percent.

If you were, it was five point three percent. It's about a twenty-twenty five percent reduction, five years after starting. This is interesting in light of the fact that the FDA did come along in the last few weeks and change the warnings on hormonal therapy and removed the black box warning suggesting it is okay to use hormonal therapy in postmenopausal women for postmenopausal symptoms and bone benefits, etc. But there's still some concern about cancer and cardiovascular risk, and maybe you wouldn't use it in people with those conditions or at high risk for those conditions. But I think this is interesting data.

This is a modest risk. I don't know that this risk would prevent me from using hormonal therapy in a postmenopausal woman. It might in a woman who's got a family history or was worried about that. You'd have to disclose that information. But I think the data is looking better about, and we need to better look at that on RheumNow in the weeks to come about how you are in fact going to use hormonal therapy going forward.

A retrospective study looked at the role of ANAs in RA patients. Specifically, we're looking at RA patients who are double positive for rheumatoid factor and CCP antibodies. What happens if they're triple positive? And now you find out that they're ANA positive, you know, twenty percent of RA patients are ANA positive, but they're in this study of a fairly large cohort, showed that being triple positive was associated with significantly higher disease activity scores, both at baseline and twelve months later, and a lower chance of actually achieving remission or sustaining remission compared to those who were just, RF and CCP positive. So just the added positivity, and you know, triple positivity is bad in I think almost every disease.

It basically says heightened immunologic activity, that you wish weren't there, what's it doing? It's doing bad things, at least in this cohort study of RA patients. Again, we're on the topic of ANA. What about ANA positivity in lupus? This was studied by over 2,000 patients who, from China, who looked at first trimester women and found ANA positivity to be fourteen point seven percent.

That's what I teach. The population rate for ANA positivity based on how the test is developed should be five for no more than six percent. If you apply those same cutoffs to a sick population, an elderly population, it's like threefold higher. To a hospitalized population, threefold higher. And to a pregnant population, threefold higher, fourteen point seven percent.

The most common titer was one to 100 low titer. Most common pattern was a speckled pattern, we all see this. ANA positivity in this cohort study was associated with smoking, ages 30 to 34, being multiparous, having thyroid disease, and having hypertension. I like all those, except I don't the head scratcher on hypertension. Not sure what that is, but that's what they found.

So this week we reported on Michelle Petrie's ARD study. It was an article written by MedPage Today, saying that twenty five hydroxy vitamin D levels, do influence outcomes in lupus. This was the Hopkins lupus cohort that Michelle's been following serially over time, and a lot of people there at Hopkins are doing great work on lupus. Seventeen sixty eight patients, and they compared those who had low vitamin d, less than twenty nanograms, versus those who had normal thirty to thirty nine nanograms per, ml, and they showed that if you were low, less than 20, you had a significantly higher mortality rate and cardiovascular event rate. So the ones with the low levels had a rate of death rate of eight point six per 1,000 patient years versus the normal rate, two point seven.

That's not good, that's almost threefold higher. So it's actually about twofold higher, has a ratio of two point o five for death, and for cardiovascular event, it's two point nine eight, a threefold higher risk. So I'm not a big fan of vitamin d research. I do believe in supplementation for bone and immunologic reasons. My problem that I'm seeing a therapist about is that I just don't see the data that giving vitamin D fixes a problem.

Show me the data. Now show me two lupus cohorts that have a low level and another, and they all have low levels and half don't get treated and half do get treated. And again, they're kind of saying this, but this is retrospective. It's not quite the same as a prospective study. But I'll believe this, and I certainly will be monitoring vitamin D levels and treating hypovitaminosis D in my lupus patients mainly because of concern over these outcomes.

I like the report this week from the Auto, Inflammatory, Disease Alliance, Registry, included in that registry, which is many thousands of patients are patients with Behcet's disease, and they cherry picked three twenty eight Behcet's patients who presented with mucocutaneous manifestations. And they then looked to see how often do they get multi organ involvement, meaning more than mucosal disease, right? And now we're talking about phlebitis and brain and all kinds of other organs being involved. And what they showed was I thought interesting. Risk of multi organ disease in the future was not associated with minor aphthous ulcers.

Minor oral ulcers in the mouth had no future risk. However, if you had major and minor, now you had a 12 fold higher risk of future organ and multi organ involvement. Also, if you had major oral aphthous ulcerations, your risk of multi organ involvement went up when you also had genital aphthous ulcers. It went up two and a half fold. Pseudofolliculitis, again threefold.

And a positive family history of Behcet's, it went up almost threefold. Not all Behcet's patients are going be mild genital and oral ulceration that you can manage with steroids, colchicine, Epimelast, whatever. I like this report on rheumatology supply and demand between 02/2024, published in seminars of arthritis and rheumatism. They used NRMP match data between in that era, and they basically found a lot of things that should make us really encouraged. We're very worried about a manpower shortage as the population is aging, arthritis frequency, rheumatic disease frequency is going up, autoimmune frequency is going up, but are the programs and the training, and the state says, yes, we are doing so much better when it comes to training, people for the future, but we're still falling short.

Nonetheless, rheumatology programs went up from 99 to 127, that's a 28% increase. Training positions, number of positions that we have went up from 181 to two seventy six, that's a 52% increase. The number of applicants has gone up from two forty nine in 2009 to three fifty nine in 2024, again a 48% increase. And the number of unfilled positions in adult rheumatology went down from 7% to 1%. And not surprisingly, rheumatology has become competitive.

There are more people that are not matching with their first choice. Meaning getting your first choice went down from 49% to 33%. Getting your fourth choice went up from like 11 to 17%, 11 to 18%. Rheumatology has become an interesting competitive fellowship and career path, And there are a lot of reasons for that, but this article does point out we are still falling short when it comes to the future of rheumatology and meeting the needs of the population, whether that be for care or for education. So I think, and for this reason, I think that this is why RheumNow, in the month of December, is going to do a month long campaign on advanced practice providers.

We have a month that's going to be devoted to nurse practitioners and physician assistants, and all matters important to them, and why rheumatologists should be hiring them to meet the demands of their practice. The campaign is going to be called Partners in Care. We're going to talk about APP careers, roles, manpower, and where they fit in healthcare and where they fit in rheumatology practice. We're going to do a lot of disease management in difficult cases, go over diagnostics and therapeutics, talk about complications and comorbidities. We're going to have four Tuesday night rheumatologists that are going to go over these issues, I think you're going to really enjoy them.

Again, that's Tuesday night 7PM in the month of December. Tune in, be there, it's going to be great. I great panelists who you're going to love to hear from. We're going to do four of those. We're going to do at least 12 videos in our therapeutic update series called Underserved and Undertreated and Underserved, and that's going to be a really interesting set of videos.

A lot of blogs, vlogs, and plenty of APP QD clinics. Don't forget, RheumNow live is coming February 2026. Fly in a DFW. You know, you can fly in a DFW if you buy a ticket now from either Chicago or Atlanta for like a 150, a $160. Registration is a discounted registration that ends next week.

Get the early bird registration. If you're a fellow or an APP, it's only $55. It goes up two or three fold after that. Just look at the program and you're going to want to attend and come to Dallas for this meeting. Just as we begin Saturday morning, February seventh, our first session starting at 08:30 on Rheumatoid Arthritis, mortality in RA from Elena Mayasadova from the Mayo Clinic where they have all the data and all the insights.

Second lecture, the mucosal hypothesis of rheumatoid arthritis. This is the hot thing in rheumatology coming out of the University of Colorado, and we have Kristen Demarell, who's leading that charge at the U of Denver, U of Colorado in Denver. And lastly, the master himself, Jeff Sparks, talking about ILD in RA. And then we go into step talks, placebos and rheumatology. Andreas Kirschbaum from Austria, great lecture.

Disease modification and osteoarthritis from Tahina Nyogi from Boston. And then we go, after that, diet and obesity, mitigating, risk for Rheum patients undergoing orthopedic surgery from Susan Goodman. We go to lunch, we come back and have a fabulous session on psoriatic arthritis. That's one third, one morning from the meeting and you see it's star studded, topics, you got to be there. That's it for this week on RheumNow, tune in next week, we'll see you.