Keys to Mastery (5.2.2025) Save

Doctor. It's 05/02/2025. This is the RheumNow podcast. Hi, I'm Doctor. Jack Cush, executive editor with roomnow.com.

May is lupus month. May is the month we're going to do a big lupus campaign. More on that later. Today, we'll talk about a new FDA approval, and a diabetes drug that works in osteoarthritis, but it's not the one you think. But first, a message.

Great rheumatologists go to great rheumatology meetings. Now for the first time ever, RheumNow Live On Demand is available. We'll have more coming up after today's podcast.

Let's start with an FDA announcement. The FDA this week approved upadacitinib or RINVOQ for use in giant cell arteritis, based on the data from the SELECT GCA study. We started talking about that a few meetings ago. A very successful study of patients getting either fifteen milligrams or seven point five milligrams of I'm sorry, fifteen milligrams or placebo of upadacitinib or RINVOQ to treat patients with active giant cell arteritis, and fifteen milligrams per day was shown to be highly effective. This is the ninth indication for upadacitinib, and it's now in the package insert.

No new safety signals, no new precautions were advised. These patients were often being treated, as you would imagine, for giant saltiritis with steroids and had a weaning or tapering regimen employed in those studies that was successful. Again, the question is, how are you going to fit this in? Will this be steroid sparing therapy? This is a second drug that's been FDA approved for use in GCA, and I think this is a big advance, whether you use tocilizumab or whether you use, upadacitinib.

We have a lot of lupus, reports this month because it is lupus month, we have a big lupus campaign. One such report comes from a study of African American, children from the South who were compared to a multi ethnic group. This is forty five patients with, lupus, childhood lupus, who were African American. And it turns out that patients who were African American had significantly higher disease activity and greater damage over time. They started out with high SLIC scores of 8.4, SLETEI scores of 13.

With treatment and follow-up, the SLETE eye dropped from 13 to 7.4 at six months to 4.7, but still high at one year. So childhood lupus is bad, much worse than adult lupus, but then it turns out that if you are African American, you're going to also do worse, and that's been shown in adult cohorts, and because this is a pediatric rheumatology lupus report, they put in there that the average distance that these kids were traveling for their room visits was 75 miles. There's a serious shortage of pediatric rheumatologists and care for kids with childhood lupus. I like this report about predictors of bacterial infection. A single center study of 116, juvenile SLE patients diagnosed with bacterial arthritis.

That was seen actually in seventeen percent of those one hundred and sixteen that had a bacterial infection. Looking at many, many different biomarkers, what best predicted bacterial infection, it turns out it was procalcitonin. You know, we talk about this as a measure, we don't do it very much. It's not widely used, it probably should be used. It was compared to the CBC, it was compared to sed rate and CRP, the neutrophil to lymphocyte ratio, the platelet to lymphocyte ratio, ferritin levels.

While those other markers have value, their cutoffs not determined, were not determined by this study. By this study, it showed a procalcitonin level of greater than 0.9 nanograms per ml was predictive of those who would develop bacterial infection. I looked up the incidence of gout this week. As you know, gout incidence and prevalence has increased over time with the obesity epidemic, with dietary changes, you know, at one point it was eight million, then it was nine million. The most recent report comes from NHANES twenty seventeen-twenty eighteen, where The U.

S. Prevalence of gout is twelve point one million adults. This is a significant increase from twenty eleven-twelve when the gout prevalence was three point six in the population, and this went up to five point one percent in twenty seventeen-twenty eighteen. The interesting thing about the most recent change in the last few NHANES evaluations was the doubling of the rate of gout amongst Asian Americans going from three point three to six point six percent. That a sharp increase, and it takes us up to twelve million people who have gout in our society.

Another report about gout this week looked at what happens to gout after the emergency room visit. So one hundred and fifty nine patients showing up with gout flares in the emergency department were studied and showed that only thirty five percent of them, had a follow-up outpatient visit after their emergency room visit. This is horrible. This is one of the big problems in gout management, is that the patients themselves are not good at follow-up. We're not good at ensuring their follow-up, and follow-up obviously means better care over time, less use of the emergency room, better prevention, and that's one of the problems.

Those who are less likely to or actually more likely to show up in follow-up were those who are married, those who had no comorbidities, those who were on colchicine, those who were older. I guess being married, being wiser, being on therapy made the patient's management of their own gout a little bit more responsible and adult like, maybe? I always like to put up the data about the risk of cancer with the drugs we use in RA patients or other inflammatory arthritis. This was looked at in the Dan Bio Register, a Danish Register, as you know, does fabulous work. They had seven twenty RA patients who had a prior solid cancer.

These included breast, colon, bladder, melanoma, lung, endometrial cancers, and they were in remission from their cancer, but then went on to receive a biologic, either TNF or any or actually a number of different biologics, and they found out specifically that TNF inhibitor use or rituximab use had no increased risk of cancer recurrence. The same was seen with the other biologics that were under study. Specifically, patients who had breast cancer had no breast cancer recurrence, that was increased over the control. So again, this goes along with what we've said. Patients with solid tumors who have cancer should be treated as if they didn't have a solid tumor when it comes to their RA or biologic therapy.

Use whatever you want. There's not one that's preferred, there's not one that's better, there's not one that's worse. Treat them as you should. Another study about RA and RA ILD looked at the association with ANCA antibodies. We've talked about this before, a study of one hundred and four RA ILD patients found that thirty two percent of them had ANCA positive autoantibodies.

Twenty nine of those were in fact P ANCA positive, not C ANCA, and when compared to the RA ILD patients who were ANCA negative, the ANCA positive RAILDs not so good. Worse disease, more pulmonary symptoms, more ANA positivity, worse PFTs, more exacerbations, more bronchiectasis, worse honeycombing on CT of the chest. ANCA in RAILD, usually P ANCA, which would be myeloperoxase, probably a poor prognostic finding, right? There is that evidence about these RA ILD patients where you should be doing KL6 as a biomarker to see where those patients are. That wasn't studied here, but I want to remind you of that other biomarker that's also new and out there, new to us rheumatologists at least.

Immune checkpoint inhibitors are used, they cause autoimmune syndromes, we call immune related adverse events or IRAE. There's now reports of IRAE with the resultant manifestation being myasthenia gravis. The interesting thing about this particular report of, sixteen patients on immune checkpoint inhibitors who developed myasthenia gravis, they were from mostly lung, and like more than nine of those sixteen were from lung tumors, that the patients who had myasthenia gravis, eleven of the sixteen also had overlap myositis, and that, these occurred roughly a month or two after the onset of therapy. All were given steroids, most were given immunosuppressors or plasma exchange. The problem is that the outcomes were bad.

Only two responded to the therapies given. Six of the sixteen died, and the others didn't do very well, and the ones who died, died of myasthenia complications, not of cancer complications. Kind of a bad manifestation of IRAE, don't you think? Pregnancies in the news. The Norwegian pregnancy data set called RevNatus, a study of four seventeen births in three fifty women with axial spondyloarthritis, looked at breastfeeding.

Good news, eighty six percent of them at the time of delivery were breastfeeding, out to six weeks, but that went down seventy percent by six months, thirty eight percent at twelve months. That's kind of normal, but compared to when they compared those who didn't go on breastfeeding, there were differences. The non breastfeeders had more C sections, double the rate of C sections, higher as DAS CRP levels of 2.6 versus 2.2, and the breastfeeders higher CRP levels, more pain. Maybe the interpretation here is AS patients, ex SPA patients who are in pain, highly active, they're just not as likely to go on breastfeeding, and then I think that suffers, that the patient's going to suffer in many ways, but also the offspring is going to suffer. So again, I guess the point is make sure your patients are well controlled.

There's no reason a patient with axSpA can't be aggressively treated when they're pregnant with whatever drugs that you want to use. Again, if you don't have a healthy mother, you're not going to have a healthy baby, and I think we've said that many times before. We put up some data this week about the cost of drugs that, were incurred in 2024 in The United States, where, pharmaceutical spending reached $8.50, sorry, $8.00 6,000,000,000 in 2024. That's a 10% increase over that, experienced in 2023. What were the most expensive drugs?

I put up about 10 or 12 of the most expensive, led by the GLP-one agonists, semaglutide and, tirzepatide. Semaglutide, 54,000,000,000 spent in 2024, Tirzepatide almost 32,000,000,000, my goodness, that's $86,000,000,000 We thought they were spending a lot in 2020, what was it, 2022, when Humira sales were at $22,000,000,000 Well, don't worry, there's a lot of our drugs on the list too, and that would include adalimumab, now $28,000,000,000 with a minority of that being due to brand name Humira, and the rest of it, I would guess around $910,000,000,000. I don't know the exact number, but that's my guess, with the majority of that being biosimilar sales. So that's kind of good news, is it not? Other room drugs in the list, ustekinumab 17,000,000,000, rizanquizumab 16,000,000,000, etanercept still in the list at 10,000,000,000, and secukinumab at 7,700,000,000, upadacitinib at 7,000,000,000.

So we make the top 20 drugs. Don't worry. Two big reports this week. I think the most important one came from JAMA about the efficacy of metformin in patients with osteoarthritis of the knee. So a study, it's a small study, and there's been reports before of metformin's use being, advantageous in a lot of autoimmune situations, and it was sort of a, you know, bystander use or co therapy, and then looked at other outcomes, immune outcomes, inflammatory outcomes.

In this study of one hundred and seven overweight or obese patients who did not have diabetes, by the way, they were randomized to receive either placebo or two grams a day of metformin, and it turns out that after six months, the metformin patients had a significant decrease in their knee pain scores by, a 31 change on a scale of zero to 100, compared to placebo that only had a 19 change, or 18.9. So the difference there is about 11.5 points, and that was significant, but the trialist had chosen 15 points as a clinically meaningful change in OA knee pain. So it did not achieve that, but everyone's kind of excited about it, including the authors saying this was significant results, whether it's clinically meaningful, they had patients who had positive reports. So, it looks like it was encouraging, and it's in line with what has been reported before, but again, this is a small study. They have shown that, other studies that have shown that patients on metformin had less need for knee joint replacement and hip joint replacement, a thirty percent less need, and there are other examples where metformin may have a role.

Now, why does it work? Is it simply lowering blood glucose levels has these effects, or is it that there's another immune or anti inflammatory effect? More studies are needed to know that. This month we have a lot of planned content on lupus. We began with a great blog by Lisa Samaritano, who, as you know, led the ACR Reproductive Guidelines publication.

Lisa at Hospital for Special Surgery wrote a really good blog about contraception in SLE that I would strongly recommend you read. Lupus patients who get pregnant have horrible outcomes. Lupus patients who get pregnant, often were never on contraceptions of any sort, that contraceptive use is woefully deficient in lupus, and could be used and could be used safely. She states in here that effective long acting reversible contraceptives include IUDs, subdermal, progestin implants. There are oral contraceptives, and those are very, very effective.

There are oral contraceptives, both progestin only and mixed estrogen progestin that can be used with almost the same degree of efficacy and that they can be used even in patients with APS. The first two options, the implants and the IUDs, can certainly be used in patients with APS. So, I think it's important for you to read that if you're managing young women with lupus to get up to date on what the conversation is between you and your patients who have lupus and want to get pregnant or will become pregnant sometime in the future. I want to remind you that this month, May is lupus month, you'll see a lot of content from the RoomNow about lupus. Our theme to our campaign this month that is sponsored by Aurinia, thank you Aurinia, is our campaign is called The Keys to Mastery, and what we're going to present is basically giving you the keys to mastering lupus.

We're going to have 40, over 40 contributors, the best and brightest in the lupus world who are going to be doing blogs, videos, webinars, journal clubs, podcasts, talking about contraception, pregnancy, cardiovascular risk, type one lupus, type two lupus. What's that all about? Steroid use, new rules on steroid use, mental health, psychosocial issues, immunologic aberrations in lupus, cutaneous SLE, pediatric SLE, the antiphospholipid syndrome, and a big effort covering, lupus nephritis advances and also our need for renal biopsies. We're going to hear from nephrologists about their approach, how they manage CKD even in the face of new lupus nephritis, GLP-one and SGLT-two drugs and their benefits, biomarkers, CAR T cell, more, more, more. Next Tuesday, this upcoming Tuesday, and every Tuesday this month, we're going to have a Tuesday night rheumatology webinar.

We're going to lead off this first episode with the authors of the Obentuzumab in Active Lupus Nephritis, New England Journal article, I think it's called the Regency Report, and the voclosporin versus placebo, the AURORA-one trial. Those papers were authored by their lead authors, Doctor. Richard Fury and Doctor. Brad Rovan, a rheumatologist and nephrologist, and they're going to take some questions from you, and we're going to send you some questions to ask them. So, want to be there.

If you're a rheumatologist, you'll get an invite. You can attend the Zoom webinar on Tuesday night, seven p. M. Eastern Time. That'll be four p.

M. Pacific Time, and if you're not going to be on the Zoom webinar, you can watch it on YouTube, LinkedIn, Facebook, and also Twitter. We're going to post the recorded versions on our website and on those same social media channels. So, be there for Journal Club this week. We hope you enjoy it.

Tune in next week for more on lupus and great news in rheumatology. Take care. Wait, here's a message.

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