DERM on RheumNow (June 2026) Save

Welcome to the RheumNow podcast for June 26. I'm Jack Cush, executive editor of RheumNow.com. This podcast is for dermatologists about dermatology issues that we cover on RheumNow.com. We've got a lot of overlap between us. We do a lot of consulting and sharing of patients, hence my sharing information with you. Tell your colleagues in dermatology, especially your NPs and PAs about this podcast. It's a great way to stay abreast of what's important and what's new in dermatology and biologics and drug safety, etc.

I think the big news this month that you may not be aware of is that the FDA has approved a generic version of Xeljanz. Breenidge Pharmaceuticals is the manufacturer. They make the pills in Spain. They were approved for both the five and 10 milligram dose of tofacitinib, not the extended 11 milligram dose, for use in both adults and children with the same disorders for which tofacitinib is currently approved. It's available now at a pharmacy near you. Will you use it? What will be the savings? Will it expand the use of JAK inhibitors? My goodness, the use of JAK inhibitors in dermatology is just gargantuan compared to what we're doing in rheumatology. You've got so many indications approved and soon to be approved. It would be important to stay abreast of the availability of generic tofacitinib. By the way, tofacitinib has been generic and available in Southeast Asia, India, Pakistan, a lot of countries for a few years now and the pills there are dirt cheap, really cheap. Will they be cheap here like methotrexate cheap? Not likely. But what if it was? What if it was as cheap as any other immunosuppressant or DMARD? Would you not use it? If it was a lot cheaper than the trade drug, would you not use it? Again, we'll find out over time what this is going to mean to your practice.

A population-based study looked at the risk of psoriasis based on pollution. Here we're looking specifically at particulate matter, looking at the size of the pollutants PM2.5 and PM10, and shows that in a population-based study at least a 19% increased risk of psoriasis. This was both with short-term exposure, and the people who seem to be at greater risk were those who live in urban areas — not surprisingly — younger people, lower socioeconomic group people, ever smokers, and those who had allergies seem to have higher risk of developing. So just like in rheumatology, many of our disorders, not just rheumatoid arthritis, have shown that pollution, particulate matter, smoking, environmental triggers are triggers to immune activation. I assume in someone who's predisposed genetically, but waiting for that exposure that sets off the key and lock that turns on the immune response that goes wrong and becomes an autoimmune and inflammatory disorder. Will this become part of therapy in the future? It's possible. People working in environmental medicine are working at this.

I like this report about the risk of TB when you take an IL-23 inhibitor. As you know, when you use any biologic, especially IL-23s — the IL-12/23s, the ustekinumab drugs, now a ton of biosimilars — would use the IL-17 inhibitors, all four and soon to be five of those. All three of the IL-23 inhibitors, they all have the package insert recommendation that you should test for TB prior to use of the drug. Oh, by the way, and you're talking to a guy who — and you could talk to the podcast, that's okay, no one's going to worry too much — you're talking to a guy who knows a lot about TB. I've worked with the world's best TB people on committees and at the FDA. There's no guideline that says — other than NPF guidelines, which I don't agree with — that says that you need to do annual TB testing. No. And of course, that was a bad idea when you were doing TST, PPDs, because you would induce immunogenicity. But even if you're doing IGRA assays — QuantiFERON, T-SPOT — it's still not indicated. You do it once and you're done. If it's positive, you respond to it. When you're done, you only do it when risk changes, meaning they go to Kolkata and do medical relief work with lower socioeconomic groups and in risky populations. You take a trip to India and visit the Taj Mahal with your camera — no, you don't get tested or treated after that. You do get tested after coming back from exposure or a high-risk situation.

Anyway, let me get to the report. I just went off on a rant. Sorry about that. This is a report of 34 studies in all different IL-23 inhibitors showing no risk. Basically, there were 34 studies in psoriasis showing no new cases of TB. And you know, if it happened, it would get reported, right? That's almost a selection bias — a selection bias in favor of knowing the real safety. But no new cases. One case out of 34 studies, thousands of patients, with one reactivation of TB. We call that LTBI.
or latent TB infection. In eight studies with psoriatic arthritis, no new cases, no reactivation cases. So does that mean you don't need to do TB testing? No. The package insert says you got to do it. But it should tell you what you do when TB is on the table.

I've taught from my many learnings, teachings, and writings that the risk of TB and opportunistic infection is really highest in people receiving TNF inhibitors. You need TNF to make a granuloma and to sustain a granuloma. You inhibit TNF, granulomas break down. Those bugs get out and spread, right? Is it just TNF? Yes, it's TNF, TNF, TNF, TNF. A little bit of gamma interferon and maybe alpha interferon. And I think alpha interferon is a significant risk, right? So when you have a TB situation or opportunistic situation and you're wondering what drug can I use, don't use a TNF inhibitor. Everything else is okay, including the IL-17 inhibitors, IL-23 inhibitors. This study addresses the IL-23 inhibitors.

We just got back from — not the ACR — the EULAR meeting in London, the first week of June. Great meeting, a number of important presentations, a lot of them on psoriatic arthritis. We've talked about the TOGETHER PsA study. Izokibep coupled with a GLP-1 has a significant benefit over the IL-17 inhibitor alone. That was covered.

The BOLD study — I think I mentioned it in the last podcast. The full data was presented as a late breaker by Joe Merola. He's one of yours, a dermatologist from Harvard and now Southwestern. He's also a rheumatologist. Who's going to claim him? I know Joe Merola. I want him on my team.

He presented the data of this — I think important landmark study in rheumatology. You've got tons of head-to-head trials in dermatology. We have none or very few. This is a head-to-head of bimekizumab against risankizumab in patients with psoriatic arthritis. I think it was 30–40% of them had previously received a TNF inhibitor. And it's important — 553 patients randomized to receive either drug. The primary endpoint was an ACR50, a high-level joint endpoint at week 16. Significant benefit of bimekizumab over the IL-23 drug — ACR50 of 49% versus 38%. That's P equals 0.0058. The advantage was maintained out to week 24.

Interestingly, other outcomes — skin outcomes and secondary joint outcomes — there might have been a numeric advantage for bimekizumab, but it was not significant. This included minimal disease activity, PSSI 100s, DAPSA, and a few others. So why? There are theories, but we now await the paper. This is an important study that now you can point to your rheum colleagues and say you might want to look at that head-to-head BOLD study — bimekizumab versus risankizumab.

The other big study that will affect practice is the RA-BRIDGE and RA-BRANCH. Why am I talking about RA? Oh my god, you know he's a rheumatologist — can't help himself. This is a large-scale FDA-mandated study of baricitinib and the risk of venous thromboembolic events, VTE.

Let me give you a prelude and tell me that I'm wrong or tell me that I'm right. Most of my good friends who are medical dermatologists — after the release of the ORAL Surveillance study done with tofacitinib that then ended up changing the package inserts for all JAK inhibitors, saying that you must use a JAK inhibitor after a TNF inhibitor because of a higher number of cardiovascular and malignancy and serious infectious events with the JAK inhibitor compared to the TNF inhibitor — that's been out there and it's changed practice. It had a tremendous effect on dermatology use of JAK inhibitors. It had a modest effect on rheumatology use. Why? Well, we use maybe a lot more JAK inhibitors, but we looked at many of the reports that came after that, that looked at the analyses to show who exactly was at risk.

The entry criteria for ORAL Surveillance was over age 50 or 55 with a cardiovascular risk factor, right? But it turns out the people who had the highest risk of all those three bad things — cardiovascular events, MACE events, malignancies, lymphoma and lung cancer especially, also some skin cancer, and then serious infectious events, hospitalizable infections — the people who got those bad outcomes were over 65 with a prior history of MI or cardiovascular event who were smokers.

So now apply that to all your patients that use a JAK inhibitor. How many of them are over 65, smokers, with a prior MI? Yeah, it's a small number of your population. Your 37-year-old with atopic dermatitis — no problem. Your 29-year-old, very attractive lawyer who's lost all her hair from alopecia universalis can go on a JAK, you know. Do you have to try a TNF inhibitor before the JAK if the TNF inhibitor is indicated for that disorder? Yes, I think you should, just to be in compliance with the package insert. But for alopecia areata, alopecia universalis, TNF
numbers are not indicated. I'd go right to Jack's. Why wouldn't you? So, RA BRIDGE and RA BRANCH — and remember ORAL SURVEILLANCE was what, 4,500 patients followed four years, double-blind randomized placebo-controlled trial of tofacitinib versus two different TNF inhibitors. Same design for the RA BRIDGE and RA BRANCH study, 3,500 patients followed for almost four years. The primary endpoint achieving a certain number of VTE events, either pulmonary emboli or DVTs. They stopped the study prematurely because they weren't going to change the results, and they showed unequivocally that baricitinib at both doses, 2 milligrams a day and 4 milligrams a day, significantly increased the VTE events. 3,600 patients followed for up to 6 years, 11,000 patient years of follow-up. Again, the entry criteria was having one prior VTE — having had a prior VTE, you're more likely to get it in the future. That's why they included those over age 60, BMI greater than 30, or if you were age 50 to 59 and overweight with a BMI greater than 25. And again, this was a non-inferiority study with an upper limit of non-inferiority of 1.8. This exceeded that, which means that the JAK inhibitor was not non-inferior, meaning there were more events — significantly more events. And again, the hazard ratio was 1.6, exceeded the upper confidence limit at 2.6, and that was true for VTE only. It did not show an increased risk of MACE. It did not show an increased risk of cancer or opportunistic infections. And where it didn't show these risks, there was no difference between the low dose and the high dose. There was a marginally but significant increased risk of serious infections.

So this is follow-up data to ORAL SURVEILLANCE that should give you either confidence, or if you're Chicken Little and you're worried about this, you're more worried about using these drugs. You know, send them to the rheumatologist or don't use those drugs at all. When I've asked rheumatologists their interpretation of the study — does it give them more confidence or not? — I am getting a split message. You know, I consider myself an expert on this because I've been on the FDA advisory committees, and when they submitted the tofacitinib study, I study these issues all the time. I have less worry based on this data. But my colleagues are split. Some say less worry, some waffle and are still worried. You have to decide for yourself, but know that RA BRANCH and RA BRIDGE are out there.

My last report — no, two more reports. Probiotics in psoriatic arthritis. You know, we see goofy things on diet and whatnot. I'm a big believer, not in probiotics, but a low-gluten, low-carbohydrate diet as being tremendously effective in psoriasis. We did an uncontrolled study — we didn't publish it, ask me sometime about it — but this study, it's called the MEDISPA study. It examined the effects of probiotic therapy on 66 PsA patients with moderate activity receiving placebo or a probiotic with just Lactobacillus and Bifidobacterium, 12-week study. The primary outcome was either lowering of the disease activity or achieving remission with a PASDAS less than 3.2. The placebo was better than the probiotic, 65% versus 43%. So you might say to your patients, doesn't look like probiotics do anything. I would say this isn't the study that I would have done. You know, to have an effective probiotic, you need to have five or more strains, 14–15 billion CFUs or bugs in there. They don't have to be live, they don't have to be refrigerated, whatever. I'm still okay with probiotics, but this study proved that it didn't work.

Another interesting study looked at a stepwise approach to treating CLE. This came from Professor Wittmann at EULAR. And he really showed me something that was important that I don't pay enough attention to. Smoking is a bad, bad player in rheumatoid arthritis and many inflammatory arthropathies. We know smoking is a bad player in autoimmune disease. In his presentation he showed smoking reduces the efficacy of antimalarial drugs — significantly reduces the efficacy. So if your patient's on an antimalarial and they're not doing well, number one, do a hydroxychloroquine level — you can get that now — to see if they're taking the drug, and then ask them if they're smoking. But if they're a smoker, it also worsens skin activity, and not only the severity of skin, but also the development of organ damage beyond the skin. So these are important lessons coming out of EULAR that I hope you'll find useful for your practice. That's it for this week. Tell your colleagues about the Derm on RheumNow podcast.