DERM on RheumNow Podcast (September 2025) Save

Hi, this is dermonroomnow.com. I'm Doctor. Jack Cush, executive editor of roomnow.com. This podcast is dedicated to those of you who are dermatologists and skin deep HCPs. RheumNow covers a lot of dermatology, so we're doing a dermatology podcast.

This week on the podcast we'll be discussing hydroxychloroquine, the safety of JAK inhibitors versus TNF inhibitors, the SMART study about how to best use methotrexate, what do I think about diets, especially vegan diets, and could that help you? And then what about the safety of IL-seventeen inhibitors? And lastly, news on alopecia areata. So, let's start with the SMILE study. That was just published this past week.

The SMILE study is a randomized, placebo controlled trial of hydroxychloroquine in patients with incomplete lupus. It's a phase two, multi center trial. Took a number of years accrue this data. It was sort of started and hampered by COVID. Ultimately they included one hundred and eighty seven patients who had incomplete lupus, meaning they were ANA plus they had one or two SLIC criteria, but did not qualify to meet criteria for lupus.

They basically analyzed the data on half the patients being on hydroxychloroquine and placebo. Mean age was about 33 years. They were mostly female, as you would imagine. And if you looked at the end, there was no difference in progression to lupus if you were on hydroxychloroquine or on placebo. About twenty percent of the patients ultimately progressed to lupus, and it was not significant.

Those who did become lupus were notable for having, a new malar rash, oral ulcers, joint involvement and pleurisy basically meeting all the criteria for lupus. So, this is really disappointing because we, and I'm sure you see a fair number of patients who have some features of LE, and they have ANAs, and it's always been thought it's got to be safe to use hydroxychloroquine, and it is. It's just that it doesn't work, and that's the surprising thing. There'll be sub analyses on this to figure out maybe why it didn't work, but right now, just that's all we can say. A big meta analysis, systematic review, looked at the safety of JAK inhibitors versus TNF inhibitors when used in head to head trials in patients with IMiDs, including skin indications.

This was published in, I believe, JAMA Network Open. And in the end, in these head to head studies, there was no difference when it came to the risk of serious infections. The rate being about three per one hundred patient years in both groups. Or malignancies: about one per one hundred patient years in both groups. Or MACE: Major Adverse Cardiac Events 0.7 per one hundred patient years, not significant.

The only thing that was significant between these two when they were in head to head trials, there was a higher risk of VTE, venous thromboembolic events, if you're on a JAK inhibitor. And it was low, but it was still significant for JAKs, and we know that to be true. But this is sort of data that one puts in perspective what the actual risks of serious infections and MACE events and malignancies are: it's low, and that in contrast to the oral surveillance data found in tofacitinib, this does not show much of a risk. But again, this is not a prospective trial. This is a meta analysis of head to head trials.

Still useful data. The SMART study was an important study in rheumatology I think you should know about. It was done in India. It was a single blind open label study that compared the outcomes in RA patients who were either treated with twenty five milligrams once a week of methotrexate, or twenty five milligrams methotrexate given in split doses. So this is a one time dose versus a split dose.

You know this all started in dermatology. You were the first to use methotrexate, and the earliest regimens were point two five milligrams, one pill, given q12 hours times three. The idea being that it would be safer or better tolerated. And actually what it did was it gave you more toxicity, and then I guess rheumatology and dermatology ultimately got around to doing single dose. But we know that when you use doses above fifteen milligrams or above, that there's very variable absorption.

You know, it can be as low as 30%, as high as 80%, and it is not predictable. At doses below fifteen, it's pretty good absorption, and a lot of people say that at fifteen or above you should probably go with parenteral. But then there's this idea of split dose oral. So in this study of two fifty three patients, people were started at fifteen, quickly escalated to twenty five, and they found that by week sixteen there was a significant benefit for those that got the split dose oral. Because we know that when you do that it's the same as giving parenteral, and that you have really almost a 100%, 90 plus percent absorption.

And, and yes, there might be more toxicity when you do that, but in this study, the split dose patients, were less likely to need a second DMARG. So, at sixteen weeks, if they didn't respond, with a certain disease activity level, then you could add in a second DMARD. Well, they were less likely to use that on split dose oral compared to single dose oral, and that there was more transaminitis with split dose oral. So again, if you are going use methotrexate and you get to fifteen, don't give it as six pills once a week on Friday, give it as three bid on Friday, and the patients will get more drug and presumably do better for whatever you're treating them for. An analysis of a French database that contains thirty four thousand patients treated with an IL-seventeen inhibitor, and it was over a five year period for psoriasis, psoriatic arthritis, ankylosing spondylitis and JIA.

They basically did this analysis to look at the safety in these thirty four thousand patients on IL-seventeen, and reported that there was no significant association between IL-seventeen inhibitor use and major adverse cardiac events in the first six months of use, and they compared that to what you see with TNF inhibitors, which we know do not carry an increased risk of cardiovascular events. In fact, TNF inhibitors will lower the risk of cardiovascular events. And here it was not different. Now this is important, I guess, for dermatology because you've experienced this in your literature, especially with briakinumab, which was another ustekinumab like IL-twelve twenty three inhibitor, that didn't make it to market because of concerns about cardiovascular risk. But ustekinumab made it to market with no increased risk of cardiovascular events.

Subsequently IL-seventeen inhibitors have not been shown to do this, whether they're an A or an F or an AF inhibitor. The same can be said for the IL-twenty three inhibitors that it looks good as far as cardiovascular safety. Another report came out, a press release from AbbVie this week, on their JAK inhibitor upadacitinib showing results of a phase three, it's called the Up Dot AA trial, meaning upadacitinib and alopecia areata, showing that at fifteen and thirty milligrams a day that forty five and fifty five percent respectively achieved a salt score of less than 20, which means that there was 80% or more scalp coverage with new hair. These were results at week twenty four. This is encouraging.

I would assume that they're going to go take this to the FDA, and right now you have three drugs that are FDA approved for use in alopecia areata. We use the baricitinib, but we're not familiar with ridicitinib and diruxolitinib, which is like ruxolitinib, and their trade names are Litfullo and Lexelvi. Maybe you know that, I'm not familiar with that. But it looks like upadacitinib is on its way to becoming a fourth one that will be included. Last report is on anifrolumab.

This is the type one alpha interferon therapy that has been FDA approved for use in lupus. I put up a report this week of an open label study of fifteen patients with cutaneous lupus that had active disease despite being on hydroxychloroquine and steroids, topical steroids, and they had failed multiple DMARDs. They were all treated with anifrolimab, three hundred milligrams IV q4 weeks. All of them improved. Their classy A scores decreased from 16 to one, their classy D from five to four.

These were all significant findings. I said we need double blind randomized controlled trials on this, and we certainly do, but this is not the first time. Anifrolimab looks very, very good at controlling skin disease and lupus. This is not the first report, there are multiple reports. And also in the news this week was, Anafrolimab, which is Safnello is its trade name.

It's an IV drug, but they reported the results of a phase three safnello or anifrolimab study in lupus, and that looks good. So, coming soon to a dermatology clinic near you might be sub q anifrolimab that you could use for cutaneous lupus, should that be something you're interested in. I'll leave you with what I think is an inspirational quote from Margaret Mead. Never doubt that a small group of thoughtful committed citizens can change the world. Indeed it's the only thing that ever has.

We'll see you next month with Derm on RheumNow.