Adam Friedman, MD, FAAD: Exploring the Utilization of Immunomodulators as Therapeutic Interventions in Chronic Spontaneous Urticaria

Adam Friedman, MD, FAAD, professor and chair of dermatology at GW School of Medicine and Health Sciences, chaired a session at the 2024 American Academy of Dermatology Annual Meeting titled, "Immunomodulators and Biologics for Treating Tumors and Inflammatory Skin Diseases."

Friedman spoke with Dermatology Times to discuss clinical pearls from his session and what he looks forward to in the future of the field.

"Look to the future--look to the stars, which are going to be pretty close. We got some new and amazing stuff coming relatively soon. ... Let's not forget about the underdogs," Friedman said, considering his hopes for a future of dermatology where more understudied disease states with fewer available FDA-approved therapies can have their time in the sun.

Transcript

Adam Friedman, MD, FAAD: Hi, I'm Dr Adam Friedman, professor and chair of dermatology at GW School of Medicine and Health Sciences. It was really fun to chair again, the session titled, "Immunomodulators and Biologics for Treating Tumors and Inflammatory Skin Diseases." This year, I had the great fun of talking about chronic spontaneous urticaria. But before diving into the practical pointers that I hope the audience took away from my talk, I just want to take a step back and have maybe a mushy Hallmark moment regarding the session in its own right.

Now, this session has been around many, many years, and I was very fortunate to take over from the great Neil Bhatia. I think the fact that this session been around for a long time highlights how it is such an exciting time to be a dermatologist, that the number of biologics, small molecule inhibitors, and even the off-label use of oldies but goodies continue to emerge for both well-known and well-treated diseases, but also the stuff that really doesn't get their day in the sun. I think that the fact that we need sessions like this to talk the latest and greatest, the fact that each year, I've been able to talk on a different disease date and how these classes of medications can be translated to the bedside, is really quite remarkable and only highlights that there's more to come.

The other piece, I want to comment on: Fortunately for me, I have many wonderful mentors, Dr Bhatia, one of them, being able to hand this off to me, I've been able to pay it forward as well and bring on Dr George Hahn, who is my very first student dating back from when I was a resident, and now co-chairs this session with me, so I just want to highlight that the American Academy of Dermatology Annual Meeting and even what has become the innovations meeting, the summer meeting, is a great opportunity to both to get involved but also to pay it forward and pull others into the fray to get engaged with education.

All right, enough tears; we can move on from the sappiness, and let's talk about chronic spontaneous urticaria, a disease state that affects so many, is so well-known for its burden and its unique burden in that as opposed to every other disease we manage, I would argue there are very few of any other things that can go from 0 to 60 in nanoseconds. What do I mean by this? You can be walking around, you can be Netflix and chilling, it doesn't matter. You could be completely clear, and all of a sudden, in a matter of milla, nano, however many seconds, you can be covered head to toe in wheals, and what I mean by wheals, I mean those dermal, edematous, burny, itchy plaques that are moving around doing whatever they want. I think that unpredictability adds another level of anxiety to this disease.

So what do we do about it? What are we as dermatologists doing about it? Well, it's interesting. One would think that this would be very much in our wheelhouse, but often dermatologists maybe shy away from chronic spontaneous urticaria. Could it be because our treatment options are somewhat limited? Yeah, maybe. We like to hit diseases and hit them hard and get people better. So innovation has been lacking in this area until recently. First line, no question, are going to be your second generation and non-sedating antihistamines.

The pearl here is ramp it up. Do not follow the label. We are rule breakers. You want to go to fourfold the recommended dose within a matter of weeks of seeing that patient for the first time. I would even argue: another little pointer is vitamin D seems to augment and improve the impact of antihistamines, and vitamin D deficiency may even be a marker of CSU activity. Still not fully fleshed out, but there are some interesting data supporting this mentality.

Getting to the core of this session: immunomodulators, immunosuppressants, biologics, are second line, and we're going to initiate this pretty quickly, because roughly 50% of patients will not respond to your fourfold recommended dose of antihistamines. That's going to be omalizumab. Omalizumab has evolved over the years. Historically, we had to really lay eyes on these patients and keep them around for that very rare risk of anaphylaxis, like 0.2% of patients, yet any percent is still a percent. So the issues of having patients stick around for 2 hours afterwards, having to stir this very viscous liquid up, it really hindered the busy dermatology practice.

Fast forward to just a couple of years ago, things have changed. We now have it in a prefilled syringe. The dosing is not based on pretreatment IgE, or even weight-based dosing, and we only have to keep a patient in the office for 3 visits, and if there's no problem, no problemo: They can go home and they can self inject. I think one of the greatest innovations with omalizumab has been making it easier to use. Yet even with maximum dosing or even off-label updosing, I sometimes have patients on 450 milligrams per dosing time. We still have patients who don't get there. Roughly about 25 to 30% of patients are not 100% clear, and that is the goal. We want patients clear, not even worrying about it, and so then we turn to off-label medications.

Now, there was some recent guidelines published out of Europe, really pushing us away from any of the off-label immunosuppressants other than cyclosporine. But we do have some nice evidence supporting mycophenolate mofetil, coming out of NYU. Gotta give Dr Soter, Nick Soter, a wonderful shout out for his great work in CSU.

We have some data on methotrexate, even narrowband UVB, dapsone, colchicine, so while if we're not going to utilize or if not effective, in terms of thinking about omalizimab, we do have third line options, most notably cyclosporine, which certainly works quickly and works well. But the patient has to come off of it. The current guidance is you want to get patients off of it after 6 months, and then you got to transition to something else. That may be where the kind of looked down upon immunosuppressants like methotrexate, like mycophenolate mofetil, or some of these others, may really play a role. So I think it's important to be creative, and also get pumped because we got some new stuff coming out.

We have a small molecule inhibitor shortly coming out going after BTK, Bruton's tyrosine kinase, which is a intracellular target. We have some biologics that we know quite well, like dupilumab that should hopefully have a lateral indication in the near future. So I think we should be excited about CSU, we should be getting these patients into our office, we should be very visible and purposeful that CSU is for you and me, because right now a lot of these patients are going elsewhere. I think that we have all the tools to both educate patients, but also to be efficient, treat them the right way, minimize laboratory testing, which I did talk a little about in my lecture, but I'm not going to hit on here, though.

The key message, and I have to throw another practical pearl out there: Less is more. Do not do the million dollar workup. Less is certainly more, but the key messages here are pile it on, dose escalate with your antihistamines, turn to omalizumab, FDA-approved biologic for CSU in the United States currently, and then look to the future--look to the stars, which are going to be pretty close. We got some new and amazing stuff coming relatively soon.

Dermatology Times: What are you most excited about with respect to the future of dermatology?

Friedman: When I'm asked what I'm excited about when it comes to the future of dermatology, I think I'm kind of an underdog type of guy. I root for the underdogs. I root for the disease states that have nothing FDA approved or don't get that front page splash, that so many of the diseases that have too many drugs for which we're really good at treating these diseases. I am hopeful that we will see some lateralization, especially with some of the small molecule inhibitors, such as JAK inhibitors, TKY2 inhibitors.

Outside the favorites, the cool group of derm diseases like psoriasis, atopic dermatitis: I want to see them for hidradenitis suppurativa, though certainly we're seeing more options coming out. I want to see lichen planus. I want to see cutaneous lupus, scarring alopecias, where currently, we're using these advanced therapies off-label, but because they're off the label, 1.) we don't have great guidance on how to monitor, how to follow, how to certainly get approved. But I think also getting a patient on board with what we think will be great for them certainly will be a lot easier when you have an FDA approval, that seal of approval. But also, we know more about the safety of these medications in this patient population. So I think we're going to see, my hope is, an explosion of orphan diseases, getting indications, and I don't care if they're lateral therapy for other things. Great: makes it even faster and easier, in my opinion, from an FDA perspective. But that's where I want to see us head, is really paying attention to diseases that have extraordinary burden, but may not have the sex appeal as a disease state that already has, like, 13 medications, so let's not forget about the underdogs.

[Transcript has been edited for clarity.]