Treatment Options for PN

Raj Chovatiya, MD, PhD: To the point about treatments, oftentimes when we’re seeing patients with PN [prurigo nodularis] for those who are listening and watching out there, we’re usually thinking about, you hear this word, this big, sexy word, “neuroimmune,” thrown about. That composes the 2 things that we’re thinking about. We’re trying to work on the immune inflammation aspect of the disease. We’re trying to work on the nerve aspect of the disease. Oftentimes, you can very roughly parse our treatments falling into both of these categories. Dr Shawn Kwatra, maybe you can take us on a little walk-through when you’re thinking about first, second, and third steps in terms of trying to get somebody’s PN under better control, or at least their symptoms. What are some of those immunologic agents and neuro agents that you’re working with? What are the common things that dermatologists might use or rather some of the less-common things that maybe someone would only use if they came to see you?

Shawn Kwatra, MD: It’s a great question, Dr Raj Chovatiya. Oftentimes, as you guys all know, we start with topical steroids for most things in dermatology, including prurigo nodularis. What I would contend is that topical steroids are less effective in prurigo nodularis than almost all other inflammatory skin conditions. One of the reasons is because the nodule has so much hyperkeratosis and dead skin on top that it’s very hard to even penetrate the nodule to where the action is at. The action in prurigo nodularis is mostly in the upper dermis. There’s some activity in the epidermis, but really the upper dermis is where that activity is at. It’s very hard to get topical steroids in there. As we all know, intralesional steroids tend to work pretty well in prurigo nodularis, but the question is how many nodules are you going to inject? You can do maybe 10, maybe 20, or maybe you can do hundreds, but probably not. Then also in the skin of patients of color, we’re worried about hyperpigmentation, atrophy, things like that. Those are the first steps.

I found that other topical agents tend to not be very effective. I’ve stopped using many of the other topicals that are available. In terms of oral and systemic agents, I do have several patients on phototherapy for their PN. What I’ve noticed is, it can be very slow to start with. Oftentimes, I would combine that. Before we had an FDA -approved therapy, I would often do methotrexate orally around 15 mg a week, and alongside that, do phototherapy. Then I’ve had several folks who’ve been able to, later on, be just on phototherapy and have them be more controlled. For severe disease, that’s when you really need a systemic agent.

Now we have methods that are FDA-approved, like I mentioned, methotrexate, cyclosporine. There is also the neuroaxis for prurigo nodularis. Agents like gabapentin, and pregabalin have all been thrown around. What I found is that those agents aren’t usually that effective as monotherapies. I think we’re learning a little bit more that targeting the immune access primarily is, in some ways, a better mechanism of action. Although, we know that they’re totally connected both in the neuro and the immune axis. There’s also some data on some JAK [Janus kinase] inhibitors that may be effective because they’re able to modulate both pathways associated with type 2 inflammation, and beyond that. IL-22 [interleukin-22] we know is expressed from CD4 [cluster of differentiation 4], CD8 T-cells, IL-31 is important. There may be even a role for IL-17, as well. That’s the overall big outlook.

I really try to stay away from steroids in all patients, in particular in PN patients with type 2 diabetes and hypertension. I really try to stay away from prednisone or intramuscular Kenalog. I was giving a talk about PN, and someone told me, you could just give them Kenalog 3 times a year and they’d be clear. I would still contend there are so many side effects of it. I’m always looking for steroid-sparing options. That’s a big key for me. That’s pretty much my outlook. Dr Sarina B. Elmariah, do you have any other thoughts about that? I know that you use a lot of other off-label stuff. What are your thoughts on treatment?

Sarina B. Elmariah, MD, PhD: Yes. I definitely agree with you that the goal is to avoid steroids where we can. I will employ phototherapy for patients when it’s covered and it’s easy for them to access. Where I know that they can be consistently treated. Maybe, unlike you, I do tend to use a lot of neuromodulators. I feel that the combination of neural-targeting therapy with immunotherapy has really worked the best. I achieve the most rapid and profound responses.

I do want to highlight, with the approval of dupilumab, but even looking back at other medications that we classically think of as being just immunomodulatory. Many of them have a neural impact. If you even think about drugs like thalidomide, still to this day, for different disorders people don’t even know exactly how it works. It clearly has a neural effect. In so many patients, 1 of the side effects of it is that you can get neuropathy. It obviously has an immune impact. Dupilumab we’re seeing is a drug that will clearly have an anti-TH2 [type II helper T cells] modulatory effect. Part of that TH2 access is controlling nerve sensitivity, if you will.

Hearkening back to the term neural sensitization. You reduce the nerve sensitivity to other itch factors. I will often use low-dose neuromodulators like gabapentin or tricyclic antidepressants or other agents, SSRIs [selective serotonin reuptake inhibitors], and SNRIs [serotonin and norepinephrine reuptake inhibitors] in order to control the nerve component while I’m loading with phototherapy or methotrexate. I do try to steer clear of cyclosporine when I can. In recent months, and even previously off-label if I was using dupilumab, now that again has superseded some of the more aggressive immunotherapies. I think the combination idea is where, or choosing an agent that seems to have an impact on both axes, is beneficial to patients.

Transcript edited for clarity