Dupilumab for Adults With Prurigo Nodularis: A Critical Review

Gil Yosipovitch, MD, is a professor and Stiefel Chair in Medical Dermatology. He is also the director at the Miami Itch Center, Dr Phillip Frost Department of Dermatology and Cutaneous Surgeryat the University of Miami Miller School of Medicine.

Transcript:

What are the primary symptoms and impacts of prurigo nodularis?
Dr Yosipovitch: First and foremost, itching, significant itching and second with nodular lesions. So, you have to have both of them to be defined as prurigo nodularis lesions with itching that are prolonged. The definition is that at least six weeks, but these patients have for years these lesions with significant edge.

Why is treating prurigo nodularis challenging with currently available therapies?
Dr Yosipovitch: So, I have to mention now things have changed, but until two years ago, we didn't really have any treatments that are targeted and specific. And this was very difficult to deal with because none of the treatments were amazingly good or the treatments were significantly associated with adverse effects. They were strong immunosuppressants. They were a drug that I used for many years was thalidomide. It's kind of a scary drug to deal with because it's causing birth defects in women and it's also causing neuropathy. But the patients were so miserable and you had to treat them. So that's why we had to deal with very miserable patients that were suffering day and night, low self-esteem and really no good treatments.

How does dupilumab function in the treatment of inflammatory skin conditions, specifically prurigo nodularis?
Dr Yosipovitch: We know that in PN there's a narrow immune dysregulation, and one of the issues is that there's type two inflammation that is clearly a major key factor in the disease itself. So the dupilumab has been approved for atopic eczema because it's targeted type two inflammation by targeting the IL four and IL 13 cytokines. And when you block that, you block that cascade of type two inflammation. So, you don't have to have atopic eczema to benefit from this drug if the pathophysiology involves type two inflammation.

What have recent clinical trials shown regarding the efficacy of dupilumab for prurigo nodularis?
Dr Yosipovitch: So, it's quite effective in reducing first, as I mentioned, itch is the major problem with patients are affected by, and it starts very early to have an effect on reducing itch. And I would say the majority of the patients respond to it.

In addition, you see that the lesions, it takes more time, but the lesions with the nodule lesions, they were scarred, nodular, they resolve, and in a period of a couple of months they have, I would say, quite significant number clearing of the skin. And this is something that even in the previous, when I described the previous treatments, it was almost impossible to think of. So, it changed totally the trajectory of this disease.

What are some advantages of dupilumab in managing prurigo nodularis compared to other treatments?
Dr Yosipovitch: I think first of all, efficacy, and second, is safety. I mean, we all know that dupilumab is a very safe drug. So clearly using a drug that has a good safety profile, and I have to mention that dupilumab in Atopics, we know one of the side effects is conjunctivitis with the PN patients. We don't see that the rarely, even some PN patients may have atopic, but clearly that's not a problem in the majority of these patients. So again, we feel comfortable in using it and I don't see any other additional problems using this drug.

What future research is needed to better understand the long-term efficacy of dupilumab for prurigo nodularis?
Dr Yosipovitch: So, I think one of the issues, the study was designed for patients who had a PN but did not have some of the comorbidities that could be associated with patients in PN, like patients with chronic kidney disease, that they have end stage renal disease that are having PN or patients who had neuropathies that can have PN. So I personally would like to know whether this drug would work well for these patients too. I suspect that yes, but we'll need to know in the future. And this, I don't think that the company would design the study. So we as dermatologists are we'll have to try and explore that and provide that information so our colleagues or others will be able to use it. And that's one of the issues. The long-term effect of this drug will be evaluated. It was just launched two years ago, so clearly we'll have more information, but I don't see any problems with the use.

What the question would be once is whether we could have a longer duration of or durability of a drug. Maybe some of the patients will not need the drug for the rest of their lives, or we can have spread, like some patients with atopic eczema, use it not every two weeks, but a longer periods of time. So that is what we call real world data. The dermatologist will have to provide and report.

What else would you like to share with your colleagues regarding the use of dupilumab for adult patients with prurigo nodularis?
Dr Yosipovitch: Don't hesitate to use it. I now see dupilumab, and now there is also a drug just launched both of these drugs, extremely safe. I really would abandon the use of other drugs that I've used in the past because I think they would cover the majority of PN patients for sure. There'll be some patients, like in any drug, there's no a hundred percent efficacy. But I don't see myself using the older drugs anymore because these drugs are just unbelievable, effective and safe.