The SOLO 1 and 2 Dupilumab Trial

Elaine Siegfried, MD: Dupilumab is a targeted IL-4 [interleukin-4] receptor blocker. So it’s very much an anti-type 2 immunity drug. And one of the emerging issues with dupilumab is that it’s being used for people who don’t have textbook atopic dermatitis. As discussed, atopic dermatitis is a phenotype, and there are many people though who have chronic inflammatory skin disease that you can’t really tell whether they have atopic dermatitis or not. Some of them have contact dermatitis, allergic contact dermatitis. Some of them have some component of psoriasis, which is a totally different drug immunologically.

And so one day when we have a better biomarker to try to distinguish between what the immunologic background is for these people who have total body inflammatory skin disease, it’ll be a little bit better. But for a subset of people who were put on dupilumab, they developed some complications. One of the emerging ones that didn’t really come out in the clinical trials is this kind of facial accentuation. The body will totally clear up and they’ll get this facial rash. And most of us think that that’s probably a subset of contact dermatitis.

Because adults in the dupilumab trial all did really well, we think that dupilumab probably works for some subset of contact dermatitis, but not all of it. So that might be one of the problems for people who don’t respond 100%. There are other issues too, but people are very concerned about whether it has an impact on your immune health in general to do this kind of a type 2 immunologic blockade. My personal feeling is that it makes it better.

When you have immune dysfunction that features overexpression of type 2 immunity, I think it makes you more susceptible for herpes and molluscum and staphylococcus aureus colonization and when you kind of correct that, this probably helps that.

The definitive trials for adolescent atopic dermatitis that were completed probably a year ago now, the results of those trials were very similar to the adult trials. One of the problems with both the adult trials and the adolescent trials was that the primary endpoint—which is the investigator global assessment [IGA], which is just a 5-point scale measuring clear, almost clear, mild, moderate, to severe disease, right? It’s just a static primary endpoint that investigators have to use.

Then there’s also an improvement in the eczema area severity index, called the EASI [eczema area and severity index] score. And that endpoint was somewhat modified from the psoriasis trials. We had a lot of experience with psoriasis trials. So again, the investigator global assessment and the percentage improvement in EASI scoring, or the endpoints that we used to monitor improvement. But this was the first big systemic trial that we’ve ever had an opportunity to generate or analyze data for. And the numbers frankly didn’t look as good as what all of us…see for patients and what patients experience with improvement.

So the trials were pretty similar to the adult trials. There’s about a 60%, a 2-point improvement in the IGA score, meaning you had to get from moderate to severe, to clear or almost clear, over a 4-month period…compared with placebo. So placebo effect in adolescents; there was 1 difference from the adult trials is that the placebo effect in adolescents was much lower. In adults, and again maybe the adults had some component of allergic contact dermatitis and they just stopped using whatever it was they were using when they came into the trial. So there was a bigger placebo response, whereas the adolescents had a smaller placebo response. But about the same degree of improvement as the adults did in those trials.

And while it was impressive and certainly enough to gain FDA approval, thank goodness, because we needed a new drug in this space, I think those results don’t really reflect the true efficacy.

The other aspect of any trial is safety, and the safety was great for both the adolescent and the adult trials, very similar. The adverse events of note were this unexpected conjunctivitis in about 10% of adolescents, just like 10% of adults. We don’t still really understand what that conjunctivitis is all about. For most people it was transient or they could tolerate it or use some eye drops, and nobody stopped the drug for that reason.

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