Clinical update on the treatment of atopic dermatitis: SOLO 1 and SOLO 2 dupilumab Phase 3 data
Recent publication of data from the SOLO 1 and SOLO 2 studies of dupilumab has increased our understanding of clinical outcomes used to assess atopic dermatitis. Dr Kenneth Gordon considers the clinical implications of these data for the future management of atopic dermatitis.
Hi my name is Ken Gordon, I’m a dermatologist at Northwestern University. I’d like to talk to you today about a new medication for atopic dermatitis called dupilumab. Recently in New England Journal of Medicine there was an article published of two studies of dupilumab for moderate to severe atopic dermatitis. Now this article has far-reaching implications, not only for the medication itself but for the understanding of atopic dermatitis.
Dupilumab is a medication that blocks one subunit of the interleukin-4 receptor. This blocks the ability of both interleukin-4 and interleukin-13, to have this pathophysiological effect on atopic dermatitis. What's important about this study however is not just so much the physiology suggesting that this medication works for the disease, but also the implication for understanding how clinical trials are done and the meaning of clinical trials in atopic dermatitis. Because this is the first of hopefully a number of new Phase 3 registry development trials for atopic dermatitis with multiple new medications, we don't quite know how the data will stack up over time. In reference with psoriasis, in years gone by when we had early biologics, we didn't know what a PASI 75 really meant or what we were able to reach in the future.
In this study, with two studies (the SOLO 1 and SOLO 2 study), it was found that dupilumab worked in getting the primary endpoint of an Investigator Global Assessment [IGA] about 35–40% of the time and then IGA of 0 or 1 which means clear or almost clear. Likewise the EASI scores (which was the primary second endpoint) reached statistical significance against placebo, at or right about EASI 75, of anywhere around 50%. What that means however for new development for atopic dermatitis is unclear. We really don't know based on comparisons to other Phase 3 development programs how far we can push that or is this medication going to be as good as we can get for atopic dermatitis—a very very important point. A couple of other specifics of the study I think need to be brought out. First of all there were two dosing periods: one was dosing at every other week and one was dosing every week for dupilumab. It turns out the two doses seem to behave about the same, that there seems to be about equal efficacy between the two doses.
What's more, and very importantly, the safety record of dupilumab for the 16-week trial seems very very good. There were no signals that would bring out any concern to me. What that means for long-term therapy for atopic dermatitis is still unclear. One other point that I think is really important is how this study was performed. It was a placebo-controlled trial without concomitant medications. There is some question as to whether atopic dermatitis trials should allow patients to have topical corticosteroids for example. In this case it was chosen not to have those concomitant medications which resulted in, I think, a very clean outcome in the clinical trial results suggesting, I think, that the way this study was done with a true monotherapy study is probably for the best. So I think the conclusions of the study are clear: dupilumab does work for atopic dermatitis and improves when in comparison to placebo in this monotherapy placebo-controlled trial. We don't know the implications for the long-term safety but the short-term safety seems quite good. But what's even more important is we're going to have to get a detailed understanding of what is the levels of care and the level of clearance that we want in atopic dermatitis studies in the future. And this is just the first of the studies that will hopefully lead us to a better understanding of how we treat the disease. Thank you very much.
- September 25th 2016
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