Andrew Blauvelt, MD, MBA, reviews clinical implications from the phase 3 LIBERTY AD CHRONOS study examining the efficacy of dupilumab plus topical corticosteroids in adult patients with moderate to severe atopic dermatitis.
Andrew Blauvelt, MD, MBA: In another recent paper that was published, we looked at the LIBERTY AD CHRONOS study, and the CHRONOS study was one of the phase 3 dupilumab [Dupixent] studies, and this was the study that also had topical corticosteroids. In the first portion of CHRONOS, we had some patients doing placebo shots plus topical steroids, and then another group getting dupilumab shots and topical steroids. So topical steroids versus dupilumab plus topical steroids. This is called CHRONOS, and it was originally published in The Lancet. There have been a lot of sub-analyses looking at this particular study, and in a recent analysis, we looked at the individual body areas and the individual signs of AD [atopic dermatitis] in those body areas over a 52-week period. What do I mean by that? When we do an EASI [Eczema Area and Severity Index] score for eczema area severity index, it’s broken down into 4 body parts: the head and neck area, the trunk, the upper extremities, and the lower extremities. And then within each of those 4 body areas, there are signs of AD that are scored: erythema, population or induration, excoriation, and lichenification. We make scores for each 1 of those signs within each 1 of those 4 body areas. So you come up with 16 numbers and then you calculate an eventual score. What has been reported before is the total EASI scores. In this particular recent paper, we looked at what happens in the head and neck and what happens in the upper extremities. What happens in the trunk specifically, and what happens in the lower extremities and what happens to each of those signs? What happens to erythema on the head and neck? What happens to like lichenification on the trunk and so forth? For all 16 of those individual parameters, we looked at them individually over the course of 52 weeks. What’s interesting about that, and why would we do something like that? There have been a number of reports now of facial erythema caused or occurring during dupilumab therapy. I consider this an uncommon side effect. Most of my personal experience with dupilumab with facial erythema has been residual atopic dermatitis. That is my opinion, and my experience is that, most of the time, if patients have facial redness and they’re on dupilumab, it has been due to residual atopic dermatitis, and I’ve treated that accordingly with some supplemental topical therapy. However, there are other cases, and it’s less common, where it’s clearly not atopic dermatitis: it’s new-onset sometimes facial erythema, and some reports suggest that it occurs in up to 5% of patients on dupilumab. It’s 1 of the reasons why we wanted to do this particular sub-analysis. We wanted to look at what in particular is happening on facial erythema and other facial signs in this large trial. The bottom-line result is that in all 16 parameters, erythema, induration, exploration, and lichenification, and within all 4 body parts, we see nice improvement over the course of 52 weeks. Now, 1 small caveat is that head and neck responded less, well if you will, compared to other body parts, so there was still anywhere from 55% to 60% improvement in the head and neck scores over the course of 52 weeks. We saw, for example, maybe in the 70% range improvement in other body areas. The head and neck perhaps didn’t do quite as well as other body parts, but it still did very well in all the individual parts of the score. The caveat of this data is that overall, if you look at clinical trial data from a large number of patients in this particular trial—and they were using topical steroids, by the way, hydrocortisone on the face if needed, patients quote-unquote do well in all body areas—1 of the caveats of this data is that it doesn’t capture individuals. It doesn’t say that there are not some individuals in this trial who may not have done well on the face. It doesn’t capture the data on the individual level. It’s just a global look at the data, but nevertheless, the global data looks good in that dupilumab works in all body areas over the course of 1 year with the addition of topical steroids.
When we looked at the time course of improvement in these individual body areas, what we found is that most of the response, if you will, most of the gain and improvement occurs in the first 4 to 8 weeks, and then what we see over time is that the curves steady out and remain durable and solid over the course of 52 weeks. This is helpful, I think, to know that when you start a new therapy like dupilumab with some topical steroids, you would expect to get the most gain at the beginning of the trial. It doesn’t mean you can’t get any gain later, but the majority of their response is going to come in that first few months of therapy, and that’s what you can tell your patients.
Transcript Edited for Clarity