Melinda Gooderham, MD, MSc, FRCPC, Peterborough Regional Health Centre in Ontario, Canada, discusses recent trials and studies that have been conducted on emerging therapies for patients with atopic dermatitis.
For a patient population with very sensitive skin, having a well-tolerated therapy is extremely important, says Melinda Gooderham, MD, MSc, FRCPC, dermatologist and clinical researcher at Peterborough Regional Health Centre in Ontario, Canada.
How do emerging therapies work to address the underlying causes of atopic dermatitis?
These emerging therapies can be more targeted, such as interleukin-13, which we know is a key cytokine in the pathophysiology of atopic dermatitis. We can block with nemolizumab interleukin-31 which is a key itch cytokine in atopic dermatitis causing the most burdensome symptom for our patients.
To have those targeted therapies that block either the inflammation or the itch that's leading to the impairment of quality of life of our patients in a safe way, I think, is a win-win situation—to have the efficacy along with the safety.
For the topicals, they are not quite as targeted. They are blocking, usually, cell signaling, in some sense, to reduce inflammation, reduce inflammatory cytokines; some improve the skin barrier. For example, tapinarof reduces inflammatory cytokine production; it also reduces oxidative stress and improves skin barrier proteins. So, we're addressing a number of issues in the pathophysiology, such as skin barrier dysfunction and dysregulated immunity.
What clinical trials or studies have been conducted on these emerging therapies, and what are the next steps?
Each of the emerging therapies have to have duplicate studies and registrational studies. For topical roflumilast, we have INTEGUMENT I and INTEGUMENT II. They're basically identical studies to see if you can replicate the results in 2 different locations and different populations.
The results were slightly different. We can't compare one to the other because of the duration of therapy, the patient selection. I think about 30% to 32% of patients achieved IGA [Investigator’s Global Assessment] success with topical roflumilast over 4 weeks.
With tapinarof, we had the 2 studies; the ADORING 1 and ADORING 2 studies. Again, looking at replication of results, with about 40% IGA success over 8 weeks of therapy. So again, greater than placebo, very effective safety, very well tolerated. Really, the only adverse event that we saw in greater than 5% of patients was folliculitis, which we knew from the psoriasis trials. They call it a follicular event; it's not a classic folliculitis that we would see. But overall, well tolerated by patients. This is a population with very sensitive skin who have a lot of burning and stinging with other treatments. So, to have a well-tolerated therapy is really important.
For the lebrikizumab trials, we have the 2 replicated registrational studies, ADvocate 1 and ADvocate 2, which were monotherapy studies. But we also have the ADhere study, which was lebrikizumab vs placebo with the addition of topical corticosteroids. This is done in a large number of patients to show the efficacy and safety. Those results were presented at the meeting.
And then we have nemolizumab, where in Japan it has actually already received approval for pruritis in atopic dermatitis. We don't have it approved here in North America, and the registrational studies have not yet been published. We know that they met their primary end point and that the medication was more effective than the placebo, but we don't have the results for that those trials yet.