Dupilumab is a monoclonal antibody approved for use in patients with atopic dermatitis that is not well controlled with topical treatments, or who are unable to use topical treatments. It was a pleasure to talk with Prof Amy Paller (Northwestern University Feinberg School of Medicine; Lurie Children’s Hospital of Chicago, Chicago, IL, USA) about the key takeaways from the LIBERTY AD PRESCHOOL and the ongoing open-label extension trial, which is investigating the safety of dupilumab treatment in patients aged 6 months to 5 years with moderate-to-severe atopic dermatitis.
The abstract ‘Treatment-Emergent Adverse Events in Patients Aged 6 Months to 5 Years With Moderate-to-Severe Atopic Dermatitis Treated With Dupilumab in an Open-Label Extension Clinical Trial.’ was presented at AAD 2023, 17-21 March, 2023.
This information is brought to you by Touch Medical Media and is not sponsored by, nor a part of, the AAD. Â
Questions
- What is already known about the clinical utility of dupilumab in the treatment of atopic dermatitis in children? (0:21)
- What were the key takeaways from the LIBERTY AD PRESCHOOL parent study? (1:12)
- What were the aims, eligibility and methodology of the open-label extension clinical trial? (2:01)
- What were the main findings of this extension trial? (2:59)
- How will these findings be used to inform future treatment decisions and what questions remain unanswered? (4:15)
Disclosures: Amy Paller discloses consultancy for Aegerion Pharma, Azitra, BioCryst, Boehringer-Ingelheim, Bristol Myers Squibb, Castle Creek, Eli Lilly, Janssen, Krystal, LEO Pharma, Novartis, Regeneron, Sanofi/Genzyme, Seanergy, TWI Biotechnology, UCB, grant/research support from AbbVie, Dermavant, Eli Lilly, Incyte, Janssen, Krystal, UCB, and other financial or material support from DSMB: AbbVie, Abeona, Catawba, Galderma, InMed.
Support: Interview and filming supported by Touch Medical Media Ltd. Interview conducted by Atiya Henry.
Filmed in coverage of the 2023 AAD Annual Meeting.
Click here for more content on atopic dermatitis.
Transcript
Hi, I’m Amy Paller, professor and chair of the Department of dermatology at Northwestern university, Feinberg School of Medicine and a pediatric dermatologist at the Lurie Children’s Hospital of Chicago.
What is already known about the clinical utility of dupilumab in the treatment of atopic dermatitis in children? (0:21)
Dupilumab was the first systemic agent that was targeted for atopic dermatitis. Before that, we just had immunosuppressant medications, including systemic steroids, which we really try never to use in children for atopic dermatitis, but is still the most broadly used by far among the systemic agents. Dupilumab became available as a biologic targeting interleukin 4 receptor several years back, first for adults, then for adolescents, and most recently in June of 2022, it became available for those youngest children with atopic dermatitis six months of age to under six.
What were the key takeaways from the LIBERTY AD PRESCHOOL parent study? (1:12)
So the LIBERTY AD PRESCHOOL study was the study that was pivotal for the approval of dupilumab for children six months of age through five years of age. This is a study in which children were treated with either weight based dupilumab or with placebo. And of course, the dupilumab not only came out on top by far, but also proved to be as safe in that study, which was a 16 week phase III double blind randomized control study, as it had been in the previous trials in children, adolescents and adults.
What were the aims, eligibility and methodology of the open-label extension clinical trial? (2:01)
So those children who had been on the LIBERTY AD study whose parents decided to move forward with the open label trial were eligible. Of course, that included children who were on placebo and had not done well as a result and they were able to move into the open label trial. In addition to children who had been treated with dupilumab, whose parents chose to continue. The aims of the open label extension clinical trial, are primarily those looking for safety, ensuring that over time, no new red flags develop for a medication, but also to see whether there was continued efficacy of the medication in those children who had responded during the first 16 week trial of the parent study.
What were the main findings of this extension trial? (2:59)
So the young children who were in this trial were treated with dupilumab on an every four week basis that is weight based, either 200 milligrams or would be 300 milligrams. In general, we have those who are 5 to less than 15 kilograms treated with 200 milligrams and those who are 15 kilograms to less than 30 kilograms treated with 300 milligrams. I will also add that in the parent study there was no loading dose used for these younger children and they did just fine without needing that extra second shot of the doubling of the dose for loading. In this open label extension trial, what was found in this group is that there was continued safety. There wasn’t any new adverse event that came up at all. And in fact, the long term extension, the patients were just continued and largely continued to have the same efficacy or better than what was seen in the 16 week trial.
How will these findings be used to inform future treatment decisions and what questions remain unanswered? (4:15)
So I think that the trial that was pivotal as well as the open label extension gives us further reassurance about the use of a systemic medication dupilumab in this very young age group. There is no other medication that is available in this age group on label for atopic dermatitis. But I will also mention that this was a large study, and used a biologic in a very young age group. I believe that this was the first study ever with these numbers, as it treated a common disease, that used a biologic in this age group. So that was pretty much unprecedented. And now we have the open label continuing study, continuing to show that safety. I think that this is the first of other studies that will come, but since no other agent is really close to that age group yet, we need to wait for a while before we see results in these very young children with other agents. The important factor about this age group is not just the tremendous safety and the lack of need for any blood monitoring for this systemic medication in this age group or any other. We also have some special considerations. This is, first of all, an age group where live immunizations are given. There has been no testing, including in this study, for the safety of live immunizations with this medication. Now, this medication targets the type 2 immune system. And we don’t know that that system has anything to do with response or the safety in managing vaccinations that are live. There’s been testing in adults on dupilumab that has shown that they’re perfectly able with killed vaccines to mount immune responses. But there’s been no study of live vaccines. And in fact, it is this age in children six months through under five years, where they, at least in the United States, get the series of two immunizations against measles, mumps, rubella and varicella. This is a study that’s now being planned to move forward that will be run jointly with investigators who really, as do I, want to ensure that safety and the take of the vaccines. I have every expectation that it will be fine, based on several anecdotal reports now of children who did get the live vaccine while using the medication. But a trial is in order. Secondly, we also have a very young age group getting the dupilumab. And the other question that raises is whether there is any effect on the immune system as it’s developing early enough that we can change the course of the atopic dermatitis and even possibly cure it in these moderate to severely affected young children. And also whether we can prevent, with the early use of this medication, the development of other forms of atopy – asthma, eosinophilic esophagitis or even later allergic rhinitis – that develop in these children as part of their probably multimorbidity set up where they’re more susceptible to all of these diseases. And yet we know that dupilumab not only works for atopic dermatitis, but for a wide variety of these type II immune mediated disorders. That too will require years of longitudinal study to try to figure out whether this population treated early with a highly effective and yet safe agent can be prevented from having what’s been called the atopic march – the later development of these other forms of atopic. So these are two really exciting possibilities for children that first of all, they can continue to get their live vaccination and very importantly, that it may change the course of the atopic dermatitis and change the potential for atopic march, that having this available and having it available long term based on these results will enable.
Subtitles and transcript are autogenerated.
