Insights on the Application of Dupilumab for Pediatric Patients Aged 6 to 11 Years With Moderate to Severe Atopic Dermatitis

Following her recent study, Dr Abigail Cline discusses current literature to assess reported efficacies, side effects, and risks of using dupilumab to treat atopic dermatitis (AD) in pediatric patients.

Abigail Cline, MD, PhD, FAAD, is a board-certified dermatologist affiliated with NYC Health + Hospitals/Coney Island and Lincoln Medical Center in New York, NY.

What is the current literature assessing reported efficacies, side effects, and risks of using dupilumab to treat AD in pediatric patients?

We found that there were 4 trials with a total of 512 patients with AD ranging from ages 6 to 11, and all these trials involved both dupilumab vs placebo. Two of the trials used dupilumab monotherapy, while another 2 used dupilumab plus topical corticosteroids, which were found using PubMed, as well as using clinicaltrials.gov.

Can you describe the Eczema Area and Severity Index (EASI), Scoring Atopic Dermatitis (SCORAD) index, Pruritis Numeric Rating Scale (P-NRS), Investigator's Global Assessment (IGA), and Children's Dermatology Life Quality Index (CDLQI), and how they’re used to assess outcome measures?

There are a lot of outcome measures used in clinical trials to assess efficacy of medications. The first and most common one is the EASI score, and this allows us to assess the severity and extent of AD. You evaluate the body surface area affected by eczema, as well as the intensity of the eczema in that area, such as erythema, induration, excoriation, and lichenification. Typically, the score ranges from 0 to 72, with 72 meaning that there’s a higher severity of disease.

Next is the SCORAD score, which combines both subjective and objective assessments. The subjective assessment is provided by the patient and includes the intensity of symptoms, such as itching and sleep loss, while the objective component evaluates the extent and intensity of the skin disease. This usually ranges from 0 to 103, with, again, the higher scores indicating more severe disease.

The next one is the P-NRS, which is actually a very simple scale ranging from 0 to 10 that is commonly used to measure itching specifically in AD.

Continuing to IGA, which is my favorite, this is a scale from 0, or clear, to 4, which is severe. It’s a subjective assessment tool that’s very handy for clinical trials, but also even for clinical applications.

Finally, there’s the CDLQI. This is a questionnaire specifically designed for pediatric patients to assess the impact of the skin condition on their quality of life, and it has 10 questions that explore the emotional, social, and functional aspects of living with AD. The score ranges from 0 to 3, with the higher score indicating greater negative impact on the child’s quality of life.

What further research is needed to evaluate dupilumab’s effectiveness and the occurrence of adverse effects?

Dupilumab is wonderful, and I have a lot of experience with it. I'm sure almost all our health care providers in dermatology have experienced not only prescribing dupilumab, but managing patients treated with it. However, further studies are always needed. We need to combine both clinical and real-world data to really get a full picture of dupilumab. Some areas for future studies include long-term safety and efficacy. Meaning that, even though a lot of trials can last up to a year, we still need to know the longer impact of being on dupilumab.  This not only shows us the durability of the treatment option, but also if there are any late onset adverse effects.

The next is comparative studies. There are more and more medications hitting the AD pathway, and it’s for the benefit of both patients and physicians to have comparative studies that would compare dupilumab to some of these newer medications. This helps us to not only see the relative effectiveness, but also their safety profile and how to better create a flow chart in terms of therapy options. Specifically, I'm thinking of the Janus kinase inhibitors and the other AD biologics that are a targeting eye of our team.

Next is subgroup analysis. It has been very controversial in dermatology, but not all patients are represented equally in clinical trials. By further investigating specific patient subgroups who are receiving dupilumab therapy, we can better see its effectiveness, as well as its safety profile. We can explore factors such as age, disease severity, disease duration, comorbidities, and race. This is real-world data that can really help us identify which patients have a better or less treatment response.

Also, we should look at post marketing registries. I know that we have them for psoriasis, and some do exist for dupilumab that we can see in real-world studies. This involves analyzing data from routine clinical practices to see the real-world data for dupilumab, which gives us insight into the efficacy and safety in a diverse patient population, ranges of age, and comorbidities. It really helps us to validate and expand upon the findings within a clinical trial.

Then there are the long-term effects both on growth and development. AD usually affects children, and so dupilumab is approved for ages 6 months and older. We need to know what's going to happen with those children 10 years down the line if they're still on dupilumab, and we need to see what are the even longer than usual effects on growth and development.

Finally, there is the adverse effects profile. There can be some very rare adverse effects to some medication that you really only start to understand once it's thousands to tens of thousands of patients being treated with that medication. As dupilumab becomes more utilized within dermatology practices, and as more and more patients can get on it, we really need to monitor for any rare or serious adverse effects that can emerge from this.

All of these are ways in which we can further understand the role of dupilumab within dermatology and within our toolbox of treating AD.

Are there any tips or insights you would like to share with your dermatologist colleagues regarding the application of dupilumab for pediatric patients with moderate to severe AD?

As much as I love dupilumab, you must find the right patient. Dupilumab can be very difficult, especially for children, because it is a subcutaneous injection. You need to find the right patient with severe enough AD and parents who have enough insight to agree and use this medication.

The next is age and weight considerations. We always think of this when we give medications for pediatric patients, especially systemic ones, and this is because there is an age requirement of at least 6 months of age and older with weight requirements.

I think the biggest one is informed consent and shared decision-making. In terms of pediatric patients, it’s not just getting consent from the patient, it's also getting consent from the parent. You must work together as a team with the patient's parents or guardians, and you must explain the potential risks and benefits of dupilumab. You must make sure that they understand the treatment goals and the expected outcomes, as well as the potential adverse effects.

We are managing AD, and this is not a cure. This is something that the patient may have to be on for years or even lifelong. Trying to get those expectations through not only to the patient, but their family really helps to create a more collaborative therapeutic environment and a better understanding of treatment duration and monitoring. For patients with dupilumab, I typically tell them, "Give it at least 3 months before we start to see any improvement." That can be a long time. A lot of parents think, "Oh, once they take the injection, it really should be very quick." That's not how dupilumab works.

Typically, we give them 3 months and we try to see if there's any improvement, then we take it step by step from there. That's why we need to have routine follow-up visits with our patients because we need to provide them with the opportunity to discuss if they're having any adverse events, if they no longer feel comfortable, or if they want to continue. It's working hand in hand with the patient throughout their treatment course.

Then there are also adverse effects and safety monitoring. Dupilumab, by in large, is safe, but you still want patients and parents to know that there can be adverse effects such as injection site reactions, conjunctivitis, or upper respiratory infections. We really must educate patients and their families just to be aware that these side effects can occur.

With AD, I like to take a multidisciplinary approach where we're collaborating not only with the the pediatrician, but also any allergists for severe AD, because we want to provide comprehensive care for these patients. We like to work together with them to make sure that their pediatrician and allergist are aware that we are starting dupilumab as well as adverse effects that may occur and how dupilumab can help with other pediatric conditions such as asthma and allergic rhinitis.

Lastly is patient and family support because dupilumab and AD can both really impact a patient's quality of life. We like to explain to patients that even though dupilumab can really improve a lot, it's still going to be management. They still likely need to use topical steroids. They’re still going to have to see a dermatologist because AD is such a lifelong condition. Patients get educational materials, they join support groups, and they really try to address the emotional and psychosocial aspects of living with this chronic skin condition. We want to empower the pediatric patient so that, when they become teenagers and adults, they’re equipped with better medical insight on how to manage it.

Reference
Balboul S, Kahn J, Tracy A, Peacock A, Cline A. The application of dupilumab to pediatric patients aged 6–11yrs with moderate-to-severe atopic dermatitis whose disease is not adequately controlled: the clinical data so far. Drug Des Devel Ther. Published online May 1, 2023.