Dupilumab for Pediatric Atopic Dermatitis: Tips From Dr Amy Paller

As an immune-mediated inflammatory disease, atopic dermatitis (AD) often requires an intensive approach to care. While diligent basic skin care practices and topical therapies can be effective for mild to moderate disease, worsening disease severity requires more advanced therapies to alleviate signs and symptoms such as dry skin and itch.

Dupilumab, an injectable biologic that inhibits IL-4 and IL-13, was approved by the FDA inn 2017 to treat moderate to severe AD in adults whose disease is not adequately controlled with topical prescriptions or if those treatments are contraindicated.¹ In 2019, dupilumab’s indication was expanded to include patients with AD aged 12 to 17 years,² and most recently, the therapy was approved to treat AD in patients as young as 6 years.³ The advanced therapy, the first available in the market to treat AD, offers an effective option for pediatric patients with severe disease.

Amy Paller, MD, MS, is president of the International Society of Pediatric Dermatology, a past president of the International Eczema Council and the Pediatric Dermatology Research Alliance (PeDRA), and former chair of the Scientific Advisory Board of the National Eczema Association. Additionally, she is the Walter J. Hamlin Professor and Chair of dermatology, professor of pediatrics, and principal investigator of the National Institutes of Health-funded Skin Biology and Disease Resource-based Center at Northwestern University’s Feinberg School of Medicine. She joined The Dermatologist to share her insights and perspectives on dupilumab in pediatric AD.

What impact can dupilumab and other emerging advanced therapies for AD have on caregiver quality of life?
There is no question that AD is a disease that does not just impact the child who is affected but impacts the entire family. It changes family dynamics; it affects the siblings and their relationship with the child, their time with the parent, and how children are treated within the family.

It is a disorder that not only increases anxiety and depression in parents but also is a financial drain. AD can also be a huge time burden because of the topical care required, along with all the extra attention the child may need to help avoid triggers. AD has several comorbidities, which can also affect the family, even when the AD is in better control. Getting the burden of AD down is a benefit, not just for the child, but for the entire family.

Children often have a fear of needles—what advice can you offer when it comes to helping patients and their caregivers overcome this fear to receive dupilumab?
We are fortunate that the need for injection is typically the only issue with dupilumab. I remind the child and family that we do not have to do laboratory testing. Certainly, we were checking laboratory tests monthly with the immunosuppressants—and getting labs drawn every 4 weeks can be more uncomfortable than getting an every 4-week injection of dupilumab, often requiring multiple sticks.

Of course, that conversation does not help with the fear. Practically, we can use topical anesthetizing agents to diminish the discomfort of getting the needle into the skin and reduce the fear. I will sometimes do that for the first few injections. Once kids get past these first few doses, they seem to feel that the injection just becomes one more thing to do in their care plan, and the anesthetizing cream is often dropped. It helps to make sure that the dupilumab is not too cold for the injection—take it out of the refrigerator for 5 to 10 minutess.

We often will administer the first-time injection in the office and distract the child. When we give a loading dose (split between two injections), the parent or caregiver will do the second one. This goes a long way in making the parent feel more comfortable and in making the child see that a trusted individual is able to do this and carry it on thereafter.

I will say that there are some families in whom the child really needs dupilumab but the child is still so wild and fearful that it cannot be administered at home. We do have some families who come in once a month to get that injection in the office; these are the most difficult ones for everyone and distraction techniques are the best we can do with limited relief.

Two recent abstracts presented at AAAAI 2021 highlighted efficacy of dupilumab in children with AD and allergic rhinitis or asthma, respectively.^4,5 Could you describe the general efficacy of dupilumab when it comes to alleviating symptoms of other atopic diseases?
We know dupilumab is already approved and has shown to be highly effective and commercially available for adolescents with asthma. Studies are underway regarding use of dupilumab as an adjunct to subcutaneous immunotherapy for adults with allergic rhinitis. Anecdotally, we have heard from patients on dupilumab who find they need less medication to treat their other allergic disorders. Unfortunately, the studies for AD have not captured well the effects of asthma and studies for asthma have not captured well the effects on AD in those subpopulations.

It is also important to realize that the severity of these comorbidities is not necessarily the same as the severity of the AD. Many of our children with AD who have other atopic comorbidities do not necessarily have severe asthma or allergic rhinitis.

That said, it is important to recognize that about 90% of the children—whether with severe AD and aged 6 to 12 years, or with moderate to severe disease and aged 12 years or older—had some other form of atopy. So, dupilumab could be a win-win beyond the AD for those children who suffer from more than one atopic disorder.

One thing we do know is that the drug works just as well for the AD in children with and without these various other atopic disorders.

Is there anything else you would like to share with your colleagues?
We are in such an exciting time related to treatment of atopic dermatitis in children, based on our growing understanding of the basis for the disease, including the differences that are age-based. Dupilumab was the first targeted agent, but we are now looking forward to the availability other injectables that will provide choices for families of children with atopic dermatitis.

The other major new approach is the Janus kinase (JAK) inhibitors, which look to be as promising in efficacy as dupilumab and offer an oral option that can easily be stopped and restarted. However, with pediatric patients, it is all about safety. Despite their many advantages, many dermatologists will use JAK inhibitors selectively until more experience accrues.

References
1. Sanofi and Regeneron announce FDA approval of Dupixent® (dupilumab), the first targeted biologic therapy for adults with moderate-to-severe atopic dermatitis. News release. Sanofi Regeneron; March 28, 2017. Accessed May 27, 2021. https://www.globenewswire.com/news-release/2017/03/28/946002/0/en/Sanofi-and-Regeneron-Announce-FDA-Approval-of-Dupixent-dupilumab-the-First-Targeted-Biologic-Therapy-for-Adults-with-Moderate-to-Severe-Atopic-Dermatitis.html

2. FDA approves Dupixent® (dupilumab) for moderate-to-severe atopic dermatitis in adolescents. News release. Sanofi Regeneron; March 11, 2019. Accessed May 27, 2021. https://www.prnewswire.com/news-releases/fda-approves-dupixent-dupilumab-for-moderate-to-severe-atopic-dermatitis-in-adolescents-300810264.html

3. Sanofi: FDA approves Dupixent® (dupilumab) as first biologic medicine for children aged 6 to 11 years with moderate-to-severe atopic dermatitis. News release. Sanofi Regeneron; May 26, 2020. Accessed May 27, 2021. https://www.globenewswire.com/news-release/2020/05/26/2038798/0/en/Sanofi-FDA-approves-Dupixent-dupilumab-as-first-biologic-medicine-for-children-aged-6-to-11-years-with-moderate-to-severe-atopic-dermatitis.html

4. Beck L, Wollenberg A, Paller A, et al. Dupilumab improves signs and symptoms of severe atopic dermatitis in children aged 6-11 years with and without comorbid allergic rhinitis. J Allergy Clin Immunol. 2021;147(2):AB144. doi:10.1016/j.jaci.2020.12.523

5. Boguniewicz M, Sher L, Paller A, et al. Dupilumab improves signs and symptoms of severe atopic dermatitis in children aged 6-11 years with and without comorbid asthma. J Allergy Clin Immunol. 2021;147(2):AB32. doi:10.1016/j.jaci.2020.12.151