Pharmacists play key roles in navigating prior authorizations and other limits on utilization, as well as educating and listening to patients and caregivers.
Listening to the experiences of patients and caregivers is crucial when treating pediatric atopic dermatitis (AD), according to experts during a presentation at the 2023 Asembia Summit.
AD is a long-term skin condition characterized by an inflamed and pruritic rash that tends to wax and wane, according to presenter Alyssa Wu, PharmD, BCPPS, AE-C, flares can be worsened by factors such as patient-specific allergens, and it occurs most commonly inside the elbows, behind the knees, and in the front of the neck.
It occurs in between 10% and 20% of children in the United States, although there is an increased incidence in children with comorbidities such as asthma. In 90% of affected individuals, symptoms develop before age 5. Some children may outgrow it before age 18, but AD remains a lifelong condition in between 20% and 40% of patients. Etiology appears to be related to both genetics and environmental factors.
“A loss-of-function mutation in the filaggrin gene that encodes an epidermal structural protein can be inherited, and what this leads to is a decreased level of skin barrier molecules,” Wu explained. “So, this makes it a lot easier for those irritants and allergens to make it past that first line of defense, and this also causes issues with moisture and water retention, as well.”
Notably, the full impact of AD cannot be estimated based on skin signs alone. Sleep disturbances are common and increase with disease severity. On average, children with mild to moderate AD lose 50 minutes of sleep per night, and 60% of caregivers wake up a minimum of 2 times per night to care for their child with AD.
Caregivers also report heightened anxiety due to conflicting treatment and management recommendations, as well as concerns about adverse effects and worry about the child’s well-being. The session included caregiver perspectives from Ashley Ellis, PharmD, MBA, whose daughter was diagnosed with severe AD when she was very young. Even as a pharmacist, Ellis said the impact of the diagnosis and treatments has been challenging.
“I felt a lot of guilt and shame because the area where I worked the most was primary care…and I know how to get those patients better,” Ellis said. “But I don’t even know how to get my own child better. It’s a lot to deal with for sure.”
Goals of treatment are to reduce the rash, with the ultimate goal of eliminating it, although that may not be possible in all patients, Wu said. Additionally, treatments aim to resolve itching, improving overall quality of life (QoL) for both the child and caregiver, and prevent worsening or further exacerbations. Pharmacists should carefully consider the mechanisms of action of available treatments, as well as age-appropriate indications.
Quite a few topical treatments are available. Wu said ointments are preferred, followed by creams and lotions, but she emphasizes that whatever the child will tolerate is acceptable. For example, high school-aged children may refuse greasier options, such as Vaseline, because of social embarrassment, so lotions may be a better option.
Steroids are the first-line option, varying from low to high potency. Phosphodiesterase 4 inhibitors, such as crisaborole ointment 2%, are FDA-approved for use in patients aged 3 months and older with mild to moderate AD.
Wu noted that this is an important option for especially young children because other treatments, such as topical calcineurin inhibitors, are often approved for children aged 2 years and older. Challenges with topical options include frequent administration adherence, stinging or burning, and caregivers’ concerns about steroids and boxed warnings.
Non-topical treatments are also well-established. Oral antihistamines are an option, although it is important to consider sedating versus non-sedating options. These can primarily be used to help with nighttime itching, thereby improving sleep quality. Other, older options, including cyclosporine, methotrexate, azathioprine, mycophenolate mofetil, and ultraviolet light, are less frequently used.
“If you think about these agents, these medications, you think about a lot of adverse effects that come with these therapies,” Wu said. “So, my patients, especially my parents, are very reluctant to use these types of agents. Luckily, with use of newer systemic agents, their use has really gone down drastically.”
Omalizumab is one such new option. The humanized monoclonal antibody inhibits immunoglobulin E (IgE) binding to high affinity receptors on both basophils and mast cells. In the ADAPT trial, treatment with omalizumab reduced AD severity and improved QoL in children with high IgE at baseline.
Dupilumab is a particularly exciting newer option, Wu said, calling it the “workhorse” of her clinic. As a monoclonal antibody that inhibits interleukin (IL)-4 and IL-13, dupilumab was approved in 2017 for moderate to severe AD and has been expanded to include those aged 6 months and older since then. In October 2022, an additional formulation was approved as a single-dose pre-filled pen for at-home administration in patients 2 years and older with AD.
The LIBERTY AD PRESCHOOL trial examined dupilumab in children aged 6 months to 5 years with uncontrolled moderate to severe AD. Two-thirds of participants had a 75% or greater improvement in the Eczema Area and Severity Index (EASI) score in AD compared with topical steroids.
Further, the LIBERTY AD PED-OLE trial in adolescents aged 12 to 18 years showed that approximately 71% of participants were up-titrated to every-2-week dosing based on body weight due to inadequate response. At week 52, 43% achieved an Investigator Global Assessment score of 0 or 1, signaling clear or almost-clear skin, as well as 81% achieving EASI-75.
Ellis said her daughter has had significant success with dupilumab, although access became a challenge once it received FDA approval in her age group, their FDA compassionate use ended, and insurance denied the claim. Her expertise as a pharmacist was essential to ensure continued access, and these issues can be common challenges for many patients and their families.
“With my training as a pharmacist, I was able to spring into action…I was able to gather her medical records and her prescription records for the past 4 years and show her oral corticosteroid use, injectables, and topical,” Ellis said. “So, between that and the medical records showing how severe her case of AD was, she was approved very quickly.”
Additional biologics include tralokinumab, which is currently approved for adults and has active pediatric studies; lebrikizumab, which has FDA Fast Track Designation and is expected to reach the market later this year; and nemolizumab, which has showed a marked improvement in rash, itch, and sleep disturbances in an open-label, 16-week study.
Two key JAK inhibitors are also showing promise for the treatment of AD. Upadacitinib was previously approved for rheumatoid arthritis and active psoriatic arthritis and was approved in January 2022 for moderate to severe AD in adults and children aged 12 years and older weighing 40 kg or more who did not experience adequate disease control with other therapies. Similarly, abrocitinib was previously approved for AD in adults and was approved in February 2023 for use in adolescents aged 12 years and older with moderate to severe AD.
Wu noted that some caregivers express concerns about the boxed warnings associated with JAK inhibitors, although she said it is important to note that the populations in those clinical trials differ from the pediatric AD population.
“The 2 [boxed warnings] that come up the most often [with caregivers] are the higher rate of cardiovascular death and thrombosis,” Wu said. “These were mostly from the rheumatoid arthritis studies; these are usually patients that are much older than my pediatric AD patients and they also have a lot more comorbidities, usually.”
As Ellis noted, navigating the complex financial landscape with all of these treatments can be particularly challenging. Increased out-of-pocket expenses in pediatric AD are associated with poorer disease control as well as increased allergic and infectious comorbidities, explained presenter Dana McCormick, RPh, FAMCP.
“There are some unique economics as it relates to pediatric patients,” McCormick said. “There’s been a fair amount of research over the past several years about the economic burden and health care utilization with pediatric patients specifically.”
Additionally, racial disparities are persistent. McCormick noted that there is a higher prevalence of AD in Black children than in White children, as well as increased disease severity. Black children are also 6 times more likely than White children to have severe and treatment-resistant AD.
“One of the things that [the Institute for Clinical and Economic Review] talked about [in a 2021 report] is encouraging specialty societies to help educate physicians on the differential diagnosis and being able to diagnose kids of different skin colors, so that children of color can be diagnosed earlier and have treatment earlier so their disease doesn’t progress,” McCormick said.
For all patients, pharmacists play key roles in navigating prior authorizations and other limits on utilization, as well as educating and listening to patients and caregivers. Listening to their concerns is particularly important as the most accessible health care providers, Ellis said.
“As a caregiver of someone with eczema—and I think it’s important for us to remember as providers—in the end, the eczema belongs to [my daughter],” Ellis said. “As she’s getting older, now that she’s 12, that shared decision-making that we’re talking about…I’m trying more and more to transfer that responsibility over to her.”
Wu A, McCormick D, Ellis A. Reducing the Clinical and Caregiver Burden of Moderate to Severe Pediatric Atopic Dermatitis Through Improved Access to Treatments. Presented at: Asembia Summit 2023. May 1, 2023. Accessed May 1, 2023.