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Combating Moderate-to-Severe Pediatric Atopic Dermatitis: Considerations for Pharmacists

INTRODUCTION

Atopic dermatitis (AD) is a chameleon of a skin disorder, sometimes called eczema or atopic eczema, and presenting differently at various ages, easily confused with other skin diseases (TABLE 1), and always associated with intense itching.¹ It is also as common and visible as obesity in children in high-income countries, affecting up to 20% of kids.^2-4 Unfortunately, its global prevalence is growing, although it seems to be stabilizing in developed countries.¹ AD can develop at any age, but it tends to start in early childhood, typically between ages 3 to 6 months. Up to 10% of adults have AD, and it can be either persistent or new onset.^5,6

The focus of this continuing education activity is AD’s pathophysiology, epidemiology, and signs and symptoms in pediatric patients, including the appropriate use of newly approved therapeutic agents and management of symptoms and flares.

Epidemiology

AD’s prevalence in children is high, with up to one-fifth of American children affected.^2,3 It appears that AD’s prevalence is leveling off in developed countries but increasing in low- and middle-income countries.² Researchers have looked at the sum of environmental influences over time (called the exposome) with regard to AD and determined that environmental factors are important in its etiology. Of most importance, they indicate air pollutants (airborne particulate matter, tobacco smoke, and organic compounds), allergens, and microbiota (bacteria, viruses, and fungi) have contributed to AD’s increasing incidence.⁸

Other interesting evidence has underscored environmental influences that affect children. For example, when East and West Germany reunified in 1990, AD’s prevalence was higher in East Germany, possibly because more children attended daycare as infants there than in West Germany before unification.⁹ Both trends (higher incidence of AD and early daycare) continued after reunification.¹⁰

It also appears that children who live in urban areas are more likely to develop AD than those in rural areas and farming households.¹⁰ Over the years, many researchers have proposed a “hygiene hypothesis” as a possible explanation for AD, with people of lower socioeconomic status and children who come from families with a greater number of siblings disproportionally affected.^1,11,12 AD’s prevalence tends to be lower in areas of the United States (US) with high humidity, temperature, and ultraviolet light exposure.¹³ Black Americans (17%) are more likely than white Americans (11%) to develop AD.^1,14

Pathophysiology

AD is a complex disease that is the manifestation of several factors and causes. Genetics have a profound influence, with evidence that multiple mechanisms are at play at the genetic level. Patients frequently report a personal or family history, or both, of atopic disease (eg, asthma, allergic rhinitis, atopic dermatitis) or specific immunoglobulin E (IgE) reactivity.¹⁵ A family history of any atopic disease, but especially relatives who have AD, is the strongest risk factor for developing the disorder.¹⁶ If a twin has AD, the chances are 75% that the other twin will also have it,¹⁷ and researchers have isolated 34 loci that cumulatively account for roughly 20% of AD heritability.¹⁸ The multiple genes in these genomic regions participate in immune responses, T-cell activation, innate immunity, and the epidermal differentiation complex that produces skin barrier genes.¹⁹

Researchers consider loss-of-function mutations in the gene encoding filaggrin (FLG) the most important and common genetic variant; filaggrin is a major structural protein in the epidermis and contributes to the skin barrier.²⁰ The FLG gene encodes preprotein profilaggrin.^21,22 Individuals heterozygous for the mutation experience a 50% decrease in protein expression; homozygous mutations lead to a total loss of protein.^20,23 These mutations elevate the risk of developing AD 3 to 5 times, and predispose affected individuals to asthma and peanut allergy. Between 20% and 40% of patients with AD have FLG loss-of-function mutations, so researchers suspect other genes are also involved.^22,24-26

Genetics alone do not explain AD’s mechanisms. AD’s increasing global burden suggests environmental factors. As noted previously, people with AD have a strong tendency for comorbid asthma, allergic rhinitis, and food allergy, dubbed the “Atopic Triad.” Atopy is generally defined as a genetic tendency to develop the classic allergic diseases: atopic dermatitis, allergic rhinitis, and asthma. In general, it would involve the ability to overproduce IgE in response to common environmental proteins (ie, dust mites, pollen, foods).²⁷ Although the word atopy suggests IgE-mediated allergic reactions, not all patients with AD possess IgE-mediated allergic sensitization. For this reason, experts have suggested using the term “eczema” as an umbrella term for atopic and non-atopic forms of AD. However, most clinicians use these terms synonymously.^28,29

Patients with AD consistently have greater than normal transepidermal water loss and pH changes in all of their skin (not just the areas affected by AD), an observation called epidermal barrier dysfunction.^30,31 Their skin is more permeable, loses its hydration faster, and has less lipids than the skin of people who do not have AD.^31-34 One model of AD’s pathogenesis indicates it may begin with a genetically predetermined skin barrier defect, which manifests as dry skin.³² Subsequently, patients experience an overexpression of pro‐inflammatory cytokines and their immune systems activate innate lymphocyte subsets and antigen‐presenting cells (TH2 and TH22). It’s clear now that interleukin (IL)‐4 and IL‐13 drive eosinophil and mast cell recruitment and increase IL‐31 secretion. IL-31, a cytokine, is crucial to the itch sensation. Barrier disruption and eczematous skin inflammation increases as patients develop transcutaneous sensitization to environmental allergens and bacterial infections, especially Staphylococcus aureus. Type 2 immune activity in the skin exacerbates underlying barrier defects.^34,35

To summarize, the dysfunctional epidermal barrier, skin microbiome abnormalities, and a predominantly type-2-skewed immune dysregulation create a vicious cycle of dryness and itching^36,37:

• Skin barrier weakness (often pursuant to filaggrin deficiency) promotes inflammation and T-cell infiltration
• S aureus colonization or infection damages the skin barrier and induces inflammatory responses
• Microbial colonization (usually with S aureus and Malassezia yeasts) creates dysbiosis (microbial imbalances)
• Local TH2 immune responses disrupt the barrier function, promote itching, and facilitate dysbiosis, which creates a hospitable environment for Staphylococcus, especially S aureus.^36,37

Signs, Symptoms, and Severity

AD’s clinical features, severity, and course are heterogeneous. To diagnose AD, medical providers rely on clinical features since no lab tests are available to definitively diagnose the disorder.³⁸ The 3 features essential to diagnosis are 1) eczematous lesions, 2) intense pruritus, and 3) chronic or relapsing disease course.³⁹ In addition, AD waxes and wanes, with patients experiencing often unexplained flares. Most patients with AD experience widespread skin dryness.

AD lesions typically change with age, often presenting acutely in infants with poorly defined swollen erythema, vesicles, excoriations (abraded areas, usually due to scratching in AD), and serous (clear, thin, watery) exudate. Infants usually have widely distributed skin involvement that spares the buttocks but includes the face (typically the cheeks) and trunk. Around age 2, eczema tends to localize and exhibit the hallmarks of a chronic condition. The erythema pales, the skin becomes dry with certain areas undergoing lichenification (thickening) in areas of chronic inflammation, and the lesions begin to lack definition and migrate to the flexor surfaces (joints that bend). As these patients enter adolescence and adulthood, the eczema is usually diffuse, but localized lesions affecting hands, eyelids, and flexures are also typical. In adults, AD takes many forms; chronic hand eczema or head-neck dermatitis alone or eczema of the upper trunk, shoulders, and scalp are possible.^1,39

AD, so common in infancy, sometimes resolves in early childhood, but experts describe its trajectory as variable. It may include early transient disease, relapsing-remitting flares, chronic persistent symptoms, or long periods of remission.^40,41 Active AD that persists into adulthood is common, however, and adults can develop new onset AD.^42,43 Factors associated with persistent AD (but not necessarily disease severity) include concurrent asthma, hay fever, or both; young age of onset; low socioeconomic status; and non-white ethnicity.^5,44

Quality of Life Issues

People who have AD are at elevated risk of a wide range of health and psychosocial outcomes.¹ AD has a weighty impact on quality of life (QoL) for children and their families and caregivers. The Global Burden of Disease Study identified AD as the skin disease with the most profound population-level disability among skin diseases.⁴⁵ A large US population-based, cross-sectional study compared moderate-to-severe AD with common chronic illnesses; outcomes associated with AD were worse than those for heart disease and diabetes.⁴⁶ In children and young adults, AD confers considerable declines in physical, emotional, and social functioning.⁴⁷ Among chronic childhood conditions specifically, AD ranked second to cerebral palsy with respect to QoL measures.⁴⁷

People who have AD often experience allergic eye disease, such as keratoconjunctivitis, keratoconus (an abnormal cone-shaped protrusion of the cornea of the eye), and cataracts. Among American adults with AD, a survey found that they were 4.38 times more likely to contract conjunctivitis than healthy people.⁴⁸

Patients often have significant knowledge deficits about their AD, experience stigma associated with AD’s manifestations, and struggle with associated medical conditions that cause physical limitations and adherence barriers. Financial hardship limits some patients’ ability to achieve therapy goals.⁴⁹

Good quality surveys indicate that patients with AD spend a considerable amount of their day (2 to 3 hours) on treatment regimens. Such a large investment of time interferes with hobbies, entertainment, and vacations. For parents and caregivers, this time drain strains relationships and out-of-pocket expenses can be tremendous (most insurers do not cover moisturizers and over-the-counter [OTC] products). Adherence at or above 90% is a treatment goal. In AD, adherence to topical therapies exceeds 90% at the start of treatment but decreases to approximately 30% at 8 weeks.^49,50 This elevates risk of poor treatment response and unnecessary treatment escalation and related costs.

A good way to summarize QoL is to use the term “cascading issues.” AD frequently creates a vicious cycle that begins with the time required to apply topicals and the itching associated with the condition. Patients cannot sleep, and their wakefulness disturbs other people in their homes, and then leads to mental health issues, missed work and school, or social isolation.^47,49-52

CURRENT TREATMENTS FOR PEDIATRIC AD

Like many other skin diseases, management generally follows a stepwise pattern, starting with trigger avoidance. Patients, and especially children, may find that certain things aggravate their AD and precipitate flares, and once identified, these triggers should be avoided. These may be irritants like rough or scratchy fabrics, soaps and detergents, and anything that is drying. Exposure to specific foods, inhalants, or contact allergens can trigger flares. Cold and dry weather, infections, and stress have also been implicated.^53,54

Moisturizers

Most patients with AD experience xerosis (dry skin), and moisturization is a constant and time-consuming need that increases hydration of the epidermis to reduce xerosis, itch, and flares. (Patients or their caregivers will need to moisturize liberally 2 to 3 times a day and after bathing.) It may also reduce the need for anti-inflammatory medication if applied regularly and well.^55,56 The amount of time it takes to moisturize can be an adherence barrier, so health care providers need to consider patients’ skin type, body area, dryness, and inflammation level. Critical in the choice is patient preference.^56,57

Although the market is flooded with moisturizers with proprietary ceramide, essential fatty acid, emollient, occlusive, and humectant combinations, guidelines do not recommend any one product.⁵⁶ Fragrance-free moisturizers with few ingredients tend to reduce the likelihood of irritation or allergy. Traditional moisturizers are available in a variety of delivery systems, including lotions, gels, creams, and ointments, and each delivery system has pros and cons. For example, preservatives can sting when applied to irritated skin and most ointments are preservative-free, but many patients find them too greasy. Creams, however, are more pharmaceutically elegant, but contain preservatives, thus increasing the chance of stinging. Guidelines do not indicate an optimal amount or frequency for moisturizer application, but generally, patients should apply them liberally and frequently until xerosis resolves.³⁹

Bleach Baths

Pharmacists are often surprised to learn that a bleach bath is widely accepted as an effective adjunct therapy for AD. Since the 18th century, people have used sodium hypochlorite—bleach—as a disinfectant and antiseptic. When mixed with water, bleach generates concentration-dependent activity against gram-negative and gram-positive bacteria, spores, fungi, and viruses. The American Academy of Dermatology (AAD) recommends that patients with AD who have visible signs of infection bathe in bleach baths for 5 to 10 minutes, 2 to 3 times a week.⁵⁸

Bleach baths seem to improve symptoms through antimicrobial, anti-inflammatory, and antipruritic effects.⁵⁸ An appropriate concentration is 0.005% bleach, or one-half cup of 6% common household bleach in a standard 150-liter (40 gallon) bathtub full of tepid water. Pharmacists should remind patients or caregivers to measure the amount of bleach they add to a lukewarm bath with a precise measuring cup or spoon; pharmacists should warn against estimating the amount of bleach. Too much bleach can inflame skin and too little bleach may be ineffective. After the bath, patients should pat the skin dry without rubbing, apply AD medication, and moisturize.⁵⁸

Topical Corticosteroids

All of the medications approved for children are also approved for adults. This continuing education activity will focus on pediatric dosing and dosage forms.

Guidelines recommend topical corticosteroids (TCS) as first-line, anti-inflammatory treatment.^39,59 Used appropriately, these medications reduce inflammation and redness. Adverse effects, which are rare with proper use, include skin atrophy, purpura (subcutaneous [SC] bleeding), striae (parallel grooves or scratches), telangiectasias (spider veins), dyspigmentation, and facial acneiform changes.⁶⁰ Systemic adverse effects (eg, hypothalamic-pituitary-adrenal suppression and growth retardation) are rare with topical use.⁶¹

In the US, TCS are grouped into 7 classes, from highest (I) to lowest (VII) based on the specific corticosteroid’s ability to cause vasoconstriction.³⁹ The formulation employed also affects potency, with more opaque formulations generally stronger. Charts describing these classes and the TCS that fall into each class are readily available in standard pharmaceutical references. Prescribers should use less potent TCS once or twice daily when patients have milder disease, are younger, or have flexural and facial skin involvement unless they are prescribing short-term treatments for a severe flare. For acute relief, patients can apply TCS under wet wrap dressings (ie, 2 layers of cotton bandages or garments, with a wet inner layer and a dry outer layer) to enhance penetration and skin hydration.⁶²

Although TCS-associated risks are low, many patients and caregivers report steroid-phobia. One survey found that 72.5% of individuals worried about using TCS on their own or their child’s skin, causing 24% to interrupt therapy.⁶³ These concerns, in general, are unwarranted. If individuals use TCS correctly, adverse effects are rare.

Steroid-Free Topicals

Despite the fact that in most cases steroid phobia is unwarranted and TCS are safe and effective, researchers have looked for steroid-free options for AD. Steroids, while effective, do not target AD’s underlying causes. Targeted therapies should be as (or more) effective than shotgun approaches.

In 2016, the US Food and Drug Administration (FDA) approved crisaborole 2% ointment (Eucrisa), a topical phosphodiesterase 4 (PDE-4) inhibitor for treatment of patients aged 3 months or older with mild-to-moderate AD.⁶⁴ Inhibiting the enzyme PDE-4 results in increased intracellular cyclic adenosine monophosphate levels. In phase 3 randomized trials, researchers measured improvements using the Investigator Static Global Assessment (ISGA); 32% of patients assigned to crisaborole improved to have clear or almost clear skin with at least a 2-point improvement in ISGA scores. No serious adverse effects occurred; the drug’s most common adverse effects include pain and paresthesia at the application site occurring in less than 1% of participants.^65,66 Crisaborole decreases pruritis, which may lower the risk of infection and scarring and improve patients’ QoL.⁶⁷ Patients apply a thin layer of crisaborole twice daily on affected areas.⁶⁴

The topical calcineurin inhibitors tacrolimus and pimecrolimus have clinical effectiveness equal to or less than moderately potent TCS. Their advantages over TCS include no skin atrophy and usefulness at susceptible sites, including intertriginous areas (armpits, upper thighs and genitals, skin folds of the breasts, and between fingers and toes) or the face.⁶⁸ Patients sometimes apply TCS and topical calcineurin inhibitors to previously active sites for 2 days every week to reduce flares, particularly when flares occur on the same body sites repeatedly.^69,70

Tacrolimus (Protopic) is available as a 0.03% and 0.1% ointment, but only the 0.03% formulation is FDA approved in children 2 to 15 years of age who are non-immunocompromised.⁷¹ It is considered second-line, short-term (its long-term safety has not been established), noncontinuous therapy for moderate-to-severe AD.⁷¹ Based on data from systemic use of calcineurin inhibitors, prolonged use of topical tacrolimus is not recommended due to the potential for increased risk of infections, lymphomas, and skin malignancies. Patients apply tacrolimus twice daily to affected skin only. Pharmacists should note that this product’s labeling includes a Medication Guide that must be given to patients with each prescription fill or refill.⁷¹

The FDA approved pimecrolimus (Elidel) cream 1% as a second-line therapy for mild-to-moderate AD in children 2 years of age and older.⁷² This cream is used short-term in individuals who failed or did not respond to topical treatments or when other treatments are not advisable.⁷² In phase 3 trials in pediatric patients, 11% of participants withdrew in the first 6 weeks, with 1.5% discontinuing participation due to adverse events. At 12 months, 32% had withdrawn with 3% discontinued due to adverse events. Children with AD may complain about burning and pruritus for a few days when they start treatment.⁶⁸ The most common adverse effects in pivotal trials were application site burning, headache, influenza, pyrexia, cough, and viral infection.⁷² Patients apply pimecrolimus twice daily to affected areas only, and this product also requires a Medication Guide.⁷²

Labeling on the topical calcineurin inhibitors has created controversy; the specific concern is the warnings about immunosuppression. Experts from leading institutions worldwide issued a consensus statement in 2015. They indicated that short- and long-term studies enrolling more than 4000 infants younger than 2 years of age have shown efficacy and sustained response of long-term intermittent pimecrolimus use in infants.⁷³ These experts note its advantages over TCS (eg, no risk of skin atrophy, impaired epidermal barrier function, or enhanced percutaneous absorption). Studies have documented no evidence of systemic immunosuppression in infants. (A very recent study [N = 8000] looked at tacrolimus use and also found no increased risk of cancer in children with AD.⁷⁴) The authors also note that evidence from clinical studies, epidemiological investigations, and postmarketing surveillance indicate no safety concerns. They recommend reconsideration of the boxed warning and current age limit.⁷³

Ruxolitinib (Opzelura) cream 1.5% is a Janus kinase (JAK) inhibitor for the treatment of mild-to-moderate AD in non-immunocompromised individuals 12 years of age and older.⁷⁵ The Janus kinases are a family of intracellular, non-receptor tyrosine kinases (enzymes). It, too, is used short-term in individuals who failed or did not respond to other topical treatments or when other treatments are contraindicated. The most common adverse effects found during the clinical trials were nasopharyngitis, bronchitis, ear infection, and urticaria. In phase 2 studies, researchers found that ruxolitinib cream was well tolerated and lead to prompt, persistent improvements in AD, more so than a TCS. Patients who used ruxolitinib cream twice daily had mean local Eczema Area and Severity Index (EASI) reductions of 71.6% versus 15.5% for vehicle and 59.8% for triamcinolone at week 4. They experienced only mild or moderate adverse events.^76,77 Its labeling indicates patients should apply a thin layer twice daily to affected areas of up to 20% body surface area (BSA), patients should use less than 60 g per week or 100 g every 2 weeks. It carries a boxed warning for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis. The labeling requires a Medication Guide.⁷⁵

Phototherapy

If disease control cannot be achieved with topical measures, prescribers often consider 4 to 12 weeks of arrow-band ultraviolet B radiation or medium-dose ultraviolet phototherapy.⁷⁸ Long-term adverse effects (eg, photodamage, melanoma induction and skin carcinogenesis) can be cumulative. The need to visit a health care facility for frequent treatments is an adherence barrier.⁷⁸

Systemic Therapies

Prescribers should use systemic corticosteroids only to treat flares for a short period of time or when starting another systemic therapy.⁷⁹

The traditional systemic immunosuppressives for AD include azathioprine, cyclosporine, methotrexate, and mycophenolate mofetil, with all used off-label with no long-term data or head-to-head comparisons available.⁷⁹ Efficacy and safety data from randomized controlled trials is strongest for cyclosporine, which has a faster onset of action that the others and is associated with a mean improvement of clinical severity scores of 55% from baseline after 6 to 8 weeks of treatment.^80,81 Most guidelines recommend continuous use of less than 1 to 2 years because of the risk of end-organ toxicity and malignancy.^39,79,80,82

Azathioprine and methotrexate seem to be effective and safe off-label treatments for severe AD, even in children.⁸³ It can take up to 8 and 12 weeks to see optimal benefit for azathioprine and methotrexate, respectively.⁸⁴

The evidence for mycophenolate mofetil in AD is scant, but it appears to have a favorable safety profile and some evidence of efficacy. Generally, it is considered an alternative treatment option for patients who fail to respond to or cannot tolerate other oral immunosuppressives.³⁹

The oral JAK inhibitor upadacitinib (Rinvoq) is approved for treatment of refractory, moderate-to-severe AD in adult and pediatric patients aged 12 years and older weighing at least 40 kg (88 lbs) who did not respond to or have contraindications to other systemic therapies.⁸⁵ Available as extended-release tablets, upadacitinib has been associated with serious infections, mortality, malignancy, cardiovascular events, and thrombosis, which are detailed in its boxed warning. In children who weigh at least 40 kg (88 lbs), the initial dose is 15 mg orally once daily. Prescribers can increase the dose to 30 mg once daily if the patient does not achieve an adequate response. This medication also requires a Medication Guide.⁸⁵

Among AD’s multiple immune pathways, strong activation of type 2 immune responses appears to be a dominant mechanism that generates IL-4 and IL-13.^86,87 Targeting type 2 pathways has emerged as a reasonable and successful therapeutic strategy. Dupilumab (Dupixent) is a fully human monoclonal antibody administered SC that inhibits IL-4 and IL-13 signaling.⁸⁸ The FDA approved dupilumab for treatment of uncontrolled moderate-to-severe AD in patients 6 months of age and older.⁸⁹ Dupilumab has shown reductions in pruritis and depression, which improve patients’ QoL.⁹⁰ Dupilumab’s most common adverse effects are injection site reactions, conjunctivitis, blepharitis, oral herpes, keratitis, eye pruritus, other herpes simplex virus infection, dry eye, and eosinophilia.⁸⁸ Pharmacists should note that ocular complaints (in particular transitory conjunctivitis) are common and have been reported in up to 28% of trial participants⁹¹ and up to 38% of patients treated in real-world settings.^92-95 Topical anti-inflammatory ocular medications may relieve symptoms and circumvent the need to discontinue dupilumab.⁹⁵

Dupilumab’s dosing is weight based (TABLE 2) and not necessarily intuitive. Pharmacists should note that the loading dose for patients aged 6 to 17 years who weigh between 30 and 60 kg is different than that for patients who weigh less or more, and the dosing intervals change as children gain weight.⁸⁸

CONSIDERATIONS FOR PHARMACISTS

A successful AD treatment plan must address hydration, skin barrier restoration, and prevention of skin infection.^49,50 To meet these goals, pharmacists need to provide patient and caregiver education. One question that pharmacists seem to struggle with is the age at which to begin including children in counseling. By 5 to 7 years of age, most children have developed enough mental capacity to understand basic medication instructions, so their participation in counseling can start.⁹⁶ As children age, pharmacists can work with caregivers to determine how much children need to know and how much responsibility they can assume. Pharmacists need to remember some other basic counseling points when dealing with children and adolescents who have AD and their caregivers. First, the primary prescriber and pharmacist should both obtain a good history (including what has worked, what has not worked).

Points that pharmacists will need to cover with patients and caregivers include the basics of AD and the importance of adherence to treatment.^97-99 They need to know which treatments are chronic in nature, how they can prevent flares, and which treatments are used for flares. Patients who do not understand the disease or its various treatments may over- or underuse topical treatments, which are both technically nonadherence. Patients and caregivers must apply moisturizers chronically and consistently even if they have no active disease flare, so they have no “treatment holiday.”^97-99 When SC medication is prescribed, patients will need redundant counseling on administration technique.

To address these patient needs, written AD action plans—also known as eczema action plans (EAPs)—are fast becoming a standard of care in AD. These plans specify what to do as maintenance and during flares of every severity. They differentiate between the face and the body, since some treatments are not used on the face (ie, high-potency TCS). Pharmacists can find many versions of the AD action plan online, and studies indicates that they increase adherence and patient satisfaction.^97-99 (An example of an action plan is available through the AAD at https://www.aad.org/public/diseases/eczema/childhood/treating/know-control.) AD action plans often do not consider patient/caregiver preferences (eg, vehicle, frequency of application, type of preparation) for topical treatments. When health care providers ignore patients’ preferences, patients become dissatisfied, adhere poorly, and experience treatment failure.¹⁰⁰

A cornerstone of the pharmacist’s responsibilities is ensuring that patients know the differences in therapies. Often, topical prescriptions are labeled "apply to affected areas.” For all products used for AD, patients need to know if they can use them on the face, groin, and underarms or if the product should not be used on those areas.⁸⁰

The out-of-pocket costs associated with AD can be considerable. Patients may need guidance to find appropriate moisturizers they can afford. The vehicle in which a topical product is prepared can have a significant impact on the patients’ acceptance and ability to adhere with directions.¹⁰¹ For this reason, asking about patient preference should be a first step. TABLE 3 describes the different vehicles; these points apply to moisturizers and medication-containing products.¹⁰¹ One clinical pearl is that the unscented products for patients who have sensitive skin are usually located on the shelves that are not at eye level (rather, they are near the floor or on upper shelves).

It goes without saying that pharmacists need to perform their basic duties, including monitoring for food and drug interactions, helping patients manage any adverse effects that develop, and using motivational interviewing to ensure patients can overcome any barriers.

Finally, pharmacists can provide assertive input to their formulary committees. In a 2019 survey, 85 US health plan officers identified AD as 1 of the top 4 conditions with the greatest financial impact to their plans.¹⁰² This puts medications used to treat AD squarely in the spotlight for ongoing review. Most plans support their formulary decisions with comparative effectiveness research (CER), but little CER is available for AD. Most of the medications used to treat AD are costly. Patients may incur copay or coinsurance costs that add to their out-of-pocket costs.¹⁰²

In addition, many medications are subject to prior authorization. Prior authorization has 6 goals: 1) control for inappropriate use, 2) manage products by indication, 3) promote preferred agents, 4) provide for step therapy, 5) reduce cost to the plan, and 6) drive rebate contracts.¹⁰³ Pharmacists who provide frontline care and those who contribute to formulary decisions need to ensure that prior authorization decisions are evidence-based. Increasingly, health plans are using patient reported outcomes and real-world evidence to make initial coverage decisions or reexamine decisions as the market expands and more data is accrued.¹⁰⁴ Monitoring constantly and gathering data about patient needs is critical if formularies are to remain responsive and responsible for patients who have AD.

CONCLUSION

Affecting 9.6 million children in the US, AD creates a significant physical, psychosocial, and financial burden for patients and their families. Several new drugs have navigated clinical trials and obtained FDA approval recently. Pharmacist’s skills—providing comprehensive education, therapy management, ongoing monitoring of adverse events, and drug-drug interaction prevention—are essential in the treatment process. Knowledge of the most recent therapies for pediatric AD and their place in therapy is crucial for pharmacists to deliver comprehensive pharmaceutical care, improve children’s QoL, and promote ideal treatment outcomes.

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