Clinical Review

Update on Pediatric Atopic Dermatitis

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Evolving Practices and Therapies

Bathing Practices
There has long been much controversy regarding best bathing habits for patients with AD. In a 2009 study, cutaneous hydration was quantified after various bathing and moisturizing regimens.18 The study showed clear benefits of emollient application on skin hydration, either after bathing or without bathing. Bathing followed by emollient applications did not decrease skin hydration in contrast to bathing without emollient application.18

There are limited studies evaluating bathing frequency in pediatric patients, and many families receive conflicting information regarding best practice. In one study that surveyed 354 parents, more than 75% of parents/guardians who had seen multiple providers for their child’s AD reported a substantial amount of confusion and frustration from conflicting advice on bathing frequency.19 Cardona et al20 undertook a randomized clinical trial of frequent bathing and moisturizing vs less-frequent bathing and moisturizing in pediatric patients with AD aged 6 months to 11 years. Patients were divided into 2 groups: 1 being bathed twice daily with immediate moisturizer application and the other being bathed twice weekly followed by moisturization, then a switch to the other method. Patients used standardized topical corticosteroids (TCSs) in both groups. There were significant improvements in scoring AD and other objective measures during the frequent bathing time period vs infrequent bathing; in the group that bathed more frequently, SCORAD (SCORing Atopic Dermatitis) decreased by 21.2 compared with the group that bathed less frequently (95% confidence interval, 14.9-27.6; P<.0001). These findings suggest that more-frequent bathing with immediate moisturization is superior as an acute treatment intervention for improving AD disease severity in comparison to less-frequent bathing with immediate moisturization.20

Expanding Treatment Options

Topical Phosphodiesterase Inhibitors
There are several new and evolving topical therapies in AD. Crisaborole ointment 2% is a steroid-free phosphodiesterase inhibitor approved in 2016 by the US Food and Drug Administration (FDA) for mild to moderate AD in patients aged 2 years and older. A recent multicenter, open-label, single-arm study in 137 infants (CrisADe CARE 1) evaluated the pharmacokinetics and efficacy of crisaborole ointment 2% applied twice daily for 4 weeks in pediatric patients aged 3 months to less than 24 months of age with mild to moderate AD.21 The study had 2 cohorts: one with a minimum of 5% body surface area involvement and another (the pharmacokinetic cohort) with a minimum of 35% body surface area involvement. Both cohorts demonstrated similar efficacy data. From baseline to day 29, the mean percentage change in eczema area and severity index (EASI) score was 57.5%, and an investigator global assessment (IGA) score of clear or almost clear with at least a 2-grade improvement was achieved in 30.2% of patients. Crisaborole systemic exposures in infants were comparable with those in patients aged 2 years or older. Patients tolerated crisaborole well, with a 4% rate of burning, which was similar to other studies in children and adults but perhaps lower than seen in clinical practice. Pharmacokinetic studies did not show any remarkable noticeable concern with accumulation of propylene glycol absorption.21

Based on the CrisADe CARE 1 study data, in March 2020 the FDA extended the indication of crisaborole ointment 2% from a prior lower age limit of 24 months to approval for use in treating mild to moderate AD in children as young as 3 months, making it the first nonsteroidal topical anti-inflammatory medication to be approved in children younger than 2 years in the United States.

Evolving Topical Therapies

Topical Janus Kinase Inhibitors
Ruxolitinib is a potent inhibitor of Janus kinase 1 (JAK-1) and Janus kinase 2 (JAK-2) and has been developed in topical formulations. In recent phase 3 clinical trials of patients with AD aged 12 years and older with mild to moderate disease (TRuE-AD1 and TRuE-AD2), more than half of the patients treated with either ruxolitinib cream in a 0.75% or 1.5% concentration reached EASI-75 after 8 weeks of treatment.22 Additionally, more patients treated with topical ruxolitinib reached an IGA score of clear to almost clear than patients treated with vehicle at the end of treatment. Thus far, it appears to be very well tolerated, significantly decreases EASI score (P<.0001), and improves overall pruritus.22

Delgocitinib is a topical pan-JAK inhibitor that blocks several cytokine-signaling cascade pathways. It was first developed and approved in Japan in an ointment formulation for use in patients with AD aged 16 years and older.23 The efficacy and safety profile of delgocitinib is currently being evaluated in pediatric patients with AD in Japan. In a recent phase 2 clinical study of 103 Japanese patients aged 2 to 15 years with moderate to severe AD, patients were randomized to receive either delgocitinib ointment in 0.25% or 0.5% concentrations or vehicle ointment twice daily for 4 weeks. The proportion of patients with a modified EASI-75 score was 38.2% (13/34) in the 0.25% group and 50.0% (17/34) in the 0.5% group vs 8.6% (3/35) in the placebo group. More patients treated with delgocitinib ointment received an IGA score of clear or almost clear than patients treated with vehicle at the end of treatment. Overall, both delgocitinib groups demonstrated superior improvement in clinical symptoms and signs without notable side effects.24

Tapinarof is a topical therapeutic aryl hydrocarbon receptor agonist. In a recent phase 2 randomized study of 2 concentrations and 2 frequencies of tapinarof cream vs vehicle in 247 randomized patients aged 12 to 65 years with moderate to severe disease, tapinarof demonstrated greater success with both concentrations than vehicle at all visits beyond week 2.25 Additionally, in patients treated with tapinarof cream 1%, nearly 50% reached an IGA score of clear to almost clear with at least a 2-grade improvement. More than 50% of patients achieved EASI-75 improvement at 12 weeks of treatment with tapinarof cream 1% used daily. These findings suggest that tapinarof may be an efficacious and well-tolerated treatment for both adolescents and adults with AD; however, large confirmation trials are needed to further investigate.25

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