Safety, Effectiveness, and Pharmacokinetics of Crisaborole in Infants Aged 3 to < 24 Months with Mild-to-Moderate Atopic Dermatitis: A Phase IV Open-Label Study (CrisADe CARE 1)

Abstract

Background Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis (AD).Objectives The aim of this study was to evaluate the safety, effectiveness, and pharmacokinetics (PK) of crisaborole in infants aged 3 to < 24 months with mild-to-moderate AD in an open-label study. Methods Infants (3 to < 24 months) with Investigator's Static Global Assessment (ISGA) of mild (2) or moderate (3) and percentage of treatable body surface area (%BSA) ≥ 5 received crisaborole twice daily for 28 days; a cohort with moderate AD per ISGA and %BSA ≥ 35 were included in a PK analysis. Endpoints included safety (primary), efficacy, and PK (exploratory). Results Included were 137 infants total (mean age [SD], 13.6 months [6.42]), with 21 in the PK cohort (12.7 months [6.58]). Treatment-emergent adverse events (TEAEs) were reported for 88 (64.2%) patients (98.9% rated as mild/moderate). TEAEs were considered treatment-related for 22 patients (16.1%); most frequently reported were application site pain (3.6%), application site discomfort (2.9%), and erythema (2.9%). ISGA clear/almost clear with ≥ 2-grade improvement at day 29 was achieved by 30.2% of patients. From baseline to day 29, mean percentage change in Eczema Area and Severity Index score was − 57.5%, and mean change in Patient-Oriented Eczema Measure total score was − 8.5. Crisaborole systemic exposures in infants were characterized and, based on nonlinear regression analysis, were comparable with that in patients aged ≥ 2 years.Conclusions In this open-label study, crisaborole was well tolerated and effective in infants (3 to < 24 months) with mildto-moderate AD with systemic exposures similar to patients aged ≥ 2 years. Clinical Trial Registration NCT03356977.William C. Ports: Affiliation at the time of this study. Electronic supplementary materialThe online version of this article (https ://doi.org/10.1007/s4025 7-020-00510 -6) contains supplementary material, which is available to authorized users.

DRM02, a novel phosphodiesterase-4 inhibitor with cutaneous anti-inflammatory activity

“…56,57 Important features of crisaborole in these trials were its low systemic exposure and mild treatment-related adverse events that spontaneously resolved in 16%-57% of patients. 58,59 Further, crisaborole reduced expression of inflammatory mediators and improved skin barrier function in atopic dermatitis patients, 60 indicating that PDE4 inhibition may be an effective approach to restore the epidermal barrier, at least under some circumstances.…”

New treatments in atopic dermatitis

“…16,17 A subsequent phase 4 open-label study of 137 infants 3 to less than 24 months with mild-to-moderate AD revealed crisaborole ointment to achieve the end point of the Investigator's Static Global Assessment in 30.2% of the patients with a safety profile similar to that in older children. 18 Crisaborole 2% ointment was approved by the FDA in 2016 for treatment of mild-to-moderate AD in children 2 years and older, with the indication extended in March 2020 to infants 3 months of age and older.…”

Practical Approach for the Diagnosis and Treatment of Chronic Pruritus

“…24 This drug was also recently shown to be well tolerated and effective in infants. 25 In addition to treating atopic itch, crisaborole 2% ointment has newly been shown to demonstrate superior efficacy to vehicle ointment for the treatment of intertriginous, anogenital, and facial psoriasis. 26 Crisaborole is generally well-tolerated but is commonly associated with application-site pain (ie, burning or stinging).…”