Crisaborole and its Potential Role in Treating Atopic Dermatitis: Overview of Early Clinical Studies

Abstract

Atopic dermatitis (AD), a chronic, relapsing, inflammatory skin disease that is characterized by intense pruritus and eczematous lesions with up to 90% of patients presenting with mild to moderate disease. Current topical treatments for AD have not changed in over 15 years and are associated with safety concerns. In AD, overactivity of phosphodiesterase 4 (PDE4), leads to inflammation and disease exacerbation. Crisaborole Topical Ointment, 2%, is a novel, nonsteroidal, topical anti-inflammatory PDE4 inhibitor currently being investigated for the treatment of mild to moderate AD. Preliminary studies in children and adults demonstrated favorable efficacy and safety profiles. Crisaborole may represent an anti-inflammatory option that safely minimizes the symptoms and severity of AD and that can be used for both acute and long-term management.

Atopic dermatitis yardstick: Practical recommendations for an evolving therapeutic landscape

“…Crisaborole 2% topical ointment, the most recent addition to topical agents for treating mild to moderate AD, provides an improved risk-benefit profile that might be appropriate for some patients. [66][67][68][69][70] The following comments reflect the most recent data and the authors' combined clinical experience with these agents.…”

“…67 Chemically, crisaborole is a unique boron-based compound-a benzoxaborole-and the configuration of boron within the compound enables synthesis of a low-molecular-weight molecule (251 Da) that facilitates the effective penetration of crisaborole through human skin so that it can target PDE4. 67,70 Systemic exposure varies according to the cutaneous surface treated. Crisaborole is rapidly and substantially metabolized to inactive metabolites, limiting continued exposure and systemic PDE4 inhibition.…”

“…Crisaborole is rapidly and substantially metabolized to inactive metabolites, limiting continued exposure and systemic PDE4 inhibition. 67,68,70 The clinical efficacy and safety of crisaborole 2% ointment were established in 2 large, randomized, controlled phase 3 clinical trials in the United States. 67,68 A total of 1,522 subjects (≥2 years old) were included, all with mild to moderate AD at baseline, according to the ISGA score (mild, 2; moderate, 3).…”

“…68 The significant decrease in pruritus with crisaborole 2% ointment confirmed previous findings from 2 post hoc pooled analyses of phase 1 and 2 studies, lending support to a possible role for PDE4 in regulating itch through neuronal pathways. 68,70 More data are needed to determine whether crisaborole modulates itch indirectly through anti-inflammatory mechanisms and/or directly through PDE4-induced neuronal inhibition. 68 Treatment with crisaborole was well tolerated, with similar rates of adverse events reported for patients treated with crisaborole and those treated with vehicle alone.…”

“…Application site pain (burning, stinging) occurred in at least 1% of patients. [67][68][69][70] Pediatric considerations. Children at least 2 years old were included in clinical trials.…”