JDD_Sanofi_Leaderboard

Demographics and Baseline Disease Characteristics of Early Responders to Crisaborole for Atopic Dermatitis

June 2020 | Volume 19 | Issue 6 | Original Article | 619 | Copyright © June 2020


Published online May 29, 2020

Linda F Stein Gold MDa, Liza Takiya PharmDb, Chuanbo Zang PhDc, Paul Sanders PhDd, Steven R. Feldman MD PhDe

aDepartment of Dermatology, Henry Ford Health System, Detroit, MI bMedical Affairs, Pfizer Inc., Collegeville, PA cBiostatistics, Pfizer Inc., Collegeville, PA dClinical Development and Operations, Global Product Development, Pfizer R&D UK Ltd., Surrey, United Kingdom eDepartment of Dermatology, Wake Forest School of Medicine, Winston-Salem, NC

Abstract
Introduction: Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis (AD). This post hoc, pooled analysis identified demographic characteristics associated with early response to crisaborole.
Methods: Early response was defined as day 8 Investigator’s Static Global Assessment (ISGA) success (clear [0] or almost clear [1] with ≥2-grade improvement), ISGA clear/almost clear, or Severity of Pruritus Scale (SPS) response (≥1-point improvement). Correlations between early response and day-29 response were calculated.
Results: Patients were more likely to be early ISGA success responders if they were aged <12 years (P=0.0023), were white (P=0.0316), had moderate baseline disease by ISGA (P=0.0003), had not received prior AD treatment (P=0.0213), had disease duration shorter than or equal to the median (≤6.45 years; P=0.0349), or did not concurrently use antihistamines (P=0.0148). Similar early response results were observed for patients achieving ISGA clear or almost clear; however, they were more likely to have mild baseline disease by ISGA (P<0.0001) or mild percentage of treatable body surface area involvement (5 to <16; P<0.0001). Patients aged <12 years (P=0.0001) or with moderate baseline disease (P=0.0475) were more likely to be early responders based on SPS criteria. By all 3 definitions, patients who achieved early response at day 8 were more likely to be responders at day 29 (P<0.0001).
Conclusion: Based on this analysis, patients aged <12 years were more likely to be early responders to crisaborole per all 3 definitions. Early response to crisaborole was a predictor of response at day 29.
Clinical Trial Registration: ClinicalTrials.gov, NCT02118766 and NCT02118792

J Drugs Dermatol. 2020;19(6): doi:10.36849/JDD.2020.5095

THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

INTRODUCTION

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by eczematous lesions and pruritus that occurs in approximately 15%-30% of children and 2%-10% of adults worldwide.1,2 AD causes psychological, social, quality-of-life, and financial burden to patients and their families, often related to intense pruritus.3 Despite the impact of the disease, adherence to AD treatment may be poor, related to a lack of patient understanding of the disease, improper topical medication application that can lead to reduced effectiveness, and fear of topical corticosteroids, among other reasons.4

Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate AD. In 2 large, randomized, double-blind, vehicle-controlled phase 3 clinical studies (AD-301: NCT02118766; AD-302: NCT02118792), a greater proportion of crisaborole-treated patients than vehicle-treated patients had improvement in global disease severity, as measured by Investigator’s Static Global Assessment (ISGA) success (defined as ISGA of clear [0] or almost clear [1] with ≥2-grade improvement) at day 29.5 In both studies, differences in ISGA success rates were observed between crisaborole and vehicle as early as day 8 of treatment, which was the first day of postbaseline clinical assessment.5 Crisaborole-treated patients also achieved improvement in pruritus earlier than vehicle-treated patients, and the improvement was sustained until day 29.6

Patients with AD may become frustrated if improvement is not observed early in the course of treatment and may discontinue treatment prematurely if the signs and symptoms of the disease do not seem to improve.7 Suboptimal management of AD can lead to flares1 and, potentially, an increased risk for comorbidities, such as allergies, infections, depression, and autoimmune disease.8 Therefore, it may be valuable to identify factors that predict early treatment response with crisaborole.