Crisaborole and atopic dermatitis skin biomarkers: An intrapatient randomized trial.
J Allergy Clin Immunol
; 144(5): 1274-1289, 2019 11.
Article
em En
| MEDLINE
| ID: mdl-31419544
ABSTRACT
BACKGROUND:
Crisaborole ointment 2% is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis (AD). The mechanism of action of crisaborole and its effects on lesional measures of disease severity are not yet well defined.OBJECTIVE:
This phase 2a, single-center, vehicle-controlled, intrapatient study was designed to further characterize the mechanism of action of crisaborole through evaluation of clinical efficacy and changes in skin biomarkers in adults (n = 40) with mild-to-moderate AD.METHODS:
Two target lesions were randomized in an intrapatient (11) manner to double-blind crisaborole/vehicle applied twice daily for 14 days. Patients then applied crisaborole (open-label) to all affected areas for 28 days. Punch biopsy specimens were collected for biomarker analysis at baseline, day 8 (optional), and day 15.RESULTS:
Crisaborole treatment resulted in early improvement in lesional signs/symptoms versus vehicle, with improvement in pruritus (pruritus numeric rating scale) observed as early as 24 hours after the first application. Crisaborole-treated lesions showed significant percentage improvement from baseline in lesional transcriptomic profile compared with vehicle at day 8 (91.15% vs 36.02%, P < 10-15) that was sustained until day 15 (92.90% vs 49.59%, P < 10-15). Crisaborole significantly modulated key AD biomarkers versus vehicle, including TH2 and TH17/TH22 pathways and epidermal hyperplasia/proliferation. Molecular profiles and epidermal pathology normalized toward nonlesional skin and correlated with clinical changes in lesion severity and barrier function.CONCLUSION:
Crisaborole reversed biomarker profiles of skin inflammation and barrier function, with associated improvements in clinical efficacy measures, highlighting the therapeutic utility of targeting phosphodiesterase 4 in patients with AD.Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Pele
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Compostos de Boro
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Anti-Inflamatórios não Esteroides
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Células Th2
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Junções Íntimas
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Compostos Bicíclicos Heterocíclicos com Pontes
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Dermatite Atópica
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Células Th17
Tipo de estudo:
Clinical_trials
Limite:
Adolescent
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Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Allergy Clin Immunol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Canadá