Crisaborole and atopic dermatitis skin biomarkers: An intrapatient randomized trial

Robert Bissonnette, Ana B. Pavel, Aisleen Diaz, John L. Werth, Chuanbo Zang, Ivana Vranic, Vivek S. Purohit, Michael A. Zielinski, Bonnie Vlahos, Yeriel D. Estrada, Etienne Saint-Cyr Proulx, William C. Ports, Emma Guttman-Yassky

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


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 (1:1) 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.

Original languageEnglish
Pages (from-to)1274-1289
Number of pages16
JournalJournal of Allergy and Clinical Immunology
Issue number5
StatePublished - Nov 2019


  • Atopic dermatitis
  • biomarker
  • crisaborole
  • gene expression
  • inflammation
  • phosphodiesterase 4
  • pruritus
  • transcriptome
  • transepidermal water loss


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