Crisaborole and atopic dermatitis skin biomarkers: An intrapatient randomized trial

J Allergy Clin Immunol. 2019 Nov;144(5):1274-1289. doi: 10.1016/j.jaci.2019.06.047. Epub 2019 Aug 13.


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.

Trial registration: NCT03233529.

Keywords: Atopic dermatitis; biomarker; crisaborole; gene expression; inflammation; phosphodiesterase 4; pruritus; transcriptome; transepidermal water loss.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Biomarkers / metabolism
  • Biopsy
  • Boron Compounds / therapeutic use*
  • Bridged Bicyclo Compounds, Heterocyclic / therapeutic use*
  • Cell Proliferation
  • Dermatitis, Atopic / drug therapy*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Ointments
  • Signal Transduction
  • Skin / drug effects
  • Skin / metabolism*
  • Skin / pathology
  • Th17 Cells / immunology*
  • Th2 Cells / immunology*
  • Tight Junctions / drug effects
  • Tight Junctions / metabolism*
  • Young Adult


  • Anti-Inflammatory Agents, Non-Steroidal
  • Biomarkers
  • Boron Compounds
  • Bridged Bicyclo Compounds, Heterocyclic
  • Ointments
  • crisaborole

Associated data