title: Post Hoc Analyses of the Effect of Crisaborole Topical Ointment, 2% on Atopic Dermatitis: Associated Pruritus from Phase 1 and 2 Clinical Studies.
abstract: BACKGROUND
  Two post hoc analyses assessed the antipruritic activity of crisaborole topical ointment, 2% (crisaborole; Anacor Pharmaceuticals, Inc., Palo Alto, CA), a first-in-class boron-based phosphodiesterase-4 inhibitor in development for treatment of mild to moderate atopic dermatitis (AD).
  
  
  METHODS
  Two pooled analyses included data from 4 studies evaluating crisaborole in AD (study 1, phase 1b, systemic exposure, safety, and pharmacokinetics [PK] under maximal-use conditions in children and adolescents; study 2, phase 2a, safety and PK in adolescents; study 3, phase 2a, efficacy and safety in adults; study 4, phase 2, efficacy and safety in adolescents). Pooled data from studies 1 and 2 included whole body assessments; studies 3 and 4 included target lesion assessments. Pruritus severity was evaluated using a 4-point rating scale (0=none to 3=severe). Efficacy assessments included percent change from baseline in pruritus severity scores at days 8 (first pooled assessment), 15, 22, and 29 (whole body assessments) or days 15 (first pooled assessment), 22, and 29 (target lesions). Paired t-tests comparing change from baseline against zero were used to calculate P values. Categorical shifts in pruritus severity were also assessed (no to mild pruritus, 0-1.5; moderate to severe pruritus, 2-3).
  
  
  RESULTS
  In the pooled analysis of studies 1 and 2 (N=57), the percent change from baseline in pruritus severity scores were 63.0% and 64.9% at days 8 and 29, respectively (P<0.001 for each). Similar results were observed in the pooled analysis of studies 3 and 4 (N=67). In both analyses, most patients had mild to no pruritus from the first time point assessed through the remainder of treatment.
  
  
  CONCLUSIONS
  Treatment with crisaborole topical ointment, 2% resulted in statistically significant reductions in pruritus severity at the first time point evaluated in both analyses. These findings provide preliminary evidence of the antipruritic activity of crisaborole topical ointment, 2%.
authors.forename: Zoe Diana
authors.initials: ZD
authors.lastname: Draelos
authors.forename: Linda F
authors.initials: LF
authors.lastname: Stein Gold
authors.forename: Dedee F
authors.initials: DF
authors.lastname: Murrell
authors.forename: Matilda H
authors.initials: MH
authors.lastname: Hughes
authors.forename: Lee T
authors.initials: LT
authors.lastname: Zane
mesh_terms: D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D000368:Aged; D001896:Boron Compounds / Q000008:administration & dosage* / Q000737:chemistry; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage* / Q000737:chemistry; D002648:Child; D002675:Child, Preschool; D017321:Clinical Trials, Phase I as Topic / Q000379:methods*; D017322:Clinical Trials, Phase II as Topic / Q000379:methods*; D003876:Dermatitis, Atopic / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D004339:Drug Compounding; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009824:Ointments; D011537:Pruritus / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001896:Boron Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D009824:Ointments; C543085:crisaborole