title: Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults.
abstract: BACKGROUND
  Additional topical treatments for atopic dermatitis (AD) are needed that provide relief while minimizing risks.
  
  
  OBJECTIVE
  We sought to assess the efficacy and safety of crisaborole ointment, a phosphodiesterase 4 inhibitor, in two phase III AD studies (AD-301: NCT02118766; AD-302: NCT02118792).
  
  
  METHODS
  Two identically designed, vehicle-controlled, double-blind studies enrolled and randomly assigned (2:1, crisaborole:vehicle) patients aged 2 years or older with an Investigator's Static Global Assessment (ISGA) score of mild or moderate for twice-daily application for 28 days. The primary end point was ISGA score at day 29 of clear (0)/almost clear (1) with 2-grade or greater improvement from baseline. Additional analyses included time to success in ISGA score, percentage of patients achieving clear/almost clear, reduction in severity of AD signs, and time to improvement in pruritus.
  
  
  RESULTS
  More crisaborole- than vehicle-treated patients achieved ISGA score success (clear/almost clear with ≥2-grade improvement; AD-301: 32.8% vs 25.4%, P = .038; AD-302: 31.4% vs 18.0%, P < .001), with a greater percentage with clear/almost clear (51.7% vs 40.6%, P = .005; 48.5% vs 29.7%, P < .001). Crisaborole-treated patients achieved success in ISGA score and improvement in pruritus earlier than those treated with vehicle (both P ≤ .001). Treatment-related adverse events were infrequent and mild to moderate in severity.
  
  
  CONCLUSIONS
  Short study duration was a limitation.
  
  
  CONCLUSIONS
  Crisaborole demonstrated a favorable safety profile and improvement in all measures of efficacy, including overall disease severity, pruritus, and other signs of AD.
authors.affiliation: Northwestern University, Feinberg School of Medicine, Chicago, Illinois. Electronic address: APaller@nm.org.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Paller
authors.affiliation: Rady Children's Hospital-San Diego, San Diego, California; University of California, San Diego, La Jolla, California.
authors.forename: Wynnis L
authors.initials: WL
authors.lastname: Tom
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lebwohl
authors.affiliation: Anacor Pharmaceuticals, Inc, Palo Alto, California.
authors.forename: Robin L
authors.initials: RL
authors.lastname: Blumenthal
authors.affiliation: National Jewish Health, Denver, Colorado; University of Colorado School of Medicine, Denver, Colorado.
authors.forename: Mark
authors.initials: M
authors.lastname: Boguniewicz
authors.affiliation: Clinical Research Partners, Richmond, Virginia.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Call
authors.affiliation: Rady Children's Hospital-San Diego, San Diego, California; University of California, San Diego, La Jolla, California.
authors.forename: Lawrence F
authors.initials: LF
authors.lastname: Eichenfield
authors.affiliation: Jordan Valley Dermatology and Research Center, West Jordan, Utah.
authors.forename: Douglass W
authors.initials: DW
authors.lastname: Forsha
authors.affiliation: Pi-Coor Clinical Research, Burke, Virginia.
authors.forename: William C
authors.initials: WC
authors.lastname: Rees
authors.affiliation: Oregon Health and Science University, Portland, Oregon.
authors.forename: Eric L
authors.initials: EL
authors.lastname: Simpson
authors.affiliation: Anacor Pharmaceuticals, Inc, Palo Alto, California.
authors.forename: Mary C
authors.initials: MC
authors.lastname: Spellman
authors.affiliation: Henry Ford Health System, Detroit, Michigan.
authors.forename: Linda F
authors.initials: LF
authors.lastname: Stein Gold
authors.affiliation: Pennsylvania State University, Hershey, Pennsylvania.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Zaenglein
authors.affiliation: Anacor Pharmaceuticals, Inc, Palo Alto, California.
authors.forename: Matilda H
authors.initials: MH
authors.lastname: Hughes
authors.affiliation: Anacor Pharmaceuticals, Inc, Palo Alto, California.
authors.forename: Lee T
authors.initials: LT
authors.lastname: Zane
authors.affiliation: University of Texas Health Science Center Houston, Houston, Texas.
authors.forename: Adelaide A
authors.initials: AA
authors.lastname: Hebert
mesh_terms: D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D000368:Aged; D001896:Boron Compounds / Q000009:adverse effects* / Q000627:therapeutic use*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000009:adverse effects* / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000009:adverse effects* / Q000627:therapeutic use*; D003876:Dermatitis, Atopic / Q000150:complications / Q000188:drug therapy*; D003879:Dermatologic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009824:Ointments; D011537:Pruritus / Q000188:drug therapy / Q000209:etiology; D055815:Young Adult
chemical_list: D001896:Boron Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003879:Dermatologic Agents; D009824:Ointments; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C543085:crisaborole
keywords: atopic dermatitis; crisaborole ointment; eczema; phosphodiesterase 4; pruritus; topical therapy