title: Improved clinical outcome and biomarkers in adults with papulopustular rosacea treated with doxycycline modified-release capsules in a randomized trial.
abstract: BACKGROUND
  Patients with rosacea have increased amounts of cathelicidin and protease activity but their usefulness as disease biomarkers is unclear.
  
  
  OBJECTIVE
  We sought to evaluate the effect of doxycycline treatment on cathelicidin expression, protease activity, and clinical response in rosacea.
  
  
  METHODS
  In all, 170 adults with papulopustular rosacea were treated for 12 weeks with doxycycline 40-mg modified-release capsules or placebo in a multicenter, randomized, double-blind, placebo-controlled study. Clinical response was compared with cathelicidin and protease activity in stratum corneum samples obtained by tape strip and in skin biopsy specimens obtained from a random subset of patients.
  
  
  RESULTS
  Treatment with doxycycline significantly reduced inflammatory lesions and improved investigator global assessment scores compared with placebo. Cathelicidin expression and protein levels decreased over the course of 12 weeks in patients treated with doxycycline. Low levels of protease activity and cathelicidin expression at 12 weeks correlated with treatment success. Low protease activity at baseline was a predictor of clinical response in the doxycycline treatment group.
  
  
  CONCLUSIONS
  Healthy control subjects were not studied.
  
  
  CONCLUSIONS
  Improved clinical outcome correlated with reduced cathelicidin and protease activity, supporting both the mechanism of doxycycline and the potential of these molecules as biomarkers for rosacea.
authors.affiliation: Department of Dermatology, University of California-San Diego, School of Medicine, La Jolla, California. Electronic address: adinardo@ucsd.edu.
authors.forename: Anna
authors.initials: A
authors.lastname: Di Nardo
authors.affiliation: Galderma Laboratories LP, Fort Worth, Texas.
authors.forename: Anna D
authors.initials: AD
authors.lastname: Holmes
authors.affiliation: Department of Dermatology, University of California-San Diego, School of Medicine, La Jolla, California.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Muto
authors.affiliation: Therapeutics Clinical Research, San Diego, California; Department of Veterans Affairs San Diego Healthcare System, San Diego, California.
authors.forename: Eugene Y
authors.initials: EY
authors.lastname: Huang
authors.affiliation: Galderma Laboratories LP, Fort Worth, Texas.
authors.forename: Norman
authors.initials: N
authors.lastname: Preston
authors.affiliation: Galderma Laboratories LP, Fort Worth, Texas.
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Winkelman
authors.affiliation: Department of Dermatology, University of California-San Diego, School of Medicine, La Jolla, California.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gallo
mesh_terms: D000284:Administration, Oral; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002214:Capsules; D054804:Cathelicidins / Q000378:metabolism*; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004318:Doxycycline / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D045726:Metalloproteases / Q000378:metabolism*; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012016:Reference Values; D018570:Risk Assessment; D012393:Rosacea / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D002214:Capsules; D054804:Cathelicidins; D003692:Delayed-Action Preparations; D045726:Metalloproteases; D004318:Doxycycline
keywords: biomarker; cathelicidin; doxycycline; kallikrein; matrix metalloproteinase; papulopustular; rosacea; serine protease