title: Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1).
abstract: BACKGROUND
  Apremilast works intracellularly to regulate inflammatory mediators.
  
  
  OBJECTIVE
  ESTEEM 1 evaluated efficacy/safety of apremilast at 30 mg twice a day for moderate to severe plaque psoriasis.
  
  
  METHODS
  This phase III, multicenter, double-blind, placebo-controlled study randomized adults (2:1) to apremilast or placebo. At week 16, the placebo group switched to apremilast through week 32, followed by a randomized treatment withdrawal phase to week 52. Binary end points were analyzed using χ(2) test; continuous end points used analysis of covariance.
  
  
  RESULTS
  In all, 844 patients were randomized (n = 282, placebo; n = 562, apremilast). At week 16, significantly more patients taking apremilast achieved 75% or greater reduction from baseline Psoriasis Area and Severity Index score (PASI-75) (33.1%) versus placebo (5.3%, P < .0001; primary end point). Most (61.0%) patients rerandomized to apremilast at week 32 achieved PASI-75 at week 52 versus 11.7% rerandomized to placebo. Of patients rerandomized to apremilast at week 32, mean percentage change from baseline PASI score was -88% to -81% (weeks 32-52). During the placebo-controlled period, 55.7% and 69.3% of patients randomized to placebo and apremilast, respectively, had 1 or more adverse events. Most adverse events were mild/moderate in severity. No new significant adverse events emerged with continued apremilast exposure versus the placebo-controlled period.
  
  
  CONCLUSIONS
  Data were limited to 52 weeks and may not generalize to nonplaque psoriasis.
  
  
  CONCLUSIONS
  Apremilast was effective in moderate to severe plaque psoriasis.
authors.affiliation: Probity Medical Research, Waterloo, Ontario, Canada. Electronic address: kapapp@probitymedical.com.
authors.forename: Kim
authors.initials: K
authors.lastname: Papp
authors.affiliation: Dermatologikum Hamburg, Hamburg, Germany.
authors.forename: Kristian
authors.initials: K
authors.lastname: Reich
authors.affiliation: Department of Dermatology, Saint Louis University School of Medicine, Saint Louis, Missouri.
authors.forename: Craig L
authors.initials: CL
authors.lastname: Leonardi
authors.affiliation: Physicians Skin Care, PLLC, Louisville, Kentucky; Mount Sinai Medical Center, New York, New York.
authors.forename: Leon
authors.initials: L
authors.lastname: Kircik
authors.affiliation: University of Rome Tor Vergata, Rome, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Chimenti
authors.affiliation: Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Richard G B
authors.initials: RG
authors.lastname: Langley
authors.affiliation: Celgene Corporation, Summit, New Jersey.
authors.forename: ChiaChi
authors.initials: C
authors.lastname: Hu
authors.affiliation: Celgene Corporation, Summit, New Jersey.
authors.forename: Randall M
authors.initials: RM
authors.lastname: Stevens
authors.affiliation: Celgene Corporation, Summit, New Jersey.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Day
authors.affiliation: Northwestern University, Chicago, Illinois.
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Gordon
authors.affiliation: University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Korman
authors.affiliation: Dermatology Center, Salford Royal Hospital, University of Manchester, Manchester, United Kingdom.
authors.forename: Christopher E M
authors.initials: CE
authors.lastname: Griffiths
mesh_terms: D000284:Administration, Oral; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D058988:Phosphodiesterase 4 Inhibitors / Q000008:administration & dosage*; D011565:Psoriasis / Q000188:drug therapy*; D012720:Severity of Illness Index; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D058988:Phosphodiesterase 4 Inhibitors; D013792:Thalidomide; C505730:apremilast
keywords: ESTEEM; apremilast; clinical trial; phosphodiesterase 4 inhibitor; psoriasis; treatment