title: Oral ponesimod in patients with chronic plaque psoriasis: a randomised, double-blind, placebo-controlled phase 2 trial.
abstract: BACKGROUND
  We assessed the efficacy, safety, and tolerability of ponesimod, an oral, selective, reversible modulator of sphingosine 1-phosphate receptor 1, in patients with moderate to severe chronic plaque psoriasis.
  
  
  METHODS
  Between Sept 22, 2010, and Oct 24, 2012, patients with psoriasis area and severity index (PASI) scores higher than 10 were enrolled into this multicentre double-blind, phase 2 study. They received 20 mg or 40 mg ponesimod or placebo once daily for 16 weeks. Those with at least 50% reduction in PASI score at 16 weeks and who were receiving ponesimod were rerandomised to receive maintenance ponesimod therapy or placebo until week 28. The primary endpoint was reduction in PASI score from baseline of at least 75% (PASI75) at week 16. This study is registered with ClinicalTrials.gov, number NCT01208090.
  
  
  RESULTS
  Of 326 patients initially randomised (20 mg ponesimod n=126, 40 mg ponesimod n=133, and placebo n=67) PASI75 was achieved at week 16 in 58 (46·0%), 64 (48·1%), and nine (13·4%), respectively. The treatment effect was significant for the two ponesimod doses (both p<0·0001). Of 219 patients who entered the maintenance period, PASI75 was achieved by week 28 in 35 (71·4%) of 49 who continued on 20 mg ponesimod and 41 (77·4%) of 53 on 40 mg ponesimod, and in 19 (42·2%) of 45 who swapped from 20 mg to placebo and 19 (40·4%) of 47 from 40 mg to placebo. Ponesimod was associated with dyspnoea, raised liver enzyme concentrations, and dizziness.
  
  
  CONCLUSIONS
  Significant clinical benefit was seen at week 16 that increased with maintenance therapy.
  
  
  BACKGROUND
  Actelion Pharmaceuticals.
authors.affiliation: Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Vaclavkova
authors.affiliation: Department of Dermatology, University of Rome "Tor Vergata", PTV-Policlinico di Tor Vergata, Rome, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Chimenti
authors.affiliation: Department of Dermatology, Charles University, Third Faculty of Medicine, Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Arenberger
authors.affiliation: Department of Dermatovenerology and Oncodermatology, Semmelweis University, Budapest, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Holló
authors.affiliation: Department of Dermatology, Municipal Hospital Hietzing, Vienna, Austria.
authors.forename: Paul-Gunther
authors.initials: PG
authors.lastname: Sator
authors.affiliation: Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.
authors.forename: Michel
authors.initials: M
authors.lastname: Burcklen
authors.affiliation: Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.
authors.forename: Mylène
authors.initials: M
authors.lastname: Stefani
authors.affiliation: Actelion Pharmaceuticals Ltd, Allschwil, Switzerland. Electronic address: daniele.dambrosio@actelion.com.
authors.forename: Daniele
authors.initials: D
authors.lastname: D'Ambrosio
mesh_terms: D000284:Administration, Oral; D002908:Chronic Disease; D004311:Double-Blind Method; D006801:Humans; D011565:Psoriasis / Q000188:drug therapy*; D013844:Thiazoles / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D013844:Thiazoles; C550169:ponesimod