title: Tofacitinib versus etanercept or placebo in moderate-to-severe chronic plaque psoriasis: a phase 3 randomised non-inferiority trial.
abstract: BACKGROUND
  New therapeutic options are needed for patients with psoriasis. Tofacitinib, an oral Janus kinase inhibitor, is being investigated as a treatment for moderate-to-severe chronic plaque psoriasis. In this study, we aimed to compare two tofacitinib doses with high-dose etanercept or placebo in this patient population.
  
  
  METHODS
  In this phase 3, randomised, multicentre, double-dummy, placebo-controlled, 12-week, non-inferiority trial, adult patients with chronic stable plaque psoriasis (for ≥12 months) who were candidates for systemic or phototherapy and had a Psoriasis Area and Severity Index (PASI) score of 12 or higher and a Physician's Global Assessment (PGA) of moderate or severe, and had failed to respond to, had a contraindication to, or were intolerant to at least one conventional systemic therapy, were enrolled from 122 investigational dermatology centres worldwide. Eligible patients were randomly assigned in a 3:3:3:1 ratio to receive tofacitinib 5 mg or 10 mg twice daily at about 12 h intervals, etanercept 50 mg subcutaneously twice weekly at about 3-4 day intervals, or placebo. Randomisation was done by a computer-generated randomisation schedule, and all patients and study personnel were masked to treatment assignment. The co-primary endpoints were the proportion of patients at week 12 with at least a 75% reduction in the PASI score from baseline (PASI75 response) and the proportion of patients achieving a PGA score of "clear" or "almost clear" (PGA response), analysed in the full analysis set (all patients who were randomised and received at least one dose of study drug). This study is registered with ClinicalTrials.gov, number NCT01241591.
  
  
  RESULTS
  Between Nov 29, 2010, and Sept 13, 2012, we enrolled 1106 eligible adult patients with chronic plaque psoriasis and randomly assigned them to the four treatment groups (330 to tofacitinib 5 mg twice daily, 332 to tofacitinib 10 mg twice daily, 336 to etanercept 50 mg twice weekly, and 108 to placebo). Of these patients, 1101 actually received their assigned study medication (329 in the tofactinib 5 mg group, 330 in the tofacitinib 10 mg group, 335 in the etanercept group, and 107 in the placebo group). At week 12, PASI75 responses were recorded in 130 (39·5%) of 329 patients in the tofacitinib 5 mg group, 210 (63·6%) of 330 in the tofacitinib 10 mg group, 197 (58·8%) of 335 in the etanercept group, and six (5·6%) of 107 in the placebo group. A PGA response was achieved by 155 (47·1%) of 329 patients in the tofacitinib 5 mg group, 225 (68·2%) of 330 in the tofacitinib 10 mg group, 222 (66·3%) of 335 in the etanercept group, and 16 (15·0%) of 107 in the placebo group. The rate of adverse events was similar across the four groups, with serious adverse events occurring in seven (2%) of 329 patients in the tofacitinib 5 mg group, five (2%) of 330 in the tofacitinib 10 mg group, seven (2%) of 335 in the etanercept group, and two (2%) of 107 in the placebo group. Three (1%) of 329 patients in the tofacitinib 5 mg group, ten (3%) of 330 in the tofacitinib 10 mg group, 11 (3%) of 335 in the etanercept group, and four (4%) of 107 patients in the placebo group discontinued their assigned treatment because of adverse events.
  
  
  CONCLUSIONS
  In patients with moderate-to-severe plaque psoriasis, the 10 mg twice daily dose of tofacitinib was non-inferior to etanercept 50 mg twice weekly and was superior to placebo, but the 5 mg twice daily dose did not show non-inferiority to etanercept 50 mg twice weekly. The adverse event rates over 12 weeks were similar for tofacitinib and etanercept. This study indicates that in the future tofacitinib could provide a convenient and well-tolerated therapeutic option for patients with moderate-to-severe plaque psoriasis.
  
  
  BACKGROUND
  Pfizer Inc.
authors.affiliation: Sorbonne Paris Cité Université Paris Diderot, Department of Dermatology, APHP Hôpital Saint-Louis, Paris, France. Electronic address: herve.bachelez@sls.aphp.fr.
authors.forename: Hervé
authors.initials: H
authors.lastname: Bachelez
authors.affiliation: Radboud University Nijmegen Medical Center, Nijmegen, Netherlands.
authors.forename: Peter C M
authors.initials: PC
authors.lastname: van de Kerkhof
authors.affiliation: Federal Academic Teaching Hospital of Feldkirch, Feldkirch, Austria.
authors.forename: Robert
authors.initials: R
authors.lastname: Strohal
authors.affiliation: State Research Center of Dermatology and Venereology, Ministry of Health, Moscow, Russia.
authors.forename: Alexey
authors.initials: A
authors.lastname: Kubanov
authors.affiliation: University of Chile Clinical Hospital, Department of Dermatology, Santiago, Chile; Probity Medical Research, Waterloo, ON, Canada.
authors.forename: Fernando
authors.initials: F
authors.lastname: Valenzuela
authors.affiliation: Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea.
authors.forename: Joo-Heung
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Soloviev's Clinical Hospital for Urgent Medical Care, Yaroslav, Russia.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Yakusevich
authors.affiliation: Department of Dermatology, University of Rome, Rome, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Chimenti
authors.affiliation: Pfizer Inc, Groton, CT, USA.
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Papacharalambous
authors.affiliation: Pfizer Inc, Groton, CT, USA.
authors.forename: James
authors.initials: J
authors.lastname: Proulx
authors.affiliation: Pfizer Inc, Groton, CT, USA.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Gupta
authors.affiliation: Pfizer Inc, Groton, CT, USA.
authors.forename: Huaming
authors.initials: H
authors.lastname: Tan
authors.affiliation: Pfizer Inc, Groton, CT, USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Tawadrous
authors.affiliation: Pfizer Inc, Groton, CT, USA.
authors.forename: Hernan
authors.initials: H
authors.lastname: Valdez
authors.affiliation: Pfizer Inc, Groton, CT, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Wolk
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011565:Psoriasis / Q000188:drug therapy*; D011743:Pyrimidines / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007074:Immunoglobulin G; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D018124:Receptors, Tumor Necrosis Factor; C479163:tofacitinib; D000068800:Etanercept