title: The relationship between pruritus and the clinical signs of psoriasis in patients receiving tofacitinib.
abstract: OBJECTIVE
  Tofacitinib is a novel, oral Janus kinase inhibitor being investigated for psoriasis. This study assessed the relationship between pruritus and clinical signs of psoriasis (assessed by Physician's Global Assessment [PGA]) in patients with moderate-to-severe chronic plaque psoriasis receiving tofacitinib.
  
  
  METHODS
  In this 16-week (12-week treatment period, 4-week observation period), double-blind, placebo-controlled, phase IIb study (NCT00678210), 197 patients were randomized to tofacitinib 2, 5 or 15 mg BID, or placebo. Pruritus was patient assessed using the Itch Severity Score (ISS), a 0-10 (10=worst itching) rating scale recorded daily from baseline to week 2 and at study visits. Mediation modeling was used to determine relationships between ISS (average score weeks 2-12), PGA (average score weeks 2-12) and treatment groups.
  
  
  RESULTS
  Mediation analysis showed that 70.2-80.5% (p<0.001 versus placebo) of tofacitinib's effect on pruritus was direct, and mostly independent of improvements in erythema, induration and scaling. ISS measurements had acceptable test-retest reliability. Correlation analyses with clinical outcomes supported the validity of the ISS as a pruritus measure.
  
  
  CONCLUSIONS
  Tofacitinib has a direct, beneficial effect on patient-reported pruritus independent from improvements in clinician-reported psoriasis severity signs. The ISS demonstrated favorable psychometric characteristics, supporting its use as a pruritus assessment tool.
authors.affiliation: Pfizer Inc , Groton, CT , USA.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Bushmakin
authors.forename: Carla
authors.initials: C
authors.lastname: Mamolo
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Cappelleri
authors.forename: Michelle
authors.initials: M
authors.lastname: Stewart
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011537:Pruritus / Q000188:drug therapy*; D011565:Psoriasis / Q000188:drug therapy*; D011594:Psychometrics; D011743:Pyrimidines / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D015203:Reproducibility of Results; D016896:Treatment Outcome
chemical_list: D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib
keywords: Erythema; induration; mediation modeling; plaque psoriasis; pruritus; scaling; tofacitinib