title: Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, in the treatment of psoriasis: a Phase 2b randomized placebo-controlled dose-ranging study.
abstract: BACKGROUND
  Tofacitinib is a novel, oral Janus kinase inhibitor under investigation as a potential treatment for plaque psoriasis.
  
  
  OBJECTIVE
  This Phase 2b, 12-week, dose-ranging study (A3921047, NCT00678210) aimed to characterize the exposure-response, efficacy and safety of tofacitinib vs. placebo in patients with moderate-to-severe chronic plaque psoriasis.
  
  
  METHODS
  One hundred and ninety-seven patients were randomized. The primary endpoint was the proportion of patients achieving a ≥ 75% reduction in the Psoriasis Area and Severity Index (PASI 75) score at week 12.
  
  
  RESULTS
  At week 12, PASI 75 response rates were significantly higher for all tofacitinib twice-daily groups: 25·0% (2 mg; P < 0·001), 40·8% (5 mg; P < 0·0001) and 66·7% (15 mg; P < 0·0001), compared with placebo (2·0%). Significant increases in the proportion of PASI 75 responses were seen by week 4 and were maintained at week 12. Exposure-response over the 0-15 mg tofacitinib twice-daily dose range was successfully characterized. PASI 50, PASI 90 and Physician's Global Assessment response rates were also higher for tofacitinib vs. placebo. The most frequently reported adverse events (AEs) were infections and infestations: 22·4% (2 mg twice daily), 20·4% (5 mg twice daily), 36·7% (15 mg twice daily) and 32·0% (placebo). Discontinuations due to AEs were 6·0%, 2·0%, 4·1% and 6·1% of patients in the placebo, and 2, 5 and 15 mg twice-daily tofacitinib groups, respectively. Dose-dependent increases from baseline in mean serum high-density lipoprotein, low-density lipoprotein and total cholesterol, and decreases in haemoglobin and neutrophils were observed.
  
  
  CONCLUSIONS
  Short-term treatment with oral tofacitinib results in significant clinical improvement in patients with moderate-to-severe plaque psoriasis and is generally well tolerated.
authors.affiliation: Probity Medical Research, 135 Union Street East, Waterloo, ON N2J 1C4, Canada. kapapp@probitymedical.com
authors.forename: K A
authors.initials: KA
authors.lastname: Papp
authors.forename: A
authors.initials: A
authors.lastname: Menter
authors.forename: B
authors.initials: B
authors.lastname: Strober
authors.forename: R G
authors.initials: RG
authors.lastname: Langley
authors.forename: M
authors.initials: M
authors.lastname: Buonanno
authors.forename: R
authors.initials: R
authors.lastname: Wolk
authors.forename: P
authors.initials: P
authors.lastname: Gupta
authors.forename: S
authors.initials: S
authors.lastname: Krishnaswami
authors.forename: H
authors.initials: H
authors.lastname: Tan
authors.forename: J A
authors.initials: JA
authors.lastname: Harness
mesh_terms: D000284:Administration, Oral; D000328:Adult; D002908:Chronic Disease; D003879:Dermatologic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D053616:Janus Kinase 3 / Q000037:antagonists & inhibitors*; D008297:Male; D010880:Piperidines; D011565:Psoriasis / Q000188:drug therapy*; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D003879:Dermatologic Agents; D010880:Piperidines; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib; D053616:Janus Kinase 3