title: Treatment of plaque psoriasis with an ointment formulation of the Janus kinase inhibitor, tofacitinib: a Phase 2b randomized clinical trial.
abstract: Most psoriasis patients have mild to moderate disease, commonly treated topically. Current topical agents have limited efficacy and undesirable side effects associated with long-term use. Tofacitinib is a small molecule Janus kinase inhibitor investigated for the topical treatment of psoriasis.
  
  
  
  This was a 12-week, randomized, double-blind, parallel-group, vehicle-controlled Phase 2b study of tofacitinib ointment (2 % and 1 %) applied once (QD) or twice (BID) daily in adults with mild to moderate plaque psoriasis. Primary endpoint: proportion of patients with Calculated Physician's Global Assessment (PGA-C) clear or almost clear and ≥2 grade improvement from baseline at Weeks 8 and 12. Secondary endpoints: proportion of patients with PGA-C clear or almost clear; proportion achieving Psoriasis Area and Severity Index 75 (PASI75) response; percent change from baseline in PASI and body surface area; change from baseline in Itch Severity Item (ISI). Adverse events (AEs) were monitored and clinical laboratory parameters measured.
  
  
  
  Overall, 435 patients were randomized and 430 patients received treatment. The proportion of patients with PGA-C clear or almost clear and ≥2 grade improvement from baseline at Week 8 was 18.6 % for 2 % tofacitinib QD (80 % confidence interval [CI] for difference from vehicle: 3.8, 18.2 %) and 22.5 % for 2 % tofacitinib BID (80 % CI: 3.1, 18.5 %); this was significantly higher vs vehicle for both dosage regimens. No significant difference vs vehicle was seen at Week 12. Significantly more patients achieved PGA-C clear or almost clear with 2 % tofacitinib QD and BID and 1 % tofacitinib QD (not BID) at Week 8, and with 2 % tofacitinib BID at Week 12. Pruritus was significantly reduced vs vehicle with 2 % and 1 % tofacitinib BID (starting Day 2), and 2 % tofacitinib QD (starting Day 3). Overall, 44.2 % of patients experienced AEs, 8.1 % experienced application site AEs, and 2.3 % experienced serious AEs. The highest incidence of AEs (including application site AEs) was in the vehicle QD group.
  
  
  
  In adults with mild to moderate plaque psoriasis, 2 % tofacitinib ointment QD and BID showed greater efficacy than vehicle at Week 8, but not Week 12, with an acceptable safety and local tolerability profile.
  
  
  
  NCT01831466 registered March 28, 2013.
authors.affiliation: K Papp Clinical Research and Probity Medical Research Inc, Waterloo, ON, Canada.
authors.forename: Kim A
authors.initials: KA
authors.lastname: Papp
authors.affiliation: Innovaderm Research, Montreal, QC, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Bissonnette
authors.affiliation: SKiN Centre for Dermatology and Probity Medical Research Inc, Peterborough, and Queens University, Kingston, ON, Canada.
authors.forename: Melinda
authors.initials: M
authors.lastname: Gooderham
authors.affiliation: Wake Forest Baptist Health, Winston-Salem, NC, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Feldman
authors.affiliation: Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Iversen
authors.affiliation: Southern California Dermatology, Santa Ana, CA, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Soung
authors.affiliation: Dermatology Consulting Services, High Point, NC, USA.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Draelos
authors.affiliation: Pfizer Worldwide Biopharmaceuticals, Global Innovative Pharma Business, Groton, CT, USA.
authors.forename: Carla
authors.initials: C
authors.lastname: Mamolo
authors.affiliation: Pfizer Worldwide Biopharmaceuticals, Global Innovative Pharma Business, Groton, CT, USA.
authors.forename: Vivek
authors.initials: V
authors.lastname: Purohit
authors.affiliation: Pfizer Worldwide Biopharmaceuticals, Global Innovative Pharma Business, Groton, CT, USA.
authors.forename: Cunshan
authors.initials: C
authors.lastname: Wang
authors.affiliation: Pfizer Worldwide Biopharmaceuticals, Global Innovative Pharma Business, Groton, CT, USA. william.c.ports@pfizer.com.
authors.forename: William C
authors.initials: WC
authors.lastname: Ports
mesh_terms: D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors; D008297:Male; D008875:Middle Aged; D009824:Ointments; D010880:Piperidines / Q000008:administration & dosage*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology; D011743:Pyrimidines / Q000008:administration & dosage*; D011758:Pyrroles / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D009824:Ointments; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib; D053612:Janus Kinases
keywords: CP-690,550; Dermatology Life Quality Index; Itch; PASI; Physician’s Global Assessment; Pruritus; Psoriasis; Psoriasis Area and Severity Index; Tofacitinib; Topical