title: Tofacitinib withdrawal and retreatment in moderate-to-severe chronic plaque psoriasis: a randomized controlled trial.
abstract: BACKGROUND
  Tofacitinib is an oral Janus kinase inhibitor being investigated for the treatment of moderate-to-severe plaque psoriasis.
  
  
  OBJECTIVE
  To compare outcomes following tofacitinib withdrawal with outcomes of continuation.
  
  
  METHODS
  In this phase 3 study (NCT01186744), patients received tofacitinib 5 mg (n = 331) or 10 mg (n = 335) twice daily for 24 weeks. The patients who achieved both ≥ 75% reduction in Psoriasis Area and Severity Index (PASI 75) score from baseline and Physician's Global Assessment (PGA) of 'clear' or 'almost clear' (PGA response) received a placebo (withdrawal) or the previous dose. At relapse (> 50% reduction in the PASI improvement during initial treatment) or week 40, the patients received the initial dose.
  
  
  RESULTS
  Initial treatment: 33·5% and 55·2% achieved both PASI 75 and PGA responses with tofacitinib 5 and 10 mg twice daily, respectively, making them eligible for the treatment-withdrawal period. Withdrawal: 56·2%, 62·3%, 23·3% and 26·1% maintained PASI 75 responses with tofacitinib 5, 10 mg, placebo (5 mg) and placebo (10 mg) twice daily, respectively; 49·9%, 63·9%, 22·9% and 18·0% maintained PGA responses; and 92·3%, 93·0%, 32·8% and 42·9% did not relapse. Elevations in low-density lipoprotein-cholesterol levels following initial treatment (mean increase: 8·71 mg dL(-1) with 5 mg twice daily, 10·26 mg dL(-1) with 10 mg twice daily) were reversed upon withdrawal. Retreatment: 36·8% and 61·0% of patients who relapsed achieved PASI 75 responses with tofacitinib 5 or 10 mg after 16 weeks; 44·8% and 57·1% regained PGA responses.
  
  
  CONCLUSIONS
  Patients who received continuous treatment maintained a response more effectively when compared with placebo recipients. Safety profiles were comparable in both the continuous treatment group and retreatment group. Of those patients who relapsed, up to 60% recaptured a response with tofacitinib.
authors.affiliation: Innovaderm Research, Montreal, QC, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Bissonnette
authors.affiliation: Aarhus University Hospital, Aarhus, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Iversen
authors.affiliation: Department of Medicine/Dermatology, UCLA School of Medicine, Los Angeles, CA, U.S.A.
authors.forename: H
authors.initials: H
authors.lastname: Sofen
authors.affiliation: Salford Royal Hospital, Manchester Academic Health Science Centre, University of Manchester, Manchester, U.K.
authors.forename: C E M
authors.initials: CE
authors.lastname: Griffiths
authors.affiliation: Skin and Cancer Foundation Inc., The University of Melbourne, Carlton, Vic., Australia.
authors.forename: P
authors.initials: P
authors.lastname: Foley
authors.affiliation: Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: R
authors.initials: R
authors.lastname: Romiti
authors.affiliation: Pfizer Inc, Groton, CT, U.S.A.
authors.forename: M
authors.initials: M
authors.lastname: Bachinsky
authors.affiliation: Pfizer Inc, Groton, CT, U.S.A.
authors.forename: S T
authors.initials: ST
authors.lastname: Rottinghaus
authors.affiliation: Pfizer Inc, Groton, CT, U.S.A.
authors.forename: H
authors.initials: H
authors.lastname: Tan
authors.affiliation: Pfizer Inc, Groton, CT, U.S.A.
authors.forename: J
authors.initials: J
authors.lastname: Proulx
authors.affiliation: Pfizer Inc, New York, NY, U.S.A.
authors.forename: H
authors.initials: H
authors.lastname: Valdez
authors.affiliation: Pfizer Inc, Groton, CT, U.S.A.
authors.forename: P
authors.initials: P
authors.lastname: Gupta
authors.affiliation: Pfizer Inc, Collegeville, PA, U.S.A.
authors.forename: L
authors.initials: L
authors.lastname: Mallbris
authors.affiliation: Pfizer Inc, Groton, CT, U.S.A.
authors.forename: R
authors.initials: R
authors.lastname: Wolk
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002908:Chronic Disease; D003879:Dermatologic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D063868:Patient Outcome Assessment; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011565:Psoriasis / Q000188:drug therapy*; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D011788:Quality of Life; D019233:Retreatment; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003879:Dermatologic Agents; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib