Tofacitinib withdrawal and retreatment in moderate-to-severe chronic plaque psoriasis: a randomized controlled trial

Br J Dermatol. 2015;172(5):1395-406. doi: 10.1111/bjd.13551. Epub 2015 Apr 2.

Abstract

Background: Tofacitinib is an oral Janus kinase inhibitor being investigated for the treatment of moderate-to-severe plaque psoriasis.

Objectives: 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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Chronic Disease
  • Dermatologic Agents / administration & dosage*
  • Dermatologic Agents / adverse effects
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Middle Aged
  • Patient Outcome Assessment
  • Piperidines / administration & dosage*
  • Piperidines / adverse effects
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / adverse effects
  • Psoriasis / drug therapy*
  • Pyrimidines / administration & dosage*
  • Pyrimidines / adverse effects
  • Pyrroles / administration & dosage*
  • Pyrroles / adverse effects
  • Quality of Life
  • Retreatment
  • Treatment Outcome
  • Young Adult

Substances

  • Dermatologic Agents
  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Pyrroles
  • tofacitinib

Associated data

  • ClinicalTrials.gov/NCT01186744