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.

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.

• Authors: R Bissonnette, L Iversen, H Sofen, C E M Griffiths, P Foley, R Romiti, M Bachinsky, S T Rottinghaus, H Tan, J Proulx, H Valdez, P Gupta, L Mallbris, R Wolk
• Journal: The British journal of dermatology (Br J Dermatol) Vol. 172 Issue 5 Pg. 1395-406 ( 2015) ISSN: 1365-2133 [Electronic] England
• PMID: 25418186 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 British Association of Dermatologists.

Chemical References

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

Topics

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