A randomized phase 2a efficacy and safety trial of the topical Janus kinase inhibitor tofacitinib in the treatment of chronic plaque psoriasis

Abstract

Background: Tofacitinib (CP-690,550) is a novel Janus kinase inhibitor in development as an oral formulation for the treatment of several inflammatory diseases including psoriasis.

Objectives: This phase 2a study aimed to assess the efficacy, systemic safety, local tolerability and systemic pharmacokinetics of topical tofacitinib in mild-to-moderate plaque psoriasis.

Methods: Two tofacitinib ointment formulations were evaluated in this multicentre, double-blind, vehicle-controlled trial (NCT01246583). Seventy-one patients were randomized 2 : 1 : 2 : 1 to 2% tofacitinib ointment 1, vehicle 1, 2% tofacitinib ointment 2 and vehicle 2, each administered twice daily for 4 weeks to a single fixed 300 cm(2) treatment area containing a target plaque with or without one or more nontarget plaques and normal skin.

Results: The primary endpoint of percentage change from baseline in the Target Plaque Severity Score at week 4 demonstrated statistically significant improvement for ointment 1 [least squares mean (LSM) -54.4%] vs. vehicle 1 (LSM -41.5%), but not ointment 2 (LSM -24.2%) vs. vehicle 2 (LSM -17.2%). Secondary endpoints (target plaque area and Itch Severity Item) improved similarly for tofacitinib ointment vs. corresponding vehicle. Adverse event (AE) occurrence was similar across treatment groups. All AEs were mild or moderate and none were serious or led to subject discontinuation. One application-site AE (erythema) was reported. Tofacitinib mean systemic exposure was minimal and was greater for ointment 1 than for ointment 2.

Conclusions: Tofacitinib ointment 1 was well tolerated and efficacious compared with vehicle for the treatment of plaque psoriasis. Further study of topical tofacitinib for psoriasis treatment is warranted.

Fig 1

CONSORT diagram. BID, twice daily.

Fig 2

Target Plaque Severity Score (TPSS) percentage change from baseline for (a) tofacitinib ointment 1 vs. vehicle 1 and (b) tofacitinib ointment 2 vs. vehicle 2 (full analysis set, no imputation). *Statistically significant (one-sided 90% upper confidence limit < 0); standard error bars may overlap at the prespecified statistical significance level. LSM, least squares mean.

Fig 3

Target plaque photographs at baseline and week 4 for a patient receiving (a) ointment 1 and (b) vehicle 1. Ointment location is left leg above the knee; baseline Target Plaque Severity Score (TPSS) = 8; week 4 TPSS = 3 (–62·5%). Vehicle location is left leg above the knee; baseline TPSS = 7; week 4 TPSS = 6 (–14·3%).

Fig 4

Target Plaque Severity Score (TPSS) – induration, erythema and scaling subscore changes from baseline for tofacitinib ointment 1 vs. vehicle 1 (a, c, e) and ointment 2 vs. vehicle 2 (b, d, f) (full analysis set, no imputation). *Statistically significant (one-sided 90% upper confidence limit < 0); standard error bars may overlap at the prespecified statistical significance level. LSM, least squares mean.