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

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 ointment2 and vehicle 2, each administered twice daily for 4weeks to a single fixed 300cm(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<bold>4</bold>%] vs. vehicle 1 (LSM -41<bold>5</bold>%), but not ointment 2 (LSM -24<bold>2</bold>%) vs. vehicle 2 (LSM -17<bold>2</bold>%). 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.