Efficacy and safety of the Janus kinase 1 inhibitor PF-04965842 in patients with moderate-to-severe psoriasis: phase II, randomized, double-blind, placebo-controlled study.

Background PF-04965842 is an oral Janus Kinase 1 inhibitor being investigated for treatment of plaque psoriasis. Objectives To evaluate the efficacy, safety and tolerability of PF-04965842 in patients with moderate to severe plaque psoriasis. Methods Patients in this phase 2, placebo-controlled study (NCT02201524) were randomised to receive placebo, 200 mg once-daily (QD), 400 mg QD, or 200 mg twice-daily (BID) PF-04965842 for 4 weeks. The primary endpoint was change from baseline in Psoriasis Area Severity Index (PASI) at Week 4. Study enrolment was discontinued on 25 June 2015 due to changes in the sponsor's development priorities. Results Fifty-nine patients were randomised and received at least one dose of PF-04965842 or placebo. The estimated treatment effect (active-placebo PASI change from baseline) and 90% CI at Week 4 was –5·1 (–9·2, –1·0), –5·6 (–9·6, –1·6) and –10·0 (–14·2, –5·8) for the 200 mg QD, 400 mg QD and 200 mg BID groups, respectively. At Week 4, the proportion of patients achieving PASI75 was 17% for the placebo and 200 mg QD groups, 50% for the 400 mg QD group and 60% for the 200 mg BID group. There were more abnormal laboratory test results of clinical interest (low neutrophil, reticulocyte and platelet counts) in the 200 mg BID group vs the QD treatment groups. No serious infections or bleeding events related to neutropenia or thrombocytopenia, respectively, were reported. Conclusions These results suggest that treatment with PF-04965842 improves symptoms and is well tolerated in patients with moderate to severe psoriasis. This article is protected by copyright. All rights reserved.