Ixekizumab Is Effective in Subjects With Moderate to Severe Plaque Psoriasis With Significant Nail Involvement: Results From UNCOVER 3

August 2016 | Volume 15 | Issue 8 | Original Article | 958 | Copyright © August 2016

Ellen B. Dennehy PhD,a Lu Zhang MS,a David Amato DO,a Orin Goldblum MD,a and Phoebe Rich MDb

aEli Lilly and Company, Indianapolis, IN
bOregon Health and Science University Center for Health and Healing, Portland, OR

Abstract
BACKGROUND: Ixekizumab, a monoclonal antibody that selectively targets interleukin-17A, has been established as safe and effective in 3 Phase 3 trials for the treatment of moderate to severe plaque psoriasis. The lifetime incidence of psoriatic nail disease is 80%-90% of patients, and approximately 50% of patients with psoriasis have nail involvement.
MATERIALS AND METHODS: The design of UNCOVER-3, a Phase 3, multicenter, double-blind, placebo- and active-controlled trial that evaluated the efficacy and safety of ixekizumab for moderate to severe psoriasis, has been published previously. Patients were randomized to receive blinded placebo, etanercept (50 mg twice weekly) or 80 mg ixekizumab every 2 weeks (IXEQ2W) or every 4 weeks (IXEQ4W) for 12 weeks. At week 12, all patients were assigned to open-label ixekizumab 80 mg every 4 weeks through week 60. In this 60-week post hoc subset analysis, we evaluated only those patients with significant baseline nail involvement, defined as fingernail NAPSI ≥16 and at least 4 fingernails involved.
RESULTS: Ixekizumab Q2W or Q4W resulted in greater improvement in nail psoriasis than placebo or etanercept by week 12 of administration, as measured by percent NAPSI reduction (IXEQ2W 39% improvement, IXEQ4W 40%, etanercept 28%, placebo -4.7%). At week 24, significantly more patients receiving ixekizumab exhibited no signs of nail involvement (IXEQ2W/Q4W 34%, IXEQ4W/Q4W 30%). Similar gains were observed at 60 weeks in all treatment groups.
CONCLUSION: Ixekizumab led to improvement in fingernail psoriasis by week 12 compared with placebo. Continued improvement in fingernail psoriasis with ixekizumab was observed, with >50% of patients achieving complete fingernail psoriasis resolution (NAPSI=0) at week 60.

J Drugs Dermatol. 2016;15(8):958-961.

INTRODUCTION

The safety and efficacy of ixekizumab, a monoclonal antibody that selectively targets interleukin-17A, have been established in 3 Phase 3 trials for the treatment of moderate to severe plaque psoriasis. We report a 60-week post hoc analysis of patients in the UNCOVER-3 trial with significant fingernail psoriasis involvement, defined as Nail Psoriasis Severity Index (NAPSI) ≥16 with ≥4 fingernails involved. Nail psoriasis is widely acknowledged to be a more difficult-to-treat manifestation of localized disease. The lifetime incidence of psoriatic nail disease is 80%-90% of patients, and approximately 50% of patients with psoriasis have nail involvement.1-4

METHODS

The induction study design for UNCOVER-3 has been published previously.3 Briefly, UNCOVER-3 was a Phase 3, multicenter, double-blind, placebo- and active-controlled trial that evaluated the efficacy and safety of ixekizumab in patients with moderate to severe psoriasis. Patients were randomized to receive blinded placebo, etanercept (50 mg twice weekly), or 80 mg ixekizumab as 1 subcutaneous injection every 2 weeks (IXEQ2W) or every 4 weeks (IXEQ4W) for 12 weeks, following an ixekizumab 160-mg starting dose. At week 12, all patients were assigned to open-label ixekizumab 80 mg every 4 weeks through week 60. The placebo group received a 160-mg starting dose of ixekizumab while the etanercept group underwent a 4-week washout period prior to starting ixekizumab 80 mg Q4W. This trial is registered with ClinicalTrials.gov, number NCT01646177.
In this post hoc subset analysis, we evaluated only those patients with significant baseline nail involvement, defined as fingernail NAPSI ≥16 and at least 4 fingernails involved.4 Patients were analyzed according to the treatment to which they were assigned at week 0 regardless of compliance (intention-to-treat population).The primary efficacy variable was the total fingernail NAPSI score (sum of NAPSI scores of all 10 fingernails, total score 0-80). The primary objective of this analysis was to evaluate the efficacy of ixekizumab compared with placebo and etanercept on total fingernail NAPSI percent change from baseline to week 12 in patients with severe nail disease. The secondary objective was to examine the effect of