Efficacy and Safety of Ixekizumab in a Randomized, Double-blinded, Placebo-controlled Phase IIIb Study of Patients With Moderate-to-severe Genital Psoriasis

C. Ryan; A. Menter; L. Guenther; A. Blauvelt; R. Bissonnette; K. Meeuwis; J. Sullivan; J.C. Cather; G. Yosipovitch; A.B. Gottlieb; J.F. Merola; K. Callis Duffin; S. Fretzin; O.O. Osuntokun; R. Burge; A.N. Naegeli; F.E. Yang; C.-Y. Lin; K. Todd; A. Potts Bleakman; on behalf of the IXORA-Q Study Group

Disclosures

The British Journal of Dermatology. 2018;179(4):844-852. 

In This Article

Abstract and Introduction

Abstract

Background: Genital psoriasis (GenPs) is a common, debilitating and difficult-to-treat manifestation of plaque psoriasis. However, few controlled, interventional studies of GenPs exist.

Objectives: To determine the efficacy of ixekizumab vs. placebo in patients with moderate-to-severe GenPs with ≥ 1% involved body surface area (BSA).

Methods: Patients with moderate-to-severe GenPs, defined as a baseline static Physician's Global Assessment of Genitalia (sPGA-G) score of ≥ 3, with BSA ≥ 1% were randomized 1 : 1 to receive placebo (n = 74) or the recommended dosing of ixekizumab (n = 75). Major outcomes included the percentage of patients achieving 0 or 1 scores on the sPGA-G (primary end point), overall sPGA, GenPs Sexual Frequency Questionnaire (GenPs-SFQ) item 2, and ≥ 3–point improvement from baseline on the GenPs itch numerical rating scale.

Results: At week 12, ixekizumab was superior to placebo for sPGA-G 0/1 (73% vs. 8%, P < 0·001), overall sPGA 0/1 (73% vs. 3%, P < 0·001), GenPs-SFQ item 2 score of 0 or 1 (78% vs. 21%, P < 0·001) and genital itch (60% vs. 8%, P < 0·001). No candidiasis was reported, no deaths occurred and one (1%) serious adverse event was reported in a patient receiving placebo.

Conclusions: Ixekizumab was superior to placebo for the treatment of moderate-to-severe GenPs with BSA ≥ 1%. The safety profile of ixekizumab was consistent with previous studies in moderate-to-severe plaque psoriasis.

Introduction

Up to 63% of patients with psoriasis experience genital skin involvement at some point during the course of their disease.[1] Genital psoriasis (GenPs) is a particularly challenging manifestation of psoriasis with significantly greater negative impacts on sexual health and quality of life than in patients with psoriasis with no genital involvement.[1–3] Nevertheless, GenPs often remains undiagnosed due to insufficient evaluation of patients for genital involvement and a reluctance of patients and healthcare providers to discuss GenPs.[4]

The sensitive genital skin limits treatment options because many standard topical or ultraviolet-based treatments for psoriasis are either contraindicated or not well tolerated on genital skin. Current treatment guidelines support systemic therapies for GenPs when other treatment options fail, even in patients with lower body surface area (BSA) involvement.[5] However, interventional clinical studies for GenPs are sparse.[6–9] Therefore, there is an unmet clinical need for effective therapies for GenPs when topical therapies are ineffective or not well tolerated.

Ixekizumab results in rapid achievement of high clinical response rates that persist over long-term treatment of patients with moderate-to-severe plaque psoriasis.[10–12] However, the efficacy of ixekizumab for GenPs is unknown. We report the efficacy and safety results from the 12–week blinded treatment period of a randomized, double-blinded, phase IIIb clinical trial investigating the impact of ixekizumab on GenPs severity, sexual health and health-related quality of life (HRQoL) in patients with ≥ 1% involved BSA and moderate-to-severe GenPs, as defined by a baseline score of 3 (moderate) or more on the static Physician's Global Assessment of Genitalia (sPGA-G).

The primary outcome measure (sPGA-G) was developed for assessment of the severity of GenPs and was validated using data from the screening and baseline visits of IXORA-Q. Herein we provide results for the assessment of the psychometric properties of the sPGA-G (Appendix S1, Table S1 and Table S2; see Supporting Information). A description of the conceptualization, development methodology and content validity of the sPGA-G has been published previously.[13]

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