Efficacy and Safety of Ixekizumab in a Phase III, Randomized, Double-Blind, Placebo-Controlled Study in Paediatric Patients With Moderate-to-Severe Plaque Psoriasis (IXORA-PEDS)

A.S. Paller; M.M.B. Seyger; G. Alejandro Magariños; J. Bagel; A. Pinter; J. Cather; S. Keller; C. Rodriguez Capriles; R. Gontijo Lima; G. Gallo; C.A. Little; E. Edson-Heredia; L. Li; W. Xu; K. Papp

Disclosures

The British Journal of Dermatology. 2020;183(2):231-241. 

In This Article

Abstract and Introduction

Abstract

Background: Plaque psoriasis affects children and adults, but treatment options for paediatric psoriasis are limited.

Objectives: To evaluate the efficacy and safety of ixekizumab (IXE ), a high-affinity monoclonal antibody that selectively targets interleukin-17A, for moderate-to-severe paediatric psoriasis.

Methods: In a randomized, double-blind, placebo-controlled, phase III study (IXORA -PEDS ), patients aged 6 to < 18 years with moderate-to-severe plaque psoriasis were randomized 2 : 1 to weight-based dosing of IXE every 4 weeks (IXE Q4W, n = 115) or placebo (n = 56) through week 12, followed by open-label IXE Q4W. Coprimary endpoints were the proportions of patients at week 12 achieving ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) and those achieving a static Physician's Global Assessment score of 0 or 1 (sPGA 0,1).

Results: IXE was superior (P < 0·001) to placebo for both coprimary endpoints of PASI 75 (IXE Q4W, 89%; placebo, 25%) and sPGA (0,1) (IXE Q4W, 81%; placebo, 11%). IXE was also superior for all gated secondary endpoints, including PASI 75 and sPGA (0,1) at week 4, improvement in itch, and complete skin clearance. IXE Q4W provided significant (P < 0·001) improvements vs. placebo in quality of life and clearance of scalp and genital psoriasis. Responses at week 12 were sustained or further improved through week 48. Through week 12, 45% (placebo) and 56% (IXE ) of patients reported treatment-emergent adverse events. One serious adverse event was reported (IXE ), one patient discontinued due to an adverse event (placebo) and no deaths were reported.

Conclusions: IXE was superior to placebo in the treatment of moderate-to-severe paediatric psoriasis, and the safety profile was generally consistent with that observed in adults.

Introduction

Paediatric plaque psoriasis affects approximately 1% of children and adolescents, and is estimated to occur first before 20 years of age in 35–50% of adults with plaque psoriasis.[1–3] Paediatric psoriasis can be associated with reduced quality of life and a higher incidence of multiple comorbidities, including psoriatic arthritis, obesity, diabetes, Crohn's disease, ulcerative colitis and psychiatric comorbidities.[4] Thus, early recognition and treatment of paediatric psoriasis are important for overall health and quality of life.

As there have been few clinical studies of paediatric psoriasis, treatment options are limited and often used off-label. Topical therapies comprise first-line treatment, followed by phototherapy for moderate-to-severe paediatric psoriasis.[5] Systemic treatments are recommended for moderate-to-severe paediatric psoriasis recalcitrant to topical therapies.[5,6] Nonbiologic systemic treatments such as methotrexate or ciclosporin are used, but they may not be well tolerated or provide adequate efficacy.[5,6]

Ixekizumab (IXE) is a high-affinity monoclonal antibody that selectively targets interleukin-(IL)-17A. The objective of this study was to evaluate the efficacy and safety of IXE for moderate-to-severe plaque psoriasis in paediatric patients aged 6 to < 18 years. Prior to the current study, two tumour necrosis factor inhibitors (etanercept and adalimumab) and one IL-12/23 antagonist (ustekinumab) were approved for paediatric psoriasis.[7] Based on the findings from this study, IXE was recently approved by the US Food and Drug Administration (FDA) for moderate-to-severe paediatric psoriasis in addition to previously approved indications for adult patients with moderate-to-severe plaque psoriasis, active psoriatic arthritis and ankylosing spondylitis.

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