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 )

Abstract

Summary 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. What is already known about this topic? Paediatric psoriasis affects approximately 1% of children and can negatively impact health‐related quality of life. Treatment options for paediatric psoriasis are typically limited to off‐label treatments and approved systemic biologics. Ixekizumab, a high‐affinity monoclonal antibody that selectively targets interleukin‐17A, is approved for moderate‐to‐severe plaque psoriasis in adults and was recently approved by the US Food and Drug Administration for moderate‐to‐severe paediatric psoriasis. What does this study add? Ixekizumab resulted in rapid and statistically significant improvements over placebo in skin involvement, itch and health‐related quality of life, which persisted through 48 weeks of treatment in paediatric patients with moderate‐to‐severe plaque psoriasis. The safety profile of ixekizumab was generally consistent with that seen in adults. Ixekizumab may be an additional potential therapeutic option and an additional class of biologic therapy (interleukin‐17A antagonist) for the treatment of moderate‐to‐severe paediatric psoriasis. Plain language summary available online

Therapeutic update of biologics and small molecules for scalp psoriasis: a systematic review

“…7,18,36 Further phase III trials included the UNDERCOVER-1, Investigations on the pediatric populations were carried out too. 41 The IXORA-PEDS phase III trial included patients aged from 6 to 17 years and treated with the pediatric dosage of ixekizumab (weight-based) versus placebo. 41 The majority (89%, n = 152) had scalp involvement.…”

“…The IXORA‐PEDS phase III trial included patients aged from 6 to 17 years and treated with the pediatric dosage of ixekizumab (weight‐based) versus placebo 41 . The majority (89%, n = 152) had scalp involvement 41 . A statistically significant difference was reported between the two arms, as 69% of patients in the ixekizumab group reached a PSSI of 0 (16% for the placebo; difference ixekizumab vs placebo, 95% CI: 52.6% [39.1‐66.2], P < .001) 41 .…”

Efficacy and Safety of Ixekizumab with or Without Methotrexate in Biologic-Naïve Patients with Psoriatic Arthritis: 52-Week Results from SPIRIT-H2H Study

“…Ixekizumab (IXE) is a high-affinity monoclonal antibody that selectively targets IL-17A and is approved for the treatment of moderateto-severe plaque psoriasis (PsO), PsA, ankylosing spondylitis, non-radiographic axial spondylarthritis, and pediatric PsO [18][19][20][21]. SPIRIT-H2H (ClinicalTrials.gov: NCT03151551) is a 52-week trial evaluating the efficacy and safety of IXE versus adalimumab (ADA), a TNFi, in bDMARD-naïve patients with active PsA and inadequate response to csDMARDs.…”

Biologic Treatments of Psoriasis: An Update for the Clinician

“…Ixekizumab was shown to be superior to placebo in the treatment of moderate‐to‐severe pediatric psoriasis, and the safety profile was generally consistent with that observed in adults. 29 …”