Efficacy and safety of ixekizumab in a phaseIII, randomized, double-blind, placebo-controlled study in paediatric patients with moderate-to-severe plaque psoriasis (IXORA-PEDS)

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, phaseIIIstudy (IXORA-PEDS), patients aged 6 to < 18 years with moderate-to-severe plaque psoriasis were randomized 2 : 1 to weight-based dosing ofIXEevery 4 weeks (IXEQ4W,n= 115) or placebo (n= 56) through week 12, followed by open-labelIXEQ4W. Coprimary endpoints were the proportions of patients at week 12 achieving >= 75% improvement in Psoriasis Area and Severity Index (PASI75) and those achieving a static Physician's Global Assessment score of 0 or 1 (sPGA0,1). Results IXEwas superior (P< 0 center dot 001) to placebo for both coprimary endpoints ofPASI75 (IXEQ4W, 89%; placebo, 25%) andsPGA(0,1) (IXEQ4W, 81%; placebo, 11%).IXEwas also superior for all gated secondary endpoints, includingPASI75 andsPGA(0,1) at week 4, improvement in itch, and complete skin clearance.IXEQ4W provided significant (P< 0 center dot 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 IXEwas 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.