The Study On Efficacy And Safety Of Secukinumab Combined With Dupilumab Treating Pediatric Patients With Netherton Syndrome

Background:Netherton Syndrome(NS)is a rare disease,which is a hereditary ichthyosis.NS is caused by loss-of-function mutations in the gene SPINK5,which leads to the loss of LEKTI activity,making KLK5,KLK7,and KLK14 hyperactive after the loss of inhibition,promoting the rapid degradation of desmocollin,accelerating the decomposition and exfoliation of keratin,and ultimately leading to skin barrier defect and repeated skin inflammation.The disease is characterized by congenital erythroderma,hair abnormalities,and severe Psoriatic-like/atopic dermatitis-like lesions with atopic manifestations accompanied by growth retardation and increased susceptibility to infection.At present,there is no effective treatment for NS,topical drugs are not enough to achieve satisfy the curative efficacy,and there is the risk of drug overabsorption.Systemic use of tretinoin and immunosuppressive agents cannot bring obvious and lasting curative effect.Currently,biological agents alone have not achieved satisfactory results in the treatment of NS.NS has atopic manifestations,while IL-36 and IL-23/Th17 immune signaling axes are common in psoriasis and NS.Based on the idea that NS is a mixed inflammation of type Ⅱ and IL-17A,It is expected that the combination of IL-17A antagonist(secuchiumab)and IL-4R antagonist(Dupriliumab)targeting type Ⅱ inflammation will bring benefits.Therefore,we designed a treatment plan of " The study on efficacy and safety of secukinumab combined with dupilumab treating pediatric patients with Netherton syndrome".Objectives:(1)To summarize the clinical characteristics of NS pediatric patients in China;(2)To evaluate the efficacy and safety of the treatment.Methods:This is an open-label,single-arm clinical study(ChiCTR2200065139)in which investigators collected clinical data and summarized their clinical characteristics in NS pediatric patients who met the enrollment criteria.The patients were treated according to protocol and followed for 24 weeks.During the study,investigators performed efficacy and safety observations in NS pediatric patients.Results:The main clinical manifestations of NS pediatric patients were congenital erythroderma,pruritic eczematous-like rash and/or erythematous plaque surrounded by a double-edged scale,bamboo hair,growth-faltering and atopic manifestations.The results of the treatment study showed that after 24 weeks of treatment with secukinumab combined with dupilumab in NS pediatric patients,the mean percentage changes of IASI score in 7 patient was 71.94%s from baseline;The average level of pruritus decreased from 7.49 points to 2.5 points.50%of the patients had a decrease in IGA of 3 points or more.At the same time,the height and weight gap between the patient and the same age children was significantly reduced.Conclusions:Treatment of NS pediatric patients with secukinumab combined with dupilumab can quickly and safely control clinical symptoms and itch.