Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Saint Louis University and Cardinal Glennon Children's Hospital, St. Louis, MO, USA.
J Eur Acad Dermatol Venereol. 2021 Feb;35(2):464-475. doi: 10.1111/jdv.16928. Epub 2020 Nov 8.
Dupilumab has demonstrated efficacy and acceptable safety in adults and children (aged 6-17 years) with moderate-to-severe atopic dermatitis (AD), but effective systemic therapy with a favorable risk-benefit profile in younger children remains a significant unmet need.
To determine the pharmacokinetics, safety and efficacy of single-dose dupilumab in children with severe AD aged ≥6 months to <6 years.
This open-label, multicenter, phase 2, sequential, two-age cohort, two-dose level study (LIBERTY AD PRE-SCHOOL; NCT03346434) included an initial cohort of older children aged ≥2 to <6 years, followed by a younger cohort aged ≥6 months to <2 years. Pharmacokinetic sampling, safety monitoring and efficacy assessments were performed during the 4-week period after a single subcutaneous injection of dupilumab, in two sequential dosing groups (3 mg/kg, then 6 mg/kg). The use of standardized, low-to-medium potency topical corticosteroids was allowed.
Forty patients were enrolled (20/age cohort, 10/dose level within a cohort) between December 20, 2017 and July 22, 2019. Within each age cohort, pharmacokinetic exposures after a single injection of dupilumab increased in a greater than dose-proportional manner. At week 3, treatment with 3 and 6 mg/kg dupilumab reduced scores of mean Eczema Area and Severity Index by -44.6% and -49.7% (older cohort) and -42.7% and -38.8% (younger cohort), and mean Peak Pruritus NRS scores by -22.9% and -44.7% (older cohort) and -11.1% and -18.2% (younger cohort), respectively. At week 4, improvements in most efficacy outcomes diminished in both age groups, particularly with the lower dose. The safety profile was comparable to that seen in adults, adolescents and children.
Single-dose dupilumab was generally well tolerated and substantially reduced clinical signs/symptoms of AD. Slightly better responses were seen in older than younger children. The pharmacokinetics of dupilumab were non-linear, consistent with previous studies in adults and adolescents.
度普利尤单抗在中重度特应性皮炎（AD）的成人和儿童（6-17 岁）中显示出疗效和可接受的安全性，但在年龄较小的儿童中，仍存在有效的全身治疗方法和有利的风险效益比，这是一个重大的未满足需求。
确定单剂量度普利尤单抗在 6 个月至<6 岁重度 AD 儿童中的药代动力学、安全性和疗效。
这项开放标签、多中心、2 期、序贯、两年龄队列、两剂量水平研究（LIBERTY AD PRE-SCHOOL；NCT03346434）包括一个年龄较大的队列（≥2 至<6 岁），然后是一个年龄较小的队列（≥6 个月至<2 岁）。在单次皮下注射度普利尤单抗后 4 周内进行药代动力学采样、安全性监测和疗效评估，在两个连续剂量组（3mg/kg，然后 6mg/kg）中进行。允许使用标准化的中低效外用皮质类固醇。
2017 年 12 月 20 日至 2019 年 7 月 22 日期间，共招募了 40 名患者（每个年龄队列 20 名，每个队列内 10 名/剂量水平）。在每个年龄队列中，单次注射度普利尤单抗后的药代动力学暴露呈剂量依赖性增加。在第 3 周，3mg/kg 和 6mg/kg 度普利尤单抗治疗分别使平均湿疹面积和严重程度指数评分降低了-44.6%和-49.7%（年龄较大的队列）和-42.7%和-38.8%（年龄较小的队列），平均 Peak Pruritus NRS 评分降低了-22.9%和-44.7%（年龄较大的队列）和-11.1%和-18.2%（年龄较小的队列）。在第 4 周，两个年龄组的大多数疗效指标的改善均减弱，特别是低剂量组。安全性与成人、青少年和儿童中的安全性一致。
单剂量度普利尤单抗总体耐受性良好，可显著减轻 AD 的临床体征/症状。年龄较大的儿童比年龄较小的儿童反应略好。度普利尤单抗的药代动力学是非线性的，与之前在成人和青少年中的研究一致。
