Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Ann and Robert H. Lurie Children's Hospital, Chicago, IL, USA.
Am J Clin Dermatol. 2024 Jul;25(4):655-668. doi: 10.1007/s40257-024-00859-y. Epub 2024 May 14.
Pediatric patients with moderate-to-severe atopic dermatitis (AD) often experience a high disease burden and have a high risk of persistent disease. Standard-of-care immunosuppressive systemic treatments have been used off-label for AD in pediatric patients despite concerns for suboptimal safety with continuous use and risk of relapse upon discontinuation. The biologic agent dupilumab is the first systemic treatment approved for moderate-to-severe AD in children as young as 6 months. Long-term safety and efficacy data in this patient population are needed to inform continuous AD management.
The purpose of this work was to determine the long-term safety and efficacy of dupilumab treatment up to 1 year in an open-label extension (OLE) study [LIBERTY AD PED-OLE (NCT02612454)] in children aged 6 months to 5 years with moderate-to-severe AD who previously participated in the 16-week, double-blind, phase 3 LIBERTY AD PRESCHOOL trial (NCT03346434 part B; parent study) and were subsequently enrolled in PED-OLE.
In PED-OLE, patients received dupilumab every 4 weeks according to a weight-tiered regimen (body weight ≥ 5 kg to < 15 kg: 200 mg; ≥ 15 kg to < 30 kg: 300 mg).
Data for 142 patients were analyzed, 60 of whom had completed the 52-week visit at time of database lock. Mean age at baseline was 4.1 y [SD, 1.13; range, 1.0-5.9 years]. A majority (78.2%) of patients reported ≥ 1 treatment-emergent adverse event (TEAE), most of which were mild or moderate and transient. The most frequently reported TEAEs were nasopharyngitis (19.7%), cough (15.5%), and pyrexia (14.1%). One TEAE led to treatment discontinuation (severe urticaria, which resolved in 1 day). By week 52, 36.2% of patients had achieved an Investigator's Global Assessment score of 0/1 (clear/almost clear skin), and 96.6%, 79.3%, and 58.6% had at least 50%, 75%, or 90% improvement, respectively, in Eczema Area and Severity Index scores.
Consistent with results seen in adults, adolescents, and older children (aged 6-11 years), treatment with dupilumab for up to 1 year in children aged 6 months to 5 years with inadequately controlled moderate-to-severe AD demonstrated an acceptable long-term safety profile and sustained efficacy. These results support the long-term continuous use of dupilumab in this patient population.
ClinicalTrials.gov Identifiers: NCT02612454 and NCT03346434 (part B).
患有中重度特应性皮炎（AD）的儿科患者通常疾病负担较重，且疾病持续存在的风险较高。尽管连续使用标准治疗方案中的免疫抑制性全身治疗药物的安全性存在顾虑，且停药后存在复发风险，但这些药物仍被超适应证用于儿科患者的 AD 治疗。生物制剂度普利尤单抗是首个获批用于 6 个月及以上中重度 AD 儿童患者的全身性治疗药物。需要了解该患者人群的长期安全性和疗效数据，以指导 AD 的持续管理。
本研究旨在评估在一项开放标签扩展（OLE）研究[LIBERTY AD PED-OLE（NCT02612454）]中，度普利尤单抗治疗 6 个月至 5 岁中重度 AD 儿童患者长达 1 年的长期安全性和疗效，这些患者先前参与了为期 16 周、双盲、III 期 LIBERTY AD PRESCHOOL 试验（NCT03346434 部分 B；母研究），随后入组 PED-OLE。
在 PED-OLE 中，根据体重分层方案（体重≥5 kg 至＜15 kg：200 mg；≥15 kg 至＜30 kg：300 mg），每 4 周给予度普利尤单抗治疗。
对 142 例患者的数据进行了分析，截至数据库锁定时，其中 60 例患者完成了 52 周的访视。基线时的平均年龄为 4.1 岁[标准差（SD），1.13；范围，1.0-5.9 岁]。大多数（78.2%）患者报告了≥1 次治疗后出现的不良事件（TEAE），大多数为轻度或中度且为一过性的。最常报告的 TEAE 为鼻咽炎（19.7%）、咳嗽（15.5%）和发热（14.1%）。1 例 TEAE 导致治疗中止（严重荨麻疹，1 天内缓解）。在第 52 周时，36.2%的患者达到了研究者全球评估评分 0/1（皮肤完全或几乎完全清除），96.6%、79.3%和 58.6%的患者分别至少有 50%、75%和 90%的 Eczema Area and Severity Index 评分改善。
与成人、青少年和年龄较大的儿童（6-11 岁）的研究结果一致，在 6 个月至 5 岁中重度 AD 控制不佳的儿童中使用度普利尤单抗治疗长达 1 年，显示出可接受的长期安全性和持续疗效。这些结果支持该患者人群长期连续使用度普利尤单抗。
ClinicalTrials.gov 标识符：NCT02612454 和 NCT03346434（部分 B）。
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