Eshtiaghi Panteha, Gooderham Melinda J
Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
SKiN Centre for Dermatology, Peterborough, ON, Canada.
Core Evid. 2018 Feb 23;13:13-20. doi: 10.2147/CE.S133661. eCollection 2018.
Atopic dermatitis (AD) is a recurrent, pruritic inflammatory skin disease with complex immunopathogenesis characterized by a dominant T2 response. Dupilumab is an interleukin (IL)-4 receptor alpha antagonist that subsequently blocks IL-4 and IL-13 signaling. It has recently been approved for the treatment of adult patients with moderate-to-severe AD whose current treatment options are limited.
This article reviews the evidence of clinical efficacy, safety, and patient-reported out-come (PRO) measures from Phase I-III trials of dupilumab in adult patients with moderate-to-severe AD.
Results from clinical trials of dupilumab in adults with moderate-to-severe AD have shown that weekly or biweekly dupilumab injections significantly improve clinical and PROs. Transcriptome and serum analyses also found that dupilumab significantly modulates the AD molecular signature and other T2-associated biomarkers, compared with placebo. Additionally, concomitant use of dupilumab with topical corticosteroids (TCS) results in a greater improvement in signs and symptoms of AD than with dupilumab use alone. Throughout the trials, common adverse events were headaches, conjunctivitis, and injection site reactions. These were consistently mild-moderate and occurred with similar frequency between the treatment and placebo groups.
In adult patients with moderate-to-severe refractory AD, monotherapy or concomitant use of dupilumab with TCS holds great promise to significantly improve clinical outcomes and quality of life of the patient. Ongoing studies of dupilumab will help determine the clinical efficacy and safety profile of its long-term use. Finally, further economic evidence is warranted to compare the long-term costs and benefits of dupilumab with other currently available treatments for moderate-to-severe AD.
特应性皮炎（AD）是一种复发性、瘙痒性炎症性皮肤病，免疫发病机制复杂，以T2反应占主导为特征。度普利尤单抗是一种白细胞介素（IL）-4受体α拮抗剂，随后可阻断IL-4和IL-13信号传导。它最近已被批准用于治疗目前治疗选择有限的中度至重度AD成年患者。
本文回顾了度普利尤单抗治疗中度至重度AD成年患者的I-III期试验的临床疗效、安全性及患者报告结局（PRO）指标的证据。
度普利尤单抗治疗中度至重度AD成年患者的临床试验结果表明，每周或每两周注射度普利尤单抗可显著改善临床症状和PRO。转录组和血清分析还发现，与安慰剂相比，度普利尤单抗可显著调节AD分子特征及其他T2相关生物标志物。此外，度普利尤单抗与外用糖皮质激素（TCS）联合使用比单独使用度普利尤单抗能更显著改善AD的体征和症状。在整个试验中，常见的不良事件为头痛、结膜炎和注射部位反应。这些不良事件一直为轻至中度，在治疗组和安慰剂组中的发生频率相似。
在中度至重度难治性AD成年患者中，度普利尤单抗单药治疗或与TCS联合使用有望显著改善患者的临床结局和生活质量。度普利尤单抗正在进行的研究将有助于确定其长期使用的临床疗效和安全性。最后，需要进一步的经济学证据来比较度普利尤单抗与其他目前可用的中度至重度AD治疗方法的长期成本和效益。
