Ameer Omar Z, Mansour Ghaith K, Al-Amoudi Raghad S, Abu-Owaimer Fahmi M
Department of Pharmaceutical Sciences, College of Pharmacy, Alfaisal University, Riyadh, Saudi Arabia.
Department of Physiology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
Front Pharmacol. 2025 Aug 6;16:1631321. doi: 10.3389/fphar.2025.1631321. eCollection 2025.
Type 2 (T2) inflammation underlies a substantial subset of moderate-to-severe asthma, contributing to persistent symptoms and frequent exacerbations. Dupilumab, a fully human immunoglobulin G subclass 4 (IgG4) monoclonal antibody, targets the interleukin-4 receptor alpha (IL-4Rα), thereby inhibiting both interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling-which are key cytokines driving T2 inflammation. This review examines the formulation, pharmacological profile, clinical efficacy, safety, and cost-effectiveness of dupilumab in the treatment of asthma, with an emphasis on its role across T2-high and selected T2-low phenotypes. Dupilumab displays nonlinear pharmacokinetics, with approximately 61% bioavailability and a prolonged half-life that supports biweekly subcutaneous (SC) administration. Clinical trials have demonstrated significant reductions in asthma exacerbation rates, improvements in forced expiratory volume in one second (FEV), and decreased oral corticosteroid (OCS) dependence in adults and children with moderate-to-severe asthma. The benefits are particularly robust in patients with elevated eosinophil counts or fractional exhaled nitric oxide (FeNO), although efficacy extends to some patients with T2-low profiles. Reported safety data show a favorable profile, with mild adverse events, such as injection-site reactions and nasopharyngitis, being the most common. Nonclinical studies using surrogate antibodies in animal models revealed no evidence of systemic toxicity, reproductive harm, or carcinogenicity, reinforcing the drug's high therapeutic index. From a pharmacoeconomic perspective, dupilumab has been found to be cost-effective in Japan compared to other biologics such as benralizumab and mepolizumab for asthma treatment. It has also shown cost-effectiveness in countries such as South Korea and the United Kingdom, particularly among patients with frequent exacerbations or chronic OCS use. However, in settings such as the United States and Colombia, high drug acquisition costs limit its cost-effectiveness unless its use is restricted to high-risk populations. In summary, dupilumab provides a targeted and generally well-tolerated treatment option for severe asthma. It is approved as an add-on maintenance therapy for patients aged ≥6 years with moderate-to-severe asthma, particularly those with T2 inflammation. By maximizing clinical and economic benefits through precision-guided patient selection, dupilumab's dual IL-4/IL-13 blockade makes it a versatile biologic-especially suited for T2-high and overlapping asthma phenotypes or patients with comorbidities such as nasal polyps, eosinophilic esophagitis, and atopic dermatitis.
2型（T2）炎症是中度至重度哮喘相当一部分病例的发病基础，导致症状持续和频繁发作。度普利尤单抗是一种全人源免疫球蛋白G4（IgG4）单克隆抗体，靶向白细胞介素-4受体α（IL-4Rα），从而抑制白细胞介素-4（IL-4）和白细胞介素-13（IL-13）信号传导，这两种细胞因子是驱动T2炎症的关键细胞因子。本综述探讨了度普利尤单抗治疗哮喘的制剂、药理学特征、临床疗效、安全性和成本效益，重点关注其在T2高表型和部分T2低表型中的作用。度普利尤单抗呈现非线性药代动力学，生物利用度约为61%，半衰期延长，支持每两周皮下注射给药。临床试验表明，中度至重度哮喘的成人和儿童使用度普利尤单抗后，哮喘发作率显著降低，一秒用力呼气容积（FEV）改善，口服糖皮质激素（OCS）依赖减少。对于嗜酸性粒细胞计数或呼出一氧化氮分数（FeNO）升高的患者，益处尤为显著，尽管疗效也扩展到一些T2低表型的患者。报告的安全性数据显示情况良好，最常见的是轻度不良事件，如注射部位反应和鼻咽炎。在动物模型中使用替代抗体进行的非临床研究未发现全身毒性、生殖损害或致癌性的证据，这进一步证明了该药物的高治疗指数。从药物经济学角度来看，与其他治疗哮喘的生物制剂如贝那利珠单抗和美泊利珠单抗相比，度普利尤单抗在日本已被证明具有成本效益。在韩国和英国等国家也显示出成本效益，特别是在频繁发作或长期使用OCS的患者中。然而，在美国和哥伦比亚等地区，高昂的药物采购成本限制了其成本效益，除非将其使用限制在高风险人群中。总之，度普利尤单抗为重度哮喘提供了一种有针对性且耐受性普遍良好的治疗选择。它被批准作为≥6岁中度至重度哮喘患者，特别是那些有T2炎症患者的附加维持治疗药物。通过精准指导患者选择，最大化临床和经济效益，度普利尤单抗对IL-4/IL-13的双重阻断使其成为一种多功能生物制剂，尤其适用于T2高型和重叠性哮喘表型或伴有鼻息肉、嗜酸性粒细胞性食管炎和特应性皮炎等合并症的患者。
