Exploring Dupilumab for Asthma: From Mechanistic Insights to Clinical Outcomes, Safety and Cost-Effectiveness

Omar Z Ameer^1*Ghaith K Mansour¹Raghad S Al-Amoudi¹Fahmi M Abu-Owaimer²

• ¹College of Pharmacy, Alfaisal University, Riyadh, Saudi Arabia
• ²College of Medicine, Alfaisal University, Riyadh, Saudi Arabia

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, key cytokines driving T2 inflammation.This review examines the formulation, pharmacologic profile, clinical efficacy, safety, and costeffectiveness of dupilumab in the treatment of asthma, with 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 supporting biweekly subcutaneous (SC) administration. Clinical trials have demonstrated significant reductions in asthma exacerbation rates, improvements in forced expiratory volume in one second (FEV₁), and decreased oral corticosteroid (OCS) dependence in adults and children with moderate-to-severe asthma. Benefits are particularly robust in patients with elevated eosinophils or fractional exhaled nitric oxide (FeNO), though 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 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 was found to be cost-effective in Japan when compared to other biologics such as benralizumab and mepolizumab for asthma treatment. In countries like South Korea and the United Kingdom, dupilumab has also shown cost-effectiveness, particularly among patients with frequent exacerbations or chronic oral corticosteroid (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 highrisk populations. In summary, dupilumab provides a targeted and generally well-tolerated treatment option for severe asthma. It is approved as add-on maintenance therapy for patients aged ≥6 years with moderate-to-severe asthma, particularly those with type 2 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.