dupilumab + mepolizumab + benralizumab

This is a combination of three monoclonal antibody biologics—dupilumab, mepolizumab, and benralizumab—each targeting different components of type 2 inflammation. Dupilumab is an anti-IL-4 receptor alpha antibody that inhibits signaling of both interleukin-4 (IL-4) and interleukin-13 (IL-13), key drivers in allergic and eosinophilic inflammation. Mepolizumab targets interleukin-5 (IL-5), reducing eosinophil production and survival. Benralizumab binds to the IL-5 receptor alpha on eosinophils, leading to their direct depletion via antibody-dependent cell-mediated cytotoxicity. These agents are individually approved for severe asthma with an eosinophilic phenotype and other type 2 inflammatory diseases; however, their combined use is not standard practice but has been reported in case studies for refractory or overlapping conditions such as severe asthma with comorbidities like chronic rhinosinusitis with nasal polyps or eosinophilic granulomatosis with polyangiitis[1][2][4]. The rationale for combining these drugs lies in targeting multiple pathways within type 2 inflammation when monotherapy fails.