Background Dupilumab, a fully human monocolonal antibody, blocks the shared receptor component for interleukin (IL) 4 and IL 13, key and central drivers of type 2 inflammation in multiple diseases. The efficacy and safety of dupilumab in asthma have been demonstrated up to 52 weeks in phase 2 and phase 3 studies. This open-label extension (OLE) study (NCT02134028) assessed long-term safety and efficacy of dupilumab in adult and adolescent patients who had completed a dupilumab asthma study (phase 2b DRI, phase 2 EXPEDITION, phase 3 QUEST, or phase 3 VENTURE). Methods Patients with moderate-to-severe or oral corticosteroid (OCS)-dependent severe asthma received add on subcutaneous dupilumab 300 mg every 2 weeks (q2w) up to 96 weeks. Treatment-emergent adverse events (TEAEs), annualized rate of severe asthma exacerbations (AER) during the treatment period, change from parent study baseline (PSBL) in forced expiratory volume in 1 second (FEV1), and biomarkers up to Week 96 were assessed. Results 2,282 patients were enrolled overall. Patient safety profile was consistent with the parent studies (Table). The low unadjusted AER and improvement in FEV1 observed in the parent studies were sustained during the OLE. Similar efficacy was seen in patients with elevated type 2 biomarkers from DRI/QUEST. By Week 96, blood eosinophils decreased to below-PSBL levels in patients from DRI/QUEST and were near-PSBL levels in patients from VENTURE; total IgE levels decreased by 82% (median percent change from PSBL). Conclusion Long-term use of dupilumab was well tolerated and showed sustained efficacy in asthma patients up to 96 weeks.