BACKGROUND: Dupilumab is an IL-4Rα antibody approved for treatment of severe asthma. Real-world data on the continuation and cessation patterns of dupilumab and long-term treatment efficacy are scarce. OBJECTIVE: We sought to analyze real-world, long-term treatment outcomes and to evaluate trajectories of patients continuing or discontinuing dupilumab therapy over a 3-year period. METHODS: This multicenter, retrospective, real-world cohort study included patients with severe asthma who started dupilumab before March 2021. Data on asthma control, medication, lung function, and annualized exacerbation rates were collected at baseline and 3, 12, and 36 months after initiation of dupilumab therapy. Asthma remission was assessed at 12 months and 36 months after dupilumab initiation. RESULTS: Of 160 included patients, 95 patients (59%) continued dupilumab therapy for 36 months; 65 patients (41%) discontinued therapy after a median time of therapy of 8 months. Patients who continued dupilumab for 36 months had significant reductions in annual exacerbations (-1; P < .0001) and oral corticosteroid dose (-5.5 mg/day; P < .001) as well as significant improvements in asthma control (asthma control test +5; P < .0001) and lung function (percent predicted of FEV1 +7%; P < .001) compared with baseline. Of patients who continued dupilumab, 30% achieved remission at 12 months, and 26% achieved remission at 36 months. Of the 65 patients who discontinued therapy, 55 switched to another antibody, and 10 did not receive further antibody treatment. CONCLUSIONS: Dupilumab represents an effective long-term treatment option for patients with severe asthma, with sustained treatment effects up to 36 months. Importantly, a relevant proportion of patients achieved remission in this pretreated population.