Several therapeutic strategies have been established to achieve maximal remission and improve quality of life in patients with chronic spontaneous urticaria. We previously reported dupilumab as a novel therapy for antihistamine-refractory chronic spontaneous urticaria patients who failed to respond to administration of omalizumab at increased doses for longer durations. This is the first case series to report data on the long-term duration of chronic spontaneous urticaria remission after discontinuation of dupilumab in patients who were able to obtain controlled chronic spontaneous urticaria. Six patients diagnosed with chronic spontaneous urticaria, who failed to respond to antihistamines and prolonged therapy with omalizumab at increased doses, were followed in this study for up to 34 months following initiation of dupilumab therapy. By demonstrating the maintenance of chronic spontaneous urticaria remission with dupilumab following discontinuation of therapy, in 67% of the patients, over an observation period up to 22 months, this case series highlights dupilumab's potential disease-modifying efficacy in patients affected by this disease.