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Background: Although there are many studies presenting the efficacy of omalizumab in severe asthma, the data about the optimal treatment duration are still debated. Objective: In this study, we aimed to investigate the clinical effects of omalizumab discontinuation after 5 years of treatment in patients with omalizumab super-responders, the persistence of response and to compare the features of patients, whose symptoms are still well controlled and those who relapsed and re-treated with omalizumab. Methods: Clinical and laboratory data of 100 adult patients diagnosed with allergic severe asthma and treated with omalizumab between 2008 and 2020 were evaluated retrospectively. Demographic, clinical, functional, and laboratory parameters of the patients who were re-treated with omalizumab and those who did not need to be re-treated were compared. Results: There were 14 super-responder patients, who were treated with omalizumab for 5 years, and the treatment was discontinued then. Omalizumab was not restarted in 9 patients (64%) and was restarted in 5 (36%) patients. No significant difference was presented between these two groups in terms of demographic, clinical, functional, and laboratory parameters. The baseline total IgE levels of patients, who were re-treated with omalizumab, was found to be higher than those who were not, but this difference was not statistically significant (440 [229–864] IU/mL vs. 164 [85–293] IU/mL; p = 0.053, respectively). Conclusion: One of 3 patients was re-treated with omalizumab due to loss of asthma control after discontinuation of the treatment. Therefore, omalizumab's immunomodulatory effect may seem to persist in a majority of cases after discontinuation. Also, higher baseline total IgE levels might help to predict the cases that need re-treatment after discontinuation. [ABSTRACT FROM AUTHOR]