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Background: An important subpopulation in allergic rhinitis is represented by patients with severe form of disease that is not responsive to drug treatment. It has been reported that grass pollen subcutaneous immunotherapy is effective in drug-resistant patients. In a real-life study, we evaluated the efficacy of 5-grass pollen tablets in patients with grass pollen-induced allergic rhinitis not responsive to drug therapy. Methods: We carried out this multicenter observational study in adults and adolescents with grass-induced allergic rhinitis not responsive to drug therapy who were treated for a year with 5-grass pollen tablets. Clinical data collected before and after sublingual immunotherapy (SLIT) included Allergic Rhinitis and its Impact on Asthma (ARIA) classification of allergic rhinitis, response to therapy, and patient satisfaction. Results: Forty-seven patients entered the study. By ARIA classification, three patients had moderate to severe intermittent allergic rhinitis, ten had mild persistent allergic rhinitis, and 34 had moderate to severe persistent allergic rhinitis. There were no cases of mild intermittent allergic rhinitis before SLIT. After SLIT, 33 patients had mild intermittent allergic rhinitis, none had moderate to severe intermittent allergic rhinitis, seven had mild persistent allergic rhinitis, and seven had moderate to severe persistent allergic rhinitis. The mean medication score decreased from 4.2±1.3 before to 2.4±2.0 after SLIT (P<0.01), representing a reduction of 42%. The response to treatment before SLIT was judged as poor by 70% of patients and very poor by 30%. Patient satisfaction was significantly increased after SLIT (P<0.01). Conclusion: In real life, most patients with grass pollen-induced allergic rhinitis not responsive to drug treatment can achieve control of the condition with one season of treatment using 5-grass pollen tablets. [ABSTRACT FROM AUTHOR]