Background/Objectives: To evaluate the tolerability and effectiveness of subcutaneous immunotherapy (SCIT) with a glutaraldehyde-polymerized undiluted mixture of grass and olive pollen in adults and children with allergic respiratory disease in routine clinical practice. Methods: Observational, ambispective, controlled multicenter study including patients ≥ 5 years with allergic rhinitis/rhinoconjunctivitis +/− asthma due to olive and grass pollen. Patients initiating SCIT with Olea europaea/grass pollens undiluted mixtures were included in the O&G group, and those continuing symptomatic treatment in the untreated (UT) group. Safety (primary objective) was assessed as the incidence of adverse reactions. Effectiveness variables (symptoms, control, and medication use) were compared during the pollen season before and after AIT; patients and investigators reported perceived satisfaction. Results: We included 218 patients in the O&G group (children, 23.4%; adolescents, 13.8%; adults, 62.8%) with a mean (SD) age of 26.5 (15.6) years, and 94 in the UT group. At the time of evaluation, patients had received treatment for a mean (SD) of 10.6 (2.5) months. Seventeen patients (7.8%) experienced 18 adverse reactions in total, all local (12 in adults, 6 in children; mean overall rate: 0.8%). Rhinitis frequency shifted from predominantly persistent to intermittent (−64.6% in persistent) (p < 0.0001), with significantly improved intensity and control overall and across age groups in the O&G group but not in the UT group. Patients with asthma symptoms decreased by −46.6% (p < 0.0001), along with improved asthma classification, treatment steps, and control overall (O&G group), and across most age groups. Changes in conjunctivitis symptoms followed a similar trend. Symptomatic medication use significantly decreased overall (O&G group) and across specific age groups. Patients and investigators perceived decreased symptoms and medication use after AIT. Conclusions: SCIT with a glutaraldehyde-polymerized undiluted allergen mixture of olive/grass pollen extract demonstrated safety and effectiveness to treat allergic rhinitis and asthma in adults and children in a real-world setting.

Dupilumab has demonstrated efficacy in type 2 severe asthma in clinical trials. Real-world data, particularly from Spain and including patients with prior biologic failure, remains limited. This study evaluated the effectiveness and safety of dupilumab in a Spanish cohort with type 2 severe asthma over 12 months. Retrospective, multicenter observational study in adult and adolescent patients (≥12 years) with type 2 severe asthma treated with dupilumab for at least six months. Clinical data, including exacerbations, lung function (FEV₁), Asthma Control Test (ACT), quality of life (Mini-AQLQ), systemic corticosteroid use, and biomarkers (total IgE, eosinophil count, FeNO), were collected at baseline, 6, and 12 months. The EXACTO scale was used to assess response in non-oral corticosteroid (OCS)-dependent patients at 12 months. Subgroup analyses included chronic rhinosinusitis with nasal polyps (CRSwNP) and OCS-dependent patients at baseline. A total of 156 patients were included; 54.5% had received prior biologic therapies. Significant improvements (p<0.005) from baseline to 12 months were observed in exacerbations (1.43 to 0.20 per year), FEV₁ (2530.10 to 2824.59 mL), ACT (15.84 to 21.31), and Mini-AQLQ (27.24 to 74.27). Total IgE and FeNO significantly decreased whereas blood eosinophilia increased. In non-OCS-dependent patients (n=78), 56.4% were good or super-responders according to the EXACTO scale. CRSwNP patients (n=66) significantly improved in asthma and nasal symptoms. Among OCS-dependent patients (n=35), 68.6% discontinued OCS by 6 months. Comparable clinical improvements in exacerbation rates, lung function and overall response were observed in biologic-naïve and biologic-pretreated patients, consistent with similar EXACTO scores (4.92 ± 1.29 vs. 4.55 ± 1.37, respectively; p=0.166). No new safety signals were identified. This Spanish real-world study confirms sustained effectiveness and acceptable safety of dupilumab in type 2 severe asthma, including patients with prior biologic failure and comorbid CRSwNP, supporting its use in routine clinical practice.