RESUMEN
BACKGROUND: The therapeutic effectiveness of dupilumab for severe asthma in real-world settings is yet to be prospectively investigated across multiple institutions, and uncertainties persist regarding predictive factors for its effectiveness. We aimed to assess the effectiveness of dupilumab and identify predictors of its effectiveness in real-world settings using two type-2 biomarkers: FeNO concentration and blood eosinophil count. METHODS: This prospective multicenter study included 103 patients with severe asthma. Exacerbations and respiratory functions were monitored for 24 weeks. Asthma control was evaluated using the Asthma Control Questionnaire-5. Clinical symptoms and their impact on cough and sputum were assessed using the Cough and Sputum Assessment Questionnaire (CASA-Q). Subgroup analyses of type-2 biomarkers were conducted based on FeNO levels and blood eosinophil counts at baseline. RESULTS: Treatment with dupilumab led to a reduction in exacerbations and enhancement in asthma control, FEV1, and CASA-Q scores. FEV1 improvement was correlated with enhancement in the sputum domain of the CASA-Q. Patients exhibiting elevated FeNO levels and blood eosinophil counts demonstrated more significant enhancements in FEV1. CASA-Q sputum domain scores were significantly higher in the group with elevated eosinophil counts. Regression analysis revealed that FeNO levels and blood eosinophil counts are significant predictors of FEV1 improvement, with blood eosinophil counts also predicting sputum improvement in patients treated with dupilumab. CONCLUSIONS: Type-2 biomarkers may act as indicators of improvement in FEV1 and sputum outcomes among patients with severe asthma undergoing dupilumab treatment in real-world settings.
RESUMEN
BACKGROUND: Indacaterol is a novel, inhaled once-daily ultra-long-acting beta-2 agonist under development as a fixed-dose combination with an inhaled corticosteroid (ICS) for asthma treatment. This study evaluated the 24-h bronchodilator efficacy of indacaterol in Japanese patients with asthma. METHODS: Randomised, placebo-controlled, 5-period crossover study. Patients with persistent asthma (18-75 years, FEV(1) 50-85% predicted, ≥12% and 200 mL FEV(1) reversibility) receiving ICS were randomised to double-blind single dose indacaterol 150, 300, or 600 µg or placebo, with open-label salmeterol 50 µg twice-daily for one day in the 5(th) period. Primary endpoint was FEV(1)AUC(22-24h). RESULTS: Of 41 randomised patients (48.8% male; mean age: 47.8 years), 39 completed. All indacaterol doses showed significantly higher FEV(1)AUC(22-24h) than placebo (P<0.001), with treatment-placebo differences of 180, 220, and 260 mL for indacaterol 150, 300, and 600 µg, respectively (salmeterol-placebo difference 170 mL; P < 0.001). For individual time-point FEV(1), all indacaterol doses were superior to placebo from 5 min to 24h post-dose (P < 0.001). Compared with salmeterol, all indacaterol doses were superior from 5 to 30 min (P < 0.05); in addition indacaterol 300 µg and 600 µg were superior at a number of subsequent time points. Changes in safety parameters with indacaterol were similar to placebo. All indacaterol doses were well tolerated. CONCLUSION: Single dose indacaterol provided sustained 24-h bronchodilation with a faster onset of action than salmeterol and a good overall safety and tolerability profile in Japanese patients with asthma. These results are consistent with data from Caucasian populations.