Evaluation of Rapid Onset of Action of ICS/LABA Combination Therapies on Respiratory Function in Asthma Patients: A Single-Center, Open-Label, Randomized, Crossover Trial

Abstract

Introduction: Products based on inhaled corticosteroid (ICS)/long-acting b2 agonist (LABA) combinations may provide different clinical benefits. This study was conducted to compare the rapid effects of three such combination products: formoterol/fluticasone (FFC) aerosol (pMDI), formoterol/budesonide (FBC) dry powder inhaler (DPI), and vilanterol/fluticasone furoate (VFC) DPI. Methods: The study design was a three-armed, randomized, crossover study. Patients included in the study had stable moderate asthma, defined as an Asthma Control Questionnaire (ACQ) score B 0.75, and were undergoing step 2 or 3 asthma treatment as defined by JGL2015. Subjects were treated with fluticasone propionate inhaled via Diskus Ò during a 2-week washout period before randomization. At visit 2, subjects were randomly assigned in a 1:1:1 ratio to FFC, FBC, or VFC, and evaluated for changes in pulmonary function over time. At visits 3 and 4, the treatment was switched to another ICS/LABA combination in a crossover manner after a 1-week washout period. Spirometry was performed pre-dose and at 3, 10, and 30 min post-dose, and forced oscillation was implemented pre-dose and at 1, 7, 15, and 60 min post-dose. Results: Fifteen outpatients (63.3 ± 9.5 years, ACQ: 0.13 ± 0.19) completed the study. DFEV 1 at 3 min did not significantly differ among the three groups. Significant increases in FEV 1 and %FEV 1 from baseline were observed in the FFC (p = 0.004, 0.003), FBC (p = 0.014, 0.011), and VFC (p = 0.032, 0.023) groups at 30 min. Improvements in respiratory resistance at 5-20 Hz from baseline at 60 min, resonant frequency, respiratory system reactance at 5 Hz, and low-frequency reactance area from baseline were observed at 1 min in the FFC group (p = 0.014, 0.002, 0.027, 0.018, respectively). Conclusion: FFC administered using a pMDI showed favorable delivery to peripheral airways and significantly more rapid action promptly after inhalation as compared with other ICS/

An innovative corticosteroid/long-acting β2-agonist breath-triggered inhaler: facilitating lung delivery of fluticasone propionate/formoterol fumarate for the treatment of asthma

“…Consistent with the notion that FP/FORM acts throughout the airways, objective improvements in small airway ventilation heterogeneity (measured using multiple-breath nitrogen washout) have been demonstrated with FP/FORM in patients with normal spirometry characteristics but poor asthma control [30]. Delivery of FP/FORM to the peripheral airways by pMDI and the rapid onset of action after inhalation were also shown to be favorable compared with other ICS/LABA formulations delivered by DPIs [38]. The importance of small airways is increasingly recognized in the control of patients with asthma [40] 2.2.…”

“…An extensive clinical dataset exists for FP/FORM administered via a pMDI (Table 2) [29][30][31][32][33][34][35][36][37][38]. Furthermore, long-term data from two clinical studies have demonstrated good efficacy, safety, and tolerability with this ICS/LABA combination, including a low rate of exacerbations, over study periods of up to 60 weeks [33,35].…”

Comparison of User Satisfaction and Preference with Inhalant Devices Between a Pressurized Metered-Dose Inhaler and Ellipta in Stable Asthma Patients: A Randomized, Crossover Study

“…Moreover, unless the patient uses the device for a certain minimum period and has an opportunity to use another comparable device, the patient will have no basis on which to judge satisfaction or preference with regard to the device used. Different devices also exhibit different patterns of lung deposition, which may significantly affect clinical potency for lung function and individual clinical effects [ 5 , 6 ]. In this study, patient satisfaction and preference were investigated for two of the latest asthma inhalation therapy drugs in Japan: a combination of vilanterol and fluticasone delivered with an Ellipta dry powder inhaler device (VFC Ellipta), and a combination of formoterol and fluticasone delivered with a pressurized metered-dose inhaler device (FFC pMDI).…”

Key points in effective inhaler technique training for asthma and COPD patients

“…Different devices exhibit different patterns of lung deposition, which may considerably affect the individual clinical effects [8,9]. Our recent study suggested that different devices for inhaled corticosteroid and long-acting beta agonist (ICS/LABA) combination therapy showed different clinical potency for lung functions [10]. Incorrect usage of inhaler devices may cause insuffi cient drug delivery and hence insuffi cient lung deposition, thereby leading to poor clinical control and worsened adherence of the patient with asthma and COPD.…”