Initiation of maintenance treatment with salmeterol/fluticasone propionate 50/100μg bd versus fluticasone propionate 100μg bd alone in patients with persistent asthma: Integrated analysis of four randomised trials (original) (raw)
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Respiratory Medicine, 2006
Objectives: This multicentre, parallel group, double-blind, double-dummy, randomised 24-week study was designed to compare the efficacy of salmeterol/fluticasone propionate combination (SFC) 50/250 mg one inhalation twice daily (bid) with formoterol/budesonide combination (FBC) 6/200 mg two inhalations bid in patients with persistent asthma, currently receiving 1000-2000 mg/day of inhaled corticosteroids. Methods: The intent-to-treat population comprised 694 patients in the SFC group and 697 patients in the FBC group. Results: The primary endpoint, mean rate of all exacerbations over 24 weeks, was similar in both treatment groups (SFC: 2.69; FBC: 2.79; SFC/FBC ratio 0.96; 95% CL 0.84, 1.10; P ¼ 0:571). A reduction in the rate of exacerbations over time was observed in both treatment groups. Overall, there was a 30% lower annual rate of moderate/severe exacerbations in the SFC group compared with the FBC group (95% CI 0-49%, 52% reduction vs. 1% increase; P ¼ 0:059). This effect increased with time: in weeks 17-24 the moderate/severe exacerbation rate was 57% lower in the SFC group compared with the FBC group (95% CI 21-77% reduction; P ¼ 0:006). Similar improvements in lung function, asthma symptoms and rescue medication usage were seen with both treatments and both were well tolerated. Conclusions: Twice-daily treatment with SFC and FBC over 6 months significantly improved asthma symptoms and lung function in patients with persistent asthma. The rate of exacerbations was significantly reduced over time on both treatments ARTICLE IN PRESS (R. Dahl). but SFC was found to be significantly superior to FBC in reducing the rate of moderate/severe exacerbations with sustained treatment.
Respiratory Medicine, 2010
Background: The role of combination ICS/LABA as initial controller therapy in mild, persistent asthma is uncertain. Therefore, the objective of this study was to compare the efficacy of initial controller therapy with fluticasone propionate (FP) 100 mg twice daily to the efficacy of fluticasone propionate/salmeterol xinafoate (FSC) 100/50 mg twice daily in patients with persistent asthma symptoms while using as-needed SABA alone. Methods: This randomized, double-blind, parallel-group study was conducted at 45 general practice and 15 specialist centers. A total of 526 adult patients were randomized to receive FP or FSC for 24 weeks. The primary efficacy endpoint was change in morning peak expiratory flow (PEF) from baseline. Secondary efficacy endpoints included symptom-and rescue-free days; asthma exacerbation rate; asthma-related health-care utilization; and the onset of effect. Safety was assessed by monitoring adverse events. Results: Mean morning PEF was significantly greater in the FSC versus the FP group (P < 0.001); this greater effect was evident as early as the first week of treatment (P < 0.001). The percentages of symptom-free days and rescue-free days in the FSC group were 7.7% (P Z 0.009) and 8.4% (P Z 0.001) higher than the FP group, respectively. Trends toward lower exacerbation-related health care-utilization for FSC versus FP were not statistically significant and exacerbation rates were not significantly different. The incidence of adverse events was low with both treatments. a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / r m e d Respiratory Medicine (2010) 104, 510e517
Journal of Asthma, 2021
Objective: Treatment with fluticasone furoate/vilanterol (FF/VI), an inhaled corticosteroid/ long-acting β 2-agonist therapy, reduces the risk of severe asthma exacerbations and improves lung function and symptom control in patients with asthma. However, real-world data remain limited among asthma patients in the United States (US). Methods: This retrospective cohort study propensity score (PS) matched adult asthma patients initiating once-daily FF/VI 100/25 mcg with patients initiating twice-daily budesonide/ formoterol (B/F) 160/4.5 mcg using a US claims database (January 1, 2015-December 31, 2018). Asthma control was measured by the mean number of short-acting β 2-agonist (SABA) canisters dispensed per patient-year (PPY) during follow-up. Time to first, and rates of, overall and severe asthma exacerbations were also measured. Results: After PS matching, 18,531 patients receiving FF/VI were matched to 18,531 patients receiving B/F. Mean SABA canisters dispensed PPY was significantly lower for FF/VI users compared with B/F users (FF/VI: 1.47, B/F: 1.64; p < 0.001). FF/VI use resulted in 13% significantly lower risk of having an overall asthma-related exacerbation and 22% lower risk of a severe exacerbation versus B/F use (overall exacerbation hazard ratio [HR] [95% confidence interval (CI)]: 0.87 [0.82-0.92], p < 0.001; severe exacerbation HR [95% CI]: 0.78 [0.63-0.97], p = 0.027). Asthma-related exacerbation rates per 100 patient-days were also significantly lower for the FF/VI group compared with the B/F group (overall: 0.0475 vs. 0.0558, p < 0.001; severe: 0.0026 vs. 0.0033, p = 0.020). Conclusions: In real-world practice, initiation of once-daily FF/VI 100/25 mcg in adults with asthma was associated with lower use of SABA and fewer asthma-related exacerbations, which may indicate better asthma control, when compared with use of twice-daily B/F 160/4.5 mcg.
Annals of Allergy, Asthma & Immunology, 1999
Inhaled corticosteroids are the most effective therapy available today for children and adults with chronic asthma. There have been relatively few studies comparing inhaled steroids in children. In a 2-year crossover study, we compared the efficacy of inhaled fluticasone propionate (FP), 880 /tig/d (2 puffs of 220 /tig per puff) administered twice daily, with that of triamcinolone acetonide (TA), 900 /xg/d (3 puffs of 100 fig per puff administered 3 times a day). Nine children with moderate persistent asthma, with a mean age of 13 years (range, 10-18 years) and a mean duration of asthma of 8 years, initially received TA, 900 fig/d, for 1 year and then were switched to FP, 880 /¿g/d, and followed for an additional year. Pulmonary function tests (PFTs) were monitored and analyzed before and after the switch for the duration of the study. Mean percentages of those predicted for age values for forced expiratory volume in 1 second (FEVi), forced expiratory flow between 25 and 75% of vital capacity (FEF25_75%), and peak expiratory flow rate (PEFR) were compared at 1-month, 2 to 6-month, and 7 to 12-month intervals. The number of asthma exacerbations, emergency room visits, hospital admissions, and school days lost were also compared. There was significant improvement in mean asthma exacerbations per patient per year while patients were receiving FP (4.88 ± 2.93 SD vs. 2.33 ± 2.06 SD; p < 0.05). There was a trend towards improvement in the number of emergency room visits, hospital admissions, and school days lost while patients were on FP, but the difference was not significant. A significant improvement in mean percentage of those predicted for age values for FEVi was noted while patients were receiving FP (p < 0.05 for all three periods). The mean percentage of that predicted for age values for FEF2s_75% significantly improved at 1 month after the switch, but there were no significant differences during the 2 to 6-month and 7 to 12-month periods. FP, 880 fig/d, improved lung function and decreased the number of asthma exacerbations in adolescents with moderate persistent asthma when compared with a similar dosage of TA.
Annals of Allergy, Asthma & Immunology, 1999
Background: There is a paucity of data comparing the long-term safety and efficacy of long-acting inhaled beta 2-agonists versus low-dose inhaled corticosteroids in the treatment of asthma. Objective: To compare the safety and efficacy of salmeterol xinafoate, beclomethasone dipropionate (BDP), and placebo over a 6-month treatment period in patients with persistent asthma. Methods: Salmeterol (42 g twice daily), BDP (84 g four times daily), or placebo was administered via metered-dose inhaler to 386 adolescent and adult inhaled corticosteroid-naive patients in a randomized, double-blind, double-dummy, parallel-group study. Eligible patients demonstrated a forced expiratory volume in 1 second (FEV 1) from 65% to 90% of predicted values. Pulmonary function, symptom control, frequency of asthma exacerbations, bronchial hyperresponsiveness (BHR) to methacholine challenge, and adverse events were assessed. Results: There were few statistically significant differences between the two active treatments over 6 months of therapy. Asthma symptoms and lung function were significantly improved with both salmeterol and BDP compared with placebo (changes from baseline in FEV 1 of 0.28 L (SE ϭ 0.04) and 0.23 L (SE ϭ 0.04), respectively, compared with 0.08 L (SE ϭ 0.04); P Յ .014). There were no significant differences among the treatment groups with respect to the distribution of asthma exacerbations over time. Both salmeterol and BDP significantly reduced BHR compared with placebo (P Յ .033; changes from baseline of 1.29 (SE ϭ 0.26) and 1.42 (SE ϭ 0.24) doubling doses at 6 months, respectively, compared with 0.24 (SE ϭ 0.29) doubling dose for placebo). No rebound effect in BHR was seen upon cessation of any of the three treatment regimens. There were no clinically important differences in the safety profiles among the three treatments. Conclusions: Both salmeterol and BDP are effective and well-tolerated when administered for 6 months to inhaled corticosteroid-naive patients with persistent asthma.
Global Initiative for Asthma 2016–derived asthma control with fluticasone propionate and salmeterol
Annals of Allergy, Asthma & Immunology, 2019
Background: In 2004, the landmark Gaining Optimal Asthma Control (GOAL) study demonstrated that most patients can achieve asthma control through sustained treatment and that adding a long-acting b 2-adrenoreceptor agonist to an inhaled corticosteroid (ICS) is more effective than ICS alone in this regard. Definitions of asthma control have since evolved, and the consequent implications for the GOAL study findings are unclear. Objective: To evaluate the efficacy of fluticasone propionate and salmeterol and fluticasone propionate alone in achieving and maintaining asthma control, as derived from the Global Initiative for Asthma (GINA) 2016 report. Methods: In total, 3416 patients were stratified by prior medication (ICS-naive [stratum 1], low-dose ICS [stratum 2], or medium-dose ICS [stratum 3]) and randomized to receive fluticasone propionate and salmeterol or fluticasone propionate. The primary end point was the proportion of patients achieving wellcontrolled or partly controlled asthma; secondary end points included the proportion of patients achieving well-controlled asthma. Control was evaluated during the last 4 weeks of each dose titration. Results: In all strata, more patients achieved well-controlled or partly controlled asthma with fluticasone propionate and salmeterol vs fluticasone propionate alone (stratum 1: 91% vs 85%; P ¼ .003; stratum 2: 86% vs 82%; P ¼ .07; and stratum 3: 76% vs 66%; P < .001), as well as patients with well-controlled asthma (stratum 1: 64% vs 56%; P ¼ .005; stratum 2: 59% vs 41%; P < .001; and stratum 3: 40% vs 22%; P < .001). Conclusion: A markedly higher proportion of patients with uncontrolled asthma in each stratum achieved control according to GINA 2016 criteria compared with the original study criteria. The proportion of patients achieving control remained greater with fluticasone propionate and salmeterol than with fluticasone propionate alone.
Allergy and Asthma Proceedings, 2010
Clinical guidelines recommend add-on therapy with long-acting beta 2-agonists (LABA) in patients with mild-to-moderate persistent asthma whose disease is not adequately controlled with inhaled corticosteroids (ICSs) alone. For those achieving control with add-on therapy, careful reduction in ICS dose followed by withdrawal of LABA is recommended. This study was designed to compare asthma-related outcomes in patients receiving fluticasone propionate/salmeterol combination (FSC) who stepped down to a lower dose of FSC versus those who stepped down to fluticasone propionate (FP) at the same dose of FP. A retrospective observational cohort study was performed using two large health insurance claims databases spanning from January 2000 to June 2007. Subjects were age Ն12 and Ͻ65 years, had a diagnosis of asthma (International Classification of Diseases [ICD-493.xx]), and who within 1 year of initiating FSC either stepped down to a lower dose of FSC ("FSC patients") or to FP only at the same dose of FP ("FP patients"). FSC and FP patients were matched based on propensity scores to control for potential differences in baseline demographic and clinical characteristics and preindex asthma-related and costs. Of 4350 subjects identified, 3881 stepped down to a lower dose of FSC and 469 stepped down to FP. After matching, there were 447 pairs of FSC and FP patients. FSC patients had 30% fewer prescriptions for short-acting beta-agonists, a 26% lower risk of receiving systemic corticosteroids, and a 48% lower risk of asthma-related hospitalization or Emergency Department visit during follow-up. Stepping down to FP monotherapy is associated with worsening asthma symptoms and greater risk of severe asthma-related exacerbations compared with staying on FSC at a lower ICS dose.
Jama the Journal of the American Medical Association, 2001
Context: Long-acting beta(2)-agonists are prescribed for patients with persistent asthma and are sometimes used without inhaled corticosteroids (ICSs). No evidence exists, however, to support their use as monotherapy in adults with persistent asthma. Objective: To examine the effectiveness of salmeterol xinafoate, a long-acting beta(2)-agonist, as replacement therapy in patients whose asthma is well controlled by low-dose triamcinolone acetonide, an ICS. Design and setting: A 28-week, randomized, blinded, placebo-controlled, parallel group trial conducted at 6 National Institutes of Health-sponsored, university-based ambulatory care centers from February 1997 to January 1999. Participants: One hundred sixty-four patients aged 12 through 65 years with persistent asthma that was well controlled during a 6-week run-in period of treatment with inhaled triamcinolone (400 microg twice per day). Interventions: Patients were randomly assigned to continue triamcinolone therapy (400 microg twice per day; n = 54) or switch to salmeterol (42 microg twice per day; n = 54) or to placebo (n = 56) for 16 weeks, after which all patients received placebo for an additional 6-week run-out period. Main outcome measures: Change in morning and evening peak expiratory flow (PEF), forced expiratory volume in 1 second (FEV(1)), self-assessed asthma symptom scores, rescue albuterol use, asthma-specific quality-of-life scores, treatment failure, asthma exacerbation, bronchial reactivity, and markers of airway inflammation, compared among the 3 treatment groups. Results: During the 16-week randomized treatment period, no significant differences between the salmeterol and triamcinolone groups were observed for conventional outcomes of clinical studies of asthma therapy-morning PEF, evening PEF, asthma symptom scores, rescue albuterol sulfate use, or quality of life. Both active treatments were superior to placebo. However, the salmeterol group had more treatment failures than the triamcinolone group (13/54 [24%] vs 3/54 [6%]; P =.004), as well as more asthma exacerbations (11/54 [20%] vs 4/54 [7%]; P =.04), greater increases in median (interquartile range) sputum eosinophils (2.4% [0.0% to 10.6%] vs -0.1% [-0.7% to 0.3%]; P<.001), eosinophil cationic protein (71 [-2 to 430] U/L vs -4 [-31 to 56] U/L; P =.005), and tryptase (3.1 [2.1 to 7.6] ng/mL vs 0.0 [0.0 to 0.7] ng/mL; P<.001). The duration of benefit when patients were switched from active treatment to placebo after 22 weeks of randomized treatment was not significantly longer in the triamcinolone group than in the salmeterol group. Conclusions: Patients with persistent asthma well controlled by low doses of triamcinolone cannot be switched to salmeterol monotherapy without risk of clinically significant loss of asthma control.