Inhaled salmeterol/fluticasone propionate combination. A pharmacoeconomic review of its use in the management of asthma

Cost estimates from developed countries indicate that asthma accounts for up to 2% of the economic cost of all diseases. A large proportion of asthma-related costs are attributable to poor asthma control. Treatment strategies which improve clinical outcomes in patients with asthma, therefore, have the potential for significant economic benefits, and it is important to evaluate new asthma therapies for cost effectiveness. Several studies have established that salmeterol and fluticasone propionate combined in a single dry powder inhalation device are at least as effective as a combination of the 2 drugs administered via separate dry powder inhalers and more effective than monotherapy with fluticasone propionate or budesonide. Importantly, pharmacoeconomic analysis of several of these studies show that the salmeterol/fluticasone propionate combination is cost effective relative to monotherapy with fluticasone propionate or budesonide. Although the total cost of asthma management tended to be slightly higher with salmeterol/fluticasone propionate than with inhaled corticosteroid monotherapy, in most cases mean cost-effectiveness ratios were lower (i.e. more favourable) for salmeterol/fluticasone propionate than either fluticasone propionate or budesonide. Cost effectiveness was assessed according to 3 end-points: successfully treated weeks, symptom-free days and episode-free days. Mean cost-effectiveness ratios consistently favoured salmeterol/fluticasone propionate over the comparator drug for the end-point successfully treated weeks, and in most cases the other 2 end-points also favoured the combination product over the comparator. In a further study, salmeterol/fluticasone was also less costly than therapy with formoterol and budesonide administered via 2 separate inhalers. Studies of health-related quality of life (HR-QOL) using the Asthma Quality of Life Questionnaire indicate that salmeterol/fluticasone propionate produces clinically meaningful improvements in overall HR-QOL relative to salmeterol monotherapy or placebo. Improvements in overall HR-QOL were statistically significantly greater for salmeterol/fluticasone propionate than with fluticasone propionate or budesonide alone, although the differences between treatments did not exceed the threshold for clinical significance. In conclusion, short term cost-effectiveness data show that salmeterol/fluticasone propionate is more cost effective than the inhaled corticosteroids budesonide and fluticasone propionate alone. The combination product also appears to improve HR-QOL relative to placebo or salmeterol alone.     

Inhaled salmeterol/fluticasone propionate combination: a review of its use in persistent asthma

The long-acting beta2-agonist salmeterol and the corticosteroid fluticasone propionate are available as a combination inhalation device for the treatment of persistent asthma. Well designed studies in adults, adolescents and children aged > or =4 years, demonstrate that combined salmetero/fluticasone propionate 50/100, 50/250 and 50/500 microg administered via a dry powder inhaler (DPI) is clinically equivalent to concurrent delivery of the same dosages of the 2 drugs via separate DPIs. In adults and adolescents, combined salmeterol/fluticasone 50/100 and 50/250 microg twice daily produced rapid improvements in lung function that were consistently greater than those in patients receiving monotherapy twice daily salmeterol 50 microg, fluticasone propionate 100 or 250 microg or placebo in 2 well designed studies. Recipients of the combination had a significantly greater probability of completing 12 weeks of treatment than patients receiving monotherapy or placebo. The combination also produced significant improvements between baseline and end-point in all secondary outcome variables (morning and evening peak expiratory flow, daytime symptom scores, days and nights without asthma symptoms and requirements for as-needed beta-agonists) and health-related quality of life (QOL). Combination therapy was superior to monotherapy with salmeterol and placebo for all outcomes in both studies, and was superior to fluticasone propionate 100 microg for all but 1 outcome (nights without awakenings) in 1 study. Similar results were obtained in patients who had previously been using short acting beta2-agonists alone. Combined twice daily salmeterolfluticasone propionate 50/100 and 50/250 microg produced greater improvements in lung function than inhaled budesonide at higher dosages than fluticasone propionate in the combination. Combined salmeterol/fluticasone propionate 50/250 microg produced similar improvements in lung function to concurrent budesonide 800 microg plus formoterol 12 microg when given twice daily for 12 weeks. In another 12-week trial, combined salmeterol/fluticasone propionate 50/100 microg was more effective than oral montelukast 10 mg/day plus fluticasone propionate 100 microg twice daily in patients with suboptimally controlled asthma. Salmeterol/fluticasone is more cost effective than monotherapy with fluticasone propionate or budesonide. The most frequent adverse events associated with salmeterol/fluticasone propionate are headache, throat irritation, hoarseness and candidiasis. CONCLUSION: Combined salmeterol/fluticasone propionate is as effective as the 2 drugs given concurrently via separate inhalers and significantly more effective than either drug given alone at the same nominal dosage. The combination is also significantly more effective than montelukast plus fluticasone propionate or monotherapy with inhaled budesonide. Furthermore, the combination is more cost effective than inhaled corticosteroid monotherapy.     

Inhaled salmeterol/fluticasone propionate: a review of its use in asthma

Salmeterol/fluticasone propionate, administered twice daily via a multidose dry powder inhaler (Seretide/Advair Diskus), Seretide Accuhaler or metered-dose hydrofluoroalkane (chlorofluorocarbon-free) inhaler (Seretide Evohaler), is a combination of the long-acting beta(2)-adrenoceptor agonist (beta(2)-agonist) [LABA] salmeterol and the corticosteroid fluticasone propionate.Maintenance therapy with combined salmeterol/fluticasone propionate is at least as effective in improving lung function and symptoms and is as well tolerated in patients with asthma as concurrent salmeterol plus fluticasone propionate. In patients previously receiving as-required short-acting beta(2)-agonists (SABAs) or inhaled corticosteroids, salmeterol/fluticasone propionate was significantly more effective in providing asthma control than fluticasone propionate and in improving lung function and asthma symptoms than inhaled corticosteroids (at equivalent or higher dosages), salmeterol or montelukast (as monotherapy or in combination with fluticasone propionate). Salmeterol/fluticasone propionate was more effective in improving asthma symptoms than adjusted-dose budesonide/formoterol in patients with uncontrolled asthma despite treatment with inhaled corticosteroids with or without a LABA in a well designed 1-year study. In pharmacoeconomic analyses, salmeterol/fluticasone propionate compared favourably with inhaled corticosteroids and mono- or combination therapy with oral montelukast. Salmeterol/fluticasone propionate is, therefore, an effective, well tolerated and cost-effective option for the maintenance treatment of patients with asthma.     

Inhaled fluticasone propionate. A pharmacoeconomic review of its use in the management of asthma

Contemporary asthma management guidelines list inhaled corticosteroids as the preferred controller medication for patients with persistent asthma. Despite the availability of explicit guidelines, there is evidence that these agents are underused and that guidelines are not always adhered to. Fluticasone propionate is one of several inhaled corticosteroids used for the treatment of asthma. Like other agents of its class, its efficacy is backed by extensive clinical data. More recently, the quality of life of recipients of fluticasone propionate and its relative cost effectiveness have been investigated. A series of comparative analyses show that inhaled fluticasone propionate is more cost effective than oral zafirlukast and triamcinolone acetonide and slightly more cost effective than flunisolide in adult patients with asthma. Analyses used cost per symptom-free day and/or cost per successfully treated patient as outcome measures and were generally conducted from the perspective of the third-party payer. When administered at a microgram dose of half or less than budesonide (as is therapeutically appropriate), the cost effectiveness of fluticasone propionate was similar to or better than that of budesonide. In children, fluticasone propionate was more cost effective per treatment success compared with inhaled sodium cromoglycate. Quality-of-life assessments in patients with mild to moderate disease show that inhaled fluticasone propionate achieved improvements which were deemed to be clinically meaningful in patients with mild to moderate asthma; these changes were significantly greater than those achieved with oral zafirlukast, inhaled triamcinolone acetonide or placebo. Greater improvements were evident with inhaled fluticasone propionate in patients with severe disease. CONCLUSIONS: In addition to the considerable body of clinical evidence supporting the use of inhaled fluticasone propionate in patients with asthma, accumulating short term cost-effectiveness data also suggest that this agent can be administered for a similar or lower cost per outcome than other inhaled corticosteroids or oral zafirlukast. Importantly, the clinical benefits offered by fluticasone propionate in patients with persistent asthma are accompanied by clinically significant improvements in quality of life.     

Inhaled salmeterol/fluticasone propionate: a review of its use in chronic obstructive pulmonary disease

The salmeterol/fluticasone propionate dry powder inhaler (DPI) [Advair Diskus, Seretide Accuhaler] contains the long-acting beta2-adrenoceptor agonist salmeterol and the inhaled corticosteroid fluticasone propionate. In the US, twice-daily salmeterol/fluticasone propionate 50/250 microg is approved for use in adults with chronic obstructive pulmonary disease (COPD) associated with chronic bronchitis, and in the EU, the twice-daily 50/500 microg dosage is approved for use in patients with severe COPD, repeat exacerbations and significant symptoms despite bronchodilator therapy. In patients with moderate-to-severe COPD, twice-daily inhaled salmeterol/fluticasone propionate 50/250 or 50/500 microg for 24-52 weeks improves predose forced expiratory volume in 1 second (FEV1) significantly more than salmeterol monotherapy, improves postdose or postbronchodilator FEV1 significantly more than fluticasone propionate monotherapy and results in clinically significant improvements in health-related quality of life. Salmeterol/fluticasone propionate 50/500 microg significantly reduced annual COPD exacerbations, especially in severe COPD. Some corticosteroid-related adverse events were increased in recipients of fluticasone propionate with or without salmeterol versus salmeterol monotherapy or placebo; withdrawal from fluticasone propionate, including combination therapy, needs careful management to minimise COPD exacerbations. The DPI combining a corticosteroid and long-acting beta2-agonist provides benefits over monotherapy and may encourage patient compliance in COPD.     

Cost-effectiveness of salmeterol xinafoate/fluticasone propionate combination inhaler in chronic asthma

ABSTRACT

Objective: To determine where in the treatment steps recommended by the British Thoracic Society and Scottish Intercollegiate Guidelines Network (BTS/SIGN) Asthma Guideline it is cost-effective to use salmeterol xinafoate/fluticasone propionate combination inhaler (SFC) (Seretide^*) compared with other inhaled corti­costeroid (ICS) containing regimens (with and without a long acting beta?2 agonist (LABA)) for chronic asthma in adults and children.

Research design and methods: Meta-analyses of percentage symptom-free days (%SFD) were used within a cost-effectiveness model. Time spent in two asthma control health states, ‘symptom-free’ and ‘with-symptoms’ was used as the measure of differential treatment effectiveness. SFC was compared with varying doses of fluticasone propionate (FP) and beclometasone dipropionate (BDP) with or without a separate salmeterol inhaler, and with the budeson­ide/formoterol combination inhaler (BUD/FORM) (Symbicort^?). Drug costs, non-drug costs and quality adjusted life years (QALY) were incorporated into the analyses. Results are presented as cost per QALY ratios and uncertainty explored using probabilistic sensitivity analysis.

Results: Compared with an increased dose of FP in adults, SFC either ‘dominates’ (i.e. cheaper and more effective) FP or the cost per QALY is £6852. The cost per QALYs estimated in sensitivity analyses using BDP costs range from £5679 to £15?997. For children the cost per QALY for SFC 50 Evohaler* compared with an increased dose of FP is £15?739. SFC is similarly clinically effective in improving %SFDs compared with FP plus salmeterol delivered in separate inhalers (mean differences for each dose comparison of –3.9 (low) (with a 95% confidence interval (CI): –12.96; 5.16); 4.10 (medium) (95% CI: –3.01; 11.21); –0.4 (high) (95% CI: –8.88; 8.08)) and BUD/FORM (mean difference of 0.40 (95% CI –3.69; 4.49)) in adults, and a cheaper SFC option is available at all doses (annual cost savings range from £18–£427 per patient). SFC was similarly effective compared with FP plus salmeterol in separate inhalers in children under 12 and also resulted in annual cost savings of between £47 and £77. A number of other comparisons were also made and the results are available as electronic supplementary data.

Conclusions: This is the first analysis to estimate the cost-effectiveness of SFC in chronic asthma compared with multiple comparators and based on a systematic identification of relevant trials and data on %SFDs. The findings suggest that for adults and children uncontrolled on BDP 400?μg/day or equivalent it is a cost-effective option to switch to SFC (at an equivalent ICS dose) compared with increasing the dose of ICS. For adults and children aged 12 years and over who have passed this point and are uncontrolled on BDP 800?μg/day or equivalent, switching to SFC remains a cost-effective approach. Where an adult or child requires an ICS and a LABA to be co-prescribed, SFC is a cost-effective option compared with FP or BDP plus salmeterol delivered in separate inhalers. In adults who require combination therapy, SFC is a cost-effective option compared with BUD/FORM.     

Combined salmeterol/fluticasone propionate versus fluticasone propionate alone in mild asthma : a placebo-controlled comparison

BACKGROUND AND OBJECTIVE: Combined therapy with inhaled corticosteroids (ICSs) and long-acting beta(2)-adrenoceptor agonists (LABAs) is the recommended approach for the treatment of patients with asthma that is uncontrolled on ICSs alone. Additional studies are needed to assess the safety and efficacy of combination treatment with ICSs and LABAs in patients with mild asthma. The aim of this study was to compare the efficacy and tolerability of once-daily salmeterol/fluticasone propionate combination (SFC) with once-daily fluticasone propionate (FP) over a 12-week treatment period in patients with mild persistent asthma. METHODS: This was a randomized, double-blind, placebo-controlled, parallel-group, multicentre study carried out in primary care or at a hospital outpatient department and included patients 12-79 years of age with mild persistent asthma (n = 458). After a 2-week run-in period, patients were randomized to receive SFC 50 microg/100 microg (n = 149), FP 100 microg (n = 154) or placebo (n = 155) once daily in the morning for 12 weeks. The primary efficacy endpoint was patient-recorded pre-dose mean morning peak expiratory flow (PEF). Other assessments included asthma symptom scores, use of rescue medication and investigator-recorded exacerbations. Lung function was measured and assessed during clinic visits. RESULTS: For the primary efficacy endpoint of mean change in morning PEF, SFC achieved significantly greater increases from baseline than both placebo (difference in adjusted means 23 L/min; 95% CI 15.0, 30.3; p < 0.001) and FP (difference in adjusted means 14 L/min; 95% CI 6.3, 21.7; p < 0.001). Compared with those who received FP, patients in the SFC group demonstrated significantly greater improvements in mean evening PEF (95% CI 11.7, 28.1; p < 0.001), forced expiratory volume in 1 second (95% CI 0.093, 0.257; p < 0.001), forced expiratory flow between 25% and 75% of forced vital capacity (95% CI 0.242, 0.617; p < 0.001), the percentage of symptom-free days (95% CI 0.34, 0.87; p = 0.011), and the percentage of rescue medication-free days (95% CI 0.34, 0.90; p = 0.018). During weeks 5-12, 52% of patients in the SFC group achieved 'well controlled' asthma, compared with 42% and 26% of patients in the FP and placebo groups, respectively. Only one patient (receiving placebo) had a severe asthma exacerbation during the study; the frequency of adverse events was similar across the three treatment groups. CONCLUSION: Once-daily SFC 50 microg/100 microg provided significantly greater improvements in lung function and in asthma symptoms than once-daily FP 100 microg alone in patients with mild persistent asthma. However, twice-daily treatment with either SFC or ICSs plus short acting beta(2)-adrenoceptor agonists could be required to achieve guideline-defined asthma control in some patients.     

沙美特罗/丙酸氟替卡松干粉剂和丙酸氟替卡松气雾剂治疗支气管哮喘的疗效比较

目的：比较吸入沙美特罗/丙酸氟替卡松（SM/FP）干粉剂和单用丙酸氟替卡松（FP）气雾剂治疗轻中度哮喘患者的临床疗效.方法：将60例哮喘患者随机分为两组,A组吸入SM/FP,每次50μg/100μg,bid,B组吸入FP,每次125μg,bid.测定两组患者治疗前、治疗后1个月和4个月后晨间呼气峰流速（mPEF）,第1秒用力呼气容积占预计值百分比（FEV1%pre）、第1秒用力呼气容积占用力肺活量百分比（FEV1/FVC）和哮喘症状评分.结果：两组各项指标均有好转,治疗后1个月A组mPEF,FEV1%pre,症状评分较B组改善明显,第4个月两组之间各项指标均有差异（P＜0.05）.结论：联合吸入低剂量糖皮质激素和β2受体激动剂较单一吸入激素效果好.     

Co-deposition of salmeterol and fluticasone propionate by a combination inhaler

Powder mixing has been the subject of substantial research due to its importance in a variety of industrial sectors, including pharmaceuticals, food, and polymer manufacturing. Although a number of different models have been proposed in the literature, most of them are either empirical or require computationally intensive calculations that make them difficult to implement for realistic systems. The aim of this paper is to develop a simplified framework, based on compartment modeling that efficiently and accurately captures the system behavior. Using the V-blender as a model system, the compartment modeling approach was used to illustrate the effects of vessel loading on mixing as well as the impact of sampling methods on the accuracy of mixing characterization.     

Resource utilization in asthma:combined fluticasone propionate/salmeterol compared with inhaled corticosteroids

ABSTRACT

Background: Asthma management guidelines recommend low-dose inhaled corticosteroids (ICS) for initial treatment of mild persistent asthma. Instead, data from primary care practice show that many patients start on combination therapy with fluticasone propionate/salmeterol (FPS) for mild asthma. The consequences of this variance from guideline recommendations are not well described.

Objective: Compare healthcare utilization and asthma-related outcomes for patients with mild asthma who began treatment with FPS or ICS alone.

Design and data source: A retrospective analysis of asthma-related insurance claims. Patients initially treated with FPS or ICS were identified from an administrative health insurance claims database and followed for 1 year. Analyses of resource utilization 6 months before therapy initiation identified patients with mild asthma. Propensity score matching managed between-group differences in clinical characteristics and controlled for selection bias.

Outcome measures: Resource use was determined for asthma-related outpatient visits, emergency room services, hospitalizations, and medications.

Results: Demographic characteristics and comorbidities were similar for each group (FPS, n = 1888; ICS, n = 1888). During the 12?month follow-up period, total asthma-related costs were significantly higher for FPS versus ICS ($1206 vs. $804; p < 0.0001), owing primarily to significantly higher drug costs for FPS versus ICS ($677 vs. $357; p < 0.0001). The percentage of patients experiencing an exacerbation (14.0% FPS, 13.5% ICS) and the average number of exacerbations in each group (0.175 FPS, 0.164 ICS) were similar.

Conclusions: Healthcare costs were found to be lower in patients receiving ICS than in those receiving FPS, with similar health outcomes in both groups. Study limitations included the use of claims data and a proxy definition of asthma severity, and potential confounding by unobserved factors.     

Cost effectiveness of fluticasone propionate plus salmeterol versus fluticasone propionate plus montelukast in the treatment of persistent asthma

BACKGROUND: Asthma is a chronic disease, the two main components of which are inflammation and bronchoconstriction. Fluticasone propionate (FP) and salmeterol, a strategy that treats both main components of asthma, has been recently compared with FP plus montelukast in a randomised clinical trial. The present study reports economic evaluation of these two strategies. OBJECTIVE: To determine the relative cost effectiveness when persistent asthma is treated with FP/salmeterol 100/50 microg twice daily administered via a single Diskus inhaler device versus treatment with FP 100 microg twice daily via a Diskus inhaler plus oral montelukast 10mg once daily. STUDY DESIGN: A cost-effectiveness analysis was performed by applying cost unit data to resource utilisation data collected prospectively during a US randomised, double-blind, 12-week trial of FP/salmeterol (n = 222) versus FP + montelukast (n = 225). Patients were > or =15 years of age and were symptomatic despite inhaled corticosteroid (ICS) therapy. PATIENTS AND METHODS: Efficacy measurements in this analysis included improvement in forced expiratory volume in 1 second (FEV(1)) and symptom-free days. Direct costs included those related to study drugs, emergency room department visits, unscheduled physician visits, treatment of drug-related adverse events (oral candidiasis), and rescue medication (salbutamol [albuterol]). The study assumed a US third-party payer's perspective with costs in 2001 US dollars. RESULTS: Treatment with FP/salmeterol resulted in a significantly higher proportion (p < 0.001) of patients who achieved a > or =12% increase in FEV(1) than treatment with FP + montelukast (54% [95% CI 47%, 61%] vs 32% [95% CI 26%, 38%]). Lower daily costs and greater efficacy of FP/salmeterol resulted in a cost-effectiveness ratio of US6.77 dollars (95% CI US5.99 dollars, US7.66 dollars) per successfully treated patient in the FP/salmeterol group compared with US14.59 dollars (95% CI US12.12 dollars, US17.77 dollars) for FP + montelukast. In addition, FP/salmeterol achieved similar efficacy in terms of symptom-free days compared with FP + montelukast (31% [95% CI 26%, 35%] vs 27% [95% CI 23%, 32%]), but at a significantly lower daily per-patient cost (US3.64 dollars [95% CI US3.60, US3.68 dollars] vs US4.64 dollars [95% CI US4.56 dollars, US4.73 dollars]). Sensitivity analyses demonstrated the stability of the results over a range of assumptions. CONCLUSION: From a US third-party payer's perspective, these findings suggest that treating the two main components of asthma (inflammation and bronchoconstriction) with FP/salmeterol may not only be a more cost-effective strategy but may actually lead to cost savings compared with the addition of montelukast to low-dose FP in patients with persistent asthma. The results were found to be robust over a range of assumptions.     

沙美特罗替卡松吸入剂联合布地奈德治疗哮喘的疗效

目的　探究沙美特罗替卡松吸入剂联合布地奈德治疗哮喘的临床疗效,分析对患者血清白细胞介素-21（IL-21）、IL-18水平的影响。方法　选取2020年1月至2021年12月于海阳市人民医院接受治疗的86例支气管哮喘患者,采用抛硬币法进行随机分组,分为观察组（47例）和对照组（39例）。观察组男22例,女25例,年龄（43.48±5.57）岁;对照组男25例,女14例,年龄（44.39±6.01）岁。所有患者均接受常规对症治疗,在此基础上对照组采用沙美特罗替卡松吸入剂治疗,观察组采用沙美特罗替卡松吸入剂联合布地奈德治疗。比较两组患者临床疗效、临床症状改善时间,治疗前后肺功能及血清IL-21、IL-18水平变化,记录患者治疗后3个月的哮喘复发情况及治疗期间不良反应发生情况。计量资料行t检验,计数资料行χ²检验。结果　观察组的治疗总有效率为91.49%（43/47）,高于对照组的71.79%（28/39）（P<0.05）。治疗后,观察组的临床症状改善时间均短于对照组（均P<0.05）,第1秒用力呼气量（FEV₁）、FEV₁/用力肺活量（FVC）和最大呼气流速（PEF）水平高于对照组（均P<0.05）,血清IL-21、IL-18水平低于对照组（均P<0.05）。观察组的哮喘复发率为6.38%（3/47）明显低于对照组的23.08%（9/39）（P<0.05）;两组患者的不良反应发生率比较,差异无统计学意义（P>0.05）。结论　沙美特罗替卡松吸入剂联合布地奈德治疗可明显改善哮喘患者的临床症状,提高患者肺功能,且复发率低,临床疗效可靠,安全性较好,其机制可能与调节血清IL-21、IL-18水平有关。