Cost–utility analysis of reslizumab for patients with severe eosinophilic asthma inadequately controlled with high-dose inhaled corticosteroids and long-acting β2-agonists in South Korea

Objectives: We aimed to assess the cost-utility of reslizumab for patients with severe eosinophilic asthma uncontrolled with high-dose inhaled corticosteroids and long-acting β₂-agonists (ICS/LABAs) in Korea.

Methods: A Markov model with limited societal perspective was used to compare the costs and quality-adjusted life years (QALYs) of reslizumab add-on therapy with standard-of-care (high-dose ICS/LABA) and standard-of-care alone. The model adopted a 4?week cycle with the following six health states over a lifetime (60?years): controlled asthma, uncontrolled asthma, moderate exacerbation, severe exacerbation, all-cause death and asthma-related death. The population comprised adult patients (age ≥18?years) with severe eosinophilic asthma (eosinophils ≥400 cells/μL) at Global Initiative for Asthma (GINA) step 4 or 5 who had experienced at least three exacerbations in the preceding year. Model inputs were sourced from individual patient-level data from two 52?week randomized controlled trials of reslizumab (NCT01287039, NCT01285323). The model included discontinuation rules where patients uncontrolled with reslizumab add-on therapy were transitioned to the standard-of-care arm. Costs and QALYs were annually discounted at 5%. Deterministic and probabilistic sensitivity analyses were performed.

Results: Reslizumab add-on therapy was associated with increased cost (US$119,394) and improved QALYs (5.17) compared with standard-of-care alone, resulting in an incremental cost-effectiveness ratio of US$23,081 per QALY gained. Body weight, time horizon and discount rate were influential factors in the model.

Conclusions: The addition of reslizumab to high-dose ICS/LABA was cost-effective in Korean patients with severe eosinophilic asthma uncontrolled with high-dose ICS/LABA, based on the threshold of 1 gross domestic product in Korea.     

Asthma control in patients with asthma and allergic rhinitis receiving add-on montelukast therapy for 12 months: a retrospective observational study

ABSTRACT

Background: Montelukast, a potent leukotriene receptor antagonist, is approved for treatment of both asthma and allergic rhinitis (AR). No studies to date have examined whether montelukast can improve asthma control over a long period of time in patients with seasonal AR and asthma.

Objective: To evaluate asthma control and use of asthma-related medical resources by patients with inadequately controlled mild to moderate persistent asthma and seasonal AR who required addition of montelukast as part of routine care.

Methods: This multicenter, 24?month, pre–post retrospective observational study included patients receiving current inhaled corticosteroid (ICS) therapy (alone or in combination with long-acting β-agonist [LABA]), who received add-on treatment with montelukast for 12 consecutive months. The incidence of asthma attacks, defined as emergency department visit, hospitalization, or oral corticosteroid use for asthma, was compared for the year before and the year after addition of montelukast to therapy.

Results: For the 696 patients from Italy, Poland, and Spain who were included in the analyses, the proportion of patients experiencing an asthma attack declined from 31.5% in the year before to 10.1% (?p < 0.001) the year after addition of montelukast to therapy. Proportions of patients with an asthma-related emergency room visit, hospitalization, and oral corticosteroid use declined from 18.7% to 3.9%, from 5.2% to 1.4%, and from 17.5% to 5.9% (all p < 0.01), respectively. The incidence of these outcomes declined in all three countries, regardless of baseline asthma severity or asthma therapy (ICS alone or ICS + LABA). Important study limitations include the possibility of selection bias or missing medical chart data in this retrospective study design. Also noteworthy is the inclusion of only those patients who remained persistent with montelukast therapy. Therefore, the results of the study are relevant for patients who remain persistent with montelukast therapy.

Conclusions: Addition of montelukast to current ICS therapy improved long-term asthma control and resulted in substantial reductions in asthma-related resource use by patients with mild or moderate persistent asthma and concomitant seasonal AR who were persistent with montelukast therapy in this retrospective observational study.     

A re-evaluation of the role of inhaled corticosteroids in the management of patients with chronic obstructive pulmonary disease

Introduction: Inhaled corticosteroids (ICS) (in fixed combinations with long-acting β₂-agonists [LABAs]) are frequently prescribed for patients with chronic obstructive pulmonary disease (COPD), outside their labeled indications and recommended treatment strategies and guidelines, despite having the potential to cause significant side effects.

Areas covered: Although the existence of asthma in patients with asthma–COPD overlap syndrome (ACOS) clearly supports the use of anti-inflammatory treatment (typically an ICS/LABA combination, as ICS monotherapy is usually not indicated for COPD), the current level of ICS/LABA use is not consistent with the prevalence of ACOS in the COPD population. Data have recently become available showing the comparative efficacy of fixed bronchodilator combinations (long-acting muscarinic antagonist [LAMA]/LABA with ICS/LABA combinations). Additionally, new information has emerged on ICS withdrawal without increased risk of exacerbations, under cover of effective bronchodilation.

Expert opinion: For patients with COPD who do not have ACOS, a LAMA/LABA combination may be an appropriate starting therapy, apart from those with mild disease who can be managed with a single long-acting bronchodilator. Patients who remain symptomatic or present with exacerbations despite effectively delivered LAMA/LABA treatment may require additional drug therapy, such as ICS or phosphodiesterase-4 inhibitors. When prescribing an ICS/LABA, the risk:benefit ratio should be considered in individual patients.     

Budesonide/formoterol maintenance and reliever therapy: a new treatment approach for adult patients with asthma

ABSTRACT

Background: An inhaled corticosteroid (ICS) or an ICS/long-acting β₂-agonist (LABA) combination plus short-acting β₂-agonist (SABA) as needed for symptom relief is recommended for persistent asthma. Additionally, budesonide/formoterol maintenance and reliever therapy (Symbicort SMART, AstraZeneca, Sweden) has been approved for adults in the European Union. This option is well tolerated and offers greater reductions in asthma exacerbations together with similar improvements in daily symptom control, at a lower overall steroid load, compared with fixed-dose ICS/LABA plus SABA.

Scope: Two large clinical trials investigated the use of budesonide/formoterol as maintenance and reliever compared with medium or high doses of an ICS/LABA combination as controller plus SABA as reliever in adults (aged ≥ 12 years). COMPASS was a 6-month, double blind, randomized trial while COSMOS was a 1?year, dose titration study which reflected routine clinical practice. The current review focuses on the findings in both studies, among adult patients only (aged ≥ 18 years).

Findings: Among adults, the studies confirmed a 21–39% reduction in severe exacerbations in patients treated with budesonide/formoterol maintenance and reliever therapy compared with titrated salmeterol/fluticasone plus SABA (COSMOS) or fixed higher budesonide/formoterol or salmeterol/fluticasone plus SABA (COMPASS), respectively. Similar levels of daily asthma control were achieved with budesonide/formoterol maintenance and reliever therapy at a significantly lower overall steroid load compared with salmeterol/fluticasone or budesonide/formoterol plus SABA. Budesonide/formoterol maintenance and reliever therapy was as well tolerated as combination therapies.

Conclusions: In adult patients, budesonide/formoterol maintenance and reliever therapy is a safe and simplified approach to asthma management, using a single inhaler, which reduces severe exacerbations and maintains similar daily asthma control at a lower drug load compared with the traditional strategy of ICS/LABA plus SABA.     

Tiotropium for the treatment of asthma in adolescents

Introduction: Asthma is a prevalent disease affecting millions of individuals. Despite receiving guideline therapy with inhaled corticosteroids (ICS) with or without a long-acting β₂-agonist (LABA), a proportion of patients remain symptomatic or have suboptimal lung function. There is therefore an unmet need for additional therapies to improve asthma control. The long-acting anticholinergic tiotropium, delivered via the Respimat inhaler, is approved for the treatment of asthma in the EU, the USA, and other countries. Phase III investigation in adults has demonstrated that tiotropium improves lung function and asthma control, with a safety profile comparable with that of placebo.

Areas covered: Clinical trials in adolescent patients (aged 12–17 years) with moderate or severe symptomatic asthma have shown that tiotropium Respimat as add-on to ICS, with or without other maintenance therapies, is a well-tolerated and efficacious bronchodilator showing trends toward improved asthma control, similar to data in adult patients.

Expert opinion: Tiotropium Respimat may be of benefit as add-on maintenance therapy to medium- or high-dose ICS with or without LABA; however, further data are needed to directly compare the efficacy of ICS plus tiotropium versus ICS plus LABA in adolescents with symptomatic asthma, and to establish the long-term effects on airway modeling.     

Evaluating fluticasone furoate + vilanterol for the treatment of chronic obstructive pulmonary disease (COPD)

Introduction: Inhaled corticosteroid/long-acting β-2 agonists (ICS/LABA) combination inhalers have been a lifeline for a generation of chronic obstructive pulmonary disease (COPD) and asthma patients. Fluticasone furoate and Vilanterol (FF/VI) as a once-daily ICS/LABA combination have an extensive clinical trial and real-world data to support its use in COPD patients.

Areas covered: The authors provide pharmacological profiles of fluticasone furoate, vilanterol and the FF/VI fixed dose combination. Salient clinical trials evaluating efficacy and safety of the FF/VI combination, and studies demonstrating the impact on COPD exacerbation risk and mortality are also discussed.

Expert opinion: ICS/LABA combinations provide bronchodilation and decrease the frequency of COPD exacerbations. Individualizing treatment of each COPD patient based on unique phenotypes will maximize chances of therapeutic responsiveness. Asthma-COPD overlap (ACO), patients with sputum and/or blood eosinophilia, patients with a brisk bronchodilator response, and patients with frequent exacerbations are more likely to show a therapeutic response to ICS than populations who have none of these features. FF/VI will likely remain a popular ICS/LBA combination to treat COPD, as a once-daily inhaled therapy delivered via the Ellipta device popular with COPD patients, with extensive clinical trial and real-world data to support its use.     

Tiotropium bromide as add-on therapy to inhaled corticosteroids for treating asthma

Introduction: Bronchial asthma is becoming increasingly prevalent worldwide. Although first-line therapy with inhaled corticosteroids (ICS) with or without long-acting β2 agonists (LABA) has significantly improved the clinical outcomes of asthma, they cannot provide all asthmatics with good control and thus alternatives or add-on drugs are required. Tiotropium is a long-acting muscarinic antagonist that has been used to treat chronic obstructive pulmonary disease and it has been approved for treating asthma in some countries. This agent has similar bronchodilatory effects to those of LABA and might also have anti-inflammatory and anti-remodeling effects.

Areas covered: Some pivotal clinical trials have found tiotropium effective as an add-on medication for low-to-medium doses of ICS for treating symptomatic asthma and asthma that remains uncontrolled despite ICS plus LABA therapy.

Expert opinion: Whether or not tiotropium has anti-inflammatory and anti-remodeling effects in humans with asthma is an important issue. Predictors that would identify patients who would derive the maximal potential benefit from treatment with tiotropium in addition to their current therapy are also needed. Although the cardiovascular toxicity of tiotropium is less remarkable in asthma than in chronic obstructive pulmonary disease, longer and larger studies are still needed to confirm the safety of tiotropium for treating asthma.     

An assessment of asthma exacerbations in pediatric patients using a long-acting B2-agonist plus inhaled corticosteroid versus an inhaled corticosteroid alone

BackgroundAn asthma exacerbation is an anticipated sudden worsening of the disease severity, which usually does not respond to conservative therapy. The management of asthma depends on the severity of the disease symptoms, which includes an inhaled corticosteroid (ICS) and a bronchodilator. This study aimed to assess the efficacy of combining a long-acting B2-agonist (LABA) with ICS, compared to ICS alone, to reduce the incidence of asthma exacerbations in pediatric patients, diagnosed with severe persistent asthma.MethodsA retrospective analysis of the medical records was conducted for 586 children, admitted to the Emergency Department (ED) at King Abdullah Specialized Children Hospital in Riyadh, Saudi Arabia, for the management of severe persistent asthma symptoms, from January 2016 to September 2019.ResultsThe majority (n = 480, 81.9%) of the patients received fluticasone (Flovent)® as the standard of care ICS treatment for controlling asthma, and a small proportion (n = 106, 18.1%) were treated with a combination of LABA and ICS. A significant increase in the frequency of recurrent asthma exacerbation episodes occurred in the group receiving ICS alone (98.5%), compared to 67.0% in the combination group (p < 0.0001). Moderate to severe exacerbations were significantly higher in the ICS group compared to the combination group (95.6% versus 84.5%, respectively, p = 0.0005).ConclusionsThe current results confirm the substantial efficacy of the LABA/ICS combination therapy in reducing the incidence and severity of asthma exacerbations in pediatric patients, compared to ICS alone.     

Mometasone furoate vs fluticasone propionate with salmeterol: multivariate analysis of resource use and asthma-related charges

Abstract

Objective:

Although current National Asthma Education and Prevention Program (NAEPP) guidelines indicate low-dose inhaled corticosteroid (ICS) monotherapy as the preferred treatment for patients with mild persistent asthma, many patients receive ICS and long-acting β₂-agonist (LABA) combinations. The objective of the current study was to evaluate asthma-related charges in patients with mild asthma who began treatment with mometasone furoate (MF) versus those who began treatment with a fluticasone propionate/salmeterol (FPS) combination.     

New and developing non-adrenoreceptor small molecule drugs for the treatment of asthma

Introduction: Inhaled corticosteroids (ICS) alone or in combination with an inhaled long-acting beta₂-agonist (LABA) are the preferred long-term treatment for adults and adolescents with symptomatic asthma. Additional drugs include leukotriene-receptor antagonists, slow-release theophylline and the long-acting muscarinic antagonist (LAMA) tiotropium (approved in 2015). There is a need for more effective therapies, as many patients continue to have poorly controlled asthma.

Areas covered: New and developing long-acting non-adrenoreceptor synthetic drugs for the treatment of symptomatic chronic asthma despite treatment with an ICS alone or combined with a LABA. Data was reviewed from studies published up until November 2016.

Expert opinion: Tiotropium improves lung function and has a modest effect in reducing exacerbations when added to ICS alone or ICS and LABA. The LAMAs umeclidinium and glycopyrronium are under development in fixed dose combination with ICS and LABA. Novel small molecule drugs, such as CRTH2 receptor antagonists, PDE₄ inhibitors, protein kinase inhibitors and nonsteroidal glucocorticoid receptor agonists and ‘off-label’ use of licensed drugs, such as macrolides and statins are under investigation for asthma, although their effectiveness in clinical practice is not established. To better achieve the goal of developing effective novel small molecule drugs for asthma will require greater understanding of mechanisms of disease and the different phenotypes and endotypes of asthma.     

Inhaled corticosteroids as combination therapy with β-adrenergic agonists in airways disease: present and future

Inhaled corticosteroid (ICS) therapy in combination with long-acting β-adrenergic agonists represents the most important treatment for chronic airways diseases such as asthma and chronic obstructive pulmonary disease (COPD). ICS therapy forms the basis for treatment of asthma of all severities, improving asthma control, lung function and preventing exacerbations of disease. Use of ICS has also been established in the treatment of COPD, particularly symptomatic patients, who experience useful gains in quality of life, likely from an improvement in symptoms such as breathlessness and in reduction in exacerbations, and an attenuation of the yearly rate of deterioration in lung function. The addition of long-acting β-agonist (LABA) therapy with ICS increases the efficacy of ICS effects in moderate-to-severe asthma. Thus, a 800 μg daily dose of the ICS budesonide reduced severe exacerbation rates by 49% compared to a low dose of 200 μg daily, and addition of the LABA formoterol to budesonide (800 μg) led to a 63% reduction. In COPD, the effects of ICS are less prominent but there are beneficial effects on the decline in FEV₁ and the rate of exacerbations. A reduction in the rate of decline in FEV₁ of 16 ml/year with a 25% reduction in exacerbation rate has been reported with the salmeterol and fluticasone combination. A non-significant 17.5% reduction in all-cause mortality rate with ICS and LABA is reported. Chronic inflammation is a feature of both asthma and COPD, although there are site and characteristic differences. ICS targets this inflammation although this effect of ICS is less effective in patients with severe asthma and with COPD; however, addition of LABA may potentiate the anti-inflammatory effects of ICS. An important consideration is the presence of corticosteroid insensitivity in these patients. Currently available ICS have variably potent binding activities to specific glucocorticoid receptors, leading to inhibition of gene expression by either binding to DNA and inducing anti-inflammatory genes or by repressing the induction of pro-inflammatory mediators. Local side effects of ICS include oral candidiasis, hoarseness and dysphonia, while systemic side effects, such as easy bruising and reduction in growth velocity or bone mineral densitometry, are usually restricted to doses above maximally recommended doses. Use of LABA alone in patients with asthma increases the risk of asthma-related events including deaths, but this is less observed with the combination of ICS and LABA. Therefore, use of LABA alone is not recommended for asthma therapy. Future progress in ICS development will be characterised by the introduction of ICS with greater efficacy with a limited side-effect profile, and by longer-acting ICS that can be used in combination with once-daily LABAs. Other agents that could improve the efficacy of corticosteroids or reverse corticosteroid insensitivity may be added to ICS. ICS in combination with LABAs will continue to remain the main focus of treatment of airways diseases.     

Muscarinic antagonists in early stage clinical development for the treatment of asthma

Introduction: Parasympathetic neurons utilize the neurotransmitter acetylcholine to modulate and constrict airway smooth muscles at the muscarinic acetylcholine receptor. Inhaled agents that antagonize the muscarinic (M) acetylcholine receptor, particularly airway M3 receptors, have increasing data supporting use in persistent asthma.

Areas covered: Use of inhaled long-acting muscarinic antagonists (LAMA) in asthma is explored. The LAMA tiotropium is approved for maintenance in symptomatic asthma patients despite the use of inhaled corticosteroids (ICS), leukotriene receptor antagonists (LTRA) and/or long-acting beta₂ agonists (LABA). LAMA agents currently approved for chronic obstructive pulmonary disease (COPD) include tiotropium, glycopyrrolate/glycopyrronium, umeclidinium and aclidinium. These agents are reviewed for their pharmacological differences and clinical trials in asthma.

Expert opinion: Current guidelines place inhaled LAMAs as adjunctive maintenance therapy in symptomatic asthma not controlled by an ICS and/or a LTRA. LAMA agents will play an increasing role in moderate to severe symptomatic asthma patients. Additional LAMA agents are likely to seek a maintenance indication perhaps as a combined inhaler with an ICS or with an ICS and a LABA. These fixed-dose combination inhalers are being tested in COPD and asthma patients. Once-a-day dosing of inhaled LAMA agents in severe asthma patients will likely become the future standard.     

Improving asthma control in patients suboptimally controlled on inhaled steroids and long-acting β2‐agonists: addition of montelukast in an open-label pilot study

ABSTRACT

Background: Airway inflammation and symptoms often persist in asthma patients despite treatment with inhaled corticosteroids (ICS) and long-acting β₂-agonists (LABA). It is hypothesized that the leukotriene receptor antagonist montelukast, treating a pathway of inflammation distinct from that of ICS, might confer additional benefit.

Objective: To evaluate the efficacy of montelukast in improving asthma control in patients symptomatic on a fixed-association (FA) medium dose of ICS and LABA.

Methods: A 2-month, open-label, real-life observational study was undertaken by 131 Belgian pulmonologists. Patients (≥ 15 years old) suffering from persistent asthma (pre-bronchodilator FEV₁ ≥ 60% of predicted value) and insufficiently controlled on a FA therapy of fluticasone/salmeterol or budesonide/formoterol were given montelukast 10?mg daily as add-on therapy. Asthma control was assessed by the standardized Juniper asthma control questionnaire (ACQ) at baseline and after a 2-month treatment with montelukast. Global evaluation of therapy was made both by the patients and physicians.

Results: A total of 313 patients were eligible for analysis. Forty-nine per cent received inhaled fluticasone/salmeterol and the rest budesonide/formoterol. Mean ACQ score decreased significantly on montelukast (13.9 ± 5.1 at baseline versus 7.4 ± 4.7 on montelukast, p < 0.001), with a significant improvement in all individual symptom scores (?p < 0.001) and in pre-bronchodilator FEV₁ score (from 2.2 ± 1.5 to 1.6 ± 1.4; p < 0.001). Parallel to these results, 78.6% of the patients reported a global improvement of their asthma. The same proportion of improvement was observed in the global evaluation made by the physicians (κ = 0.66).

Conclusion: This pilot study suggests that addition of montelukast in patients symptomatic on a FA of ICS and LABA may result in significant improvements in asthma control. A randomised, placebo-controlled clinical trial seems warranted.     

Efficacy of add-on montelukast in patients with non-controlled asthma: a Belgian open-label study*

ABSTRACT

Objective: To evaluate the efficacy of add-on montelukast on asthma control and allergic rhinitis symptoms in asthmatic patients still symptomatic with chronic treatment with inhaled corticosteroid and long-acting β₂ agonist (ICS/LABA), irrespective of the dose.

Research design and methods: This 2-month, open-label, real-life, multicentre, observational study was undertaken by 499 general practitioners in Belgium. Patients (≥?4?years old) with uncontrolled asthma despite fluticasone/salmeterol or budesonide/formoterol therapy had oral montelukast 4, 5, or 10?mg daily added to their therapy, depending on the registered dose for their age. Asthma control, assessed by the 6-item Juniper Asthma Control Questionnaire (ACQ) was recorded at baseline and after 2?months of treatment with montelukast and the patients’ global evaluation of asthma was also recorded at the end of the study. Concomitant allergic rhinitis symptoms were evaluated according to the patients’ perception.

Results: A total of 5769 patients were eligible for analysis. Addition of montelukast was associated with significant decrease in mean (SD) ACQ score (from 1.97 [0.77] at baseline to 1.05 [0.69] after add-on treatment, p?<?0.001). There was also a significant improvement in all individual symptoms of the ACQ score (p?<?0.001). After 2?months, 89% of the patients reported global improvement of their asthma, with a good correlation between patients’ global evaluation and change in ACQ scores. Of the 2442 patients who reported allergic rhinitis symptoms at baseline, 91% showed a global improvement of their asthma symptoms and 82% in their rhinitis symptoms after adding montelukast.

Conclusion: This open-label observational study showed an improvement, after 2?months of add-on therapy with montelukast, in both asthma and allergic rhinitis symptoms in patients not adequately controlled on a fixed association of ICS/LABA.     

The efficacy and safety of three types of combination therapies in patients with moderate to very severe COPD: a systematic review and meta-analysis

Inhaled drugs, including long-acting muscarinic antagonists (LAMAs), long-acting β₂-agonists (LABAs) and inhaled corticosteroids (ICSs), are the main therapeutic options for patients with chronic obstructive pulmonary disease (COPD). We conducted a systematic review and meta-analysis to compare the efficacy and safety of LAMA+LABA+ICS, LAMA+LABA and LABA+ICS therapies. The Pubmed, Embase and Cochrane Library databases were searched for randomized controlled trials (RCTs) comparing the efficacy (moderate-to-severe exacerbations, lung function and quality of life) and safety (adverse events (AEs), severe adverse events (SAEs), withdrawals due to AEs, deaths and pneumonia) of LAMA+LABA+ICS, LAMA+LABA and LABA+ICS in COPD patients. Two investigators independently searched eligible studies and extracted relevant information. The data were analyzed using the Review Manager software, and the quality of included studies was assessed using the Cochrane risk of bias tool. A total of 27 studies were included, and majority of the studies showed low risk of bias. Moderate­to­severe exacerbations were lower after LAMA+LABA+ICS therapy compared with the LABA+ICS (RR = 0.66; 95% CI: 0.59–0.74) and LAMA+LABA therapies (RR = 0.88; 95% CI: 0.82–0.94). Lung function was significantly improved after LAMA+LABA+ICS compared with LAMA+ICS treatment. FEV1, peak FEV1 and trough FEV1 were significantly increased by 100 mL, 150 mL and 120 mL, respectively, in LAMA+LABA+ICS therapy compared with LAMA+ICS. In addition, LAMA+LABA therapy resulted in increased FEV1, peak FEV1 and trough FEV1 by 80 mL, 90 mL and 70 mL, respectively, compared with LAMA+ICS. SGRQ-total score was used to assess quality of life of COPD patients, which indicated that LAMA+LABA+ICS therapy was associated with slightly greater decrease compared with LABA+ICS (MD = –1.33; 95% CI: –2.35 to –0.30). No significant differences were found across all three treatment combinations in term of AEs, SAEs, withdrawals due to AEs and deaths. However, the risk of pneumonia was higher in the triple therapy group than that in the LABA+ICS (RR = 1.16; 95% CI: 1.01–1.33) or LAMA+LABA (RR = 1.31; 95% CI: 1.06–1.62) groups, and significantly lower in the LAMA+LABA group compared with LABA+ICS (RR = 0.64; 95% CI: 0.54–0.76). LAMA+LABA+ICS therapy offered greater efficacy and comparable safety compared with the LAMA+LABAor LABA+ICS therapies. However, triple therapy could increase the risk of pneumonia compared with LAMA+LABA or LABA+ICS therapies. People who have higher risk of pneumonia should carefully consider the use of triple therapy. LAMA+LABA therapy offered greater efficacy and lower risk of pneumonia to LABA+ICS therapy. Collectively, LAMA+LABA therapy might be a better choice than LABA+ICS.     

小剂量阿奇霉素联合沙美特罗替卡松气雾剂对慢性中度持续期哮喘患儿的疗效及依从性分析

目的 探究吸入小剂量阿奇霉素联合沙美特罗替卡松气雾剂对慢性中度持续期哮喘患儿的疗效及对其治疗依从性的影响。方法 选择2015年1月-2016年1月于郑州大学附属儿童医院进行治疗的98例慢性中度持续期哮喘患儿,按照随机数字表法将其分为观察组与对照组,每组各49例患者。对照组患儿给予沙美特罗替卡松气雾剂,1掀/次,2次/d;观察组患儿在对照组基础上增加阿奇霉素干混悬剂进行治疗,使用剂量为0.1 g/次,1次/d,连续服用3 d后停用4 d,而后继续。两组患儿治疗时间均为12周。对比两组患者治疗有效率,对比治疗前后两组患儿儿童哮喘控制测试（C-ACT）评分、哮喘用药依从性量表（MARS-A）评分、1秒用力呼气容积（FEV1）及最大呼气峰流速（PEF）,并对两组患儿治疗过程中不良反应发生率进行对比。结果 观察组患儿哮喘有效率为87.76%,对照组患儿有效率为65.31%,两组对比差异具有统计学意义（P<0.05）。治疗后两组患儿C-ACT及MARS-A得分均有所上升,对比治疗前差异具有统计学意义（P<0.05）;同时观察组患儿C-ACT及MARS-A得分均高于对照组,组间差异有统计学意义（P<0.05）。治疗后两组患儿FEV1及PEF均有提升,对比治疗前差异具有统计学意义（P<0.05）;同时观察组患者上述指标均高于对照组,组间差异有统计学意义（P<0.05）。两组不良反应发生率对比差异不具有统计学意义。结论 小剂量阿奇霉素联合沙美特罗替卡松气雾剂能够显著缓解慢性中度持续期哮喘患儿临床症状,改善患儿肺功能,同时具有较低的不良反应发生率,值得进行临床推广。     

Single inhaler triple therapy with extrafine beclomethasone,formoterol, and glycopyrronium for the treatment of chronic obstructive pulmonary disease

Introduction: Chronic obstructive pulmonary disease (COPD) management focuses on the alleviation of symptoms and prevention of exacerbations. Inhaled long acting bronchodilators and inhaled corticosteroids (ICS) are the main classes of treatment for COPD. Triple therapy with a long acting beta₂-agonist (LABA), long acting muscarinic antagonist (LAMA), and ICS is commonly prescribed for symptomatic COPD patients experiencing regular exacerbations. Triple therapy is usually administered using separate inhalers; there is little clinical trial evidence of an effect on exacerbation prevention with this approach.

Areas covered: This evaluation reviews the single inhaler extrafine combination containing beclometasone diproprionate (BDP), formoterol fumarate (FF), and glycopyrronium bromide (GB) which has been developed as a simplified triple regime. BDP/FF/GB significantly reduced exacerbation rates in three clinical trials (1-year duration) compared against LAMA monotherapy (20% exacerbation reduction), ICS/LABA combination (23% exacerbation reduction), and LAMA/LABA combination (15% exacerbation reduction).

Expert opinion: The practical benefits of single inhaler triple therapy in the real world have not been studied. However, the robust clinical trial evidence that BDP/FF/GB reduces exacerbations compared to double combination treatments and LAMA monotherapy cements triple therapy positioning as an escalation step in COPD management pathways.     

Anticonvulsant hypersensitivity syndrome: an update

Introduction: Long-acting β-agonists (LABAs) added to inhaled corticosteroids (ICS) reduce symptoms, improve lung function and enhance overall asthma control. However, several studies have indicated an increased risk of asthma mortality and asthma-related serious adverse events and the FDA recently mandated restrictions to the use of LABAs in asthma.

Areas covered: This review highlights the clinical studies on which safety analyses pertaining to salmeterol and formoterol have been based and then focuses on recent meta-analyses of safety outcomes with and without consideration of concomitant ICS.

Expert opinion: The phenomenon of masking of inflammation by LABA if ICS dose is insufficient underscores the potential for confounding in determining real safety risks. Under-treatment with ICS and differential dosing of ICS in many trials are major factors driving the LABA safety concern. The FDA meta-analysis, when stratified for mandatory ICS use, found no significant increase in the composite outcome of asthma mortality, intubations and hospitalizations. Add-on therapy with LABA is effective and safe if the dose of ICS is adequate to treat airway inflammation. LABA and ICS given in a single device will negate the possibility of LABA monotherapy which is contraindicated. The FDA has recommended that LABAs be withdrawn when control is achieved with combination therapy but recent evidence suggests this may result in loss of symptom control.     

Comparing the efficacy and safety of salmeterol/fluticasone pMDI versus its mono-components,other LABA/ICS pMDIs and salmeterol/fluticasone Diskus in patients with asthma

Introduction: Pressurized metered dose inhalers (pMDIs) are evolving to be a very effective drug delivery option in patients with airway diseases. They offer comparable lung deposition and reduced oropharyngeal deposition similar with the dry powder inhalers. As recommended by the Global Initiative for Asthma guidelines, the ideal maintenance treatment for asthma is a combination of long acting β₂-agonists (LABAs) and inhaled corticosteroids (ICSs). One of the available LABA/ICS combinations is the salmeterol/fluticasone propionate combination (SFC) and a plethora of evidence supports its clinical efficacy and safety.

Areas covered: This article focuses on the SFC hydrofluroalkane pMDI and compares the efficacy and tolerability with salmeterol and fluticasone given individually, and with other fixed-dose combinations namely formoterol/fluticasone, formoterol/beclometasone and formoterol/mometasone furoate, all delivered via pMDI. Also discussed is the efficacy and tolerability of the SFC delivered via a pMDI, as compared to the SFC via Diskus.

Expert opinion: pMDIs play an important role in inhalation therapy given the low price, low maintenance and convenience of use. LABA/ICS combinations are the preferred choice of medication for asthma treatment and will remain the mainstay for the decades to come. In our opinion, pMDI should be the choice of device to administer LABA/ICS maintenance therapy, as it is already being used by the patients for reliever therapy, which may eventually improve patient adherence and compliance.     

The place of inhaled corticosteroids in chronic obstructive pulmonary disease

SUMMARY

The role of systemic corticosteroids in the treatment of exacerbations of chronic obstructive pulmonary disease (COPD) is well established. However, despite being frequently prescribed for the treatment of COPD, the clinical utility of inhaled corticosteroids (ICS) is less clearly defined.

While individual clinical and epidemiological studies have yielded conflicting results, meta-analysis of available data suggests that ICS may reduce the frequency and severity of exacerbations, the number of hospitalisations and the mortality rate, as well as yielding improvements in lung function and health-related quality of life (HRQL) in some subgroups of COPD patients. More recently, clinical trials evaluating the effect of combination therapy with ICS and long-acting β₂-agonists (LABA) have shown significant effects on the prevention of exacerbations and HRQL. Emerging data are expected to clarify the role of ICS in the management of patients with COPD of different severities as well as the place of treatment with ICS/LABA combinations in the management of this chronic and disabling disorder.