Publications by authors named "Karen Mezzi"

18 Publications

  • Page 1 of 1

The Perception of Physicians on Gender-Specific Differences in the Diagnosis of COPD: Results from a Questionnaire-Based Survey.

Int J Chron Obstruct Pulmon Dis 2021 1;16:901-907. Epub 2021 Apr 1.

Medicines Evaluation Unit, University of Manchester, Manchester University NHS Foundations Trust, Manchester, UK.

Objective: To evaluate the perception of physicians on gender-specific differences in the diagnosis of chronic obstructive pulmonary disease (COPD) using a qualitative and anonymous questionnaire-based survey.

Methods: The survey was conducted amongst respiratory physicians attending a standalone educational conference (29-30 September 2017) using the SpotMe App. The 20-item standardized closed questionnaire had pre-coded responses to questions on physician's profile, and perception of COPD diagnosis and existing comorbidities between genders. All the responses were recorded anonymously.

Results: Of 368 physicians who downloaded the SpotMe App and had access to the survey, 132 (35.9%) completed the survey. Respondents were predominantly hospital-based (57.3%), aged 30-49 years (54.2%), male (56.5%), and from large cities (59.5%). 68.7% of physicians perceived the prevalence of COPD to be higher in men; over 50% of physicians perceived that women were more prone to the effects of smoking. More than 60% of physicians agreed that women experience more severe symptoms (anxiety and depression) and have reduced quality of life than men. Over 50% of physicians agreed that misdiagnosis/underdiagnosis of COPD in women was an important factor for gender-differences.

Conclusion: Results from this survey indicate that the understanding of COPD burden in women varies among healthcare professionals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/COPD.S271505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021252PMC
July 2021

The Impact of Exacerbation Frequency on Clinical and Economic Outcomes in Swedish COPD Patients: The ARCTIC Study.

Int J Chron Obstruct Pulmon Dis 2021;16:701-713. Epub 2021 Mar 18.

IQVIA Solutions, Real World Evidence Solutions, Copenhagen, Denmark.

Purpose: The aim of this study was to assess the association between exacerbation frequency and clinical and economic outcomes in patients with COPD.

Patients And Methods: Electronic medical record data linked to National Health Registries were collected from COPD patients at 52 Swedish primary care centers (2000-2014). The outcomes analyzed were exacerbation rate, mortality, COPD treatments, lung function and healthcare costs during the follow-up period. Based on the exacerbation rate two years before index date, the patients were initially classified into three groups, either 0, 1 or ≥2 exacerbations per year. After the index date, the classification into exacerbation groups was updated each year based on the exacerbation rate during the last year of follow-up. A sensitivity analysis was conducted excluding patients with asthma diagnosis from the analysis.

Results: In total 18,586 COPD patients were analyzed. A majority of the patients (60-70%) who either have had no exacerbation or frequent exacerbations (≥2/year) during the pre-index period remained in their group (ie, with 0 or ≥2 annual exacerbations) during up to 11 years of follow-up. Compared with having no exacerbation, mortality was higher in patients having 1 (HR; 2.06 [1.93-2.20]) and ≥2 (4.58 [4.33-4.84]) exacerbations at any time during the follow-up. Lung function decline was more rapid in patients with frequent exacerbations and there was an almost linear relationship between exacerbations frequency and mortality. Total healthcare costs were higher in the frequent exacerbation group (≥2/year) than in patients with no or one exacerbation annually (p<0.0001 for both). The results did not differ from the main analysis after exclusion of patients with a concurrent asthma diagnosis.

Conclusion: In addition to faster lung function decline and increased mortality, frequent exacerbations in COPD patients imply a significant economic burden.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/COPD.S297943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987259PMC
June 2021

Efficacy of indacaterol/glycopyrronium salmeterol/fluticasone in current and ex-smokers: a pooled analysis of IGNITE trials.

ERJ Open Res 2021 Jan 22;7(1). Epub 2021 Feb 22.

National Heart and Lung Institute, Imperial College London, London, UK.

Inhaled corticosteroids have proven to be less effective in asthmatic patients who smoke; however, there is limited information on the efficacy of inhaled corticosteroid-containing regimens in COPD patients who continue smoking. We evaluate the differential efficacy of once-daily indacaterol/glycopyrronium 110/50 µg compared with twice-daily salmeterol/fluticasone 50/500 µg in current smokers and ex-smokers with COPD. A pooled analysis of data from ILLUMINATE, LANTERN and FLAME studies was conducted to assess the efficacy of indacaterol/glycopyrronium compared with salmeterol/fluticasone in current smokers and ex-smokers with COPD. Efficacy was assessed in terms of improvements in trough forced expiratory volume in 1 s (FEV) transition dyspnoea index (TDI) focal score, St George's Respiratory Questionnaire (SGRQ) total score, reduced rescue medication use and exacerbation prevention at 26 weeks after the start of the therapy. In total, 1769 (38%) current smokers and 2848 (62%) ex-smokers were included. Patients treated with indacaterol/glycopyrronium experienced greater improvements in trough FEV salmeterol/fluticasone in both current and ex-smokers (least squares mean treatment difference, 105 mL and 78 mL, respectively). Improvements in TDI focal score, SGRQ total score and reduction in rescue medication use were also greater with indacaterol/glycopyrronium salmeterol/fluticasone in current and ex-smokers. Furthermore, indacaterol/glycopyrronium reduced all exacerbations (moderate/severe) compared with salmeterol/fluticasone, irrespective of smoking status. The difference in efficacy in favour of indacaterol/glycopyrronium was more prominent in current smokers in most cases. Indacaterol/glycopyrronium demonstrated greater efficacy salmeterol/fluticasone, and the differences were generally more prominent in current smokers suggesting smoking may reduce the effects of salmeterol/fluticasone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/23120541.00816-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897898PMC
January 2021

Inhaled corticosteroids and the risk of type 2 diabetes among Swedish COPD patients.

NPJ Prim Care Respir Med 2020 10 20;30(1):47. Epub 2020 Oct 20.

Integrative Toxicology, The National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

This study reports the association of ICS use and the risk of type 2 diabetes mellitus (T2DM) in Swedish patients with COPD using data from real-world, primary care settings. A total of 7078 patients with COPD were included in this analysis and the 5-year cumulative incidence rate per 100,000 person years was 1506.9. The yearly incidence rate per 100,000 person years ranged from 850 to 1919. Use of ICS especially at a high dose in patients with COPD was related to an increased risk of T2DM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41533-020-00207-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576803PMC
October 2020

Osteoporosis and fracture risk associated with inhaled corticosteroid use among Swedish COPD patients: the ARCTIC study.

Eur Respir J 2021 02 17;57(2). Epub 2021 Feb 17.

Intergrative Toxicology, National Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.

The effect of inhaled corticosteroids (ICS) on the risk of osteoporosis and fracture in patients with chronic obstructive pulmonary disease (COPD) remains uncertain. The aim of this study was to assess this risk in patients with COPD.Electronic medical record data linked to National Health Registries were collected from COPD patients and matched reference controls at 52 Swedish primary care centres from 2000 to 2014. The outcomes analysed were the effect of ICS on all fractures, fractures typically related to osteoporosis, recorded osteoporosis diagnosis, prescriptions of drugs for osteoporosis and a combined measure of any osteoporosis-related event. The COPD patients were stratified by the level of ICS exposure.A total of 9651 patients with COPD and 59 454 matched reference controls were analysed. During the follow-up, 19.9% of COPD patients had at least one osteoporosis-related event compared with 12.9% of reference controls (p<0.0001). Multivariate analysis in the COPD population demonstrated a dose-effect relationship, with high-dose ICS being significantly associated with any osteoporosis-related event (risk ratio 1.52 (95% CI 1.24-1.62)), while the corresponding estimate for low-dose ICS was 1.27 (95% CI 1.13-1.56) compared with COPD patients not using ICS. A similar dose-related adverse effect was found for all four of the specific osteoporosis-related events: all fractures, fractures typically related to osteoporosis, prescriptions of drugs for osteoporosis and diagnosis of osteoporosis.We conclude that patients with COPD have a greater risk of bone fractures and osteoporosis, and high-dose ICS use increased this risk further.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/13993003.00515-2020DOI Listing
February 2021

Adequacy of Therapy for People with Both COPD and Heart Failure in the UK: Historical Cohort Study.

Pragmat Obs Res 2020 2;11:55-66. Epub 2020 Jun 2.

Observational and Pragmatic Research Institute, Singapore, Singapore.

Purpose: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) often occur concomitantly, presenting diagnostic and therapeutic challenges for clinicians. We examined the characteristics of patients prescribed adequate versus inadequate therapy within 3 months after newly diagnosed comorbid COPD or HF.

Patients And Methods: Eligible patients in longitudinal UK electronic medical record databases had pre-existing HF and newly diagnosed COPD (2017 GOLD groups B/C/D) or pre-existing COPD and newly diagnosed HF. Adequate COPD therapy was defined as long-acting bronchodilator(s) with/without inhaled corticosteroid; adequate HF therapy was defined as beta-blocker plus angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker.

Results: Of 2439 patients with HF and newly diagnosed COPD (mean 75 years, 61% men), adequate COPD therapy was prescribed for 726 (30%) and inadequate for 1031 (42%); 682 (28%) remained untreated for COPD. Adequate (vs inadequate) COPD therapy was less likely for women (35%) than men (45%), smokers (36%) than ex-/non-smokers (45%), and non-obese (41%) than obese (47%); spirometry was recorded for 57% prescribed adequate versus 35% inadequate COPD therapy. Of 12,587 patients with COPD and newly diagnosed HF (mean 75 years, 60% men), adequate HF therapy was prescribed for 2251 (18%) and inadequate for 5332 (42%); 5004 (40%) remained untreated for HF. Adequate (vs inadequate) HF therapy was less likely for smokers (27%) than ex-/non-smokers (32%) and non-obese (30%) than obese (35%); spirometry was recorded for 65% prescribed adequate versus 39% inadequate HF therapy.

Conclusion: Many patients with comorbid COPD/HF receive inadequate therapy after new diagnosis. Improved equity of access to integrated care is needed for all patient subgroups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/POR.S250451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276330PMC
June 2020

COPD clinical control as a predictor of future exacerbations: concept validation in the SPARK study population.

Thorax 2020 04 10;75(4):351-353. Epub 2020 Feb 10.

National Heart Lung Institute, Airways Disease Section, Imperial College London, London, UK.

The concept of chronic obstructive pulmonary disease (COPD) control has been proposed to guide treatment decisions in COPD. In this study, we aimed to validate the prospective value of this concept in the SPARK study population. Control was assessed based on COPD stability and impact. Patients with low impact and stability during weeks 1-12 were classified as controlled, and exacerbations were measured during a 52-week follow-up. Of the 2044 patients included a majority were non-controlled (80%), frequently due to high impact. During the follow-up, the rate of moderate/severe exacerbations was significantly lower in controlled patients (rate ratio, 0.56, 95% CI 0.48 to 0.65 p<0.0001) and time-to-first moderate/severe exacerbation was significantly delayed. This study demonstrated an association between control status and risk of exacerbations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/thoraxjnl-2018-212752DOI Listing
April 2020

Gender differences among Swedish COPD patients: results from the ARCTIC, a real-world retrospective cohort study.

NPJ Prim Care Respir Med 2019 12 10;29(1):45. Epub 2019 Dec 10.

Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden.

The present study aimed to generate real-world evidence regarding gender differences among chronic obstructive pulmonary disease (COPD) patients, especially as regards the diagnosis and outcomes in order to identify areas for improvement and management and optimize the associated healthcare resource allocation. ARCTIC is a large, real-world, retrospective cohort study conducted in Swedish COPD patients and a matched reference population from 52 primary care centers in 2000-2014. The incidence of COPD, prevalence of asthma and other comorbidities, risk of exacerbations, mortality rate, COPD drug prescriptions, and healthcare resource utilization were analyzed. In total, 17,479 patients with COPD were included in the study. During the study period, COPD was more frequent among women (53.8%) and women with COPD experienced more exacerbations vs. men (6.66 vs. 4.66). However, the overall mortality rate was higher in men compared with women (45% vs. 38%), but no difference for mortality due to COPD was seen between genders over the study period. Women seemed to have a greater susceptibility to asthma, fractures, osteoporosis, rheumatoid arthritis, rhinitis, depression, and anxiety, but appeared less likely to have diabetes, kidney diseases, and cardiovascular diseases. Furthermore, women had a greater risk of COPD-related hospitalization and were likely to receive a significantly higher number of COPD drug prescriptions compared with men. These results support the need to reduce disease burden among women with COPD and highlight the role of healthcare professionals in primary care who should consider all these parameters in order to properly diagnose and treat women with COPD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41533-019-0157-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904454PMC
December 2019

Treatment response to indacaterol/glycopyrronium versus salmeterol/fluticasone in exacerbating COPD patients by gender: a post-hoc analysis in the FLAME study.

Respir Res 2019 Jan 8;20(1). Epub 2019 Jan 8.

Respiratory Medicine Department, University of Ioannina Medical School, Ioannina, Greece.

Background: The burden of chronic obstructive lung disease (COPD) is increasing in women, with recent evidence suggesting gender differences in disease characteristics and potentially in treatment outcomes.

Methods: FLAME was a 52-week randomized controlled trial in patients with severe-to-very-severe COPD and a history of exacerbations. In this post-hoc analysis, gender-based baseline differences and treatment outcomes between indacaterol/glycopyrronium 110/50 μg once daily (IND/GLY) and salmeterol/fluticasone 50/500 twice daily (SFC) were assessed in terms of rate of exacerbations, time-to-first exacerbation, lung function, health status, and rescue medication use.

Results: This post-hoc analysis included 2557 men and 805 women. Baseline characteristics differed between genders, with women being younger, having better lung function and more often experiencing ≥2 exacerbations in the previous year. Compared with SFC, IND/GLY treatment was associated with reductions in the annualized rates of moderate/severe exacerbations (rate ratio [95% CI]: 0.81 [0.73-0.91], 0.89 [0.74-1.07] in men and women, respectively). Similarly, time-to-first moderate/severe exacerbation was also delayed (hazard ratio [95% CI]: 0.79 [0.70-0.89] and 0.76 [0.63-0.91] in men and women, respectively). Results were similar for all (mild/moderate/severe) exacerbations. Improvements in lung function, health status and rescue medication use with IND/GLY vs SFC were comparable between men and women. The smaller sample size for women may account for some observed discrepancies in treatment responses.

Conclusions: Although there were gender differences in baseline characteristics, IND/GLY demonstrated similar trends for exacerbation prevention and lung function improvement in men and women with moderate-to-very-severe COPD and a history of exacerbations compared with SFC. Small differences in the effects seen between genders may be attributed to the different sizes of the two groups and need to be further evaluated in randomized trials that are appropriately powered for gender analysis.

Trial Registration: Post hoc analysis of the FLAME study. ClinicalTrials.gov number: NCT01782326 . Registered 1 February 2013.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12931-019-0972-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325763PMC
January 2019

Indacaterol/glycopyrronium versus salmeterol/fluticasone in the prevention of clinically important deterioration in COPD: results from the FLAME study.

Respir Res 2018 06 20;19(1):121. Epub 2018 Jun 20.

Respiratory Clinical Science, National Heart and Lung Institute, Imperial College London, London, UK.

Background: Chronic obstructive pulmonary disease (COPD) is a progressive disease and a composite endpoint could be an indicator of treatment effect on disease worsening. This post-hoc analysis assessed whether indacaterol/glycopyrronium (IND/GLY) 110/50 μg once daily reduced the risk of clinically important deterioration (CID) versus salmeterol/fluticasone (SFC) 50/500 μg twice daily in moderate-to-very severe COPD patients from the FLAME study.

Methods: CID was defined as ≥100 mL decrease in forced expiratory volume in 1 s (FEV) or ≥ 4-unit increase in St. George's Respiratory Questionnaire (SGRQ) total score or a moderate-to-severe COPD exacerbation. Changes from baseline in the rate of moderate and severe exacerbations, time to first moderate-to-severe exacerbation, and change from baseline in the SGRQ score, measured after Week 12 up to Week 52, were assessed by presence of early CID (CID+) or absence of CID (CID-) at Week 12.

Results: IND/GLY significantly delayed the time to CID (hazard ratio [HR] (95% confidence interval [CI]), 0.72 [0.67-0.78]; P < 0.0001), and reduced the incidences of CID versus SFC. Additionally, IND/GLY delayed the time to CID in all patient subgroups. After 12 weeks until 52 weeks, CID+ patients had a significantly higher rate of moderate-to-severe exacerbations versus CID- patients (P < 0.0001); moreover, CID+ patients experienced moderate-to-severe exacerbations significantly earlier versus CID- patients (P < 0.0001). CID+ patients had a comparable change in the SGRQ total score versus CID- patients.

Conclusions: IND/GLY reduced the risk of CID versus SFC. CID had a significant impact on long-term exacerbation outcomes in patients with moderate-to-very severe COPD and a history of ≥1 exacerbations in the previous year.

Trial Registration: Clinicaltrials.gov NCT01782326 .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12931-018-0830-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6011394PMC
June 2018

Efficacy of Indacaterol/Glycopyrronium in Patients with COPD Who Have Increased Dyspnea with Daily Activities.

Chronic Obstr Pulm Dis 2016 Sep 9;3(4):758-768. Epub 2016 Sep 9.

Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.

The Global initiative for chronic Obstructive Lung Disease (GOLD) recommends treating patients with chronic obstructive pulmonary disease (COPD) based on a combined assessment of symptom severity and airflow limitation and/or exacerbation risk. According to GOLD, patients with mild-to-moderate airflow limitation and distressing symptoms such as dyspnea should be treated with a long-acting beta2-agonist (LABA) or a long-acting muscarinic antagonist (LAMA). If symptoms persist on monotherapy, GOLD recommends a combination of bronchodilators (LABA/LAMA). We performed a post-hoc analysis of data from two 26-week, prospective clinical trials to investigate the effect of treating patients with moderate-to-severe dyspnea with the once-daily LABA/LAMA combination indacaterol/glycopyrronium (IND/GLY) 110/50 µg compared with placebo, once-daily tiotropium 18 µg, and twice-daily salmeterol/fluticasone propionate (SFC) 50/500 µg. In this analysis, a Baseline Dyspnea Index (BDI) score ≤7 was used to identify dyspneic patients. In dyspneic patients, IND/GLY significantly improved Transition Dyspnea Index (TDI) total scores compared with tiotropium (0.59 units; <0.05) and SFC (0.97 units; <0.05), and significantly increased the likelihood of a patient achieving a 1-unit improvement in TDI compared with tiotropium (odds ratio [OR] 1.87; <0.05). IND/GLY also significantly improved trough forced expiratory volume in 1 second (FEV) compared with tiotropium and SFC (<0.001 and <0.0001, respectively), and significantly reduced rescue medication use compared with tiotropium (0.001). Our analysis indicates that IND/GLY provides additional improvements in dyspnea and lung function compared with tiotropium and SFC in dyspneic patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15326/jcopdf.3.4.2016.0138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5556959PMC
September 2016

Response to Indacaterol/Glycopyrronium (IND/GLY) by Sex in Patients with COPD: A Pooled Analysis from the IGNITE Program.

COPD 2017 Aug 8;14(4):375-381. Epub 2017 Jun 8.

c Novartis Pharmaceuticals Corporation , East Hanover , NJ , USA.

In this pooled analysis, we compared the effect of indacaterol/glycopyrronium (IND/GLY) by sex versus other commonly used chronic obstructive pulmonary disease (COPD) treatments and placebo. Male and female patients with moderate-to-very-severe COPD who had participated in six randomized controlled trials were included in the analysis. Baseline demographics and disease characteristics were analyzed by sex, and any differences noted. The effects of IND/GLY versus salmeterol/fluticasone (SFC), glycopyrronium, tiotropium and placebo, on lung function and the patient-reported outcomes (health status, dyspnea, rescue medication use and symptoms) were assessed by sex after 26 weeks treatment. The analysis population comprised 4719 men and 1389 women. Most baseline parameters differed significantly between men and women. Nonetheless, despite these differences in baseline characteristics, IND/GLY significantly improved lung function versus placebo (p < 0.0001) and all active comparators (p < 0.01) in men and women. Overall, IND/GLY showed better improvement in dyspnea and health status compared with all other treatments in both sex. Greater reduction of rescue medication use was observed with IND/GLY versus placebo and other treatments (all p < 0.01 expect IND/GLY versus SFC). Although some variability was observed, improvements in health status, dyspnea, rescue medication use and symptoms were generally larger in women than in men. Irrespective of sex, IND/GLY provided superior efficacy to monotherapy or SFC in both men and women. Small differences in efficacy response by sex were observed, which should be evaluated further in prospective clinical studies. Nevertheless, the benefits observed with IND/GLY confirm dual bronchodilator as the preferred therapy in patients with moderate-to-very-severe COPD regardless of sex.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15412555.2017.1324837DOI Listing
August 2017

The effect of indacaterol/glycopyrronium versus tiotropium or salmeterol/fluticasone on the prevention of clinically important deterioration in COPD.

Int J Chron Obstruct Pulmon Dis 2017 4;12:1325-1337. Epub 2017 May 4.

Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States.

Background: Endpoints that evaluate deterioration rather than improvement of disease may have clinical utility in COPD. In this analysis, we compared the effects of different maintenance treatments on the prevention of clinically important deterioration (CID) in moderate-to-severe COPD patients.

Methods: Data were analyzed from three 26-week studies comparing indacaterol/glycopyrronium (IND/GLY) with tiotropium (TIO) or salmeterol/fluticasone (SFC). Two definitions of CID were used; each was a composite of three outcome measures typically associated with COPD. Definition 1 (D1) comprised a ≥100 mL decrease in forced expiratory volume in 1 second (FEV), a ≥4-unit increase in St George's Respiratory Questionnaire, and a moderate-to-severe COPD exacerbation. In Definition 2 (D2), a ≥1-unit decrease in transition dyspnea index replaced FEV.

Results: Using D1, IND/GLY significantly reduced the risk of first or sustained CID versus either TIO (hazard ratio 0.72 [0.61, 0.86], =0.0003 and 0.73 [0.61, 0.89], =0.001) or SFC (0.67 [0.57, 0.80] and 0.63 [0.52, 0.77], both <0.0001). With D2, IND/GLY significantly reduced the risk of first, but not sustained, CID versus TIO (0.80 [0.64 to 0.99], =0.0359 and 0.85 [0.66, 1.10], =0.2208) and both first and sustained CID versus SFC (0.73 [0.61, 0.88], =0.001 and 0.72 [0.58, 0.90], =0.0036).

Conclusion: These data confirm the utility of the CID endpoint as a means of monitoring COPD worsening in patients with moderate-to-severe COPD. Using the CID measure, we demonstrated that dual bronchodilation with IND/GLY significantly reduced the risk of CID versus either long-acting muscarinic antagonist or long-acting β-agonist/inhaled corticosteroid treatment, providing further evidence for the benefit of dual bronchodilation in this patient population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/COPD.S133307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5422319PMC
March 2018

Indacaterol/glycopyrronium in symptomatic patients with COPD (GOLD B and GOLD D) versus salmeterol/fluticasone: ILLUMINATE/LANTERN pooled analysis.

Int J Chron Obstruct Pulmon Dis 2016 14;11:3189-3197. Epub 2016 Dec 14.

Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.

Background: Indacaterol/glycopyrronium (IND/GLY) is approved for maintenance treatment of adult patients with COPD. This post hoc analysis explored the efficacy and safety of IND/GLY versus salmeterol/fluticasone (SFC) in symptomatic (Global Initiative for Chronic Obstructive Lung Disease [GOLD] B and GOLD D) patients with moderate-to-severe COPD.

Patients And Methods: Data from LANTERN and ILLUMINATE studies were pooled and analyzed. In both studies, symptomatic COPD patients were randomized to once-daily IND/GLY 110 μg/50 μg or twice-daily SFC 50 μg/500 μg. End points were pre-dose trough forced expiratory volume in one second (FEV), standardized area under the curve for FEV from 0 to 12 hours (FEV AUC hours), peak FEV, peak forced vital capacity (FVC), pre-dose trough FVC, Transition Dyspnea Index (TDI) total score, St George's Respiratory Questionnaire total score, rescue medication use and safety.

Results: A total of 1,263 patients were classified as either GOLD B (n=809) or GOLD D (n=454). At week 26, IND/GLY demonstrated statistically significant improvement in all lung function parameters versus SFC in patients in both the GOLD B and GOLD D subgroups. TDI total score and rescue medication use were significantly improved with IND/GLY versus SFC in the overall population and in the GOLD B (TDI total score only) and GOLD D (rescue medication only) subgroups. IND/GLY also reduced the rate of exacerbations in the pooled population. Overall safety profile was comparable with a higher incidence of pneumonia in the SFC-treated group.

Conclusion: In this pooled analysis, IND/GLY demonstrated superior efficacy compared with SFC in patients in the GOLD B and GOLD D subgroups and supported its use in symptomatic COPD patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/COPD.S116786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5167461PMC
August 2017

Cost-effectiveness of the LABA/LAMA dual bronchodilator indacaterol/glycopyrronium in a Swedish healthcare setting.

Respir Med 2014 Dec 2;108(12):1786-93. Epub 2014 Oct 2.

Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden.

Background: Indacaterol/glycopyrronium (IND/GLY) is a once-daily inhaled fixed-dose combination of indacaterol (IND), a long-acting β2-adrenergic agonist (LABA), and glycopyrronium (GLY), a long-acting muscarinic antagonist (LAMA) for use as maintenance treatment to relieve symptoms of chronic obstructive pulmonary disease (COPD) in adults.

Objective: To determine the economic benefits of IND/GLY compared with the free combination of indacaterol and glycopyrronium (IND + GLY), and with the fixed-dose combination of salmeterol/fluticasone (SFC), in a moderate-to-severe COPD population with low-exacerbation risk. The model-based analysis extrapolated results up to lifetime time horizon and calculated costs per quality-adjusted life year.

Methods: Assuming equal efficacy, a cost-minimisation analysis compared IND/GLY vs IND + GLY using model inputs from the double-blind, randomised SHINE trial. The double-blind, randomised ILLUMINATE and TORCH trials were used to analyse cost-effectiveness versus SFC. To consider ICS-related pneumonia events, published odds ratio comparing an ICS-exposed group to a control group of COPD patients was used. Direct and indirect drug costs as well as drug acquisition costs (in Swedish Krona [SEK]) were derived from published Swedish sources. Cost and effects were discounted with 3%. Uncertainty was assessed by one-way and probabilistic sensitivity analyses (PSA).

Results: IND/GLY was cost-saving vs IND + GLY with incremental savings of SEK (EUR) 768 (85), and 3309 (368) per patient over one and five years. IND/GLY was found to be less costly and more effective compared to SFC with cost savings of SEK (EUR) 2744 (303), 8854 (976), 13,938 (1536), 27,495 (3031) and 43,033 (4744) over one, three, five, ten years and lifetime. The PSA indicated that all iterations produced dominant results for IND/GLY.

Conclusion: IND/GLY is cost-minimising vs IND + GLY and dominates SFC in the maintenance treatment of COPD patients in Sweden. Encouraging dual bronchodilator therapy over an ICS-containing combination results in lower total costs and better outcomes compared to combination therapy including fluticasone in moderate-to-severe COPD patients with low exacerbation risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rmed.2014.09.015DOI Listing
December 2014

Lung deposition of HFA beclomethasone dipropionate in an animal model of bronchopulmonary dysplasia.

Pediatr Res 2007 Jan;61(1):21-5

INSERM U-618, Université François-Rabelais, Tours, F-37000, France.

The best delivery of a drug in ventilated neonates is obtained when using a small particle diameter solution administered via a spacer. Lung deposition of hydrofluoroalkane beclomethasone dipropionate (QVAR, 1.3 microm particles), delivered via an Aerochamber-MV15, was measured in piglets under conditions mimicking ventilated severely ill neonates (uncuffed 2.5 mm endotracheal tube; peak pressure 16 cm H2O; respiratory rate 40/min). After determining the mass and particle size distribution of the 99mTc-labeled and unlabeled drug, three lung deposition studies were performed: after 1 h of ventilation (controls, n = 18), after 48 h aggressive ventilation inducing an acute lung injury (nine piglets out of the controls), and after increasing the pressure to 24 cm H2O during drug delivery (five piglets out of the nine with acute lung injury). All piglets were then killed for lung histology. Results (median, range), expressed as a percentage of the delivered dose, were compared using an inferential or the Friedman test. While lung deposition was low, it was greater (p = 0.003) in controls (2.66%, 0.50-7.70) than in piglets with histologically confirmed acute lung injury (0.26%, 0.06-1.28) or under a high-pressure ventilation (1.01%, 0.30-2.15). Lung deposition of QVAR in an animal model of ventilated neonates is low, variable, and dramatically affected by lung injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1203/01.pdr.0000250055.26148.42DOI Listing
January 2007

[Control of asthma by treatment with inhaled corticosteroids and prolonged action beta 2-agonists in free or fixed combination. Results of the ALISE study].

Presse Med 2003 Mar;32(11):493-7

Service de pneumologie et réanimation, CHU Hôtel-Dieu, Paris.

Context: The basics of asthma treatment are well defined in the guidelines, however the criteria for the choice between fixed and free combinations of inhaled corticosteroids and long acting beta 2-agonist have not been clearly established.

Method: A modified Juniper questionnaire (using peak expiratory flow rather than maximal expiratory volume per second) was used by 421 general practitioners to assess asthma control in 861 adult patients (aged 47 +/- 17 years) having received inhaled corticosteroids and long-acting beta 2-agonist in a fixed (n = 413) or free (n = 448) combination for at least 6 weeks.

Results: Treatment groups were comparable for demographics, asthma history and severity as assessed by the physician. Despite better compliance to treatment in the fixed combination group and a mean daily dose of corticosteroids around two-fold greater compared with free combination group (913 +/- 450 micrograms/d vs 401 +/- 178 micrograms/d), the mean Juniper score was lower in the free combination group (1.60 +/- 0.94 vs 1.73 +/- 0.96) with a greater percentage of patients controlled (Juniper score < 2): 67.6% vs 60.8%. Other treatments for asthma were significantly less frequent with the free combination (14.2% vs 22.3%), as were local side effects and notably voice changes (3.3% vs 9.5%.

Comments: The apparently greater efficacy/safety ratio of the free combination was probably due to the greater severity of asthma in the patients treated with a fixed combination. This highlights the interest of free combinations as first-line therapy for patient with mild to moderate asthma.
View Article and Find Full Text PDF

Download full-text PDF

Source
March 2003
-->