scholarly journals Efficacy of umeclidinium/vilanterol versus umeclidinium and salmeterol monotherapies in symptomatic patients with COPD not receiving inhaled corticosteroids: the EMAX randomised trial

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
François Maltais ◽  
Leif Bjermer ◽  
Edward M. Kerwin ◽  
Paul W. Jones ◽  
Michael L. Watkins ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Inhaled Corticosteroids ◽  
Randomised Trial ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Short Term ◽  
Double Blind ◽  
Once Daily ◽  
Clinically Important Deterioration ◽  
Exacerbation Risk

Abstract Background Prospective evidence is lacking regarding incremental benefits of long-acting dual- versus mono-bronchodilation in improving symptoms and preventing short-term disease worsening/treatment failure in low exacerbation risk patients with chronic obstructive pulmonary disease (COPD) not receiving inhaled corticosteroids. Methods The 24-week, double-blind, double-dummy, parallel-group Early MAXimisation of bronchodilation for improving COPD stability (EMAX) trial randomised patients at low exacerbation risk not receiving inhaled corticosteroids, to umeclidinium/vilanterol 62.5/25 μg once-daily, umeclidinium 62.5 μg once-daily or salmeterol 50 μg twice-daily. The primary endpoint was trough forced expiratory volume in 1 s (FEV1) at Week 24. The study was also powered for the secondary endpoint of Transition Dyspnoea Index at Week 24. Other efficacy assessments included spirometry, symptoms, heath status and short-term disease worsening measured by the composite endpoint of clinically important deterioration using three definitions. Results Change from baseline in trough FEV1 at Week 24 was 66 mL (95% confidence interval [CI]: 43, 89) and 141 mL (95% CI: 118, 164) greater with umeclidinium/vilanterol versus umeclidinium and salmeterol, respectively (both p < 0.001). Umeclidinium/vilanterol demonstrated consistent improvements in Transition Dyspnoea Index versus both monotherapies at Week 24 (vs umeclidinium: 0.37 [95% CI: 0.06, 0.68], p = 0.018; vs salmeterol: 0.45 [95% CI: 0.15, 0.76], p = 0.004) and all other symptom measures at all time points. Regardless of the clinically important deterioration definition considered, umeclidinium/vilanterol significantly reduced the risk of a first clinically important deterioration compared with umeclidinium (by 16–25% [p < 0.01]) and salmeterol (by 26–41% [p < 0.001]). Safety profiles were similar between treatments. Conclusions Umeclidinium/vilanterol consistently provides early and sustained improvements in lung function and symptoms and reduces the risk of deterioration/treatment failure versus umeclidinium or salmeterol in symptomatic patients with low exacerbation risk not receiving inhaled corticosteroids. These findings suggest a potential for early use of dual bronchodilators to help optimise therapy in this patient group.

scholarly journals Salbutamol use in relation to maintenance bronchodilator efficacy in COPD: a prospective subgroup analysis of the EMAX trial

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
F. Maltais ◽  
I. P. Naya ◽  
C. F. Vogelmeier ◽  
I. H. Boucot ◽  
P. W. Jones ◽  
...  
Keyword(s):  
Inhaled Corticosteroids ◽  
Forced Expiratory Volume ◽  
Airflow Limitation ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Once Daily ◽  
Fractional Polynomial ◽  
Exacerbation Risk ◽  
Symptom Outcome ◽  
Post Hoc

Abstract Background Short-acting β2-agonist (SABA) bronchodilators help alleviate symptoms in chronic obstructive pulmonary disease (COPD) and may be a useful marker of symptom severity. This analysis investigated whether SABA use impacts treatment differences between maintenance dual- and mono-bronchodilators in patients with COPD. Methods The Early MAXimisation of bronchodilation for improving COPD stability (EMAX) trial randomised symptomatic patients with low exacerbation risk not receiving inhaled corticosteroids 1:1:1 to once-daily umeclidinium/vilanterol 62.5/25 μg, once-daily umeclidinium 62.5 μg or twice-daily salmeterol 50 μg for 24 weeks. Pre-specified subgroup analyses stratified patients by median baseline SABA use (low, < 1.5 puffs/day; high, ≥1.5 puffs/day) to examine change from baseline in trough forced expiratory volume in 1 s (FEV1), change in symptoms (Transition Dyspnoea Index [TDI], Evaluating Respiratory Symptoms-COPD [E-RS]), daily SABA use and exacerbation risk. A post hoc analysis used fractional polynomial modelling with continuous transformations of baseline SABA use covariates. Results At baseline, patients in the high SABA use subgroup (mean: 3.91 puffs/day, n = 1212) had more severe airflow limitation, were more symptomatic and had worse health status versus patients in the low SABA use subgroup (0.39 puffs/day, n = 1206). Patients treated with umeclidinium/vilanterol versus umeclidinium demonstrated statistically significant improvements in trough FEV1 at Week 24 in both SABA subgroups (59–74 mL; p < 0.001); however, only low SABA users demonstrated significant improvements in TDI (high: 0.27 [p = 0.241]; low: 0.49 [p = 0.025]) and E-RS (high: 0.48 [p = 0.138]; low: 0.60 [p = 0.034]) scores. By contrast, significant reductions in mean SABA puffs/day with umeclidinium/vilanterol versus umeclidinium were observed only in high SABA users (high: − 0.56 [p < 0.001]; low: − 0.10 [p = 0.132]). Similar findings were observed when comparing umeclidinium/vilanterol and salmeterol. Fractional polynomial modelling showed baseline SABA use ≥4 puffs/day resulted in smaller incremental symptom improvements with umeclidinium/vilanterol versus umeclidinium compared with baseline SABA use < 4 puffs/day. Conclusions In high SABA users, there may be a smaller difference in treatment response between dual- and mono-bronchodilator therapy; the reasons for this require further investigation. SABA use may be a confounding factor in bronchodilator trials and in high SABA users; changes in SABA use may be considered a robust symptom outcome. Funding GlaxoSmithKline (study number 201749 [NCT03034915]).

scholarly journals Single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy versus tiotropium monotherapy in patients with COPD

2021 ◽  
Vol 31 (1) ◽  
Author(s):  
Sandeep Bansal ◽  
Martin Anderson ◽  
Antonio Anzueto ◽  
Nicola Brown ◽  
Chris Compton ◽  
...  
Keyword(s):  
Health Status ◽  
Triple Therapy ◽  
Treatment Guidelines ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Fluticasone Furoate ◽  
Double Blind ◽  
Once Daily ◽  
Copd Patients ◽  
Severe Copd

AbstractChronic obstructive pulmonary disease (COPD) treatment guidelines do not currently include recommendations for escalation directly from monotherapy to triple therapy. This 12-week, double-blind, double-dummy study randomized 800 symptomatic moderate-to-very-severe COPD patients receiving tiotropium (TIO) for ≥3 months to once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 mcg via ELLIPTA (n = 400) or TIO 18 mcg via HandiHaler (n = 400) plus matched placebo. Study endpoints included change from baseline in trough forced expiratory volume in 1 s (FEV1) at Days 85 (primary), 28 and 84 (secondary), health status (St George’s Respiratory Questionnaire [SGRQ] and COPD Assessment Test [CAT]) and safety. FF/UMEC/VI significantly improved trough FEV1 at all timepoints (Day 85 treatment difference [95% CI] 95 mL [62–128]; P < 0.001), and significantly improved SGRQ and CAT versus TIO. Treatment safety profiles were similar. Once-daily single-inhaler FF/UMEC/VI significantly improved lung function and health status versus once-daily TIO in symptomatic moderate-to-very-severe COPD patients, with a similar safety profile.

scholarly journals Effects of umeclidinium/vilanterol on exercise endurance in COPD: a randomised study

2018 ◽  
Vol 4 (1) ◽  
pp. 00073-2017 ◽  
Author(s):  
John H. Riley ◽  
Chris J. Kalberg ◽  
Alison Donald ◽  
David A. Lipson ◽  
Muhammad Shoaib ◽  
...  
Keyword(s):  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Post Dose ◽  
Double Blind ◽  
Endurance Time ◽  
Obstructive Pulmonary Disease ◽  
Once Daily ◽  
Randomised Study ◽  
Residual Capacity ◽  
Exercise Endurance

This multicentre, randomised, double-blind, placebo-controlled, two-period crossover study assessed the effect of umeclidinium/vilanterol (UMEC/VI) on exercise capacity in patients with chronic obstructive pulmonary disease (COPD) using the endurance shuttle walk test (ESWT).Patients were randomised 1:1 to one of two treatment sequences: 1) UMEC/VI 62.5/25 µg followed by placebo or 2) placebo followed by UMEC/VI 62.5/25 µg. Each treatment was taken once daily for 12 weeks. The primary end-point was 3-h post-dose exercise endurance time (EET) at week 12. Secondary end-points included trough forced expiratory volume in 1 s (FEV1) and 3-h post-dose functional residual capacity (FRC), both at week 12. COPD Assessment Test (CAT) score at week 12 was also assessed.UMEC/VI treatment did not result in a statistically significant improvement in EET change from baseline at week 12 versus placebo (p=0.790). However, improvements were observed in trough FEV1 (206 mL, 95% CI 167–246), 3-h post-dose FRC (−346 mL, 95% CI −487 to −204) and CAT score (−1.07 units, 95% CI −2.09 to −0.05) versus placebo at week 12.UMEC/VI did not result in improvements in EET at week 12 versus placebo, despite improvements in measures of lung function, hyperinflation and health status.

scholarly journals Maintained therapeutic effect of revefenacin over 52 weeks in moderate to very severe Chronic Obstructive Pulmonary Disease (COPD)

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
James F. Donohue ◽  
Edward Kerwin ◽  
Sanjay Sethi ◽  
Brett Haumann ◽  
Srikanth Pendyala ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Health Outcomes ◽  
Pulmonary Disease ◽  
Inhaled Corticosteroids ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Open Label ◽  
Double Blind ◽  
Obstructive Pulmonary Disease ◽  
Long Acting

Abstract Background Revefenacin is a long-acting muscarinic antagonist that was recently approved for the nebulized treatment of chronic obstructive pulmonary disease (COPD). Although shorter duration studies have documented the efficacy of revefenacin in COPD, longer-term efficacy has not been described. In a recent 52-week safety trial, revefenacin was well tolerated and had a favorable benefit-risk profile. Here we report exploratory efficacy and health outcomes in patients receiving revefenacin 175 μg or 88 μg daily during the 52-week trial. Methods In this randomized, parallel-group, 52-week trial (NCT02518139), 1055 participants with moderate to very severe COPD received revefenacin 175 μg or 88 μg in a double-blind manner, or open-label active control tiotropium. Results Over the 52-week treatment period, both doses of revefenacin, as well as tiotropium, elicited significant (all p < 0.0003) improvements from baseline in trough forced expiratory volume in 1 s (FEV1). The trough FEV1 profile (least squares mean change from baseline) for revefenacin 175 μg ranged from 52.3–124.3 mL and the trough FEV1 profile for tiotropium ranged from 79.7–112.8 mL. In subgroup comparisons, the effect of revefenacin on trough FEV1 was comparable in patients taking concomitant long-acting β-agonists, with or without inhaled corticosteroids, with patients who were not taking these medications. There were statistically significant (p < 0.05) improvements in all measured health status outcomes (evaluated using St. George’s Respiratory Questionnaire, COPD Assessment Test, Clinical COPD Questionnaire and Baseline and Transition Dyspnea Index) from 3 months onward, in all treatment arms. Conclusions Significant sustained improvements from baseline in trough FEV1 and respiratory health outcomes were demonstrated for 175-μg revefenacin over 52 weeks, further supporting its use as a once-daily bronchodilator for the nebulized treatment of patients with COPD. Trial registration NCT02518139; Registered 5 August 2015.

scholarly journals Tiotropium and olodaterol fixed-dose combinationversusmono-components in COPD (GOLD 2–4)

2015 ◽  
Vol 45 (4) ◽  
pp. 969-979 ◽  
Author(s):  
Roland Buhl ◽  
François Maltais ◽  
Roger Abrahams ◽  
Leif Bjermer ◽  
Eric Derom ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Forced Expiratory Volume ◽  
Phase Iii ◽  
Fixed Dose ◽  
Chronic Obstructive ◽  
Double Blind ◽  
Obstructive Pulmonary Disease ◽  
Once Daily ◽  
Multicentre Phase ◽  
St George's Respiratory Questionnaire

Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials.Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-dailyviaRespimat inhaler over 52 weeks. Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0–3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks.In total, 5162 patients (2624 in Study 1237.5 and 2538 in Study 1237.6) received treatment. Both FDCs significantly improved FEV1 AUC0–3 and trough FEV1 responseversusthe mono-components in both studies. Statistically significant improvements in SGRQ total scoreversusthe mono-components were only seen for tiotropium+olodaterol FDC 5/5 μg. Incidence of adverse events was comparable between the FDCs and the mono-components.These studies demonstrated significant improvements in lung function and health-related quality of life with once-daily tiotropium+olodaterol FDCversusmono-components over 1 year in patients with moderate to very severe COPD.

scholarly journals Lung function, pharmacokinetics, and tolerability of inhaled indacaterol maleate and acetate in asthma patients

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
David Miller ◽  
Soniya Vaidya ◽  
Juergen Jauernig ◽  
Brian Ethell ◽  
Kristina Wagner ◽  
...  
Keyword(s):  
Lung Function ◽  
Systemic Exposure ◽  
Forced Expiratory Volume ◽  
Fixed Dose ◽  
Chronic Obstructive ◽  
Electronic Diary ◽  
Double Blind ◽  
Once Daily ◽  
Long Acting ◽  
Salt Forms

Abstract Background Indacaterol maleate delivered with the Breezhaler® inhalation device is a long-acting β2-agonist approved for chronic obstructive pulmonary disease. In the development of a once daily, inhaled fixed dose combination (FDC) of indacaterol, glycopyrronium bromide (a long-acting muscarinic antagonist), and mometasone furoate (an inhaled corticosteroid [ICS]) for the treatment of patients with asthma, the acetate salt of indacaterol is used instead of the maleate salt. Here, we investigated the lung function, pharmacokinetics (PK) and safety of indacaterol maleate 150 μg once daily (o.d.) and indacaterol acetate 150 μg o.d. in comparison with placebo. Methods This was a randomised, double-blind, three-period crossover study (ClinicalTrials.gov identifier, NCT03257995) in patients with asthma on background ICS therapy. Patients with percent predicted pre-bronchodilator forced expiratory volume per second (FEV1) ≥50% and ≤ 90% were included in the study. Patients received indacaterol maleate 150 μg o.d., indacaterol acetate 150 μg o.d., or placebo on top of stable background ICS in randomised sequence. Trough FEV1 was assessed after 14 days of treatment. PK of indacaterol salts were assessed at steady state after 14 days of treatment; peak expiratory flow (PEF) rate and rescue medication use were collected with a combined PEF-meter/electronic diary throughout the study. Results Of the 54 adult patients (median age of 48 years), 51 patients completed the study. Both indacaterol salts demonstrated statistically significant improvements in trough FEV1 of 186 mL (maleate) and 146 mL (acetate) compared with placebo (both P < 0.001). FEV1 AUC0-4h improved by 248 mL (maleate) and 245 mL (acetate), and PEF by 33 L/min (maleate) and 30.8 L/min (acetate) versus placebo. Systemic exposure of indacaterol (AUC0-24h,ss and Cmax,ss on Day 14) was comparable after administration of both salt forms. Both salt forms demonstrated a good safety profile and were well tolerated, with a difference in the reporting frequency of AEs of coughing (maleate, 23.5%; acetate, 0%). Conclusions In patients with asthma, indacaterol maleate and acetate elicited comparable and significant improvements in lung function compared with placebo and achieved comparable systemic exposure. Both indacaterol salts were safe and well tolerated. Trial registration ClinicalTrials.gov NCT03257995 June 06, 2017

scholarly journals Efficacy of umeclidinium/vilanterol according to the degree of reversibility of airflow limitation at screening: a post hoc analysis of the EMAX trial

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Claus F. Vogelmeier ◽  
Paul W. Jones ◽  
Edward M. Kerwin ◽  
Isabelle H. Boucot ◽  
François Maltais ◽  
...  
Keyword(s):  
Lung Function ◽  
Rescue Medication ◽  
Inhaled Corticosteroids ◽  
Full Range ◽  
Medication Use ◽  
Airflow Limitation ◽  
Chronic Obstructive ◽  
Double Blind ◽  
Once Daily ◽  
Post Hoc

Abstract Background In patients with chronic obstructive pulmonary disease (COPD), the relationship between short-term bronchodilator reversibility and longer-term response to bronchodilators is unclear. Here, we investigated whether the efficacy of long-acting bronchodilators is associated with reversibility of airflow limitation in patients with COPD with a low exacerbation risk not receiving inhaled corticosteroids. Methods The double-blind, double-dummy EMAX trial randomised patients to umeclidinium/vilanterol 62.5/25 µg once daily, umeclidinium 62.5 µg once daily, or salmeterol 50 µg twice daily. Bronchodilator reversibility to salbutamol was measured once at screening and defined as an increase in forced expiratory volume in 1 s (FEV1) of ≥ 12% and ≥ 200 mL 10−30 min post salbutamol. Post hoc, fractional polynomial (FP) modelling was conducted using the degree of reversibility (mL) at screening as a continuous variable to investigate its relationship to mean change from baseline in trough FEV1 and self-administered computerised-Transition Dyspnoea Index (SAC-TDI) at Week 24, Evaluating Respiratory Symptoms-COPD (E-RS) at Weeks 21–24, and rescue medication use (puffs/day) over Weeks 1–24. Analyses were conducted across the full range of reversibility (−850–896 mL); however, results are presented for the range −100–400 mL because there were few participants with values outside this range. Results The mean (standard deviation) reversibility was 130 mL (156) and the median was 113 mL; 625/2425 (26%) patients were reversible. There was a trend towards greater improvements in trough FEV1, SAC-TDI, E-RS and rescue medication use with umeclidinium/vilanterol with higher reversibility. Improvements in trough FEV1 and reductions in rescue medication use were greater with umeclidinium/vilanterol compared with either monotherapy across the range of reversibility. Greater improvements in SAC-TDI and E-RS total scores were observed with umeclidinium/vilanterol versus monotherapy in the middle of the reversibility range. Conclusions FP analyses suggest that patients with higher levels of reversibility have greater improvements in lung function and symptoms in response to bronchodilators. Improvements in lung function and rescue medication use were greater with umeclidinium/vilanterol versus monotherapy across the full range of reversibility, suggesting that the dual bronchodilator umeclidinium/vilanterol may be an appropriate treatment for patients with symptomatic COPD, regardless of their level of reversibility.

β 2-Adrenoceptor polymorphism and bronchoprotective sensitivity with regular short- and long-acting β2-agonist therapy

1999 ◽  
Vol 96 (3) ◽  
pp. 253-259 ◽  
Author(s):  
B. J. LIPWORTH ◽  
I. P. HALL ◽  
I. AZIZ ◽  
K. S. TAN ◽  
A. WHEATLEY
Keyword(s):  
Inhaled Corticosteroids ◽  
Forced Expiratory Volume ◽  
Double Blind ◽  
Geometric Means ◽  
Once Daily ◽  
Regular Treatment ◽  
Parallel Group ◽  
Long Acting ◽  
To Receive ◽  
Β2 Agonist

The aim of the present study was to investigate bronchoprotective sensitivity in patients receiving regular treatment with short- and long-acting β2-agonists and to evaluate any possible association with genetic polymorphism. Thirty-eight patients with stable mild to moderate asthma and receiving inhaled corticosteroids were randomized in a parallel group, double-blind, double-dummy fashion to receive 2 weeks of treatment with either formoterol (12μg once daily, 6μg twice daily or 24μg twice daily) or terbutaline (500μg four times daily). Bronchoprotection against methacholine challenge (as a provocative dose to produce a 20% fall in forced expiratory volume in 1.0 ;s: PD20) was measured at baseline (unprotected) after an initial 1 week run-in without β2-agonist, and at 1 ;h after the first and last doses of each treatment. The PD20 values were log-transformed and calculated as change from baseline. Percentage desensitization of log PD20 for first- versus last-dose bronchoprotection was calculated and analysed according to effects of treatment and β2-adrenoceptor polymorphism at codon 16 or 27. The mean degree of desensitization for bronchoprotection was comparable with all four treatments and there were no significant differences in absolute PD20 values after 2 weeks of chronic dosing. The PD20 values were (as μg of methacholine, geometric means±S.E.M.): formoterol, 12μg once daily, 99±42μg; formoterol, 6μg twice daily, 107±44μg; formoterol, 24μg twice daily, 108±45μg; terbutaline, 500μg four times daily, 88±37μg. All patients receiving formoterol, 24μg twice daily, exhibited a loss of protection greater than 30% which was unrelated to polymorphism at codon 16 or 27. For codon 16, the use of lower doses of formoterol (12μg once daily or 6μg twice daily) showed wider variability in the propensity for protection loss in patients who were heterozygous, in contrast to a more uniform protection loss seen with homozygous glycine patients. The amount of protection loss was not significantly related to polymorphism at codon 16 or 27, expressed as values (mean±S.E.M.) for percentage desensitization according to each genotype (pooled treatments): Gly-16, 66±11%; Het-16, 53±8%; Arg-16, 69±18%; Glu-27, 68±12%; Het-27, 58±8%; Gln-27, 52±12%. The results of this preliminary study showed that bronchoprotective desensitization occurred readily in response to short- or long-acting β2-agonist exposure irrespective of β2-adrenoceptor polymorphism at codon 16 or 27. Further studies with larger patient numbers are required to further evaluate the effects of polymorphisms with lower doses of regular formoterol.

scholarly journals Preventing clinically important deterioration with single-inhaler triple therapy in COPD

2018 ◽  
Vol 4 (4) ◽  
pp. 00047-2018 ◽  
Author(s):  
Ian Naya ◽  
Chris Compton ◽  
Afisi S. Ismaila ◽  
Ruby Birk ◽  
Noushin Brealey ◽  
...  
Keyword(s):  
Health Status ◽  
Lung Function ◽  
Chronic Obstructive Lung Disease ◽  
Chronic Obstructive ◽  
Double Blind ◽  
Obstructive Pulmonary Disease ◽  
Once Daily ◽  
Link Type ◽  
Clinically Important Deterioration ◽  
St George's Respiratory Questionnaire

Clinically important deterioration (CID) is a novel composite end-point (lung function, health status, exacerbations) for assessing disease stability in patients with chronic obstructive pulmonary disease (COPD).We prospectively analysed CID in the FULFIL study. FULFIL (ClinicalTrials.govNCT02345161; randomised, double-blind, double-dummy, multicentre study) compared 24 weeks of once daily, single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 µg with twice daily budesonide/formoterol (BUD/FOR) 400/12 μg in patients aged ≥40 years with symptomatic advanced COPD (Global Initiative for Chronic Obstructive Lung Disease group D). A subset of patients received study treatment for up to 52 weeks. Time to first CID event was assessed over 24 and 52 weeks using two approaches for the health status component: St George's Respiratory Questionnaire and COPD assessment test. FF/UMEC/VI significantly reduced the risk of a first CID event by 47–52% versus BUD/FOR in the 24- and 52-week populations using both CID definitions (p<0.001).The median time to first CID event was ≥169 days and ≤31 days with FF/UMEC/VI and BUD/FOR, respectively. Only stable patients with no CID at 24 weeks demonstrated sustained clinically important improvements in lung function and health status at 52 weeks versus those who had experienced CID.Once daily, single-inhaler FF/UMEC/VI significantly reduced the risk of CID versus twice daily BUD/FOR with a five-fold longer period without deterioration.

scholarly journals Modified and simplified clinically important deterioration: multidimensional indices of short-term disease trajectory to predict future exacerbations in patients with chronic obstructive pulmonary disease

2020 ◽  
Vol 14 ◽  
pp. 175346662097737
Author(s):  
Yi-yang Zhao ◽  
Cong Liu ◽  
Yu-qin Zeng ◽  
Ai-yuan Zhou ◽  
Jia-xi Duan ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Predictive Value ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Short Term ◽  
Predictive Capacity ◽  
Obstructive Pulmonary Disease ◽  
Disease Trajectory ◽  
Clinically Important Deterioration

Background and aims: Various prediction indices based on the single time point observation have been proposed in chronic obstructive pulmonary disease (COPD), but little was known about disease trajectory as a predictor of future exacerbations. Our study explored the association between disease trajectory and future exacerbations, and validated the predictive value of the modified and simplified short-term clinically important deterioration (CID). Methods: This study was a multicenter, prospective observational study. Patients with COPD were recruited into our study and followed up for 18 months. The modified CID (CID-C) was defined as a decrease of 100 mL in forced expiratory volume in 1 second (FEV1), or suffering exacerbations, or increase of 2 units in COPD Assessment Test (CAT) during the first 6 months follow-up. Simplified CID was defined when excluding CAT from the CID-C model. Results: A total of 127 patients were enrolled in our final analysis. Compared with patients without exacerbations during the period of the 6th to the 18th month, patients with exacerbations were more likely to have frequent short-term exacerbations in the first 6 months (2.14 versus 0.21, p < 0.001). The short-term exacerbations were the best predictor for future exacerbations [odds ratio (OR): 13.25; 95% confidence interval: 5.62–34.67; p < 0.001], followed by the history of exacerbation before study entry, short-term changes in FEV1 and CAT. CID-C and Simplified CID were both significantly associated with exacerbations (OR: 7.14 and 9.74, both p < 0.001). The receiver operating characteristic curves showed that the Simplified CID had slightly better predictive capacity for future exacerbation than CID-C (0.754 versus 0.695, p = 0.02). Conclusion: Disease trajectory, including both the CID-C and the Simplified CID had significant predictive value for future exacerbations. The reviews of this paper are available via the supplemental material section.

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