Dataset Information

Severe COPD Exacerbation Risk and Long-Acting Bronchodilator Treatments: Comparison of Three Observational Data Analysis Methods.

ABSTRACT:

Objective

Results from three observational methods for assessing effectiveness of long-acting bronchodilator therapies for reducing severe exacerbations of chronic obstructive pulmonary disease (COPD) were compared: intent-to-treat (ITT), as protocol (AP), and an as-treated analysis that utilized a marginal structural model (MSM) incorporating time-varying covariates related to treatment adherence and moderate exacerbations.

Study design and setting

Severe exacerbation risk was assessed over a 2-year period using claims data for patients aged ?40 years who initiated long-acting muscarinic antagonist (LAMA), inhaled corticosteroid/long-acting beta-agonist (ICS/LABA), or triple therapy (LAMA + ICS/LABA).

Results

A total of 5475 COPD patients met inclusion criteria. Six months post-initiation, 53.5 % of patients discontinued using any therapy. The ITT analysis found an increased severe exacerbation risk for triple therapy treatment (hazard ratio [HR] 1.24; 95 % confidence interval [CI] 1.00-1.53). No increased risk was found in the AP (HR 1.00; 95 % CI 0.73-1.36), or MSM analyses (HR 1.11; 95 % CI 0.68-1.81). The MSM highlighted important associations among post-index events.

Conclusion

Neglecting to adjust for treatment discontinuation may produce biased risk estimates. The MSM approach is a promising tool to compare chronic disease management by illuminating relationships between treatment decisions, adherence, patient choices, and outcomes.

SUBMITTER: Roberts MH

PROVIDER: S-EPMC4883193 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Publications

Severe COPD Exacerbation Risk and Long-Acting Bronchodilator Treatments: Comparison of Three Observational Data Analysis Methods.

Roberts Melissa H MH Mapel Douglas W DW Borrego Matthew E ME Raisch Dennis W DW Georgopoulos Larry L van der Goes David D

Drugs - real world outcomes 20150601 2

<h4>Objective</h4>Results from three observational methods for assessing effectiveness of long-acting bronchodilator therapies for reducing severe exacerbations of chronic obstructive pulmonary disease (COPD) were compared: intent-to-treat (ITT), as protocol (AP), and an as-treated analysis that utilized a marginal structural model (MSM) incorporating time-varying covariates related to treatment adherence and moderate exacerbations.<h4>Study design and setting</h4>Severe exacerbation risk was as ...[more]

PMID: 27747765

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Project description:Bronchodilation with muscarinic antagonists, β2-agonists, and inhaled corticosteroids remains the foundation of pharmaceutical treatment for patients with stable COPD. These drugs are delivered from a variety of devices, including dry powder inhalers, pressurized metered-dose inhalers, soft-mist inhalers, or nebulizers. Nebulized delivery is often preferable in patients who are elderly, are cognitively impaired, are unable to generate sufficient inspiratory force to use their inhaler, have difficulty coordinating hand-breath activity, are too dyspneic to hold their breath for a sufficient time, and/or may be acutely ill. Revefenacin, a once-daily long-acting muscarinic antagonist for nebulization recently approved by the US FDA for the treatment of patients with COPD, was discovered and developed using "duration and lung selectivity-by-design." This strategy selected a molecule with a high lung-selective index to maximize bronchodilation and limit systemic anti-muscarinic side effects. In early-phase clinical studies, revefenacin for nebulization led to a rapid onset of bronchodilation that was sustained for 24 hrs in patients with moderate to severe COPD. Revefenacin also demonstrated minimal systemic exposure and good tolerability in these studies. Statistically and clinically significant improvements in lung function (ie, peak and/or trough FEV1) relative to placebo were observed with revefenacin in Phase III clinical trials of up to 3 months in patients with moderate to very severe COPD. Revefenacin was well tolerated in Phase III clinical trials with a low incidence of systemic antimuscarinic adverse events, which is consistent with its lung-selective design. There was no evidence of an increased risk of major cardiovascular events. Patient-reported outcome data from clinical trials indicated statistically significant improvements in several disease-specific measures. Revefenacin 175 μg for nebulization provides an effective once-daily treatment option for patients with moderate to very severe COPD who require or prefer nebulized therapy.

Project description:BackgroundAcute exacerbations of chronic obstructive pulmonary disease (COPD) lead to a significant reduction in quality of life and an increased mortality risk. Current guidelines strongly recommend pulmonary rehabilitation (PR) after a severe exacerbation. Studies reporting referral for PR are scarce, with no report to date in Europe. Therefore, we assessed the proportion of French patients receiving PR after hospitalization for COPD exacerbation and factors associated with referral.MethodsThis was a national retrospective study based on the French health insurance database. Patients hospitalized in 2017 with COPD exacerbation were identified from the exhaustive French medico-administrative database of hospitalizations. In France, referral to PR has required as a stay in a specialized PR center or unit accredited to provide multidisciplinary care (exercise training, education, etc.) and admission within 90 days after discharge was assessed. Multivariate logistic regression was used to assess the association between patients' characteristics, comorbidities according to the Charlson index, treatment, and PR uptake.ResultsAmong 48,638 patients aged ≥ 40 years admitted for a COPD exacerbation, 4,182 (8.6%) received PR within 90 days after discharge. General practitioner's (GP) density (number of GPs for the population at regional level) and PR center facilities (number of beds for the population at regional level) were significantly correlated with PR uptake (respectively r = 0.64 and r = 0.71). In multivariate analysis, variables independently associated with PR uptake were female gender (aOR 1.36 [1.28-1.45], p < 0.0001), age (p < 0.0001), comorbidities (p = 0.0013), use of non-invasive ventilation and/or oxygen therapy (aOR 1.52 [1.41-1.64], p < 0.0001) and administration of long-acting bronchodilators (p = 0.0038).ConclusionThis study using the French nationally exhaustive health insurance database shows that PR uptake after a severe COPD exacerbation is dramatically low and must become a high-priority management strategy.

Project description:Background:Ideally, treatment recommendations for maintenance therapy-naïve patients with COPD should be based on studies conducted specifically in this population. We have reviewed evidence from previous studies of pharmacological treatments in maintenance therapy-naïve patients with COPD and performed a new post-hoc analysis of dual bronchodilator treatment in this population, aiming to assess the effectiveness of these interventions. Materials and methods:A literature review identified clinical trials that included analyses of patients with COPD who were maintenance therapy-naïve with long-acting ?2-agonists (LABA) or long-acting muscarinic antagonists (LAMA). Additionally, a post-hoc subgroup analysis was conducted for maintenance therapy-naïve patients with COPD in two large phase III, randomized, double-blind, 24-week trials investigating the efficacy of aclidinium bromide/formoterol fumarate (AB/FF) fixed-dose combination versus monotherapy or placebo (ACLIFORM [NCT01462942] and AUGMENT [NCT01437397]). Results:Treatment-naïve patients with COPD often represent a population of patients at the earliest stage at which most patients seek treatment. Of nine relevant studies identified, all reported positive findings for efficacy of LABA, LAMA, or LABA/LAMA treatment in maintenance therapy-naïve populations. Improvements were observed in lung function, symptoms, and health status versus monotherapy or placebo. Post-hoc analysis of ACLIFORM and AUGMENT demonstrated that AB/FF was effective in improving lung function in patients who had received no prior maintenance therapy. AB/FF showed improvements in 1 hr post-dose FEV1, trough FEV1, and patient-reported outcomes versus placebo and monotherapies. Combined with reviews of previous studies in maintenance therapy-naïve patients, these findings suggest that earlier intervention with a dual bronchodilator maintenance therapy, such as AB/FF, may provide significantly greater benefits than LAMA or LABA mono-bronchodilator therapy as a first maintenance treatment for COPD. Conclusion:These data show that therapeutic intervention is effective in treatment-naïve patients. Intervention with dual bronchodilator therapy as a first maintenance treatment for COPD may provide greater benefits than LAMA or LABA monotherapy.

Dataset Information

Severe COPD Exacerbation Risk and Long-Acting Bronchodilator Treatments: Comparison of Three Observational Data Analysis Methods.

Objective

Study design and setting

Results

Conclusion

Publications

Severe COPD Exacerbation Risk and Long-Acting Bronchodilator Treatments: Comparison of Three Observational Data Analysis Methods.

Similar Datasets

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