Rescue medication use as a patient-reported outcome in COPD: a systematic review and regression analysis

Abstract

BackgroundReducing rescue medication use is a guideline-defined goal of asthma treatment, however, little is known about the validity of rescue medicine use as a marker of symptoms in chronic obstructive pulmonary disease (COPD). To improve patient outcomes, greater insight is needed into the relationship between rescue medication use and alternative COPD outcomes.MethodsA systematic search of electronic databases (Embase®, MEDLINE® and Cochrane CENTRAL) was conducted from database start to 26 May, 2015. Studies of bronchodilator therapy with a duration of ≥24 weeks were included if they reported either mean change from baseline (CFB) in rescue medication use in puffs/day or % rescue-free days (%RFD), and at least one other COPD endpoint. Correlation and meta-regression analyses were undertaken to test the association between rescue medication use and other COPD outcomes using weighted means (weights proportional to the sample size of the treatment group) and unweighted means (equal weight for each treatment group). Each association was assessed at 6 months and study end.ResultsForty-six studies involving 46,531 patients provided mean data from 145 treatment groups for evaluation. Changes in both measures of rescue medication use were correlated with changes in trough forced expiratory volume in one second ([FEV1]; Pearson correlation coefficients |r| ≥ 0.63; p < 0.0001) and with St George’s Respiratory Questionnaire (SGRQ) score (|r| ≥ 0.70; p < 0.0001) at study end. Change in rescue medication use in puffs/day during the study correlated with annualized rates of moderate/severe exacerbations at 6 months and study end (both r = 0.66; p ≤ 0.0028). CFB in puffs/day was not well correlated with Transition Dyspnoea Index (TDI), but %RFD did correlate with TDI score at 6 months and study end (both r = 0.69; p < 0.0001). The values for CFB in puffs/day corresponding to the proposed minimal clinically important differences for trough FEV1 and SGRQ score were -1.3 and -0.6 puffs/day, respectively. A -1.0 puffs/day CFB in rescue use corresponded to a change of 0.26 events/patient-year in moderate/severe exacerbations.ConclusionThis analysis provides clear evidence of associations at a patient group level between rescue medication use and other clinically important COPD outcomes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-017-0566-1) contains supplementary material, which is available to authorized users.

<p>Evaluation of Medication Adherence and Rescue Medication Use in Non-Exacerbating Patients with COPD Receiving Umeclidinium/Vilanterol or Budesonide/Formoterol as Initial Maintenance Therapy</p>

“… 12 , 13 Rescue medication use is an important indicator of disease severity and exacerbation risk. 8 – 11 , 14 In a systematic review including 46 studies reporting rescue medication use and other outcomes in patients with COPD, rescue medication use was negatively correlated with lung function and dyspnea and positively correlated with health status over 6 months. 8 A retrospective claims-based study of patients with COPD diagnoses showed a relationship between filled prescriptions for rescue medications and exacerbations over 1 year of follow-up.…”

“…Adherence to inhaled maintenance therapy is critical to the management of COPD symptoms. 5 – 7 Greater rescue medication use is associated with worse lung function, more severe COPD symptoms, impaired health status, and increased risk of exacerbations; 8 – 11 therefore, it may be considered a marker of inadequate treatment or treatment adherence. Medications associated with increased adherence and reduced rescue medication use may, therefore, provide better control of COPD symptoms.…”

<p>The Effect of Baseline Rescue Medication Use on Efficacy and Safety of Nebulized Glycopyrrolate Treatment in Patients with COPD from the GOLDEN 3 and 4 Studies</p>

“…2 In a recent meta-analysis of 46,531 patients from 46 studies, rescue medication use correlated with clinically important COPD outcomes, including trough forced expiratory volume in 1 second (FEV 1 ), St. George's Respiratory Questionnaire (SGRQ), and annualized moderate or severe exacerbation rates. 3 While many studies have assessed the impact of treatment on rescue medication use, there are limited analyses of the impact of the level of rescue medication use at baseline on the efficacy and safety of longacting bronchodilators in patients with COPD. In one such analysis, patient stratification based on baseline use of rescue medications did not impact the efficacy and safety of QVA149 compared with placebo or salmeterol/fluticasone combination.…”

Impact of doxofylline in COPD: a pair-wise meta-analysis

“…The results of this pairwise meta-analysis confirm that doxofylline is effective and safe when administered to COPD patients. Compared to the control, doxofylline significantly improves lung function and dyspnea, and reduces the daily use of rescue medication more than the proposed minimal clinically important difference (MCID) values for COPD outcomes [42]. Similarly to all xanthines, it induces some AEs, but they are mild in severity.…”