Dataset Information

Blood eosinophil count, a marker of inhaled corticosteroid effectiveness in preventing COPD exacerbations in post-hoc RCT and observational studies: systematic review and meta-analysis.

ABSTRACT:

Background

Blood eosinophil count has been proposed as a predictor of response to inhaled corticosteroid (ICS) in the prevention of acute exacerbations of COPD. An optimal threshold of blood eosinophil count for prescribing ICS has not been agreed. Doubt has been cast on the role by observational studies. The role of inhaled corticosteroids in this relationship, independent of long-acting bronchodilators, has not been examined.

Methods

We conducted a systematic review of post-hoc analyses of randomised controlled trials (RCTs) and observational studies examining three blood eosinophil thresholds and the independent role of ICS. Included studies were categorised by the form (relative or absolute count) and cut point of eosinophil threshold used. Thresholds assessed were relative eosinophil count of 2%, and absolute counts of 150 cells/?L and 300 cells/?L. Three meta-analyses of the effect of ICS use in post-hoc analyses of RCTs based on these counts were carried out. Initial analysis included all studies of ICS vs. any non-ICS regimen. Further analysis examined the effect of ICS, independent of the effect of long-acting bronchodilators.

Results

Sixteen studies examined the association between blood eosinophil count and response of exacerbation risk to ICS, in COPD patients. Eleven studies (25,881 patients) were post-hoc analyses of RCTs. Five studies (109,704 patients) were retrospective observational studies. The independent effect of ICS on the reduction of exacerbation risk was 20% at ?2% blood eosinophil threshold (RR, 0.80; 95% CI, 0.74-0.85), 35% at ?150 cells/?L blood eosinophil threshold (RR, 0.65; 0.52-0.79), and 39% at ?300 cells/?L blood eosinophil threshold (RR, 0.61; 0.44-0.78). No association was found in four out of five observational studies.

Conclusion

This is the first systematic review to assess, in post-hoc analyses of RCTs, the independent effect of ICS in reducing the risk of COPD exacerbation across a range of blood eosinophil thresholds. Association between ICS prescription and reduced exacerbation risk at these thresholds was confirmed. The lack of association found in the observational studies questions the relevance of these observations to a "real world" COPD population. To clarify the clinical utility of this biomarker, the association should be tested in prospective effectiveness studies.

SUBMITTER: Harries TH

PROVIDER: S-EPMC6942335 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Blood eosinophil count, a marker of inhaled corticosteroid effectiveness in preventing COPD exacerbations in post-hoc RCT and observational studies: systematic review and meta-analysis.

Harries Timothy H TH Rowland Victoria V Corrigan Christopher J CJ Marshall Iain J IJ McDonnell Lucy L Prasad Vibhore V Schofield Peter P Armstrong David D White Patrick P

Respiratory research 20200103 1

<h4>Background</h4>Blood eosinophil count has been proposed as a predictor of response to inhaled corticosteroid (ICS) in the prevention of acute exacerbations of COPD. An optimal threshold of blood eosinophil count for prescribing ICS has not been agreed. Doubt has been cast on the role by observational studies. The role of inhaled corticosteroids in this relationship, independent of long-acting bronchodilators, has not been examined.<h4>Methods</h4>We conducted a systematic review of post-hoc ...[more]

PMID: 31900184

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Project description:IntroductionAssessing clinically important measures of disease progression is essential for evaluating therapeutic effects on disease stability in chronic obstructive pulmonary disease (COPD). This analysis assessed whether providing additional bronchodilation with the long-acting muscarinic antagonist umeclidinium (UMEC) to patients treated with inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) therapy would improve disease stability compared with ICS/LABA therapy alone.MethodsThis integrated post hoc analysis of four 12-week, randomized, double-blind trials (NCT01772134, NCT01772147, NCT01957163, NCT02119286) compared UMEC 62.5 µg with placebo added to open-label ICS/LABA in symptomatic patients with COPD (modified Medical Research Council dyspnea scale score ≥ 2). A clinically important deterioration (CID) was defined as: a decrease from baseline of ≥ 100 mL in trough forced expiratory volume in 1 s (FEV1), an increase from baseline of ≥ 4 units in St George's Respiratory Questionnaire (SGRQ) total score, or a moderate/severe exacerbation. Risk of a first CID was evaluated in the intent-to-treat (ITT) population and in patients stratified by Global initiative for chronic Obstructive Lung Disease (GOLD) classification, exacerbation history and type of ICS/LABA therapy. Adverse events (AEs) were also assessed.ResultsOverall, 1637 patients included in the ITT population received UMEC + ICS/LABA (n = 819) or placebo + ICS/LABA (n = 818). Additional bronchodilation with UMEC reduced the risk of a first CID by 45-58% in the ITT population and all subgroups analyzed compared with placebo (all p < 0.001). Improvements were observed in reducing FEV1 (69% risk reduction; p < 0.001) and exacerbation (47% risk reduction; p = 0.004) events in the ITT population. No significant reduction in risk of a SGRQ CID was observed. AE incidence was similar between treatment groups.ConclusionSymptomatic patients with COPD receiving ICS/LABA experience frequent deteriorations. Additional bronchodilation with UMEC significantly reduced the risk of CID and provided greater short-term stability versus continued ICS/LABA therapy in these patients.FundingGlaxoSmithKline (study number: 202067). Plain language summary available for this article.

Project description:OBJECTIVES:Presently, those outcomes that should be prioritised for chronic obstructive pulmonary disease (COPD) exacerbation studies remain unclear. In order to coordinate multicentre studies on eosinophilia-driven corticosteroid therapy for patients hospitalised for acute exacerbation of COPD (AECOPD), we aimed to find consensus among experts in the domain regarding the prioritisation of outcomes. DESIGN:A modified Delphi study was proposed to recognised COPD experts. Two brainstorming questionnaires were used to collect potential outcomes. Four subsequent rounds of questionnaires were used to rank items according to a six-point Likert scale for their importance in the protocol, as well as for being the primary outcome. Priority outcome criteria were predefined as those for which ?70% of experts indicated that the outcome was essential for interpreting study results. SETTING:COPD exacerbation management in France. PARTICIPANTS:34 experts recommended by the French Language Pulmonology Society were invited to participate. Of the latter, 21 experts participated in brainstorming, and 19 participated in all four ranking rounds. RESULTS:105 outcomes were ranked. Two achieved consensus as candidate primary outcomes: (1) treatment failure defined as death from any cause or the need for intubation and mechanical ventilation, readmission because of COPD or intensification of pharmacologic therapy, and (2) the time required to meet predefined discharge criteria. The 10 secondary priority outcomes included survival, time with no sign of improvement, episodes of hospitalisation, exacerbation, pneumonia, mechanical or non-invasive ventilation and oxygen use, as well as comorbidities during the initial hospitalisation. CONCLUSIONS:This Delphi consensus project generated and prioritised a great many outcomes, documenting current expert views concerning a diversity of COPD endpoints. Among the latter, 12 reached consensus as priority outcomes for evaluating the efficacy of eosinophil-driven corticosteroid therapy in AECOPD inpatients. STUDY REGISTRATION:The eo-Delphi project/protocol was registered on 23 January 2018 at https://osf.io/4ahqw/.

Dataset Information

Blood eosinophil count, a marker of inhaled corticosteroid effectiveness in preventing COPD exacerbations in post-hoc RCT and observational studies: systematic review and meta-analysis.

Background

Methods

Results

Conclusion

Publications

Blood eosinophil count, a marker of inhaled corticosteroid effectiveness in preventing COPD exacerbations in post-hoc RCT and observational studies: systematic review and meta-analysis.

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