Inhaled corticosteroids in COPD: friend or foe?

Agustí, Àlvar; Fabbri, Leonardo M.; Singh, Dave; Vestbo, Jørgen; Celli, Bartolomé R.; Franssen, Frits M.E.; Rabe, Klaus F.; Papi, Alberto

doi:10.1183/13993003.01219-2018

Cited by 182 publications

(192 citation statements)

References 139 publications

(211 reference statements)

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“…There has been considerable interest in whether blood or sputum eosinophilia may predict the efficacy of inhaled corticosteroids (ICS) in COPD patients . Treatment of COPD patients who have increased sputum eosinophils with increased doses of ICS did reduce exacerbations and oral corticosteroids reduce increased IL‐5 levels in sputum .…”

Section: Eosinophilic Copdmentioning

confidence: 99%

Inflammatory endotypes in COPD

Barnes

2019

Allergy

173

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Chronic obstructive pulmonary disease (COPD) is a major global health problem that is poorly treated by current therapies as it has proved difficult to treat the underlying inflammation, which is largely corticosteroid-resistant in most patients. Although rare genetic endotypes of COPD have been recognized, despite the clinical heterogeneity of COPD, it has proved difficult to identify distinct inflammatory endotypes.Most patients have increased neutrophils and macrophages in sputum, reflecting the increased secretion of neutrophil and monocyte chemotactic mediators in the lungs.However, some patients also have increased eosinophils in sputum and this may be reflected by increased blood eosinophils. Increased blood and sputum eosinophils are associated with more frequent exacerbations and predict a good response to corticosteroids in reducing and treating acute exacerbations. Eosinophilic COPD may represent an overlap with asthma but the mechanism of eosinophilia is uncertain as, although an increase in sputum IL-5 has been detected, anti-IL-5 therapies are not effective in preventing exacerbations. More research is needed to link inflammatory endotypes to clinical manifestations and outcomes in COPD and in particular to predict response to precision medicines. K E Y W O R D Sasthma-COPD overlap, eosinophil, exacerbations, interleukin-5, macrophage, neutrophil

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Section: Eosinophilic Copdmentioning

confidence: 99%

Inflammatory endotypes in COPD

Barnes

2019

Allergy

173

159

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“…Since blood eosinophil counts C 300 cellsÁll -1 could allow recognizing patients with a higher probability of taking advantage of ICS treatment, great importance is given to the use of ICS/LABA combinations when blood eosinophils are C 300 cellsÁll -1 , but also when patients are at high risk of AECOPDs (history of two or more moderate AECOPDs or one severe AECOPD in the previous year at [ 100 eosinophilsÁll -1 ) [8]. When the blood eosinophil count is \ 100 cellsÁll -1 , ICSs should not be administered unless patients are also asthmatic because at this value these drugs will probably not be able to prevent AECOPDs [26]. The real question is whether patients with 100-300 eosinophilsÁll -1 in the blood should be treated with ICSs because there is no solid documentation supporting such an approach.…”

Section: What Do These Meta-analyses Suggest?mentioning

confidence: 99%

Triple Therapy Versus Dual Bronchodilation and Inhaled Corticosteroids/Long-Acting β-Agonists in COPD: Accumulating Evidence from Network Meta-Analyses

et al. 2019

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Guidelines are mainly based on evidence of well-designed randomized controlled trials (RCTs), but there are limitations to the transferability of conclusions of RCTs to usual care mainly because the patients enrolled in RCTs are selected and not representative of the population encountered in daily practice; moreover, the research environment is substantially different from that of the real world. Because of the scarcity of data generated in large unselected populations in everyday clinical practice, the possibility of using meta-analyses can be considered. Recently, several meta-analyses have attempted to clarify the role of triple therapy containing a long-acting b-agonist (LABA), a long-acting muscarinic antagonist

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“…4,5 As many as 40% of patients with stable COPD may have eosinophilic inflammation, which is associated with an increased risk of exacerbations as well as glucocorticoid responsiveness. 6,7 Some studies have shown that elevated blood eosinophil counts are associated with an increased risk of exacerbations and that inhaled glucocorticoids are efficacious in preventing exacerbations in this population. [7][8][9][10][11] Targeted treatments to deplete blood eosinophils may also reduce the risk of COPD exacerbations.…”

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confidence: 99%

Benralizumab for the Prevention of COPD Exacerbations

et al. 2019

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T h e ne w e ngl a nd jou r na l o f m e dicine n engl j med nejm.org 1 The authors' full names, academic degrees, and affiliations are listed in the Appendix. Address reprint requests to Dr. BACKGROUNDThe efficacy and safety of benralizumab, an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody, for the prevention of exacerbations in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) are not known. METHODSIn the GALATHEA and TERRANOVA trials, we enrolled patients with COPD (at a ratio of approximately 2:1 on the basis of eosinophil count [≥220 per cubic millimeter vs. <220 per cubic millimeter]) who had frequent exacerbations despite receiving guideline-based inhaled treatment. Patients were randomly assigned to receive benralizumab (30 or 100 mg in GALATHEA; 10, 30, or 100 mg in TERRANOVA) every 8 weeks (every 4 weeks for the first three doses) or placebo. The primary end point was the treatment effect of benralizumab, measured as the annualized COPD exacerbation rate ratio (benralizumab vs. placebo) at week 56 in patients with baseline blood eosinophil counts of 220 per cubic millimeter or greater. Safety was also assessed. RESULTSIn GALATHEA, the estimates of the annualized exacerbation rate were 1.19 per year (95% confidence interval [CI], 1.04 to 1.36) in the 30-mg benralizumab group, 1.03 per year (95% CI, 0.90 to 1.19) in the 100-mg benralizumab group, and 1.24 per year (95% CI, 1.08 to 1.42) in the placebo group; the rate ratio as compared with placebo was 0.96 for 30 mg of benralizumab (P = 0.65) and 0.83 for 100 mg of benralizumab (P = 0.05). In TERRANOVA, the estimates of the annualized exacerbation rate for 10 mg, 30 mg, and 100 mg of benralizumab and for placebo were 0.99 per year (95% CI, 0.87 to 1.13), 1.21 per year (95% CI, 1.08 to 1.37), 1.09 per year (95% CI, 0.96 to 1.23), and 1.17 per year (95% CI, 1.04 to 1.32), respectively; the corresponding rate ratios were 0.85 (P = 0.06), 1.04 (P = 0.66), and 0.93 (P = 0.40). At 56 weeks, none of the annualized COPD exacerbation rate ratios for any dose of benralizumab as compared with placebo reached significance in either trial. Types and frequencies of adverse events were similar with benralizumab and placebo. CONCLUSIONSAdd-on benralizumab was not associated with a lower annualized rate of COPD exacerbations than placebo among patients with moderate to very severe COPD, a history of frequent moderate or severe exacerbations, and blood eosinophil counts of 220 per cubic millimeter or greater (Funded by AstraZeneca [GALATHEA and TERRANOVA] and Kyowa Hakko Kirin [GALATHEA]; GALATHEA and TERRANOVA ClinicalTrials.gov numbers, NCT02138916 and NCT02155660.)A BS TR AC T

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Inhaled corticosteroids in COPD: friend or foe?

Cited by 182 publications

References 139 publications

Inflammatory endotypes in COPD

Inflammatory endotypes in COPD

Triple Therapy Versus Dual Bronchodilation and Inhaled Corticosteroids/Long-Acting β-Agonists in COPD: Accumulating Evidence from Network Meta-Analyses

Benralizumab for the Prevention of COPD Exacerbations

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