Desktop Helper No. 6 - Evaluation of appropriateness of inhaled corticosteroid (ICS) therapy in COPD and guidance on ICS withdrawal - online version

In COPD, evidence supports the use of an inhaled corticosteroid (ICS) in combination with a long acting beta-agonist (LABA) or as part of a triple therapy regimen with the addition of a long acting muscarinic-antagonist (LAMA) to reduce the risk of symptomatic exacerbations.1 The effect of these regimens (ICS/LAMA/LABA and ICS/ LABA vs LABA/LAMA) is greater in patients with high exacerbation risk (≥2 exacerbations and/or 1 hospitalization in the previous year).2–4 However, until recently there has been no consistent evidence on the long-term effects of ICS on mortality or the group of patients who would benefit most. (1)

Recent studies have shown that blood eosinophil counts predict the effect of ICS in preventing future exacerbations in COPD3,5 and they can be used as a biomarker to estimate the benefits of adding ICS to regular bronchodilator treatment for individual patients. (1)

For all patients with COPD, LABDs are recommended as first-line treatment. For patients whose disease is classified as GOLD ‘D’ (i.e. symptomatic with exacerbations) with a history of asthma or with blood eosinophil counts ≥300 cells/μL, initial therapy with LABA/ICS combination may be the first choice. (1) Patients with concomitant asthma should be treated with ICS combined with a LABA. (6) After initial therapy, clinical response should be reviewed and adjustments made to pharmacological treatment, increasing or decreasing therapy, to obtain optimal symptom control. When patients with COPD are experiencing increased breathlessness and other symptoms, adjustment of therapy to ensure maximal bronchodilation is warranted. Current guidelines do not recommend ICS therapy if deterioration is driven by symptoms. (1) In COPD patients who continue to experience frequent exacerbations despite appropriate bronchodilator therapy and have blood eosinophils <100 μL-1, ICS are not recommended unless the individual patient has a history of asthma; alternative treatments such as roflumilast and azithromycin can be considered. In patients with blood eosinophils >300 μL-1, the addition of ICS to LABA therapy is recommended. For patients with blood eosinophils of 100–300 μL-1, careful consideration of the potential benefits and risks of ICS therapy should be undertaken. (7)

1. Inital treatment:

a. Well documented previous history of asthma, especially if diagnosis under 40 years’ old
b. ≥2 moderate exacerbations or 1 hospitalization in the previous year and >300 eosinophils μL⁻¹

2. Reassessment^†

a. ≥2 moderate exacerbations or 1 hospitalization in the previous year* and >300 eosinophils μL^−1*
b. ≥2 moderate exacerbations or 1 hospitalization in the previous year* and eosinophils μL⁻¹ >100 but <300 after carefully balanced risk-benefit considering:
     o Recent pneumonia
     o Confirmed bacterial colonization
     o Bronchiectasis
     o Comorbidities, especially diabetes and osteoporosis or those at risk for these conditions

† Patient not previously on ICS
* Or since previous assessment if less than 12 months

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Updated COPD guidelines support ICS withdrawal (1) and recent studies indicate ICS can be withdrawn in both low- and high-risk patients, provided adequate bronchodilator therapy is in place. (9-17) A detailed review of these studies is in preparation. If you have a specific query in the meantime, please contact IPCRG businessmanager [at] ipcrg [dot] org.

1. Global Initiative for Chronic Obstructive Lung Disease (GOLD). 2020 Global Strategy for Prevention, Diagnosis and Management of COPD. Available at: https://goldcopd.org/gold-reports/
2. Wedzicha JA, et al. Indacaterol-glycopyrronium versus salmeterol-fluticasone for COPD. NEJM 2016;374:2222–34.
3. Lipson DA, et al. Once-daily single-inhaler triple versus dual therapy in patients with COPD. NEJM 2018;378:1671–80.
4. Papi A, et al. Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomised controlled trial. Lancet 2018;391:1076–84.
5. Bafadhel M, et al. Predictors of exacerbation risk and response to budesonide in patients with chronic obstructive pulmonary disease: a post-hoc analysis of three randomised trials. Lancet Respir Med 2018;6:117–26.
6. Global Initiative for Asthma (GINA) and Global Initiative for Obstructive Lung Disease (GOLD). Asthma, COPD and asthma-COPD overlap syndrome (ACOS), 2015. Available at: https://goldcopd.org/asthma-copd-asthma-copd-overlap-syndrome/
7. Agusti A, et al. Inhaled corticosteroids in COPD: friend or foe? Eur Respir J 2018;52(6)
8. Tsiligianni I, et al. COPD patients' characteristics, usual care, and adherence to guidelines: the Greek UNLOCK study. Int J Chron Obstruct Pulmon Dis 2019;14:547–56
9. Rossi A, et al. INSTEAD: a randomised switch trial of indacaterol versus salmeterol/fluticasone in moderate COPD. Eur Respir J 2014;44:1548–56
10. Rossi A, et al. Withdrawal of inhaled corticosteroids can be safe in COPD patients at low risk of exacerbation: a real-life study on the appropriateness of treatment in moderate COPD patients (OPTIMO). Respir Res 2014;15:77
11. Magnussen H, et al. Withdrawal of inhaled glucocorticoids and exacerbations of COPD. NEJM 2014;371:1285–94
12. Suissa S, et al. Discontinuation of inhaled corticosteroids in COPD and the risk reduction of pneumonia. Chest 2015;148:1177–83
13. Watz H, et al. Blood eosinophil count and exacerbations in severe chronic obstructive pulmonary disease after withdrawal of inhaled corticosteroids: a post-hoc analysis of the WISDOM trial. Lancet Respir Med 2016;4:390–8
14. Chapman KR, et al. Long-term triple therapy de-escalation to indacaterol/ glycopyrronium in patients with chronic obstructive pulmonary disease (SUNSET): A randomized, double-blind, triple-dummy clinical trial. Am J Respir Crit Care Med 2018;198:329–39
15. Vogelmeier CF, et al. Efficacy and safety of direct switch to indacaterol/ glycopyrronium in patients with moderate COPD: the CRYSTAL open-label randomised trial. Respir Res 2017;18:140
16. Frith PA, et al. Efficacy and safety of the direct switch to indacaterol/ glycopyrronium from salmeterol/fluticasone in non-frequently exacerbating COPD patients: the FLASH randomized controlled trial. Respirology 2018; 23:1152–9
17. Buhl R, et al. Dual bronchodilation vs triple therapy in the "real-life" COPD DACCORD study. Int J Chron Obstruct Pulmon Dis 2018;13:2557–68