Review ArticleClinical Review

Inhaled Corticosteroid Treatment in Chronic Obstructive Pulmonary Disease (COPD): Boon or Bane?

Alan G. Kaplan
The Journal of the American Board of Family Medicine March 2020, 33 (2) 289-302; DOI: https://doi.org/10.3122/jabfm.2020.02.190227

Article Figures & Data

Figures

  • Figure 1.
    Figure 1.

    GOLD ABCD assessment tool. Abbreviations: CAT, COPD Assessment Test; COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 second; FVC, forced viatal capacity; GOLD, Global Initiative for Chronic Obstructive Lung Disease; mMRC, modified British Medical Research Council questionnaire.

  • Figure 2.
    Figure 2.

    Treatment options for COPD. Abbreviations: COPD, chronic obstructive pulmonary disease; ICS, inhaled corticosteroid; LABA, long-acting β2-agonist; LAMA, long-acting antimuscarinic antagonist, PdE4, phosphodiesterase-4; SABD, short-acting bronchodilator.

  • Figure 3.
    Figure 3.

    A summary of recent ICS withdrawal studies. Abbreviations: BDP, beclomethasone dipropionate; CI, confidence interval; FF, fluticasone furoate; GLY, glycopyrronium, ICS, inhaled corticosteroid; FEV1, forced expiratory volume in 1 second; IND, indacaterol; LABA, long-acting β2-agonist; LAMA, long-acting antimuscarinic antagonist; NA, not applicable; SFC, salmeterol and fluticasone; UMEC, umeclidinium; VI, vilanterol; Tio, tiotropium.

  • Figure 4.
    Figure 4.

    A proposed step-by-step approach for ICS withdrawal in patients with COPD. Abbreviations: ACO, asthma-COPD overlap; CAT, COPD Assessment Test; CCQ9, Chronic COPD Questionnaire; COPD, chronic obstrutive pulmonary disease; FeNO, fractional exhaled nitric oxide; GINA, Global Initiative for Asthma; GOLD, Global Initiative for Chronic Obstructive Lung Disease; ICS, inhaled corticosteroid; LABA, long-acting β2-agonist; LABD, long-acting bronchodilator; LAMA, long-acting antimuscarinic antagonist; mMRC, modified British Medical Research Council questionnaire; ppb, parts per billion.

Tables

  • Table 1.

    Summary of Clinical Trials Comparing LABA + LAMA with LABA + ICS

    StudyLABA + LAMA vs LABA + ICSNumber of Patients RandomizedDurationLung FunctionExacerbation
    Magnussen et al, 2012 OCTANE46Tio (18 µg once daily) + SAL (50 µg twice daily) vs SFC (50/500 µg twice daily)3448 weeksRelative to SFC, Tio + SAL:
    -lowered postdose thoracic gas volume by 182 ± 44 mL after 4 weeks (P < .0001) and 87 ± 44 mL after 8 weeks (P < .05) -nonsignificantly increased exercise endurance time (20 ± 15 seconds at 4 weeks, 15 ± 13 seconds at 8 weeks)    		Tio + SAL vs SFC 29 (8.4%) vs 24 (7.3%)
    Vogelmeier et al, 2013 ILLUMINATE25IND + GLY (110/50 μg once daily) vs SFC (50/500 μg twice daily)52226 weeksIND + GLY vs SFC: -FEV1 AUC0 to 12 hours was significantly higher (treatment difference 138 mL; 95% CI: 100 to 176; P < .0001)COPD worsening including exacerbation was the most frequent serious AE: 0.4% (1/13) vs 1.1% (3/14) for IND + GLY vs SFC groups, respectively
    Hoshino et al, 201545Tio + IND (18/150 µg once daily) vs SFC (50/250 µg twice daily)4616 weeksTio + IND vs SFC IC was significantly higher (P = .043)
    -increase in Ai/BSA (r = 0.535, P = .011) -decrease in WA/BSA (r = −0.688, P < .001), WA/Ao (r = −0.555, P = .002), and T/√BSA (r = −0.542, P = .007)    		Not reported
    Donohue et al, 201544UMEC/VI (62.5/25 µg once daily) vs SFC (50/250 µg twice daily)70712 weeksUMEC/VI vs SFC -statistically significant, clinically meaningful improvements in wmFEV1 (study 1: 74 mL; 95% CI: 38 to 110; study 2: 101 mL; 95% CI: 63 to 139) -trough FEV1 (study 1: 82 mL; 95% CI: 45 to 119; study 2: 98 mL; 95% CI: 59 to 137) (all P < .001)Infrequent exacerbations
    Singh et al, 201547UMEC/VI (62.5/25 µg once daily) vs SFC (50/500 µg twice daily)71712 weeksUMEC/VI vs SFC -wmFEV1 (80 mL; 95% CI: 46 to 113) -trough FEV1 (90 mL; 95% CI: 55 to 125) (both P < .001)UMEC/VI vs SFC n = 8 vs 3
    Zhong et al, 2015 LANTERN26IND + GLY (110/50 μg once daily) vs SFC (50/500 μg twice daily)74426 weeksIND + GLY vs SFC -superiority for trough FEV1 (treatment difference = 75 mL; 95% CI: 44 to 107) -significant improvement in FEV1 AUC0 to 4 hours (treatment difference = 122 mL; 95% CI: 90 to 154) (both P < .001)IND + GLY vs SFC n = 53 vs 81
    Beeh et al, 2016 ENERGITO43Tio + Olo (5/5 μg and 2.5/5 μg once daily) vs SFC (50/500 μg and 50/250 μg twice daily)2296 weeksTio + Olo (5/5 μg) vs SFC (50/500 μg); Tio + Olo (5/5 μg) vs SFC (50/250 μg); Tio + Olo (2.5/5 μg) vs SFC (50/500 μg); and Tio + Olo (2.5/5 μg) vs SFC (50/250 μg)
    -FEV1 AUC0 to 12 adjusted mean (S.E.): 129 mL (11); 125 mL (11); 106 mL (11); 103 mL (11) (all P < .0001)    		Not reported
    Vogelmeier et al, 2016 AFFIRM48Aclidinium + formoterol (400/12 μg twice daily) vs SFC (50/500 μg twice daily)93324 weeksAclidinium + formoterol vs SFC-superiority for peak FEV1 (treatment difference = 93 mL; P < .0001)Aclidinium + formoterol vs SFC n = 74 vs 77 no difference in incidence
    Wedzicha et al, 2016 FLAME29IND + GLY (110/50 μg once daily) vs SFC (50/500 μg twice daily)336252 weeksIND + GLY vs SFC -significantly improved trough FEV1 (treatment difference = 62 mL; P < .001)IND + GLY vs SFC Superiority for reducing the annual rate of all COPD exacerbations (3.59 vs 4.03; RR, 0.89; 95% CI: 0.83 to 0.96; P = .003)
    Roche et al, 2017 FLAME27IND + GLY (110/50 μg once daily) vs SFC (50/500 μg twice daily)204852 weeksNot reportedIND + GLY vs SFC Significant reduction in annualized rate of moderate or severe exacerbations (RR, 0.80 [P = .004] and 0.85 [P = .010], respectively) and all exacerbations (RR, 0.84 [P = .004] and 0.90 [P = .030], respectively)

    • AE, adverse event; Ai, luminal area; Ao, total area of the airway; AUC, area under the curve; BSA, body surface area; CI, confidence interval; COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 second; GLY, glycopyrronium; ICS, inhaled corticosteroid; IND, indacaterol; IC, inspiratory capacity; LABA, long-acting β2-agonist; LAMA, long-acting antimuscarinic antagonist; Olo, olodaterol; RR, rate ratio; SAL, salmeterol; S.E., standard error; SFC, salmeterol + fluticasone; T, absolute wall thickness; Tio, tiotropium; UMEC, umeclidinium; VI, vilanterol; WA, airway wall area; wm, weighted mean.

  • Table 2.

    Current Clinical Trial Evidence for ICS-Based Therapy in Patients with COPD

    Characteristics of Patients with COPDReferences
    Patients with coexistent asthma or asthma historyLim et al, 201484
    Pascoe et al, 201556
    Ishiura et al, 201553
    Lee et al, 2016 (KOLD)54
    Lipson et al, 2018 (IMPACT)51
    Patients with eosinophils <600 cells/µLRoche et al, 2017 (FLAME)27
    Chapman et al, 2018 (SUNSET)85
    Patients on LABA/LAMA who continue to exacerbateSingh et al, 2016 (TRILOGY)67
    Vestbo et al, 2017 (TRINITY)70
    Lipson et al, 2017 (FULFIL)65
    Papi et al, 2018 (TRIBUTE)71
    Halpin et al, 2018 (FULFIL)86
    Patients with eosinophils ≥300 cells/µL and a history of ≥ 1 exacerbation in previous yearWatz et al, 2016 (WISDOM)77
    Wedzicha et al, 2016 (FLAME)29
    Calverley et al, 2017 (WISDOM)76
    Papi et al, 2018 (FLAME)87
    Chapman et al, 2018 (SUNSET)85
    Anzueto et al, 2018 (FLAME)88
    Patients with severe COPD and recalcitrant symptomsBourbeau et al, 201719

    • COPD, chronic obstructive pulmonary disease; ICS, inhaled corticosteroid; LABA, long-acting β2-agonist; LAMA, long-acting antimuscarinic antagonist.

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