Early Clinically Important Improvement (ECII) and Exacerbation Outcomes in COPD Patients

Figures & data

Table 1 Definitions of ECII

ECII Definition	Lung Function (Trough FEV1)	Patient Reported Outcome
1	Improvement ≥100 mL	Reduction in SGRQ-C score ≥4 points
2	Improvement ≥100 mL	Reduction in CAT score ≥2 points

Note: ECII is defined as an improvement measured by reaching the MCID in both lung function and a patient-reported outcome at Week 4 or Week 12 compared with Day 1 measures.

Abbreviations: CAT, COPD assessment test; COPD, chronic obstructive pulmonary disease; ECII, Early Clinical Important Improvement; FEV₁, forced expiratory volume in 1 second; SGRQ-C, St. George’s Respiratory Questionnaire for COPD.

Table 2 Baseline Demographics and Clinical Characteristics (Full Analysis Set)

Characteristic	IND/GLY 110/50 µg q.d. (N = 1675)	SFC 50/500 µg b.i.d. (N = 1679)
Age, years	64.6 ± 7.89	64.5 ± 7.70
Men, n (%)	1295 (77.3)	1255 (74.7)
Current smoker, n (%)	660 (39.4)	667 (39.7)
Duration of COPD, years	7.2 ± 5.32	7.3 ± 5.44
Number of COPD exacerbations in the previous year, n (%)
0	1 (0.1)	1 (0.1)
1	1350 (80.6)	1352 (80.5)
≥2	324 (19.3)	325 (19.4)
Post-bronchodilator FEV1, % predicted	44.0 ± 9.47	44.1 ± 9.43
SGRQ-C total score	47.3 ± 15.83	47.2 ± 15.86
CAT total score	16.9 ± 7.06	16.6 ± 6.97

Note: Data presented as mean ± standard deviation unless otherwise specified.

Abbreviations: b.i.d., twice-daily; CAT, COPD assessment test; COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in 1 second; IND/GLY, indacaterol/glycopyrronium; q.d., once daily; SFC, salmeterol/fluticasone; SGRQ-C, St. George’s Respiratory Questionnaire for COPD.

Figure 1 Proportion of patients achieving ECII at Weeks 4 or 12. ECII definition 1: improvement in trough FEV₁ ≥100 mL and reduction in SGRQ-C total score ≥4; ECII definition 2: improvement in trough FEV₁ ≥100 mL and reduction in CAT score ≥2; n, number of patients who achieved ECII. N, number of patients who had Day 1 and post-baseline values (either at Week 4 or 12) corresponding to parameters used to evaluate ECII by the two definitions.

Abbreviations: CAT, COPD assessment test; COPD, chronic obstructive pulmonary disease; ECII, Early Clinical Important Improvement; FEV₁, forced expiratory volume in 1 second; SGRQ-C, St. George’s Respiratory Questionnaire for COPD.

Figure 2 Annualized rate of moderate or severe exacerbations by ECII definition at Weeks 4 and 12. The exacerbation rates were assessed from Week 4 to 52 or Week 12 to 52 in patients who achieved ECII at Week 4 or 12, respectively. ECII definition 1: improvement in trough FEV₁ ≥100 mL and reduction in SGRQ-C total score ≥4; ECII definition 2: improvement in trough FEV₁ ≥100 mL and reduction in CAT total score ≥2; n, number of patients included in this analysis. Moderate or severe COPD exacerbations starting from Week 4 or 12 and one day after date of last treatment are included.

Abbreviations: CAT, COPD assessment test; COPD, chronic obstructive pulmonary disease; ECII, Early Clinical Important Improvement; FEV₁, forced expiratory volume in 1 second; SGRQ-C, St. George’s Respiratory Questionnaire for COPD.

Figure 3 Time-to-first moderate or severe exacerbation from (A) Week 4; and (B) Week 12 to the end of treatment by ECII definitions. The time-to-first exacerbation was assessed from Week 4 to 52 or Week 12 to 52 in patients who achieved ECII at Week 4 or 12, respectively. ECII definition 1: improvement in trough FEV₁ ≥100 mL and reduction in SGRQ-C total score ≥4; ECII definition 2: improvement in trough FEV₁ ≥100 mL and reduction in CAT score ≥2. Moderate or severe COPD exacerbations starting from Week 4 or 12 and one day after date of last treatment are included.

Abbreviations: CAT, COPD assessment test; COPD, chronic obstructive pulmonary disease; ECII, Early Clinical Important Improvement; FEV₁, forced expiratory volume in 1 second; SGRQ-C, St. George’s Respiratory Questionnaire for COPD.

Figure 4 Proportion of patients achieving ECII with IND/GLY and SFC at (A) Week 4; and (B) Week 12. ECII definition 1: improvement in trough FEV₁ ≥100 mL and reduction in SGRQ-C total score ≥4; ECII definition 2: improvement in trough FEV₁ ≥100 mL and reduction in CAT total score ≥2; n, number of patients who achieved ECII at Week 4 or 12; N, number of patients corresponding to the respective treatment group included in the analysis.

Abbreviations: b.i.d., twice-daily; CAT, COPD assessment test; COPD, chronic obstructive pulmonary disease; ECII, Early Clinical Important Improvement; FEV₁, forced expiratory volume in 1 second; IND/GLY, indacaterol/glycopyrronium 110/50 μg o.d.; o.d. once-daily; OR, odds ratio; SFC, salmeterol/fluticasone 50/500 μg b.i.d.; SGRQ-C, St. George’s Respiratory Questionnaire for COPD.