The effect of indacaterol/glycopyrronium versus tiotropium or salmeterol/fluticasone on the prevention of clinically important deterioration in COPD

Figures & data

Table 1 Definitions of first and sustained CID

Definition 1a	Definition 2
First CID (any of the following):	First CID (any of the following):
≥100 mL ↓ in trough FEV1 from baseline	≥1 unit ↓ in TDI score from baseline
≥4 unit ↑ in SGRQ score from baseline	≥4 unit ↑ in SGRQ score from baseline
An on-treatment moderate-to-severe COPD exacerbation	An on-treatment moderate-to-severe COPD exacerbation
Sustained CID (any of the following):	Sustained CID (any of the following):
≥100 mL ↓ in trough FEV1 from baseline on two consecutive visits at least 4 weeks apart, or on >50% of all subsequent visits	≥1 unit ↓ in TDI score from baseline on two consecutive visits at least 4 weeks apart, or on >50% of all subsequent visits
≥4 unit ↑ in SGRQ from baseline on two consecutive visits at least 4 weeks apart, or on >50% of all subsequent visits	≥4 unit ↑ in SGRQ from baseline on two consecutive visits at least 4 weeks apart, or on >50% of all subsequent visits
On-treatment moderate-to-severe COPD exacerbation	On-treatment moderate-to-severe COPD exacerbation

Note:

a As described by Singh et al, 2016.⁷

Abbreviations: CID, clinically important deterioration; FEV₁, forced expiratory volume in 1 second; SGRQ, St George’s Respiratory Questionnaire; TDI, transition dyspnea index.

Table 2 Patient demographics and baseline characteristics in SHINE and LANTERN/ILLUMINATE studies

Characteristic	SHINE^Citation8		LANTERN/ILLUMINATE^Citation11,Citation12
	IND/GLY 110/50 µg o.d. n=474	TIO 18 µg o.d. n=480	IND/GLY 110/50 µg o.d. n=630	SFC 50/500 µg b.i.d. n=633
Age, years	64.0 (8.9)	63.5 (8.7)	64.1 (8.0)	64.5 (7.8)
Male, n (%)	362 (76.4)	360 (75.0)	522 (82.9)	520 (82.1)
Current smoker, n (%)	192 (40.5)	189 (39.4)	219 (34.8)	223 (35.2)
COPD severity, n (%)
Mild	0	0	2 (0.32)	1 (0.16)
Moderate	313 (66.0)	296 (61.7)	399 (63.33)	407 (64.30)
Severe	161 (34.0)	184 (38.3)	226 (35.87)	221 (34.91)
BDI	6.45 (0.1)	6.46 (0.1)	6.5 (0.08)	6.5 (0.08)
ICS users at baseline, n (%)	268 (56.5)	282 (58.8)	291 (46.2)	298 (47.1)
Post-bronchodilator FEV1, % predicted	55.7 (13.2)	55.1 (13.5)	55.2 (12.7)	55.3 (12.6)
Number of COPD exacerbations in previous year, n (%)
0	352 (74.3)	363 (75.6)	569 (90.3)	539 (85.2)
1	94 (19.8)	93 (19.4)	60 (9.5)	94 (14.8)
≥2	28 (5.9)	24 (5.0)	1 (0.16)	0

Note: Data presented as mean (±SD), unless otherwise specified.

Abbreviations: BDI, Baseline Dyspnea Index; b.i.d., twice daily; FEV₁, forced expiratory volume in 1 second; ICS, inhaled corticosteroid; IND/GLY, indacaterol/glycopyrronium; o.d., once daily; TIO, tiotropium; SFC, salmeterol/fluticasone.

Figure 1 Kaplan–Meier curves and HR (95% CI) of time to first CID (A) and sustained CID (B) by D1 (SHINE study⁸).

Abbreviations: HR, hazard ratio; CI, confidence interval; CID, clinically important deterioration; D1, Definition 1; IND/GLY, indacaterol/glycopyrronium; TIO, tiotropium.

Figure 2 Kaplan–Meier curves and HR (95% CI) of time to first CID (A) and sustained CID (B) by D1 (LANTERN/ILLUMINATE^11,12).

Abbreviations: HR, hazard ratio; CI, confidence interval; CID, clinically important deterioration; D1, Definition 1; IND/GLY, indacaterol/glycopyrronium; SFC, salmeterol/fluticasone.

Figure 3 Kaplan–Meier curves and HR (95% CI) of time to first CID (A) and sustained CID (B) by D2 (SHINE study⁸).

Abbreviations: HR, hazard ratio; CI, confidence interval; CID, clinically important deterioration; D2, Definition 2; IND/GLY, indacaterol/glycopyrronium; TIO, tiotropium.

Figure 4 Kaplan–Meier curves and HR (95% CI) of time to first CID (A) and sustained CID (B) by D2 (LANTERN/ILLUMINATE^11,12).

Abbreviations: HR, hazard ratio; CI, confidence interval; CID, clinically important deterioration; D2, Definition 2; IND/GLY, indacaterol/glycopyrronium; SFC, salmeterol/fluticasone.

Figure 5 HRs and 95% CI (IND/GLY versus TIO) for first and sustained CID by subgroups in SHINE⁸ using D1 (A and B) and D2 (C and D).

Abbreviations: HR, hazard ratio; CI, confidence interval; CID, clinically important deterioration; D1, Definition 1; D2, Definition 2; IND/GLY, indacaterol/glycopyrronium; TIO, tiotropium.

Figure 6 HRs and 95% CI (IND/GLY versus SFC) for first and sustained CID by subgroups in LANTERN/ILLUMINATE^11,12 using D1 (A and B) and D2 (C and D).

Abbreviations: HR, hazard ratio; CI, confidence interval; CID, clinically important deterioration; D1, Definition 1; D2, Definition 2; IND/GLY, indacaterol/glycopyrronium; SFC, salmeterol/fluticasone.

Figure S1 Kaplan–Meier curves (with numbers of subjects at risk and 95% CIs) of time to first CID: IND/GLY versus TIO: SHINE¹: (A) time to first exacerbation, (B) time to first FEV₁ ≤ −100, (C) time to first SGRQ ≥4, (D) time to first TDI ≤ −1.

Abbreviations: CI, confidence interval; HR, hazard ratio; CID, clinically important deterioration; IND/GLY, indacaterol/glycopyrronium; TDI, Transition Dyspnea Index; TIO, tiotropium; FEV₁, forced expiratory volume in 1 second; SGRQ, St George’s Respiratory Questionnaire; trtp, treatment.

Figure S2 Kaplan–Meier curves (with numbers of subjects at risk and 95% CIs) of time to first CID: IND/GLY versus SFC: LANTERN/ILLUMINATE^2,3: (A) time to first exacerbation, (B) time to first FEV₁ ≤ −100, (C) time to first SGRQ ≥4, (D) time to first TDI ≤ −1.

Abbreviations: CI, confidence interval; HR, hazard ratio; CID, clinically important deterioration; IND/GLY, indacaterol/glycopyrronium; SFC, salmeterol/fluticasone; SGRQ, St George’s Respiratory Questionnaire; TDI, Transition Dyspnea Index; trtp, treatment.

Figure S3 Kaplan–Meier curves (with numbers of subjects at risk and 95% CIs) on the component of sustained CID for (A) IND/GLY versus TIO (SHINE¹) and (B) IND/GLY versus SFC (LANTERN/ILLUMINATE^2,3).

Abbreviations: CI, confidence interval; HR, hazard ratio; CID, clinically important deterioration; IND/GLY, indacaterol/glycopyrronium; TIO, tiotropium; SFC, salmeterol/fluticasone; trtp, treatment.

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