A Real World Study to Assess the Effectiveness of Switching to Once Daily Closed Triple Therapy from Mono/Dual Combination or Open Triple Therapy in Patients with Chronic Obstructive Pulmonary Disease

Figures & data

Figure 1 Patient enrollment flow chart. (A) A total 115 patients with COPD were stepped up to triple therapy from our hospital. (B) A total 130 patients with COPD were stepped up to triple therapy in our study, eighty-four patients (84/130, 64.6%) switched to single-inhaler triple therapy.

Table 1 Baseline Characteristics of Study Patients: Group 1, The Duration from Initial Treatment of COPD to Triple Therapy Was More Than 22 Months; Group 2, The Duration from Initial Treatment of COPD to Triple Therapy Was Less Than 22 Months

	Shift to Triple ≥ 22 m (n=52) Group 1	Shift to Triple ‹ 22 m (n=63) Group 2	p-value
Age, years (SD)	64.6±10	67.9±9.9	0.075
Sex, male (%)	48(92.3)	62(98.1)	0.217
BMI, Kg/m2	23.9±4.14	22.8±4.36	0.188
Smoking, pack-years	43.1±31.5	53.6±31.9	0.089
Blood Eosinophil cells/uL	434.5±375.1	489.6±660.8	0.589
AE ≥ 1 last year (%)	16(30.8)	29(46.0)	0.096
AE, last year	0.36±0.62	0.60±0.75	0.071
Initial FEV1, L	1.31±0.39	1.23±0.57	0.402
Initial FEV1 (%)	51.5±16.37	45.8±16.39	0.066
Initial FEV1/FVC (%)	56.6±10.7	55.1±11.2	0.445
Initial RV (%)	217.3±82.0	194.3±72.7	0.244
GLOD (%)			0.063
I	3(5.8)	1(1.6)
II	23(44.2)	23(36.5)
III	22(42.3)	28(44.4)
IV	4(7.7)	11(17.5)
Group (%)			0.036
B	28(53.8)	32(50.8)
C	8(15.4)	2(3.2)
D	16(30.8)	29(46.0)
Reversible airway (%)	24(46.2)	16(25.4)	0.021
Initial CAT score	9.6±4.3	10.2±5.2	0.531
Initial mMRC ≥ 2 (%)	34(65.4)	44(71.0)	0.524
Comorbidity (%)
HTN	16(30.8)	19(30.2)	0.943
CHF	3(5.8)	4(6.3)	1.000
Asthma	3(5.8)	10(10.9)	0.137
Bronchiectasis	4(7.7)	3(4.8)	0.699
Cancer	2(3.8)	8(12.7)	0.110
Initial treatment (%)			0.003
LABA or LAMA	19(36.5)	15(23.8)
ICS/LABA	21(40.4)	14(22.2)
LABA and LAMA	12(23.1)	34(54.0)

Abbreviations: BMI, Body Mass Index; AE, Acute Exacerbation; RV, Residual Volume; GOLD, Global Initiative for Chronic Obstructive Lung Disease; CAT, COPD Assessment Test; mMRC, Modified Medical Research Council; HTN, Hypertension; CHF, Congestive Heart Failure; ICS, inhaled glucocorticoid; LABA, long-acting β2-agonist; LAMA, a long-acting muscarinic antagonist.

Figure 2 (A) The median duration from receiving initial COPD treatment to inhaled triple therapy. (B) The duration from initial treatment to triple therapy was the shortest among those who were initially treated with dual bronchodilator therapy (median, 13.1 months; 9.1–18.8) followed by those who were initially treated with ICS/LABA (median, 26.3 months; 17.5–36.5), and those who were initially treated with a mono bronchodilator (28.2 months; 23.3–42.8; p < 0.001).

Table 2 Clinical Characteristics to Predict COPD Patient with Stepping Up to Triple Therapy Early

	Univariate			Multivariate
	HR	95% CI	p-value	HR	95% CI	p-value
Age, years	1.034	0.99–1.07	0.073	1.057	1.01–1.11	0.027
Smoking, pack years	1.012	0.99–1.03	0.075	1.011	0.99–1.03	0.186
AE, last year	1.678	0.95–2.96	0.065	2.151	1.04–4.44	0.038
FEV1(%)	0.978	0.96–1.01	0.063	0.973	0.94–1.01	0.066
Group “ABCD”	1.228	0.83–1.82	0.301	1.024	0.59–1.75	0.932
Reversible airway	0.397	0.18–0.87	0.019	0.235	0.08–0.64	0.004
Asthma	3.082	0.81–11.8	0.079	10.27	1.59–66.1	0.014
Initial Treatment	1.929	1.21–3.07	0.004	1.911	1.08–3.37	0.025

Abbreviation: AE, Acute Exacerbation.

Figure 3 (A) The reasons for the 115 patients switching from initial management to triple therapy. (B) The reasons for the 56 patients switching from open to closed triple therapy.

Table 3 The Shifting Treatment Strategies from the Different Initial Treatments

	Shifting to Triple Therapy			p-value
	ICS/LABA + LAMA N=58	LAMA/LABA +ICS N=29	Closed Triple N=28
Initial treatment, n (%)				0.003
LABA or LAMA	16(27.5)	10(34.5)	8(28.5)
ICS/LABA	27(46.5)	4(13.8)	4(14.2)
LABA/LAMA	15(25.8)	15(51.7)	16(57.1)

Abbreviations: ICS, inhaled glucocorticoid; LABA, long-acting β2-agonist; LAMA, a long-acting muscarinic antagonist.

Figure 4 (A) The mean annualized rate of moderate/severe exacerbations was 0.47 and 0.45 in the previous year before and after switching from initial to open triple therapy, respectively. (Δ = −0.027, p = 0.787). (B) The mean annualized rate of moderate/severe exacerbations was 0.38 and 0.25 in the previous year before and after switching from open to closed triple therapy, respectively. (Δ = −0.132, p = 0.047).

Figure 5 (A) The CAT scores were 10.02 and 9.61 before and after switching to ICS/LABA plus LAMA, respectively. (Δ = −0.407, p = 0.325). (B) The CAT scores were 9.16 and 9.56 before and after switching to LABA/LAMA plus ICS, respectively. (Δ = 0.400, p = 0.613). (C) The mMRC scales were both 1.98 before and after switching to ICS/LABA plus LAMA, respectively. (Δ = 0, p = 1.00). (D) The mMRC scales were 1.60 and 1.96 before and after switching to LABA/LAMA plus ICS, respectively. (Δ = 0.360, p = 0.107).

Figure 6 (A) The CAT scores were 9.36 and 10.66 before and after switching to closed triple therapy from ICS/LABA plus LAMA, respectively. (Δ = 1.305, p = 0.019). (B) The CAT scores were 9.57 and 10.61 before and after switching to closed triple therapy from LABA/LAMA plus ICS, respectively. (Δ = 1.047, p = 0.351). (C) The mMRC scales were 1.88 and 1.94 before and after switching to closed triple therapy from ICS/LABA plus LAMA, respectively. (Δ = 0.055, p = 0.534). (D) The mMRC scales were 2.00 and 1.90 before and after switching to closed triple therapy from LABA/LAMA plus ICS, respectively. (Δ = −0.100, p = 0.162).

Figure 7 (A) The FEV1 values were 1.14 L and 1.25 L before and after switching to ICS/LABA plus LAMA, respectively (p =0.046). (B) The FEV1 values were 1.37 L and 1.37 L before and after switching to LABA/LAMA plus ICS, respectively (p =0.178). (C) The FEV1 were 1.25 and 1.11 before and after switching to closed triple therapy from ICS/LABA plus LAMA, respectively. (p = 0.610). (D) The FEV1 were 1.29 and 1.32 before and after switching to closed triple therapy from LABA/LAMA plus ICS, respectively. (p = 0.837).