A Comparison of the Effectiveness of Asthma Medications on Asthma Exacerbations in Real World National Cohort

Figures & data

Figure 1 Study design and period.

Figure 2 Study flow.

Abbreviations: ICS, Inhaled corticosteroid; LABA, long-acting β2-agonist; LAMA, long-acting muscarine antagonist; LTRA, leukotriene antagonist.

Table 1 Baseline Characteristics and Outcomes of Study Subjects

Characteristics		N (%)
Total		254,951 (100.0)
Sex	Male	99,327 (39.0)
	Female	155,624 (61.0)
Age	15–19	9477 (3.7)
	20–29	17,258 (6.8)
	30–39	27,800 (10.9)
	40–49	34,870 (13.8)
	50–59	46,772 (18.4)
	60–69	53,169 (20.9)
	70–79	45,199 (17.7)
	80–89	18,749 (7.4)
	90-	1657 (0.7)
CCI	1	99,648 (39.1)
	2	63,287 (24.8)
	Above 3	92,016 (36.1)
Outcomes		N (%)
Total exacerbation		107,694 (42.2)
Severe exacerbation		6379 (2.5)
ER admission for asthma exacerbation		1901 (0.8)
Total Mortality		3096 (1.21)

Abbreviations: CCI, Charlson’s comorbidity index; ER, emergency room.

Figure 3 Clinical outcomes according to asthma medication type. Reduction of asthma exacerbation at first event (A) and second event (B) adjusted by age, sex, and CCI using Cox regression analysis.

Abbreviations: HR, hazard ratio; CI, confidence interval; ICS, Inhaled corticosteroid; LABA, long-acting β2-agonist; LAMA, long-acting muscarine antagonist; LTRA, leukotriene antagonist.

Table 2 Clinical Outcomes According to the Active Ingredient of Asthma Medication

Type	Ingredient	Number	Exacerbation
			First Event		Second Event
			HR (95% CI)	P-value	HR (95% CI)	P-value
ICS	BUD	29,869	0.525 (0.512–0.539)	<0.001	0.393 (0.380–0.407)	<0.001
	CIC1	245	0.378 (0.275–0.518)	<0.001	0.295 (0.191–0.455)	<0.001
	CIC2	1753	0.389 (0.347–0.437)	<0.001	0.249 (0.210–0.296)	<0.001
	FP1	123	0.265 (0.161–0.436)	<0.001	0.223 (0.114–0.437)	<0.001
	FP2	814	0.233 (0.188–0.289)	<0.001	0.164 (0.120–0.225)	<0.001
ICS-LABA	BEC_FOR	8908	0.460 (0.439–0.483)	<0.001	0.312 (0.291–0.333)	<0.001
	BUD_FOR1	139	0.524 (0.369–0.745)	<0.001	0.352 (0.212–0.585)	<0.001
	BUD_FOR2	13,194	0.450 (0.433–0.469)	<0.001	0.293 (0.277–0.310)	<0.001
	BUD_FOR3	758	0.602 (0.521–0.696)	<0.001	0.379 (0.308–0.467)	<0.001
	FP_FOR2	1700	0.412 (0.368–0.461)	<0.001	0.237 (0.200–0.282)	<0.001
	FP_FOR3	731	0.539 (0.462–0.628)	<0.001	0.312 (0.248–0.393)	<0.001
	FP_SAL1	614	0.326 (0.265–0.402)	<0.001	0.210 (0.155–0.285)	<0.001
	FP_SAL2	9224	0.527 (0.504–0.551)	<0.001	0.398 (0.375–0.422)	<0.001
	FP_SAL3	936	0.670 (0.590–0.760)	<0.001	0.495 (0.418–0.586)	<0.001
	FF_VIL1	15,949	0.481 (0.464–0.499)	<0.001	0.320 (0.304–0.336)	<0.001
	FF_VIL2	3016	0.473 (0.436–0.513)	<0.001	0.336 (0.301–0.376)	<0.001
LAMA	Ipratropium	6501	0.595 (0.565–0.626)	<0.001	0.450 (0.420–0.482)	<0.001
	Tiotropium	1189	0.446 (0.388–0.512)	<0.001	0.334 (0.276–0.404)	<0.001
LTRA	Montelukast	134,628	0.422 (0.415–0.429)	<0.001	0.287 (0.281–0.293)	<0.001
	Pranlukast	18,493	0.398 (0.384–0.412)	<0.001	0.262 (0.250–0.276)	<0.001
Xanthine	Aminophylline	33,661	0.536 (0.523–0.549)	<0.001	0.416 (0.403–0.430)	<0.001
	Bamiphylline	6021	0.428 (0.403–0.454)	<0.001	0.325 (0.299–0.353)	<0.001
	Doxofylline	61,322	0.456 (0.446–0.465)	<0.001	0.350 (0.341–0.360)	<0.001
	Theophylline	19,870	0.486 (0.471–0.502)	<0.001	0.373 (0.357–0.389)	<0.001

Note: Adjusted by age, sex, and CCI using Cox regression analysis.

Abbreviations: HR, hazard ratio; CI, confidence interval; ICS, Inhaled corticosteroid; LABA, long-acting β₂-agonist; LAMA, long-acting muscarine antagonist; LTRA, leukotriene antagonist; BUD, budesonide 100 μg; CIC1, ciclesonide 80 μg, CIC2, ciclesonide 160 μg, FP, fluticasone propionate 100 μg; FP2, fluticasone propionate 250 μg; BUD1, budesonide 80 μg; BUD2, budesonide 160 μg; BUD3, budesonide 320 μg; BEC, beclomethasone; FOR, formoterol; SAL, salmeterol; FP3, fluticasone propionate 500 μg; FF1, fluticasone furoate 100 μg; FF2, fluticasone furoate 200 μg; VIL, vilanterol.

Table 3 Clinical Outcomes According to Combination of ICS-LABA and LTRA

Combination of ICS-LABA and LTRA			Exacerbation
ICS-LABA	LTRA	Number	First Event		Second Event
			HR (95% CI)	P-value	HR (95% CI)	P-value
BEC_FOR	Montelukast	5376	0.435 (0.408–0.463)	<0.001	0.273 (0.250–0.299)	<0.001
BUD_FOR2	Montelukast	8056	0.408 (0.387–0.430)	<0.001	0.258 (0.240–0.278)	<0.001
BUD_FOR3	Montelukast	504	0.572 (0.478–0.685)	<0.001	0.320 (0.245–0.418)	<0.001
FP_FOR2	Montelukast	961	0.371 (0.317–0.434)	<0.001	0.219 (0.174–0.277)	<0.001
FP_FOR3	Montelukast	441	0.526 (0.431–0.641)	<0.001	0.264 (0.193–0.361)	<0.001
FP_SAL1	Montelukast	282	0.305 (0.222–0.418)	<0.001	0.227 (0.149–0.346)	<0.001
FP_SAL2	Montelukast	4809	0.464 (0.435–0.496)	<0.001	0.321 (0.293–0.350)	<0.001
FP_SAL3	Montelukast	494	0.670 (0.565–0.796)	<0.001	0.404 (0.316–0.516)	<0.001
FF_VIL1	Montelukast	9264	0.456 (0.434–0.478)	<0.001	0.281 (0.262–0.300)	<0.001
FF_VIL2	Montelukast	1911	0.499 (0.452–0.551)	<0.001	0.333 (0.291–0.382)	<0.001
BEC_FOR	Pranlukast	614	0.344 (0.279–0.424)	<0.001	0.197 (0.144–0.270)	<0.001
BUD_FOR2	Pranlukast	727	0.370 (0.309–0.443)	<0.001	0.210 (0.160–0.276)	<0.001
FP_FOR2	Pranlukast	220	0.384 (0.279–0.529)	<0.001	0.159 (0.091–0.277)	<0.001
FP_SAL2	Pranlukast	436	0.396 (0.314–0.499)	<0.001	0.276 (0.201–0.379)	<0.001
FF_VIL1	Pranlukast	755	0.342 (0.283–0.414)	<0.001	0.177 (0.131–0.238)	<0.001
FF_VIL2	Pranlukast	140	0.472 (0.324–0.685)	<0.001	0.272 (0.156–0.474)	<0.001

Note: Adjusted by age, sex, and CCI using Cox regression analysis.

Abbreviations: HR, hazard ratio; CI, confidence interval; ICS, Inhaled corticosteroid; LABA, long-acting β₂-agonist; LTRA, leukotriene antagonist; BEC, beclomethasone; BUD2, budesonide 160 μg; BUD3, budesonide 320 μg; FP, fluticasone propionate 100 μg; FP2, fluticasone propionate 250 μg; FOR, formoterol; SAL, salmeterol; FP3, fluticasone propionate 500 μg; FF1, fluticasone furoate 100 μg; FF2, fluticasone furoate 200 μg; VIL, vilanterol.

Table 4 Clinical Outcomes According to the Period of Use of Asthma Medication

Type	Usage Duration	Number	Exacerbation
			First Event		Second Event
			HR (95% CI)	P-value	HR (95% CI)	P-value
ICS	< 3 months	23,148	0.411 (0.398–0.424)	<0.001	0.267 (0.254–0.279)	<0.001
	3–6 months	7324	0.680 (0.650–0.711)	<0.001	0.530 (0.500–0.563)	<0.001
	6–9 months	1597	0.922 (0.848–1.003)	0.059	0.955 (0.866–1.053)	0.355
	≥ 9 months	736	1.297 (1.162–1.448)	<0.001	1.416 (1.251–1.602)	<0.001
ICS-LABA	< 3 months	39,189	0.426 (0.415–0.436)	<0.001	0.278 (0.269–0.288)	<0.001
	3–6 months	9983	0.587 (0.563–0.611)	<0.001	0.419 (0.397–0.443)	<0.001
	6–9 months	3494	0.653 (0.612–0.697)	<0.001	0.470 (0.430–0.513)	<0.001
	≥ 9 months	2535	0.646 (0.599–0.697)	<0.001	0.481 (0.434–0.532)	<0.001
LAMA	< 3 months	5820	0.520 (0.491–0.551)	<0.001	0.377 (0.348–0.409)	<0.001
	3–6 months	1327	0.693 (0.624–0.770)	<0.001	0.551 (0.480–0.633)	<0.001
	6–9 months	340	0.831 (0.683–1.011)	0.064	0.720 (0.564–0.920)	0.009
	≥ 9 months	203	0.968 (0.762–1.230)	0.789	0.829 (0.615–1.118)	0.218
LTRA	< 3 months	134,124	0.395 (0.389–0.401)	<0.001	0.259 (0.254–0.265)	<0.001
	3–6 months	8413	0.562 (0.537–0.587)	<0.001	0.443 (0.418–0.469)	<0.001
	6–9 months	3712	0.596 (0.558–0.636)	<0.001	0.485 (0.447–0.526)	<0.001
	≥ 9 months	6933	0.628 (0.599–0.658)	<0.001	0.468 (0.440–0.497)	<0.001
Xanthine	< 3 months	112,230	0.468 (0.461–0.476)	<0.001	0.351 (0.344–0.359)	<0.001
	3–6 months	3894	0.780 (0.734–0.830)	<0.001	0.783 (0.728–0.842)	<0.001
	6–9 months	1656	0.670 (0.607–0.738)	<0.001	0.661 (0.588–0.743)	<0.001
	≥ 9 months	3194	0.600 (0.558–0.645)	<0.001	0.554 (0.506–0.606)	<0.001

Note: Adjusted by age, sex, and CCI using Cox regression analysis.

Abbreviations: HR, hazard ratio; CI, confidence interval; ICS, Inhaled corticosteroid; LABA, long-acting β₂-agonist; LAMA, long-acting muscarine antagonist; LTRA, leukotriene antagonist.