Cost-effectiveness analysis of dupilumab among patients with oral corticosteroid-dependent uncontrolled severe asthma in Japan

Figures & data

Table 1. Model cohort characteristics at model start.†

Characteristic	Benralizumab like	Mepolizumab like	Omalizumab like
Source of dupilumab clinical data	VENTURE trial		QUEST trial
Number of patients in this model	105	132	155
% of females	69.50%	65.90%	70.30%
Average age: mean (SE)	51.20 (1.04)	50.90 (1.08)	45.90 (1.07)
Mean eosinophil count (cells/μL)	444	449	434
Mean number of severe exacerbations in the previous 12 months	2.53	2.02	2.11

† Source: VENTURE trial data based on pooled data of placebo and dupilumab 300 mg; Post hoc analyses of the QUEST trial data pooled across dupilumab 300 mg and placebo 2 ml arms.

Figure 1. Model structure.

Color coding: Black: Absorbing health state; Dark gray: Treatment-related health state; White: Sub-states within treatment-related health states.

^*Add-on treatment may be any one of the following monoclonal antibodies: dupilumab, mepolizumab, benralizumab.

^†Moderate exacerbations are defined based on the loss of asthma control (LOAC) events (excluding severe exacerbation events) as collected in the QUEST trial. As such, at least one of the following criteria must be satisfied to count as a moderate exacerbation: ≥6 additional reliever puffs of salbutamol/albuterol or levosalbutamol/levalbuterol in a 24-hour period (compared with the baseline) on two consecutive days; ≥20% decrease in pre-bronchodilator forced expiratory volume in one second (FEV1) compared with the baseline; Increase in inhaled corticosteroid (ICS) dose ≥4 times than the dose at Visit 2; A decrease in AM or PM peak flow of 30% or more on two consecutive days of treatment, based on the defined stability limit. The treatment period stability limit is defined as the respective mean AM or PM peak expiratory flow (PEF) obtained over the last seven days prior to randomization (Day 1). ΔSevere exacerbations are defined based on the severe exacerbation events as collected in the dupilumab trials. As such, at least one of the following criteria must be satisfied to count as a severe exacerbation: Use of systemic corticosteroids for ≥3 days; Hospitalization or emergency room visit because of asthma, requiring systemic corticosteroids.

Table 2. Overview of the main cost inputs.

Background therapy drugs		Average cost per standard dose per day	Source
Background therapy drug costs (Average cost per standard dose per day) (¥)
Medium-dose ICS		79.72	Source: Price: Drug master list by MHLW (28); Dose: Japanese guideline (2); Package: PMDA (29) Calculation method: Multiply the average dose by the arithmetic average cost per mg
High-dose ICS		159.43
Medium-dose ICS/LABA		231.10
High-dose ICS/LABA		364.52
LABA		101.75
LTRA		189.75
LAMA		116.22
Theophylline		16.50
OCS (Prednisolone)		76.99
Add-on treatments (Cost per cycle) (¥)
Dupilumab		163,280.00 (Cost per initial cycle: 244,920.00)	Source: Price: Drug master list by MHLW (25); Dose: Japanese guideline (2) (Dupilumab, 600 mg for first administration, 300 mg for following administration, every 2 weeks; Benralizumab, 30 mg, every 4 weeks for 2 doses then every 8 weeks; Mepolizumab, 100 mg, every 4 weeks; Omalizumab, 450 mg, every 4 weeks); Package: PMDA (29) Calculation method: Multiply the dose by the arithmetic cost per mg
Benralizumab		175,767.50 (Cost per initial cycle: 351 535.0)
Mepolizumab		175 684.00
Omalizumab		136 734.00
Drug administration cost (per time) (¥)
Cost per subcutaneous/intravenous administration		1,083	Source: NHI-Fee List by MHLW (28) Calculation method: Intradermal, subcutaneous and intramuscular injection: 200 Outpatient visits (Hospitals with 200 or more beds): 730 Outpatient visits (Hospitals with less than 200 beds: 1240 Assume 70% of biologic users (severe asthma patients) takes place in hospitals with more than 200 beds
Routine visit and disease management costs (Cost per cycle) (¥)
Controlled asthma		1148.46	Source: NHI-Fee List by MHLW (28); Nagase (6) Calculation method: Resource use of outpatient visit for “Control Asthma”: Mean (SE)=1.04 (0.04); Resource use of Asthma treatment management for “Control Asthma”: Mean (SE)=1 (0.25); Resource use of outpatient visit for “Uncontrolled Asthma”: Mean (SE)=1.49 (0.09); Resource use of Asthma treatment management for “Uncontrolled Asthma”: Mean (SE)=1 (0.25)
Uncontrolled asthma		1545.81
Exacerbation costs (Cost per cycle) (¥)
Office visit	Moderate exacerbation:	95.31	Source: NHI-Fee List by MHLW (28) Calculation method: Multiply the unit resource cost by the frequency of unit resource in different departments
	Severe exacerbations:	786.91
ED visit		730 634.49
Hospitalization		573 158.05

Note. US$1=¥110.

Abbreviations: ED, emergency department; ICS, inhaled corticosteroid; LABA, long-acting beta-agonists; LAMA, long-acting muscarinic antagonists; LTRA, leukotriene receptor antagonists; MHLW, Ministry of Health, Labor, and Welfare; NHI-Fee List, National Health Insurance Fee List; OCS, oral corticosteroid; PMDA, Pharmaceutical and Medical Devices Agency; SABA, short-acting inhaled beta-agonists.

Table 3. Base case results for the benralizumab like population.

Outcome per patient	Dupilumab + background therapy	Benralizumab + background therapy	Incremental
Severe exacerbations, n	43.55	44.83	−1.27
Requiring office visit	37.16	38.25	−1.09
Requiring ED visit	2.80	2.88	−0.08
Requiring hospitalization	3.60	3.70	−0.11
Deaths, n	0.87	0.87	0
Exacerbation-related deaths	0.31	0.31	−0.01
Non-asthma deaths	0.56	0.55	0.01
Life-years	23.01	22.89	0.13
Quality-adjusted life-years	14.43	14.26	0.17
Drug acquisition costs (¥)	31 250 436	33 620 258	−2 369 821
Total costs (¥)	41 825 081	44 141 913	−2 316 832
ICER per QALY gained	–	–	Dupilumab + background therapy is dominant

Note. US$1 = ¥110. Moderate exacerbation is not included (Supplementary Table 1).

Abbreviations: ED, emergency department; ICER, incremental cost-effectiveness ratio; n, number; QALY, quality-adjusted life-years.

Table 4. Base case results for the mepolizumab like population.

Outcome per patient	Dupilumab + background therapy	Mepolizumab + background therapy	Incremental
Severe exacerbations, n	34.42	40.57	−6.15
Requiring office visit	29.37	34.62	−5.25
Requiring ED visit	2.21	2.61	−0.40
Requiring hospitalization	2.84	3.35	−0.51
Deaths, n	0.85	0.86	−0.01
Exacerbation-related deaths	0.24	0.28	−0.04
Non-asthma deaths	0.61	0.58	0.03
Life-years	23.73	23.14	0.59
Quality-adjusted life-years	15.21	14.60	0.61
Drug acquisition costs (¥)	31 842 405	31 039 284	803 121
Total costs (¥)	42 123 673	41 504 494	619 179
ICER per QALY gained (¥)	–	–	1 010 921

Note. US$1=¥110. Moderate exacerbation is not included (Supplementary Table 1).

Abbreviations: ED, emergency department; ICER, incremental cost-effectiveness ratio; n, number; QALY, quality-adjusted life-years.

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Data availability statement

All data supporting the findings of this study are available within the article and its supplementary materials.