Perspective on the Budgetary Impact of FP/FORM pMDI on Treatment and Management of Exacerbation in Moderate-to-Severe Asthma Patients in Singapore

Figures & data

Table 1 Eligible Patient Population for Fixed Dose Combinations

Item	Value	Source
Adult resident population in Singapore	3,374,500	Ministry of Health, 2017^Citation43
Current asthma prevalence	3.9%	Ministry of Health, 2010^Citation38
Diagnosed population	70.0%	Clinician input
Treated population	50.0%	Clinician input
Fulfilment in the government sector	80.0%	Assumption based on Tan et al 2016^Citation27
Moderate to severe persistent asthma population (GINA steps 3 or 4)	48.2%	Tan et al 2016^Citation27
Total population eligible for treatment with fixed dose combination in Singapore, Year 1	17,776	Calculated based on figures above

Abbreviation: GINA, Global Initiative for Asthma.

Table 2 List of ICS/LABA Fixed Combinations Included in the Model

Drug	Metered Dose (Delivered Dose)^Citation22,Citation26,Citation44,Citation45	Standard Drug List Details
FP/SAL	FP/SAL pMDI 50/25 (44/21) μg: 2 inhalations twice daily 125/25 (110/21) μg: 2 inhalations twice daily 250/25 (220/21) μg: 2 inhalations twice daily	Fluticasone propionate 50 μg/dose + salmeterol 25 μg/dose Fluticasone propionate 125 μg/dose + salmeterol 25 μg/dose Fluticasone propionate 250 μg/dose + salmeterol 25 μg/dose
	FP/SAL DPI 100/50 (93/45) μg: 1 inhalation twice daily 250/50 (233/45) μg: 1 inhalation twice daily 500/50 (465/45) μg: 1 inhalation twice daily	Fluticasone propionate 100 μg/dose + salmeterol 50 μg/dose Fluticasone Propionate 250 μg/dose + salmeterol 50 μg/dose Fluticasone Propionate 500 μg/dose + salmeterol 50 μg/dose
BUD/FORM pMDI	100/6 (80/4.5) μg: 1 inhalation twice daily or 2 inhalations once daily 200/6 (160/4.5) μg: 1–2 inhalations twice daily 400/12 (320/9) μg: 1 inhalation twice daily	1. Budesonide 80 μg/dose + formoterol fumarate dihydrate 4.5 μg/dose 2. Budesonide 160 μg/dose + formoterol fumarate dihydrate 4.5 μg/dose 3. Budesonide 320 μg/dose + formoterol fumarate dihydrate 9 μg/dose
FP/FORM pMDI	50/5 (46/4.5) μg: 2 inhalations twice daily 125/5 (115/4.5) μg: 2 inhalations twice daily 250/10 (230/9.0) μg: 2 inhalations twice daily	Not included

Abbreviations: BUD, budesonide; DPI, dry powder inhaler; FORM, formoterol fumarate; FP, fluticasone; pMDI, pressurized metered-dose inhaler; SAL, salmeterol xinafoate.

Table 3 Unit and Annual Costs of FP/SAL and BUD/FORM

	Unit Cost (SGD)	Annual Cost (SGD)	Source
FP/SAL pMDI (50 μg/25 μg 120)	$34.02	$408.20	Average of non-subsidized patient prices from public healthcare institutions as of 2018
FP/SAL pMDI (125 μg/25 μg 120)	$63.79	$765.42
FP/SAL pMDI (250 μg/25 μg 120)	$103.74	$1,244.82
FP/SAL DPI (100 μg/50 μg 60)	$35.57	$426.78
FP/SAL DPI (250 μg/50 μg 60)	$60.64	$727.68
FP/SAL DPI (500 μg/50 μg 60)	$91.55	$1,098.60
BUD/FORM pMDI (4.5 μg/160 μg 120)	$92.24	$1,106.88
FP/FORM pMDI (50 μg/5 μg 120)	$33.97	$407.66
FP/FORM pMDI (125 μg/5 μg 120)	$57.49	$689.82
FP/FORM pMDI (250 μg/10 μg 120)	$95.34	$1,144.02

Notes: The ratio of unit costs for FP/SAL DPI (100 μg/50 μg 60) and FP/SAL DPI (250 μg/50 μg 60) was used to derived the unit costs of FP/SAL pMDI (50 μg/25 μg 120) and FP/FORM pMDI (50 μg/5 μg 120) as their prices were not available.

Abbreviations: BUD, budesonide; DPI, dry powder inhaler; FORM, formoterol fumarate; FP, fluticasone; pMDI, pressurized metered-dose inhaler; SAL, salmeterol xinafoate; SGD, Singapore dollars.

Table 4 Inputs for Exacerbation Management Costs

	Value	Source
Proportion of patients with exacerbations	35.2%	Tan et al 2016^Citation27
Proportion of uncontrolled exacerbations among patients on any ICS/LABA combinations	52.7%	Price et al 2015^Citation40
Rate of exacerbations
FP/FORM	2.1%	Papi et al 2016^Citation5
FP/SAL	9.5%
BUD/FORM	10.6%
Number of uncontrolled exacerbations implications expected annually
Hospitalizations related to exacerbations	0.45	Nguyen et al 2017^Citation29
ED visits related to exacerbations	0.95
Physician visits (primary care) related to exacerbations	1.52
Outpatient specialist visits	0.95
Healthcare costs associated with uncontrolled exacerbations implications (SGD)
Hospitalization	2,977.00	Ministry of Health 2018^Citation30
ED visit	119.00	Average cost from restructured hospitals^Citation31^–^Citation34
Primary care consultation	51.50	SingHealth Polyclinics 2018^Citation35
Outpatient specialist consultation	124.18	Average cost from restructured hospitals^Citation31,Citation33,Citation34
Steroid treatment per day	0.25	Nguyen et al 2017^Citation29
Costs per patient with moderate to severe asthma per year (SGD)
Hospitalization
FP/FORM	5.23	Calculated based on figures above
FP/SAL	23.64
BUD/FORM	26.38
ED visit
FP/FORM	0.44	Calculated based on figures above
FP/SAL	2.00
BUD/FORM	2.23
Primary care consultation
FP/FORM	0.31	Calculated based on figures above
FP/SAL	1.39
BUD/FORM	1.56
Outpatient specialist consultation
FP/FORM	0.46	Calculated based on figures above
FP/SAL	2.09
BUD/FORM	2.33

Notes: The number of specialist outpatient visits assumed that once the patients have had an ED visit or hospitalization, they were usually referred to specialists. The model assumed that all patients who have had an ED visit were either hospitalized and then referred to the outpatient specialist or were referred to the outpatient specialist directly. Tan et al 2016 reported that 3 and 2 days of steroid treatment are required for patients who were hospitalized and made visits to ED or primary care. The exchange rate of SGD 1.00 to USD 0.74 for steroid treatment per day.

Abbreviations: BUD, budesonide; DPI, dry powder inhaler; ED, emergency visit; FORM, formoterol fumarate; FP, fluticasone; ICS, inhaled corticosteroid; LABA, long-acting β2 agonist; SAL, salmeterol xinafoate; SGD, Singapore dollars.

Figure 1 OCS exacerbation incidences for individual studies of ICS/LABA combinations. ICS/LABA OCS exacerbation rates are for studies 1 and 2, and in the individual studies as reported in the Cochrane by Lasserson et al, Mansur and Kaiser, Ducharme et al, and Chauhan and Ducharme.

Notes: Grey bars represent the OCS exacerbation rates reported in open-label controlled trials of FP/FORM;46,47 white dotted bars represent the OCS exacerbation rates reported in studies from Lasserson et al 2011;48 black bars represent the OCS exacerbation rates reported in studies from Ducharme et al 2010;49 white checkered bars represent the OCS exacerbation rates reported in studies from Chauhan and Ducharme 2014.50 Reprinted with permission from Papi A, Mansur AH, Pertseva T et al. Long-Term Fluticasone Propionate/Formoterol Fumarate Combination Therapy Is Associated with a Low Incidence of Severe Asthma Exacerbations. J Aerosol Med Pulm Drug Deliv. 2016;29, 346–361. The publisher for this copyrighted material is Mary Ann Liebert, Inc. publishers.⁵

Abbreviations: BDP, beclometasone; BUD, budesonide; FLN, flunisolide; FORM, formoterol fumarate; FP, fluticasone; ICS, inhaled corticosteroid; LABA, long-acting β2 agonist; OCS, oral corticosteroid; SAL, salmeterol xinafoate.

Table 5 Budget Impact Results Considering Switch from FP/SAL

	Year 1	Year 2	Year 3	Year 4	Year 5	Total
Drug costs (SGD)
Base case	16,331,938	18,144,089	20,157,280	22,393,810	24,878,451
FP/SAL scenario	16,232,203	18,031,950	20,085,159	22,044,151	24,469,817
Difference	−99,735	−112,139	−72,121	−349,659	−408,635	−1,042,289
Exacerbation management costs (SGD)
Base case	526,038	582,677	645,411	714,898	791,864
FP/SAL scenario	521,710	579,469	613,829	632,234	690,097
Difference	−4328	−3208	−31,583	−82,664	−101,767	−223,550
Total cost difference (SGD)	−104,064	−115,347	−103,704	−432,323	−510,402	−1,265,840

Abbreviations: FP, fluticasone; SAL, salmeterol xinafoate; SGD, Singapore dollars.

Table 6 Budget Impact Results Considering Switch from BUD/FORM

	Year 1	Year 2	Year 3	Year 4	Year 5	Total
Drug costs (SGD)
Base Case	16,331,938	18,144,089	20,157,280	22,393,810	24,878,451
BUD/FORM Scenario	16,202,569	18,009,987	19,868,932	21,478,202	23,773,081
Difference	−129,368	−134,102	−288,349	−915,608	−1,105,370	−2,572,797
Exacerbation costs (SGD)
Base Case	526,038	582,677	645,411	714,898	791,864
BUD/FORM Scenario	521,067	578,992	609,134	619,946	674,970
Difference	−4972	−3685	−36,278	−94,952	−116,895	−256,781
Total cost difference (SGD)	−134,340	−137,787	−324,626	−1,010,560	−1,222,265	−2,829,578

Abbreviations: BUD, budesonide; FORM, formoterol fumarate; SGD, Singapore dollars.

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