Cost-effectiveness of roflumilast in combination with bronchodilator therapies in patients with severe and very severe COPD in Switzerland

Figures & data

Figure 1 COPD cost-effectiveness model structure.

Abbreviation: COPD, chronic obstructive pulmonary disease.

Table 1 Demographic characteristic and outcomes in COPD cohort

Average age at start, yearsa	64
Male/female ratioa	0.75/0.25
Height (males), cma	171.3
Height (females), cma	161.8
COPD severity at start	100% severe (assumption)
Average FEV1% at startb	40
The annual rate of background exacerbations in the severe COPD state in any of the comparatorsc	2.0
The annual rate of background exacerbations	2.436 = 2.0 ×
in the very severe COPD stated	(1.776/1.458)
Proportion of hospital-treated exacerbations	0.155
among all exacerbations in severe COPDa	(95% C1 0.133–0.177)
Proportion of hospital-treated exacerbations	0.244
among all exacerbations in very severe COPDa	(95% C1 0.208–0.280)
SMR for background death in severe COPD^Citation13	1.5
SMR for background death in very severe COPD^Citation13	2.0
Hospital CFR, %^Citation9	7.7

Notes:^aPooled analysis from studies M2-124 and M2-125 for the LABA subgroup;⁶

b median of the FEV₁% interval for severe COPD;

c an assumption, to indicate the group of patients with a history of frequent exacerbations who continue to exacerbate in clinical practice (95% CI from studies M2-124 and M2-125 and adjusted for the rate of exacerbations of 2.0 used in the model);

d derived from the annual background rate of exacerbation in the severe COPD state of 2.0 and the ratio of the rates of exacerbations in the very severe COPD and the severe COPD states from studies M2-124 and M2-125.

Abbreviations: COPD, chronic obstructive pulmonary disease; CI, confidence interval; FEV₁, post-bronchodilator forced expiratory volume achieved in 1 second, as a percentage predicted of that for the general population; SMR, standardized mortality ratio; CFR, case fatality rate (the percent of patients who died during a hospital-treated exacerbation); LABA, long-acting β2-agonist.

Table 2 Treatment efficacy – reduction of exacerbations

Treatment	Reference regimen	RRRa	95% CIa
LAMA + roflumilast	LAMA	0.843	0.61–1.14
LABA/ICS + roflumilast	LABA/ICS	0.835	0.74–0.95b
LAMA + LABA/ICS +	LAMA + LABA/	0.841	0.74–0.95b
roflumilast	ICS

Notes:^aValues are based on Mills et al;¹²

b reduction of exacerbation rates statistically significant.

Abbreviations: RRR, relative ratios of exacerbation rates; 95% CI, 95% confidence interval; LAMA, long-acting muscarinic antagonists; LABA, long-acting beta-agonists; ICS, inhaled corticosteroids.

Table 3 Health-related utilities and utility decrements

Parameter	Value	95% CI/SE
Utility in severe COPDa	0.751	0.738–0.765
Utility in very severe COPDa	0.657	0.635–0.678
Utility decrement (annual) associated	0.010	SE = 0.007
with community-treated exacerbationb
Utility decrement (annual) associated	0.042	SE = 0.009
with hospital-treated exacerbationsb

Notes:^aData on file, Takeda Pharma AG, Pfäffikon, Switzerland, 2010;⁵

b utility decrements are based on Rutten-van Mölken et al¹⁴ and the values represent utility loss over 1 year; the loss of utility attributed to 1-month model cycle length is estimated as: 0.01 × 12 = 0.12 and 0.042 × 12 = 0.504.

Abbreviations: 95% CI, 95% confidence interval; COPD, chronic obstructive pulmonary disease; SE, standard error.

Table 4 Key model inputs: resource use and unit costs

Resource type	Cost, CHF	Proportion of patients, or frequency of use	Subtotal/total, CHFe
Hospital-treated exacerbation
Intensive care unit	19,496a	11%a	2164
Normal ward	13,848a	78%a	10,774
Ambulance transport	804a	25%a	201
Cost per hospital-treated exacerbation			13,139
Community-treated (moderate) exacerbation
GP visit (includes treatment)	121.34b	2/3 (67%)c	80.90
Accident and emergency (not leading to admission)	27.41b	1/3 (33%)c	9.14
Prednisolone 30 mg, 7-day course	0.88c	50%c	3.08
Prednisolone 30 mg, 14-day course	0.88c	50%c	6.16
Co-amoxicillin, 3 per day, 5-day course	1.90 × 3 × 5c	50%c	14.27
Co-amoxicillin, 3 per day, 10-day course	1.90 × 3 × 10c	50%c	28.54
Cost per community-treated exacerbation			142.08
Maintenance in severe COPD, monthly
Outpatient visit to respiratory physician	18.10b	Twice a yearc	3.02
Spirometry	97.40b	Twice a yearc	16.23
Influenza vaccination, annual	17.95c	75%c	1.12
Oxygen therapy	35.49c	14.6 per yearc	43.8
Maintenance in severe COPD, monthly			63.55
Maintenance in very severe COPD, monthly
Outpatient visit to respiratory physician	18.10b	Four times a yearc	6.03
Spirometry	97.40b	Four times a yearc	32.47
Influenza vaccination, annual	17.95c	75%c	1.12
Oxygen therapy	35.49c	73 a yearc	215.90
Maintenance in very severe COPD, monthly			255.52
COPD treatments			(CHF, monthly)
Roflumilast (Daxas^®) 500 mcg, 30 tabs,	78.55 per packc	1 tab daily	79.64
LAMA, Tiotropium, Spiriva^® Inhal Kaps 18 mcg 90	196.75 per packc	18 mcg daily	66.46
LABA/ICS, budesonide + formoterol, Symbicort^® 400/12, Turbuhaler 60 puffs	93.5 per packc	2 puffs daily	94.80
LABA/ICS, fluticasone + salmeterol, Seretide^® 500 Diskus 60 doses	130.2 per packc	2 puffs daily	132.01
LABA/ICS, weighted average by market share			109.59
LAMA+LABA/ICS	(CHF 66.46 + CHF 132.	01)c	176.09

Notes:^aCost values were drawn from Schramm et al¹⁸ and inflated to 2011 values;

b cost values were drawn from TARMED Suisse, version 02.04.2010:01.07.01 (July 2012);²¹

c resource use data were drawn from Oostenbrink et al;¹⁹

d costs of pharmaceuticals obtained from the Medicines Compendium of Switzerland (July 2012);²⁰

e subtotals/totals calculated from cost and proportion of patients or frequency of use. Values in bold are the subtotals of the preceding values.

Abbreviations: GP, general practitioner; COPD, chronic obstructive pulmonary disease; LAMA, long-acting muscarinic antagonists; LABA, long-acting beta-agonists; ICS, inhaled corticosteroids.

Table 5 Cost-effectiveness results and cost breakdown, base case

	LAMA + roflumilast	LAMA	Incremental	LABA/ICS + roflumilast	LABA/ICS	Incremental	LAMA + LABA/ ICS + roflumilast	LAMA + LABA/ICS	Incremental
Total cost, CHF	86,754	83,364	3390	91,470	88,161	3308	99,364	95,564	3799
Cost of maintenancea, CHF	35,857	25,481	10,376	40,917	30,279	10,638	48,533	37,682	10,851
Cost of community-treated exacerbations, CHF	2039	2331	−292b	2025	2331	−306b	2036	2331	−295b
Cost of hospital-treated exacerbations, CHF	48,858	55,552	−6694b	48,528	55,552	−7024b	48,795	55,552	−6757b
Life years (LY)	9.625	9.278	0.347	9.642	9.278	0.364	9.628	9.278	0.351
Quality-adjusted life years (QALY)	6.466	6.191	0.275	6.479	6.191	0.289	6.468	6.191	0.278
ICER, CHF per QALY	12,313			1 1,456			13,671
ICER, CHF per LY	9757			9078			10,833

Notes:^aCost of maintenance includes the monthly medical services, and the cost of COPD drugs;

b cost offset (reduction in the roflumilast arm).

Abbreviations: LAMA, long-acting muscarinic antagonists; LABA, long-acting beta-agonists; ICS, inhaled corticosteroids; ICER, incremental cost-effectiveness ratio.

Table 6 One-way sensitivity analysis: LABA/ICS + roflumilast vs LABA/ICS

Parameter	Base case and range (low estimate; base case; high estimate)	ICER at low parameter estimate	ICER at high parameter estimate, CHF per QALY gained	Variation in ICER between low and high estimates
Relative ratios of exacerbation rates	(0.74; 0.835; 0.95)a	Roflumilast dominant	84,682	N/Ab
Hospital case fatality rate, %	(0; 7.7; 15)	Roflumilast dominant	13,732	N/Ab
Cost of hospital-treated exacerbation, CHF	(10,511; 13,139; 15,767)	16,321	6591	9730
Annual discount rate, cost	(0%; 2.5%; 5%)	15,109	8973	6136
Annual discount rate, QALY	(0%; 2.5%; 5%)	8765	14,563	5798
Background rate of exacerbations in very severe COPD, per patient per year	(1.95; 2.436; 2.92)	14,409	9411	4998
Background rate of exacerbations in severe COPD, per patient per year	(1.6; 2.0; 2.4)	13,735	9586	4149
Proportion of hospital treated exacerbations among all exacerbations in very severe COPD	(0.208; 0.244; 0.280)	13,312	10,016	3296
Proportion of hospital treated exacerbations among all exacerbations in severe COPD	(0.133; 0.155; 0.177)	12,828	10,246	2582

Notes: Base case ICER for LABA/ICS + roflumilast vs LABA/ICS; CHF 11,456 per QALY gained.

a Exacerbation rate reduction statistically significant;

b in sensitivity analyses where cost-effectiveness changes to dominance, range of ICERs is not applicable.

Abbreviations: LABA, long-acting beta-agonists; ICS, inhaled corticosteroids; ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life years; COPD, chronic obstructive pulmonary disease.

Table 7 One-way sensitivity analysis: LAMA + LABA/ICS + roflumilast vs LAMA + LABA/ICS

Parameter	Base case and range (low estimate; base case; high estimate)	ICER at low parameter estimate	ICER at high parameter estimate, CHF per QALY gained	Variation in ICER between low and high estimates
Relative ratios of exacerbation rates	(0.74; 0.841; 0.95)a	637	85,689	85,052
Hospital case fatality rate, %	(0; 7.7; 15)	Roflumilast dominant	15,621	N/Ab
Cost of hospital-treated exacerbation, CHF	(10,511; 13,139; 15,767)	18,460	8808	9652
Annual discount rate, cost	(0%; 2.5%; 5%)	17,890	10,787	7103
Annual discount rate, QALY	(0%; 2.5%; 5%)	10,461	17,377	6916
Background rate of exacerbations in very severe COPD, per patient per year	(1.95; 2.436; 2.92)	16,725	11,548	5177
Background rate of exacerbations in severe COPD, per patient per year	(1.6; 2.0; 2.4)	16,057	11,713	4344
Proportion of hospital treated exacerbations among all exacerbations in very severe COPD	(0.208; 0.244; 0.280)	15,586	12,184	3402
Proportion of hospital treated exacerbations among all exacerbations in severe COPD	(0.133; 0.155; 0.177)	15,101	12,411	2690

Notes: Base case ICER for LAMA + LABA/ICS + roflumilast vs LAMA + LABA/ICS: CHF 13,671 per QALY gained.

a Exacerbation rate reduction statistically significant;

b in sensitivity analyses where cost-effectiveness changes to dominance, range of ICERs is not applicable.

Abbreviations: LAMA, long-acting muscarinic antagonists; LABA, long-acting beta-agonists; ICS, inhaled corticosteroids; ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life years; COPD, chronic obstructive pulmonary disease.

Table 8 One-way sensitivity analysis: LAMA + roflumilast vs LAMA

Parameter	Base case and range (low estimate; base case; high estimate)	ICER at low parameter estimate	ICER at high parameter estimate, CHF per QALY gained	Variation in ICER between low and high estimates
Relative ratios of exacerbation rates	(0.61; 0.843; 1.14)a	Roflumilast dominant	Roflumilast + LAMA dominated	N/Ab
Hospital case fatality rate, %	(0; 7.7; 15)	Roflumilast dominant	14,029	N/Ab
Cost of hospital-treated exacerbation, CHF	(10,511; 13,139; 15,767)	17,176	7451	9725
Annual discount rate, cost	(0%; 2.5%; 5%)	16,030	9771	6259
Annual discount rate, QALY	(0%; 2.5%; 5%)	9422	15,651	6229
Background rate of exacerbations in very severe COPD, per patient per year	(1.95; 2.436; 2.92)	15,402	10,164	5238
Background rate of exacerbations in severe COPD, per patient per year	(1.6; 2.0; 2.4)	14,721	10,337	4384
Proportion of hospital treated exacerbations among all exacerbations in very severe COPD	(0.208; 0.244; 0.280)	14,263	10,798	3465
Proportion of hospital treated exacerbations among all exacerbations in severe COPD	(0.133; 0.155; 0.177)	13,768	11,032	2736

Notes: Base case ICER for roflumilast + LAMA vs LAMA: CHF 12,313 per QALY gained.

a Exacerbation rate reduction not statistically significant;

b in sensitivity analyses where cost-effectiveness changes to dominance, range of ICERs is not applicable.

Abbreviations: LAMA, long-acting muscarinic antagonists; ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life years; COPD, chronic obstructive pulmonary disease.

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