Cost-effectiveness of tiotropium versus glycopyrronium in moderate to very severe chronic obstructive pulmonary disease in Canada, Spain, Sweden, and the UK

Figures & data

Figure 1 Markov model state transition diagram.

Note: The arrows reflect the fact that a patient can remain in the same state for several cycles.
Abbreviations: GOLD, Global Initiative for Chronic Obstructive Lung Disease; GOLD II, GOLD classification indicating moderate COPD; COPD, chronic obstructive pulmonary disease; GOLD III, GOLD classification indicating severe COPD; GOLD IV, GOLD classification indicating very severe COPD; No Ex, no exacerbation; Ex, exacerbation; SevEx, severe exacerbation.

Table 1 Source overview of clinical inputs

Clinical input	TIO	GLY
Transition probabilities
Cycles on treatment (year 0–4)	UPLIFT (TIO arm)	UPLIFT (TIO arm)a
Cycles off treatment (≥year 4)	UPLIFT (usual care arm)b	UPLIFT (usual care arm)b
Probabilities of exacerbations
Baseline risks of exacerbations	UPLIFT (TIO arm)	UPLIFT (TIO arm)
RRs	(N/A baseline applied)	SPARK RR TIO/GLYc

Notes:

a Several trials have shown comparable efficacy between tiotropium and glycopyrronium in terms of overall lung function (FEV₁).

b As there is little persistence in the effect of LAMAs after stopping treatment, transition probabilities were assumed to return to the placebo arm (usual care) probabilities in the cycle after stopping treatment.

c Applied to baseline risks of exacerbations from UPLIFT (TIO arm). Adapted from Wedzicha et al¹⁹ and Hettle et al.²⁷

Abbreviations: TIO, Tiotropium; GLY, glycopyrronium; UPLIFT, Understanding Potential Long-term Impacts on Function with Tiotropium; N/A, not applicable; RR, relative risk; FEV₁, forced expiratory volume in 1 second.

Table 2 Model transition probabilities by GOLD states

		First cycle			Subsequent cycles
		To			To
		GOLD II	GOLD III	GOLD IV	GOLD II	GOLD III	GOLD IV
TIO/GLY
From	GOLD II	0.92	0.08	0.00	0.92	0.08	0.00
	GOLD III	0.17	0.80	0.03	0.08	0.88	0.04
	GOLD IV	0.03	0.28	0.69	0.00	0.12	0.88
Off treatment
From	GOLD II	0.86	0.13	0.01	0.91	0.09	0.00
	GOLD III	0.13	0.81	0.06	0.08	0.88	0.04
	GOLD IV	0.02	0.22	0.76	0.00	0.13	0.87

Notes: For TIO and GLY cohorts, usual care probabilities were assumed to hold when off treatment. Probabilities have been recalculated to reflect 3-month probabilities. Death has been excluded, as this model carries separate mortality rates derived for each country’s population. Based on own calculations using data from Hettle et al²⁷ (derived from UPLIFT¹⁶).

Abbreviations: GOLD II, GOLD classification indicating moderate COPD; COPD, chronic obstructive pulmonary disease; GOLD III, GOLD classification indicating severe COPD; GOLD IV, GOLD classification indicating very severe COPD; TIO, Tiotropium; GLY, glycopyrronium; UPLIFT, Understanding Potential Long-term Impacts on Function with Tiotropium.

Table 3 Model probabilities of exacerbations by GOLD states

Event/GOLD	Off treatment			Tiotropium			Glycopyrronium
	II	III	IV	II	III	IV	II	III	IV
No exacerbation	0.84	0.78	0.73	0.87	0.81	0.77	0.86	0.79	0.74
Nonsevere exacerbation	0.14	0.17	0.18	0.11	0.14	0.15	0.11	0.14	0.14
Severe exacerbation	0.02	0.05	0.08	0.02	0.05	0.08	0.03	0.07	0.12

Notes: Usual care probabilities from UPLIFT were used in cycles off treatment. Probabilities reflect 3-month risks. Data from Hettle et al²⁷ (derived from UPLIFT), SPARK,¹⁹ and own calculations.

Abbreviations: GOLD, Global Initiative for Chronic Obstructive Lung Disease; UPLIFT, Understanding Potential Long-term Impacts on Function with Tiotropium.

Table 4 Drug costs (€2014) per patient per day for each country

Therapy/country	CAN	ESP	SWE	UK
Spiriva Handihaler (tiotropium 18 µg)	1.48	0.97	1.40	1.39
Seebri Breezhaler (glycopyrronium 44 µg)	1.21	0.94	1.15	1.14

Notes: Ex-rates 2014: CAN (C$ to €: 0.68), Bank of Canada⁴⁰; SWE (SEK to €: 0.11), Sveriges Riksbank⁴¹; UK (£ to €: 1.24), Bank of England.⁴² Dosing: one capsule per day. Adapted from Ontario Drug Benefit Formulary³⁵ (CAN), botplus + deductions^36,37 (ESP), the Dental and Pharmaceuticals Benefits Agency (TLV)³⁸ (SWE), and MIMS³⁹ (UK).

Abbreviations: CAN, Canada; ESP, Spain, SWE, Sweden; SEK, Swedish krona; MIMS, monthly index of medical specialties; TLV, Tandvårds- och läkemedelsförmånsverket [dental and pharmaceutical benefits agency].

Table 5 Direct costs (€2014) by GOLD state and type of event

Event/GOLD	CAN^Citation43,Citation44			ESP^Citation45,Citation46			SWE^Citation47,Citation48			UK^Citation26
	II	III	IV	II	III	IV	II	III	IV	II	III	IV
No Ex	95	284	416	366	1,060	1,751	141	333	472	150	321	531
Non-SevEx	391	580	712	669	1,363	2,054	486	678	817	153	474	684
SevEex	7,108	7,297	7,428	1,822	2,516	3,207	3,058	3,250	3,389	4,832	5,153	5,363

Notes: Ex-rates 2014: CAN (C$ to €: 0.68)⁴⁰; SWE (SEK to €: 0.11)⁴¹; UK (£ to €: 1.24).⁴² Where necessary, costs have been inflated to 2014 year prices and recalculated to reflect 3-month cycle.

Abbreviations: GOLD, Global Initiative for Chronic Obstructive Lung Disease; GOLD II, GOLD classification indicating moderate COPD; COPD, chronic obstructive pulmonary disease; GOLD III, GOLD classification indicating severe COPD; GOLD IV, GOLD classification indicating very severe COPD; CAN, Canada; ESP, Spain, SWE, Sweden; No Ex, no exacerbation; Non-SevEx, nonsevere exacerbation; SevEx, severe exacerbation; SEK, Swedish krona.

Table 6 Utility weights by GOLD state and type of exacerbation

Event/GOLD	CAN/UK			ESP			SWE
	II	III	IV	II	III	IV	II	III	IV
No Ex	0.79	0.75	0.65	0.82	0.72	0.57	0.73	0.74	0.52
Non-SevEx	0.77	0.74	0.64	0.81	0.71	0.56	0.72	0.73	0.51
SevEx	0.74	0.70	0.61	0.78	0.69	0.54	0.69	0.70	0.49

Notes: Weights for mild and moderate exacerbations were merged (averaged) if necessary to form “nonsevere exacerbation”. Utility weights were derived using the EQ-5D questionnaire. Data from Hettle et al²⁶ (CAN/UK), Miravitlles et al⁴⁹ (ESP), and Stahl et al⁵⁰ (SWE).

Abbreviations: GOLD, Global Initiative for Chronic Obstructive Lung Disease; GOLD II, GOLD classification indicating moderate COPD; COPD, chronic obstructive pulmonary disease; GOLD III, GOLD classification indicating severe COPD; GOLD IV, GOLD classification indicating very severe COPD; CAN, Canada; ESP, Spain, SWE, Sweden; No Ex, no exacerbation; Non-SevEx, nonsevere exacerbation; SevEx, severe exacerbation; EQ-5D, Euroqol 5 dimension.

Table 7 Base case results

	Tiotropium	Glycopyrronium	Difference
CAN
Costs (€)
Treatment costs	1,933	1,554	380
Direct costs	20,171	21,174	−1,003
Total direct costs	22,105	22,728	−623
Health outcomes
QALYs	6.75	6.54	0.21
Life years	9.00	8.72	0.28
ICER (€)			TIO dom
ESP
Costs (€)
Treatment costs	1,318	1,255	63
Direct costs	39,812	38,809	1,003
Total direct costs	41,129	40,063	1,066
Health outcomes
QALYs	7.77	7.52	0.25
Life years	10.47	10.14	0.34
ICER (€)			4,281
SWE
Costs (€)
Treatment costs	1,898	1,532	366
Direct costs	18,171	18,273	−102
Total direct costs	20,069	19,805	264
Health outcomes
QALYs	7.25	7.02	0.23
Life years	10.26	9.93	0.33
ICER (€)			1,137
UK
Costs (€)
Treatment costs	1,865	1,503	362
Direct costs	19,285	19,816	−531
Total direct costs	21,150	21,319	−169
Health outcomes
QALYs	7.37	7.13	0.23
Life years	9.82	9.51	0.31
ICER (€)			TIO dom

Notes: Discount rates: all costs and effects are discounted at an annual rate of CAN, 5%; ESP, 3%; SWE, 3%; and UK, 3.5%.

Abbreviations: QALYs, quality-adjusted life years; ICER, incremental cost-effectiveness ratio; CAN, Canada; ESP, Spain; SWE, Sweden; TIO dom, tiotropium dominating.

Table 8 One-way sensitivity analysis (ICER €2014)

Variable of interest	Input	CAN	ESP	SWE	UK
Base case		TIO dom	4,281	1,137	TIO dom
Discount rates	Costs: 0%, effects: 0%	TIO dom	4,505	1,442	81
	Costs: 6%, effects: 6%	TIO dom	4,039	814	TIO dom
	Costs: 6%, effects: 0%	TIO dom	2,328	475	TIO dom
Time horizon	5 years	TIO dom	1,174	TIO	TIO dom
	10 years	TIO dom	3,617	227	TIO dom
	20 years	TIO dom	4,212	1,047	TIO dom
Treatment duration	1 year	TIO dom	4,147	1,070	TIO dom
	10 years	TIO dom	4,458	1,316	TIO dom
	Life (35 years)	TIO dom	4,707	1,631	TIO dom
Sex	Males only	TIO dom	4,174	1,048	TIO dom
	Females only	TIO dom	4,364	1,213	TIO dom
Start age	40 years	TIO dom	3,504	216	TIO dom
	80 years	2,293	4,384	1,201	TIO dom
GOLD start distribution	All start in GOLD II	TIO dom	4,136	1,402	TIO dom
	All start in GOLD III	TIO dom	4,318	997	TIO dom
	All start in GOLD IV	TIO dom	4,661	770	TIO dom
Subgroup	GOLD II	TIO dom	1,421	1,276	TIO dom
	GOLD III	TIO dom	5,259	1,087	TIO dom
	GOLD IV	TIO dom	11,421	2,112	TIO dom
Mortality	GOLD state mortality = normal mortality (not adjusted for COPD)	TIO dom	4,384	1,255	TIO dom
	20% higher excess mortality (SevEx)	TIO dom	4,440	1,355	TIO dom
	20% lower excess mortality (SevEx)	TIO dom	4,088	876	TIO dom
Effect of tiotropium on SevEx	Low 95% CI from SPARKa (RR SevEx: 1.05)	9,942	5,875	12,509	10,102
	High 95% CI from SPARKa (RR SevEx: 1.97)	TIO dom	4,161	308	TIO dom
	RR SevEx: 1.00 for GOLD II patients	TIO dom	4,579	1,691	TIO dom
Direct costs of SevEx	20% higher	TIO dom	3,909	611	TIO dom
	20% lower	TIO dom	4,592	1,576	TIO dom
QoL loss of SevEx exacerbations	0% loss	TIO dom	4,309	1,145	TIO dom
	20% loss	TIO dom	4,195	1,113	TIO dom

Notes:

a Base case: RR SevEx GLY versus TIO =1.43.

Abbreviations: ICER, incremental cost-effectiveness ratio; CAN, Canada; ESP, Spain; SWE, Sweden; GOLD, Global Initiative for Chronic Obstructive Lung Disease; GOLD II, GOLD classification indicating moderate COPD; GOLD III, GOLD classification indicating severe COPD; GOLD IV, GOLD classification indicating very severe COPD; COPD, chronic obstructive pulmonary disease; SevEx, severe exacerbation; CI, confidence interval; RR, relative risk; QoL, quality of life; TIO dom, tiotropium dominating; GLY dom, glycopyrronium dominating; TIO, tiotropium; GLY, glycopyrronium.

Figure 2 Impact of RR SevEx on ICER.

Abbreviations: RR, relative risk; SevEx, severe exacerbation; ICER, incremental cost-effectiveness ratio; GLY, glycopyrronium; TIO, tiotropium; CAN, Canada; ESP, Spain; SWE, Sweden.

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