Cost-utility of denosumab for the treatment of postmenopausal osteoporosis in Spain

Figures & data

Figure 1 Markov model used to represent the possible health state transitions of Spanish women with postmenopausal osteoporosis.

Notes: The analysis time began from the initiation of fracture prevention treatment until age 100 years or death. This model was developed from Jonssen et al³³ with the analyses conducted from the perspective of the Spanish National Health Service. Springer and the original publisher, Osteoporosis International, volume 22, 2010, page 968, Cost-effectiveness of Denosumab for the treatment of postmenopausal osteoporosis, B. Jönsson, O. Ström, J. A. Eisman, A. Papaioannou, E. S. Siris, A. Tosteson, J. A. Kanis, figure 1. © International Osteoporosis Foundation and National Osteoporosis Foundation 2010. With kind permission from Springer Science and Business Media.

Table 1 Input parameters: efficacy rate (relative risk reduction) relative to placebo

Fracture site	Denosumab			Alendronate		Risedronate		Ibandronate		Strontium ranelate
	Base case (%)	Alternative analysis (%)#	>75 years (%)	Base case (%)	>75 years (%)	Base case (%)	>75 years (%)	Base case (%)	>75 years (%)	Base case (%)	>75 years (%)
Hip	40^Citation40	47^Citation42	68^Citation42	38^Citation93	0^Citation94	26^Citation93	0^Citation94	0^Citation93	0^Citation41	15^Citation93	0^Citation94
Vertebral	68^Citation40	69^Citation43	64^Citation43	44^Citation93	38^Citation94	36^Citation93	44^Citation94	49^Citation93	0^Citation41	38^Citation93	32^Citation94
Wrist*	16^Citation39	40^Citation39	16^Citation43	15^Citation93	0^Citation94	32^Citation93	0^Citation94	0^Citation93	0^Citation41	0^Citation93	31^Citation94
Other	20^Citation40	35^Citation43	16^Citation43	18^Citation93,Citation94	0^Citation94	20^Citation93	0^Citation94	0^Citation93	0^Citation41	14^Citation93	31^Citation94

Notes:

# T-score ≤2.5 or less in the femoral neck

* where specific values for wrist are not available, the value for other has been assumed.

Table 2 Fracture incidence and mortality at selected ages

Age (years)	Risk of fracture					Risk of mortality compared with population norms
	Hip	Vertebral	Wrist	Other	Hip (year 1)	Vertebral (year 1)	Hip (year 2+)	Vertebral (year 2+)	Other (year 1)
50	0.00025	0.00124	0.00225	0.00304	9.79	12.07	3.62	7.94	1.22
55	0.00023	0.00121	0.00247	0.00370	8.64	10.15	3.34	6.67	1.22
60	0.00054	0.00187	0.00293	0.00392	7.69	9.04	3.11	5.94	1.22
65	0.00104	0.00293	0.00359	0.00663	6.39	7.43	2.70	4.88	1.22
70	0.00221	0.00490	0.00459	0.00948	5.54	5.98	2.44	3.93	1.22
75	0.00496	0.00745	0.00549	0.01553	4.16	4.39	1.91	2.88	1.22
80	0.00996	0.00870	0.00637	0.02268	2.92	2.75	1.39	1.81	1.22
85	0.01817	0.01105	0.00737	0.03800	2.15	1.98	1.06	1.30	1.22
90	0.02543	0.01469	0.00837	0.05955	1.63	1.36	1.00	1.00	1.22

Table 3 Costs (2013 prices)

	Cost (€)
	Age group (years)
	50–64	65–74	75–84	≥85
Fracture site^Citation95
Hip	10,236	11,931	12,684	18,841
Vertebral	3,994	13,683	13,683	13,683
Wrist	1,981	1,981	1,981	1,981
Other	1,981	1,981	1,981	1,981
Annual drug costs (including all sales taxes)^Citation58	Cost (€)
Denosumab	417.34
Alendronate	162.82
Risedronate	283.80
Ibandronate	156.00
Strontium ranelate	595.54
Non-drug costs
Medical costs associated with hip fracture (year 2+)^Citation95	5,480
Daily cost of nursing home/long-term care^Citation57	86.95
Cost of a physician visit^Citation95	59.18
Cost of IV administration per injection^Citation57	209.33
Cost of a nurse visit^Citation57	20.67

Abbreviation: IV, intravenous.

Table 4 Utility values and treatment persistence

Fracture	Utility multiplier
First year only
Hip	0.700
Vertebral	0.590
Wrist	0.956
Other	0.902
Subsequent years
Hip	0.800
Vertebral	0.929
Time since initiation (months)	Discontinuation rates (%)
	Denosumab	Comparators
Persistence rates
6	18.6	37.2
12	13.1	26.1
18	11.2	22.4
24	9.9	19.8
30	10.2	20.5
36	15.2	30.3
Age (years)	Mean
EQ-5D mean index values (time trade-off value set)
18–24	0.981
25–34	0.970
35–44	0.942
45–54	0.919
55–64	0.894
65–74	0.857
≥75	0.729
Total	0.912

Abbreviation: EQ-5D, five-dimension European quality of life questionnaire.

Table 5 Input distributions for probabilistic sensitivity analysis

Treatment	Relative risk of fractures – treatment versus placebo
	Fracture site	Ratio	Lower CI	Upper CI
Denosumab	Hip	0.60	0.37	0.97
	Vertebral	0.32	0.26	0.41
	Wrist	0.84	0.63	1.11
	Other	0.80	0.67	0.95
Alendronate	Hip	0.62	0.40	0.96
	Vertebral	0.56	0.46	0.67
	Wrist	0.85	0.67	1.09
	Other	0.82	0.73	0.93
Risedronate	Hip	0.74	0.59	0.93
	Vertebral	0.64	0.52	0.78
	Wrist	0.68	0.43	1.07
	Other	0.80	0.72	0.90
Ibandronate	Hip	1.00	1.00	1.00
	Vertebral	0.51	0.34	0.74
	Wrist	1.00	1.00	1.00
	Other	1.00	1.00	1.00
Strontium ranelate	Hip	0.85	0.61	1.19
	Vertebral	0.62	0.55	0.71
	Wrist	1.00	0.74	1.36
	Other	0.86	0.74	0.99
Fracture type and duration	Relative standard errors of the mean
	Cost (%)		Utilities (%)
Hip fracture, year 1	5		3
Vertebral fracture, year 1	13		6
Wrist fracture, year 1	7		4
Other fracture, year 1	13		6
Hip fracture, year 2+	10		7
Vertebral fracture, year 2+	10		6
Proportion of hip fracture patients going on to long-term care	Relative standard error of the mean
	5%

Abbreviation: CI, confidence interval.

Table 6 Results of base case and sensitivity analyses

	Total costs (€)	Life-years	Life-years (adjusted)	QALYs	ICER (€/QALY): denosumab versus comparator
Base case
No treatment	23,122	20.803	15.156	11.899	6,823
Alendronate	22,980	20.818	15.166	11.920	16,294
Risedronate	23,298	20.815	15.164	11.915	4,895
Ibandronate	23,388	20.818	15.165	11.914	2,205
Strontium ranelate	23,890	20.815	15.163	11.913	Dominant
Denosumab	23,467	20.842	15.180	11.950	–
Sensitivity analysis (high fracture-risk population [T-score ≤ −2.5 at femoral neck])
No treatment	23,122	20.803	15.156	11.899	3,311
Alendronate	22,981	20.818	15.166	11.920	9,492
Risedronate	23,299	20.815	15.164	11.915	132
Ibandronate	23,389	20.818	15.165	11.914	Dominant
Strontium ranelate	23,891	20.815	15.163	11.913	Dominant
Denosumab	23,304	20.843	15.181	11.954	–
Sensitivity analysis (treatment duration extended to 10 years)
No treatment	23,122	20.803	15.156	11.899	3,817
Alendronate	22,837	20.823	15.168	11.928	11,573
Risedronate	23,307	20.819	15.166	11.921	2,077
Ibandronate	23,469	20.822	15.168	11.919	Dominant
Strontium ranelate	24,155	20.818	15.166	11.918	Dominant
Denosumab	26,680	20.862	15.192	11.979	–

Abbreviations: ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life-year.

Table 7 Incremental cost-effectiveness ratios produced in multivariate sensitivity analysis

T-score	No previous fracture				Previous fracture
	Age (years)				Age (years)
	60	65	70	75	60	65	70	75
Denosumab versus no treatment
≤−2.5	€28,002	€15,185	€1,629	Cost-saving	€2,400	Cost-saving	Cost-saving	Cost-saving
≤−3.0	€16,018	€5,808	Cost-saving	Cost-saving	Cost-saving	Cost-saving	Cost-saving	Cost-saving
≤−3.5	€5,867	Cost-saving	Cost-saving	Cost-saving	Cost-saving	Cost-saving	Cost-saving	Cost-saving
≤−4.0	Cost-saving	Cost-saving	Cost-saving	Cost-saving	Cost-saving	Cost-saving	Cost-saving	Cost-saving
Denosumab versus alendronate
≤−2.5	€42,598	€27,501	€12,772	Cost-saving	€9,890	€4,102	Cost-saving	Cost-saving
≤−3.0	€28,625	€16,487	€4,132	Cost-saving	€3,932	Cost-saving	Cost-saving	Cost-saving
≤−3.5	€16,840	€7,038	Cost-saving	Cost-saving	Cost-saving	Cost-saving	Cost-saving	Cost-saving
≤−4.0	€7,173	Cost-saving	Cost-saving	Cost-saving	Cost-saving	Cost-saving	Cost-saving	Cost-saving

Figure 2 Results of the probabilistic sensitivity analysis showing willingness to pay per quality-adjusted life-year.

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