Assessing cost-effectiveness in the management of multiple sclerosis

Figures & data

Figure 1 Costs (Euros) of multiple sclerosis by disease severity, UK 2005.

Abbreviation: EDSS, Expanded Disability Status Scale.

Table 1 Economic evaluations of disease modifying drugs in MS

Author	Intervention and disease category	Design, methods and timescales	Cost per QALY estimate	Sensitivity analysis (best-case and worse-case scenarios)	Perspective
Bose et al (2000 prices)^Citation114	Glatiramer acetate in RRMS	Decision analytic model based on patient level data from pivotal clinical trial for 6 and 8 years	$45,992 (€52,864) (6 years) $36,429 (€41,872) (8 years) Also: cost per relapse avoided of $21,977 (€25,261) (6 years) and $17,742 (€20,393) (8 years) Cost per disability unit avoided of $19,250 (€22,126) (6 years) and $14,294 (€16,429) (8 years)	Doubling the cost of relapse ∼ Cost per QALY $28,602 (€32,875) (8 years) Duration of relapse (1 month rather than 2 months) ∼ Cost per QALY $136,350 (€156,724)	Healthcare sector
Chilcott et al (2000/01 prices)^Citation98	IFNβ and glatiramer acetate in RRMS and SPMS	Markov model simulating the clinical progression of MS over 20 years	$67,808 (€77,940) to $157,477 (€181,009) (depending on therapy and dosage)	Probability that the cost-effectiveness of any of the interventions is better than $32,258 (€37,078) is between 3% and 18%	Healthcare sector
Kobelt et al (1998/99 prices)^Citation110	IFNβ-1b in SPMS	Markov model simulating the clinical progression of MS over 10 years using 3-year clinical trial data and then extrapolating	$39,250 (€45,115) (all costs included and discounted at 3%)	$62,100 (€71,379) excluding indirect costs	Societal
Kobelt et al (1998/99 prices)^Citation111	IFNβ-1b in SPMS	Markov model simulating the clinical progression of MS using 3-year clinical trial data and then natural history disease data up to 10 years	$25,700 (€29,540) (all costs included and discounted at 3%)	$44,700 (€51,379) excluding indirect costs	Societal
Kobelt et al (1998/99 prices)^Citation99	IFNβ-1b in RRMS and SPMS	Markov model simulating the clinical progression of MS using 3-year clinical trial data from both RRMS and SPMS studies and then natural history disease data up to 10 years	$6,786 (€7,800) for 3 years treatment (all costs included and discounted at 3%)	Probability that the cost per QALY over a 20-year time frame is below $43,500 (€50,000) for patients starting treatment at EDSS3.0 is 80%	Healthcare sector + societal
Phillips et al (1999 prices)^Citation102	IFNβ-1b in RRMS	Markov model to mirror disease progression and take into account the number, severity and duration of relapses; the probability of becoming disabled; the speed at which people with MS become disabled; the different costs associated with each level of disability; the different health states experienced by patients with each level of disability; and the different time horizons based on empirical information from natural history data	$36,774 (€42,269) (10 years) (direct and indirect costs); $23,548 (€27,067) (all costs) $13,065 (€15,017) (20 years) (direct and indirect costs); $4,839 (€5,562) (all costs)	$34,516 (€39,674) to $60,484 (€69,522) (10 years) (direct and indirect costs); $22,097 (€25,399) to $50,645 (€58,213) (10 years) (all costs) $11,774 (€13,534) to $21,774 (€25,028) (20 years) (direct and indirect costs); $3,387 (€3,893) to $13,226 (€15,202) (20 years) (all costs)	Societal
Lepen et al (2000 prices)^Citation113	IFNβ-1a in RRMS	Econometric model using 4-year data from the PRISMS study and projecting the data over 10 and 20 years. The model uses the AUC-EDSS as an integrated measure of disability to calculate the effectiveness of IFNβ-1a as number of EDSS months of disability saved	Total cost £243,141 (€389,711) for 10 years = cost per EDSS-month £453 (€726). At 20 years, the total costs rose to £448,602 (€719,029) with the cost per EDSS-month saved reducing to £222 (€356)	Secondary analysis in the study confirmed that using a 1 dose of 44 μg rather than 3 doses of 22 μg per week saved 15 EDSS-months over 10 years = £14,000 (€22,440) per EDSS-month saved	Healthcare sector
Touchette et al (2000 prices)^Citation119	IFNβ-1b and Mitoxantrone in SPMS and PRMS	Using existing published data including the MIMS study, EUSPMS study and utility measures from Parkin et al^Citation100 a Markov model was populated using EDSS level 3 as an entering point. The patients’ disease progression was then followed for 10 years with the cost-utility measured as cost per QALY	Compared with routine supportive care (4.9650 QALYS over 10 years costing $46,331 (€46,009)) IV MH resulted in 5.0860 QALYS costing $53,378 (€53,007). IFN produced a QALY of 5.1702 with a cost estimate of $115,833 (€115,028)	From a societal perspective, IV MH came out at $378,464 (€375,833) with IFN remaining the most costly at $433,932 (€430,916). When compared with routine supportive care, the IV MH resulted in a cost-utility ration of $58,272 (€57,867) per QALY. Seen from the societal perspective, IV MH was less costly and produced bigger QALY gains	Healthcare sector + societal
Lazzaro et al (2006 prices)^Citation112	IFNβ-1b for all CDMS	Incorporates the patients enrolled in the BENEFIT study into a 25 year epidemiological model and measures the cost of treatment of IFNβ-1b from the diagnosis of CIS compared to the cost of treatment once conversion to CDMS has happened	The QALYs gained achieved statistical significance with the 7.84 QALY gained for the CIS arm, compared to 7.49 for the untreated arm. Early treatment of IFNβ-1b is cost effective when seen form the health service point of view with the ICER of €2,574.94 falling well below the acceptable incremental QALY range of €12,000 to €60,000	Health perspective – €67,469 to €152,1772 per QALY gained. €47,686 to €132,988 from societal perspective	Healthcare sector + societal
Guo et al (2006 prices)^Citation96	IFNβ-1a in RRMS	DES populated with data mainly taken from the EVIDENCE trial. The use of the DES model, over the more commonly used Markov model was to utilize the flexibility of a DES model when comparing various treatment scenarios	The total mean costs per patient (discounted) were US$79,890 with SC IFNβ-1a, compared with US$74,485 with IM IFNβ-1a. However, even though this means an increase of US$5405 per patient, SC IFNβ-1a was estimated to save 23 relapse-free days per patient or an incremental cost-effectiveness ratio of US$10,755 per relapse prevented	SC IFNβ-1a estimated to prevent 0.50 relapses = 23 relapse-free days per patient = ICER of $10,755 per relapse prevented = $232 per relapse-free day gained	Healthcare sector
Gani et al (2006 prices)^Citation92	Natalizumab (Tysabri) in RRMS	Uses previously published data including efficacy data from the AFFIRM study to popluate a 30-year Markov model developed based on a previous model by Chilcott et al	Natalizumab results in the most cost-effective ICER of $2300 (€3,348) per QALY gained. This is in comparison with IFNβ’s ICER of £2000 (€2,911) and glatiramer acetate’s ICER of £8200 (€11,937) per QALYs gained. With a WTP threshold set at £10,000 (€14,557) per QALY, the probability of natalizumab being cost-effective are 72%, 71% and 59%. At a threshold of £30,000 (€43,671) per QALY, this increases to 89%, 90% and 94%	The authors suggest that natalizumab for patients with HARRMS is more cost-effective than interferon-b, glatiramer acetate and best supportive care if the societal WTP is higher than £8200 (€11,937) per QALY or £26,000 (€37,849) per QALY from the health perspective	Societal
Kobelt et al (2005 prices)^Citation94	Natalizumab (Tysabri) in RRMS	Uses existing literature (AFFIRM, Ontario data set and cost data from 2 previous Swedish studies to populate the Markov model to cover a 20-year time frame	From a health perspective natalizumab’s total costs are €352,175 with a cost per QALY of €38,000	When seen over 20 years from the societal perspective, the total cost of natilizamub is 609,850 (€3830 less than standard care) with a cost per QALY dominating	Societal
Bell, et al (2005 prices)^Citation118	IFNβ and glatiramer acetate in RRMS	A Markov model populated by data from the literature was developed to assess the cost-effectiveness of 5 treatment strategies for RRMS patients compared to symptom management alone. The model incorporated the EDSS scale with 7 specific transition health states with the time horizon set at 13 years (approximation of a patient’s lifetime with MS)	SC GA patients saw greater cost benefits with the incremental cost per QALY of $258,465 (€190,552) compared to $337,968 (€249,165), $416,301 (€306,916) and $310,691 (€229,056) for the IFNβ treatments respectively	Total costs for the lifetime of a patient were calculated at $295,586 (€217,919) for symptom management arm and $352,760 (€260,071), $364,267 (€268,554), $377,996 (€278,676) and $358,509 (€264,309) for each drug arm respectively. When direct medical costs were compared, the added costs of drug treatment were partially offset by cost savings in MS related medical costs. The SC GA arm saw the highest cost offset with 24% saved compared to 17%–22% cost saved by beta-interferons	Societal
Iskedjian et al (2001 prices)^Citation108	IFNβ-1a and Avonex in CDMS	A Markov model was designed to generate both the time spent in the pre-CDMS state (MLY) and QAMLY for the CEA and CUA perspectives	From the MoH perspective, the incremental cost-effectiveness of Avonex per MLY gained was CAN$53,110 (€37,658). In the CUA, the cost per QAMLY gained was CAN$227,586 (€161,371). From the societal perspective, the CEA ratio was CAN$44,789 (€31,758) per MLY gained and CAN$189,286 (€134,214) per QAMLY gained	$44,789 (€31,758) to $227,586 (€161,371)	Healthcare sector + Societal
Prosser et al (1999 prices)^Citation103	IFNβ and glatiramer acetate in non-PPMS	A state transition model was developed with a 10-year treatment duration. The main outcome for the model was net QALY gains and ICER QALY gains	From base case analysis, IFNβ-1a provided more health benefits and resulted in an ICER of $1,838,000 (€1,575,088)/QALY for men and $2,218,000 (€1,900,732)/QALY for women. Increasing the model to 40 years, the ICER for IFNβ-1a decreased to $250,000 (€214,239)/QALY for women and $235,000 (€201,385)/QALY for men	40-year model – $250,000 (€214,239)/QALY for women and $235,000 (€201,385)/QALY for men or 10-year model $1,838,000 (€1,575,088)/QALY for men and $2,218,000 (€1,900,732)/QALY for women	Societal

Abbreviations: AUC-EDSS, area under the EDSS time curve; CEA, cost-effectiveness analysis; CEA, cost-utility analysis; CDMS, clinically definite MS; CIS, clinically isolated syndrome; DES, discrete-event simulation model; EDSS, Expanded Disability Status Scale; GA, glatiramer acetate; HARRMS, highly active relapsing-remitting multiple sclerosis; ICER, incremental cost-effectiveness ratio IFNβ-1a, interferon beta-1a; IFNβ-1b, interferon beta-1a; IM, intramuscular; MH, mitoxantrone hydrochloride; MLY, monosymptomatic life years; MS, multiple sclerosis; QAMLY, monosymptomatic life years gained; QALY, quality adjusted life-year; RRMS, relapsing-remitting MS; SC, subcutaneous; SPMS, secondary progressive MS; WTP, willingness to pay.

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