Cost-Effectiveness of Multiple Sclerosis Disease-Modifying Therapies: A Systematic Review of the Literature

Table 2

Cost-effectiveness analyses of multiple sclerosis disease modifying therapies (2004–2012).

First author year	Model type; country perspective	Study pop; time horizon	Comparators	Primary effectiveness outcome	Results	Stated conclusion	QHES; score	Sponsor
Prosser; 2004 [84]	CSM^1; US societal	Non-primary progressive MS; 10 years	(1) IFNB-1a (IM); (2) IFNB-1b; (3) GA; (4) No Tx	QALYs	1 versus 4: Not CE; (>$1,800,000/QALY); 2 & 3 dominated versus 4	1–3 less CE than 4 under a wide range of assumptions.	87	National MS Society
Iskedjian; 2005 [58]	CSM^1; Canadian; MoH/societal	SDE at risk for CDMS; 15 yrs	(1) IFNB-1a (IM) + MPS (iv); (2) MPS (iv)	QAMLY	$227,586/QAMLY (MoH); $189,286/QAMLY (SoC)	1 is a reasonably CE approach to Tx of patients with a SDE. ICER improves if Tx is initiated in pre-CDMS.	69	Biogen Idec, Inc.
Perini; 2006 [109]	OLH2HCS; Italian payer (NS)	SPMS; 2 years	(1) Mitoxantrone; (2) CP	Relapse rate decrease/EDSS decrease	1: 88%/0.9 (€8171); 2: 86.4%/0.9 (€5097)	2 should be considered as a first-line rescue therapy for MS	34	Not stated
Bell; 2007 [35]	CSM^1; US societal	RRMS; Lifetime	(1) GA; (2) IFNB-1a (IM); (3) IFNB-1a (SC); (4) IFNB-1b; (5) Supportive	QALYs	1 versus 5: $258,465/QALY; 2 versus 5: $337,968/QALY; 3 versus 5: 416,301/QALY; 4 versus 5: $310,691/QALY	1 is the best DMT and resulted in better outcomes than 5 alone.	90	Teva Neuroscience, Inc.
Gani; 2008 [52]	CSM^1; UK societal	HARRMS; 30 years	(1) Natalizumab; (2) IFNB (pooled); (3) GA; (4) Supportive	QALYs	1 versus 2: £2300/QALY; 1 versus 3: £2000/QALY; 1 versus 4: £8200/QALY	1 is more CE than 2, 3 and 4 for HARRMS.	100	Biogen Idec, Inc.
Kobelt; 2008 [62]	CSM^1; Swedish societal	RRMS; 20 years	(1) Natalizumab; (2) DMDs (composite)	QALYs	1 dominates 2	For this population, 1 provides an additional health benefit at a similar cost to 2.	90	Biogen Idec Inc./Elan Pharma.
Castelli-Haley; 2009 [38]	RMCA; US payer (NS)	ITT: CDMS, GA or IFNB-1b Rx, Ins. cov.; CU: ITT + no other DMT and Rx in last 28 days of period; 2 years	(1) GA; (2) IFNB-1b	Risk of Relapse; Avg. total medical costs	ITT: 5.31% (1), 13.54% (2); CU: 2.09% (1), 10.91% (2); $48,130 (1), $53,157 (2)	RRMS patients treated with 1 have significantly lower relapse rate. Costs are lower for 1 in CU cohort.	43	Teva Neuroscience, Inc.
Chiao; 2009 [39]	CSM^2; US payer	DMT candidates with relapsing MS; 2-years (static)	(1) Natalizumab; (2) IFNB-1a (IM); (3 IFNB-1b; (4) GA; (5) INFB-1a (SC)	Relapses avoided	1 versus 2: $23,029/RA; 1 versus 3: $24,452/RA; 1 versus 4: $20,671/RA; 1 versus 5: $20,403/RA	1 was the most CE.	78	Biogen Idec, Inc./Elan Pharma.
Earnshaw; 2009 [48]	CSM^1; US healthcare; (also societal)	RRMS; Lifetime	(1) Natalizumab; (2) GA; (3) Supportive	QALYs	Healthcare: 1 versus 3: $606,228/QALY; 2 versus 3: $496,222/QALY; Societal: 1 & 2 cost saving versus 3	1 and 2 are associated with increased benefits compared with 3 at higher costs.	88	Teva Neuroscience, Inc.
Goldberg; 2009 [1]	CSM^3; US payer	RRMS; 2 years	(1) GA; (2) IFNB-1a (IM); (3) IFNB-1a (SC); (4) IFNB-1b; (5) No Tx	Relapses avoided	1 versus 5: $88,310/RA; 2 versus 5: $141,721/RA; 3 versus 5: $80,589/RA; 4 versus 5: $87,061/RA	1, 3 and 4 represent the most CE DMDs for Tx of RRMS.	86	EMD Serono, Inc
Guo; 2009 [55]	PLS^4; US payer	Relapsing MS; 4 years	(1) IFNB-1a (SC); (2) IFNB-1a (IM)	Relapses avoided/; Relapse free days gained	1 versus 2: $10,755/RA; $232/relapse free day	1 versus 2 yields greater health benefits over 4 years at a reasonable cost.	78	EMD Serono, Inc
Jankovic; 2009 [59]	CSM^1; Balkan societal	RRMS; 40 years	(1) GA (SC); (2) IFNB-1a (IM); (3) IFNB-1a (SC); (4) IFNB-1b; (5) Supportive	QALYs	>$20,000,000/QALY; (1–4 versus 5)	IMT of RRMS in a Balkan country is not CE.	46	Serbian Ministry of Science and Ecology
Kobelt; 2009 [108]	CSM^1; French societal; (also payer)	Relapsing forms; 20 years	(1) DMTs; (2) No DMT	QALYs	1 versus 2: €15,385/QALY; (Fully treated with DMT)	Cost increase with DMTs is moderate for health gained.	71	Authors declare none
Lazzaro; 2009 [66]	CSM^5; INHS/Italian societal	CIS patients; 25 years	IFNB-1b: (1) At CIS; (2) At CDMS	QALYs	INHS: €2,575 1 versus 2; Societal: 1 dominates 2	1 significantly delays conversion to CDMS and is economically advantageous.	75	Bayer Schering Pharma, Italy
Tappenden; 2009 [100]	CSM^1; US payer; (also CMS)	Medicare; beneficiaries with MS; 50 year	(1) IFNB-1a (PA); (2) IFNB-1a (SA); (3) IFNB-1a (22 ug); (4) IFNB-1a (44 ug); (5) IFNB-1b; (6) GA; (7) Supportive	QALYs	1 versus 7: $66–234k/QALY; 2 versus 7: $60–218k/QALY; 3 versus 7: $120–199k/QALY; 4 versus 7: $79–172k/QALY; 5 versus 7: $91–169k/QALY; 6 versus 7: $122–312k/QALY	Suggests prudent use of a discontinuation rule may improve CE.	100	USDHHS AHRQ
Bakshai; 2010 [33]	CSM^2; US managed care payer	Relapsing forms receiving IMT; 2 years	(1) Natalizumab; (2) IFNB-1a (IM); (3) IFNB-1b; (4) GA; (5) IFNB-1a (SC)	Relapses avoided	1 versus 2: $23,029/RA; 1 versus 3: $24,452/RA; 1 versus 4: $20,671/RA; 1 versus 5: $20,403/RA	1 is relatively CE and adds a new option for those patients for whom conventional Tx was unsuccessful.	50	Not funded
Nuijten; 2010 [78]	CSM^1; German societal	RRMS; 4 years	(1) IFNB-1a (SC); (2) IFNB-1a (IM); (3) IFNB-1b; (4) GA; (5) No Tx	Relapses avoided	1 versus 5: €51,250/RA; 2 versus 5: €133,770/RA; 3 versus 5: €54,475/RA; 4 versus 5: €71,416/RA	1 versus 5 had favorable overall CE compared with all other available DMDs for the Tx of RRMS.	79	Merck Pharma
Tappenden; 2010 [101]	CSM^1; UKNHS/PSS	SPMS; Lifetime	(1) AHSCT; (2) Mitoxantrone	QALYs	1 versus 2: £2783 to Dominated; (Cost/QALY)	1 could potentially achieve an acceptable CE, however RCTs are needed to confirm this.	100	No commercial or research funding
Noyes; 2011 [77]	CSM^1; US societal (NS)	RRMS and SPMS; 10 years	(1) IFNB-1a (IM); (2) IFNB-1b; (3) GA; (4) IFNB-1a (SC); (5) Supportive	QALYS	1–4 versus 5: All far exceeded $800,000/QALY	DMTs resulted in small health gains for the cost. Starting DMTs earlier resulted in more favorable CE results.	83	Biogen, Boston Scientific, NIH, NMSS, and USDOD
O'Day; 2011 [80]	CSM^3; US managed care payer	Relapsing MS; 2 years	(1) Natalizumab; (2) Fingolimod	Relapses avoided	1 dominates 2	1 dominates 2 in terms of incremental cost per relapse avoided.	86	Biogen Idec, Inc.
Caloyeras; 2012 [107]	CSM^1; Swedish Societal	First initial event suggestive of MS and CDMS; 50 years	(1) IFNB-1b early treatment; (2) IFNB-1b delayed treatment	QALYS	1 dominates 2	Early treatment improved patient outcomes while controlling costs. 1 dominates 2	99	Abt Bio Pharma Solutions, Inc.
Pan; 2012 [106]	CSM^1; US Societal	RRMS; 70 years	(1) IFNB-1b early treatment; (2) Placebo, market basket after 5 years	Life-Years Gained; QALYS	1 versus 2: $30,967/LY; $46,357/QALY	Treatment during early disease phase increased patient life-years and QALYs. Early treatment with IFNB-1b likely cost-effective	90	Bayer Health-Care Pharmaceuticals

Models: ¹Markov, ²Cost-effectiveness/budget impact, ³Average patient simulation, ⁴Discrete event simulation, ⁵Open cohorts epidemiology model.
Comparators: No Tx: No physician care, Supportive: Symptom management alone.
Acronyms (alphabetical): AHSCT: Autologous haematopoietic stem cell transplantation; CE: Cost effective; CDMS: Clinically diagnosed multiple sclerosis; CIS: Clinically isolated syndrome; CP: Cyclophosphamide; CSM: Cohort simulation model; CU: Continuous use; DMD: Disease-modifying drug; DMT: Disease-modifying therapy; HARRMS: Highly active relapsing-remitting multiple sclerosis; IM: Intramuscular; IMT: Immunomodulatory treatment; INHS: Italian National Health Service; ITT: Intent to treat; MLY: Monosymptomatic life years gained; MoH: Ministry of Health; MPS: Methylprednisolone; NS: Not stated; OLH2HCS: Open-labeled head-to-head clinical study; PA: Physician-administered subcutaneous; PLS: Patient-level simulation; PMPM: Per member per month; PSS: Personal Social Services; QAMLY: Quality-adjusted monosymptomatic life years gained; RA: relapse avoided; RMCA: Retrospective multivariate cohort analysis; RRMS: Relapsing-remitting multiple sclerosis; SA: Self-administered subcutaneous; SC: Subcutaneous; SDE: Single demyelinating event; SoC: Societal; SPMS: Secondary progressive multiple sclerosis; UKNHS: United Kingdom National Health Service.