Table 2: Cost-effectiveness analyses of multiple sclerosis disease modifying therapies (2004–2012).

First author yearModel type
country perspective
Study pop
time horizon
ComparatorsPrimary effectiveness outcomeResultsStated conclusionQHES
score
Sponsor

Prosser
2004 [84]
CSM1  
US societal
Non-primary progressive MS
10 years
(1) IFNB-1a (IM)
(2) IFNB-1b
(3) GA
(4) No Tx
QALYs1 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.87National MS Society

Iskedjian
2005 [58]
CSM1  
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.69Biogen Idec, Inc.

Perini
2006 [109]
OLH2HCS
Italian payer (NS)
SPMS
2 years
(1) Mitoxantrone
(2) CP
Relapse rate decrease/EDSS decrease1: 88%/0.9 (€8171)
2: 86.4%/0.9 (€5097)
2 should be considered as a first-line rescue therapy for MS34Not stated

Bell
2007 [35]
CSM1  
US societal
RRMS
Lifetime
(1) GA
(2) IFNB-1a (IM)
(3) IFNB-1a (SC)
(4) IFNB-1b
(5) Supportive
QALYs1 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.90Teva Neuroscience, Inc.

Gani
2008 [52]
CSM1  
UK societal
HARRMS
30 years
(1) Natalizumab
(2) IFNB (pooled)
(3) GA
(4) Supportive
QALYs1 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.100Biogen Idec, Inc.

Kobelt
2008 [62]
CSM1  
Swedish societal
RRMS
20 years
(1) Natalizumab
(2) DMDs (composite)
QALYs1 dominates 2For this population, 1 provides an additional health benefit at a similar cost to 2.90Biogen 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.43Teva Neuroscience, Inc.

Chiao
2009 [39]
CSM2  
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 avoided1 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.78Biogen Idec, Inc./Elan Pharma.

Earnshaw
2009 [48]
CSM1  
US healthcare
(also societal)
RRMS
Lifetime
(1) Natalizumab
(2) GA
(3) Supportive
QALYsHealthcare:
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.88Teva Neuroscience, Inc.

Goldberg
2009 [1]
CSM3  
US payer
RRMS
2 years
(1) GA
(2) IFNB-1a (IM)
(3) IFNB-1a (SC)
(4) IFNB-1b
(5) No Tx
Relapses avoided1 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.86EMD Serono, Inc

Guo
2009 [55]
PLS4  
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.78EMD Serono, Inc

Jankovic
2009 [59]
CSM1  
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.46Serbian Ministry of Science and Ecology

Kobelt
2009 [108]
CSM1  
French societal
(also payer)
Relapsing forms
20 years
(1) DMTs
(2) No DMT
QALYs1 versus 2: €15,385/QALY
(Fully treated with DMT)
Cost increase with DMTs is moderate for health gained.71Authors declare none

Lazzaro
2009 [66]
CSM5  
INHS/Italian societal
CIS patients
25 years
IFNB-1b:
(1) At CIS
(2) At CDMS
QALYsINHS: €2,575 1 versus 2
Societal: 1 dominates 2
1 significantly delays conversion to CDMS and is economically advantageous.75Bayer Schering Pharma, Italy

Tappenden
2009 [100]
CSM1  
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
QALYs1 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.100USDHHS AHRQ

Bakshai
2010 [33]
CSM2  
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 avoided1 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.50Not funded

Nuijten
2010 [78]
CSM1  
German societal
RRMS
4 years
(1) IFNB-1a (SC)
(2) IFNB-1a (IM)
(3) IFNB-1b
(4) GA
(5) No Tx
Relapses avoided1 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.79Merck Pharma

Tappenden
2010 [101]
CSM1  
UKNHS/PSS
SPMS
Lifetime
(1) AHSCT
(2) Mitoxantrone
QALYs1 versus 2:
£2783 to Dominated
(Cost/QALY)
1 could potentially achieve an acceptable CE, however RCTs are needed to confirm this.100No commercial or research funding

Noyes
2011 [77]
CSM1  
US societal (NS)
RRMS and SPMS
10 years
(1) IFNB-1a (IM)
(2) IFNB-1b
(3) GA
(4) IFNB-1a (SC)
(5) Supportive
QALYS1–4 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.83Biogen, Boston Scientific, NIH, NMSS, and USDOD

O'Day
2011 [80]
CSM3  
US managed care payer
Relapsing MS
2 years
(1) Natalizumab
(2) Fingolimod
Relapses avoided1 dominates 21 dominates 2 in terms of incremental cost per relapse avoided.86Biogen Idec, Inc.

Caloyeras
2012 [107]
CSM1  
Swedish Societal
First initial event suggestive of MS and CDMS
50 years
(1) IFNB-1b early treatment
(2) IFNB-1b delayed treatment
QALYS1 dominates 2Early treatment improved patient outcomes while controlling costs. 1 dominates 299Abt Bio Pharma Solutions, Inc.

Pan
2012 [106]
CSM1  
US Societal
RRMS
70 years
(1) IFNB-1b early treatment
(2) Placebo, market basket after 5 years
Life-Years Gained; QALYS1 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-effective90Bayer 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.