Table 4 Outcomes and Costs of included studies

Smets et al. (2023) [53]

QALYs

Ocrelizumab

635,320.02 $

-

19.2

-

-There was no clear difference in the cost-effectiveness of sequences with ocrelizumab and ofatumumab in either first- or second-line in relapsing MS

-The probability of ocrelizumab being cost-effective versus ofatumumab in first- and second-line

Ofatumumab

622,623.28 $

-

18.5

-

Matni et al. (2022) [54]

QALY, LY & ICER

Cladribine tablets

239,094.67 $

20.225

7.186

Reference

According to the cost-utility analysis, base case analysis, Sensitivity analysis and budget impact analysis, cladribine tablets are an economically dominant therapeutic strategy when compared to alemtuzumab, fingolimod, and natalizumab, at a threshold of 22,000 USD per QALY gained

Alemtuzumab

277,825.92 $

20.225

6.947

Cladribine dominant

Fingolimod

309,969.41 $

20.225

6.150

Cladribine dominant

Natalizumab

306,363.66 $

20.225

6.546

Cladribine dominant

Spelman et al. (2022) [55]

QALY, LY & ICER

Natalizumab

671,819.07 $ (Total direct cost)

20.05

7.87

Dominant

Natalizumab dominated (higher QALYs and lower costs) fingolimod in the base-case cost-effectiveness analysis (0.453 higher QALYs and £20,843 lower costs per patient)

Fingolimod

702,322.97 $ (Total direct cost)

20.15

7.42

Natalizumab (Dominant)

Espinoza et al. (2021) [38]

QALY, ICER

Natalizumab

227,506.54 $

-

9.519

$ 0

Compared with natalizumab, cladribine was associated with incremental costs and QALYs of US$70,989 and 1.875, respectively (incremental cost-effectiveness ratio [ICER] $37,861). Ocrelizumab was extendedly dominated by cladribine and natalizumab, and alemtuzumab was dominated by cladribine. A scenario analysis of a 10% discount did not modify the results substantially, but showed a decrease in the ICER of cladribine versus natalizumab (ICER $29,833/QALY)

Ocrelizumab

251,216.33 $

-

9.912

60,328.58 $

(Extended dominated)

Cladribine

301,267.79 $

-

11.394

33,772.86 $

Alemtuzumab

305,091.44 $

-

10.786

-6288.25 $ Dominated by Cladribine

Bohlega et al. (2021) [56]

QALY, LY & ICER

Cladribine

759,525.24 $

21.451

7.378

Reference

-Cladribine tablets were dominant strategy (ie, less costly and more effective) versus all the comparators

- Cladribine tablets showed an 81% to 100% probability of being cost-effective at a threshold of Saudi Riyal 225 326 per quality-adjusted life-years gained against different comparators

Alemtuzumab

861,168.34 $

21.451

7.134

 − 13.4

Dimethyl fumarate

863,402.74 $

21.451

6.371

 − 12.1

Fingolimod

894,601.38 $

21.451

6.297

 − 15.6

nterferon beta-1a (SC)

774,481.67 $

21.451

5.761

 − 2.3

Interferon beta-1a (IM)

793,151.61 $

21.451

6.225

 − 4.3

Interferon beta-1b

843,815.62 $

21.451

7.229

 − 10.6

Natalizumab

1,106,687.37 $

21.451

6.703

 − 52.9

Teriflunomide

782,583.71 $

21.451

6.121

 − 2.1

Ayati et al. (2021) [43]

QALY, LYG & ICER

Ocrelizumab

109,029.19 $

8.525

5.459

Dominate

Ocrelizumab dominated natalizumab and was associated with cost-savings of 6971 USD, longer LYG (0.004), and higher QALYs (0.27)

Natalizumab

116,145.76 $

8.521

5.192

Ocrelizumab

Dominates

Ayati et al. (2021) [44]

QALY, LYG & ICER

Cladribine

Total discounted cost per patient:

69,842.00 $

4.655

2.720 per patient

Dominate

Cladribine tablets dominated natalizumab and yielded 6,607 USD cost-saving and 0.003 additional QALYs per patient and also were cost-effective in Iran, with a probability of 57.5% and 58.6% at lower and higher limits of threshold, respectively

Natalizumab

Total discounted cost per patient:

76,449.00 $

4.655

2.716 per patient

Cladribine Dominates

Lasalvia et al. (2020) [57]

QALY & ICER

Natalizumab

75,812.51 $

-

3.01

Dominate,

-2014.84 $

Natalizumab showed lower total costs (USD 80 024 vs USD 98 137) and higher QALY yield (3.01 vs 2.94) than fingolimod, dominating it (ICER =  − $1861)

Fingolimod

106,249.46 $

-

2.944

-

Poveda et al. (2021) [39]

QALY

Cladribine

253,209.48 $

(Total cost)

-

10.39

Dominate

Cladribine tablets was the dominant treatment: lower costs (− 86,536 €) and more effective (+ 1.11 QALYs) compared to fingolimod. The probability that Cladribine Tablets was cost-effective compared to fingolimod ranged between 94.6% and 96.1% for willingness to pay from € 20,000 to € 30,000 per QALY gained

Fingolimod

392,017.87 $ (Total cost)

-

9.28

Cladribine (dominate)

Dembek et al. (2014) [27]

QALY & ICER

Best supportive care

496,769.72 $

-

13.07

Reference

Total QALYs gained per patient were greatest with intramuscular interferon beta-1a, followed by subcutaneous interferon beta-1a, Interferon beta-1b and Glatiramer acetate. The mean per-patient costs were lowest with intramuscular interferon beta-1a, followed by Glatiramer acetate, Interferon beta-1b, and subcutaneous interferon beta-1a. The ICERs for intramuscular interferon beta-1a was lowest at €168,629 per QALY gained

Intramuscular interferon beta-1a

740,101.11 $

-

13.94

279,305.22 $

Interferon beta-1b

770,855.84 $

-

13.78

384,025.01 $

Subcutaneous interferon beta-1a

879,232.81 $

-

13.85

489,674.00 $

Glatiramer acetate

760,584.94 $

-

13.57

528,067.72 $

Ginestal et al. (2023) [61]

QALY & ICER

Cladribine tablets

299,481.50 $

-

6.6577

Dominant

Cladribine tablets were the dominant treatment, with lower costs and greater effectiveness per patient, compared with dimethyl fumarate

Dimethyl fumarate

411,464.19 $

6.4657

-

Furneri et al. (2019) [28]

QALY, LYs & ICER

Natalizumab (“escalation strategy (ESC)”)

1,017,700.64 $ (Total cost)

20.10

11.19

Dominant

Early escalation to natalizumab is dominant vs. switching among immunomodulators, in RRMS patients who do not respond adequately to conventional immunomodulators

Interferons/glatiramer acetate ( “switching strategy”)

1,045,232.01 $ (Total cost)

19.67

9.67

ESC, Dominant

Cortesi et al. (2022) [60]

QALY, LYs & ICER

Interferon beta-1b

212,009.74 $

17.77

4.44

-

Compared to interferon beta-1b, siponimod seems to be cost-effective in SPMS patients and sustainable, with less than 1% overall budget increased in the next 3 years

Siponimod

254,164.12 $

18.05

5.49

28.891

Stanisic et al. (2019) [34]

QALY & ICER

Alemtuzumab

540,381.77 $

-

7.11

Dominant

Alemtuzumab yielded more QALYs, incremental QALYs, less costs compared to the other DMTs in all base-case analyses. Alemtuzumab carried the highest likelihood of being below the accepted willingness-to-pay threshold (€40,000) compared to other DMTs

Subcutaneous IFN β-1a

546,557.15 $

-

5.49

alemtuzumab VS IFN β-1a: 6173.94 $

Natalizumab

657,162.64 $

-

6.08

Alemtuzumab VS natalizumab: 116,780.87 $

Fingolimod

617,795.17 $

-

5.75

Alemtuzumab VS fingolimod:

77,413.39 $

Montgomery et al. (2022) [58]

QALY, LYs & ICER

Siponimod

481,655.67 $

16.39

3.45

-

QALYs were greater for siponimod versus all comparators. ICERs, calculated as cost per QALY, for siponimod versus natalizumab (dominant), ocrelizumab (£4,760), fingolimod (£10,033) and dimethyl fumarate (£15,837) indicated that siponimod was cost-effective at the commonly accepted willingness-to-pay threshold of £30,000/QALY

Natalizumab

499,002.87 $

16.25

2.69

Dominant

Ocrelizumab

477,175.04 $

16.26

2.79

4,760

Fingolimod

472,502.15 $

16.26

2.81

10,033

Dimethyl fumarate

467,324.25 $

16.26

2.82

15,837

Teriflunomide

451,629.84 $

16.26

2.83

33,689

Rezaee et al. (2022) [29]

QALY & ICER

Rituximab

5512.03 $

-

7.77

0.125, Dominant

Patients receiving rituximab had lower costs ($ 58,307.93 vs. $ 354,174.85) and more QALYs (7.77 vs. 7.65). In addition, the incidence of relapse by rituximab was lower compared to natalizumab (1.15 vs. 2.57). The scatter plots also showed that rituximab was more cost-effective for the patients in 100% of the simulations for the threshold of < $ 37,641

Natalizumab

36,811.05 $

-

7.65

0, Rituximub (dominant)

Becker et al. (2011) [47]

-

Intramuscular interferon beta-1a

-In the original model, costs per relapse avoided:

171,088.83 $

- In the reanalysis using the 2-year completer data, costs per relapse avoided:

94,139.24 $

-

-

-

The cost per relapse avoided for intramuscular interferon beta-1a was approximately 45% lower than in the original analysis, whereas the recreated results for the other 3 therapies differed from the original results by less than 1%

Subcutaneous interferon beta-1a

-In the original model, costs per relapse avoided:

97,288.88$

- In the reanalysis using the 2-year completer data, costs per relapse avoided:

96,723.90 $

-

-

-

Subcutaneous interferon beta-1b

-In the original model, costs per relapse avoided:

105,102.03$

- In the reanalysis using the 2-year completer data, costs per relapse avoided: 104,511.70 $

-

-

-

Glatiramer acetate

-In the original model, costs per relapse avoided:

106,609.85 $

- In the reanalysis using the 2-year completer data, costs per relapse avoided: 105,954.33 $

-

-

-

Kantor et al. (2023) [48]

ICER

Ozanimod (1 mg)

Total MS-Related Healthcare Costs Per Relapse Avoided:

843,684.00 $

-

-

823,168.00 $

Compared with other DMTs, treatment with ozanimod was associated with annual healthcare cost savings ranging from $2178 (vs fingolimod) to $8257 (vs interferon beta-1a 30 μg) based on a budget of 1 million USD

Teriflunomide (7 mg)

491,186.00 $

-

-

480,603.00 $

Teriflunomide (14 mg)

259,369.00 $

-

-

247,052.00 $

Interferon beta-1b (250 mg)

-

-

-

294,331.00 $

Interferon beta-1a (22 mcg)

-

-

-

437,919.00 $

Interferon beta-1a (30 mcg)

843,684.00 $

-

-

823,168.00 $

Interferon beta-1a (44 mcg)

338,676.00 $

-

-

333,590.00 $

Glatiramer acetate (20 mg)

158,154.00 $

-

-

154,035.00 $

Glatiramer acetate (40 mg)

110,364.00 $

-

-

105,133.00 $

Fingolimod (0.5 mg)

72,847.00 $

-

-

72,789.00 $

Dimethyl fumarate (240 mg)

-

-

-

88,468.00 $

Baharnoori et al. (2022) [13]

QALY, Yl & ICER

Total cost for the first-line therapies: Ofatumumab

603,393.83 $

28.406

9.277

-

Among first-line indicated therapies for RRMS, ofatumumab was dominant (more effective, lower costs) over teriflunomide, interferons, dimethyl fumarate, and ocrelizumab. Compared with glatiramer acetate and best supportive care, ofatumumab resulted in CERs of $24,189 Canadian dollars per QALY and $28,014/QALY, respectively. At a willingness-to-pay threshold of $50,000/QALY, ofatumumab had a 64.3% probability of being cost effective. Among second-line therapies (scenario analysis), ofatumumab dominated natalizumab and fingolimod and resulted in an ICER of $50,969 versus cladribine

Total cost for the first-line therapies: Ocrelizumab

637,352.93 $

28.383

9.145

Ofatumumab dominant

Total cost for the first-line therapies: Teriflunomide

618,809.71 $

28.170

7.950

Ofatumumab dominant

Total cost for the first-line therapies: Dimethyl fumarate

626,143.68 $

28.238

8.341

Ofatumumab dominant

Total cost for the first-line therapies: Glatiramer acetate

579,403.93 $

28.190

8.056

19,643.61 $

Total cost for the first-line therapies: Avonex

625,460.71 $

28.216

8.118

Ofatumumab dominant

Total cost for the first-line therapies: Rebif 22

613,977.78 $

28.202

8.085

Ofatumumab dominant

Total cost for the first-line therapies: Rebif 44

634,898.80 $

28.178

7.994

Ofatumumab dominant

Total cost for the first-line therapies: Betaseron

617,127.87 $

28.189

8.041

Ofatumumab dominant

Total cost for the first-line therapies: Extavia

613,156.76 $

28.189

8.032

Ofatumumab dominant

Total cost for the first-line therapies: Best Supportive Care

559,939.80 $

28.073

7.367

22,749.84 $

Total cost for the second-line therapies: Cladribine

581,239.25 $

28.311

8.742

41,391.33 $

Total cost for the second-line therapies: Natalizumab

706,381.25 $

28.382

9.138

Ofatumumab dominant

Total cost for the second-line therapies: Fingolimod

627,573.76 $

28.251

8.422

Ofatumumab dominant

Lazzaro et al. (2022) [40]

QALYs, LYs & ICER

Teriflunomide

- Healthcare sector perspective: RRMS naïve patients:

126,174.07 $

- Societal perspective:

152,187.82 $

-Healthcare sector perspective: RRMS naïve patients: 6.406

- Societal perspective: 6.406

-Healthcare sector perspective: RRMS naïve patients: 3.603

- Societal perspective:

3.603

-

Baseline CUA shows that teriflunomide in RRMS naïve patients was strongly dominant vs. experienced patients (healthcare sector perspective: − €1042.68 and + 0.480 QALYs; societal perspective: − €6782.81 and + 0.480 QALYs)

- Healthcare sector perspective: RRMS experienced patients:

127,641.15 $

- Societal perspective: 161,731.42 $

-Healthcare sector perspective: RRMS experienced patients:6.402

- Societal perspective: 6.402

-Healthcare sector perspective: RRMS experienced patients:3.123

- Societal perspective: 3.123

0.480

Pinheiro et al. (2020) [45]

QALY, & ICER

Cladribine tablets

332,546.67 $

-

3.42

Dominant

Cladribine tablets were associated with a delay in progression, resulting in a gain of 0.85 QALYs and a cost decrease of 25,935 €. Probabilistic sensitivity analysis resulted in a mean ICER of − 31,781 € per QALY and was dominant in 98.7% of the simulations

Fingolimod

404,142.19 $

-

2.58

Cladribine, Dominant

Martins et al. (2023) [33]

QALY, LYs & ICER

Ocrelizumab

For RMS: 544,039.49 $

For PPMS: 558,109.75 $

For RMS: 15.24

For PPMS: 14.13

For RMS: 3.22

For PPMS: 1.27

-

-Ocrelizumab is expected to increase (undiscounted) life expectancy of PPMS patients by 0.55 LY (25.15 vs 24.59 years) relative to BSC

- Both natalizumab and ocrelizumab can reduce the number of attacks (relapses) relative to the other compared DMTs

BSC

For PPMS:

451,126.90 $

For PPMS: 13.94

For PPMS: 0.47

133,729.41 $

Interferon β-1a

For RMS:

512,571.75 $

For RMS: 15.05

For RMS: 2.11

28,349.12 $

Dimethyl fumarate

For RMS:

532,077.14 $

For RMS: 15.08

For RMS: 2.29

12,862.84 $

Glatiramer acetate

For RMS:

525,298.92 $

For RMS: 15.04

For RMS: 2.02

15,616.86 $

Teriflunomide

For RMS:

514,460.90 $

For RMS: 15.06

For RMS: 2.16

27,904.81 $

Fingolimod

For RMS: 593,567.77 $

For RMS: 15.06

For RMS: 2.15

Dominant

Natalizumab

For RMS: 598,975.76 $

For RMS: 15.21

For RMS: 2.92

Dominant

AlRuthia et al. (2021) [49]

-

Oral agents

10,819.76 $

-

-

Dominant

The use of orally administered agents was dominant (e.g., more effective and less costly), with average annual cost savings of USD − 4336.65 and 8.11% higher rate of effectiveness when compared with Rebif®. With regard to the use of MABs in comparison to Rebif®, MABs were associated with higher cost but a better rate of effectiveness, with an average additional annual cost of USD 1381.54 and 43.11% higher rate of effectiveness. The use of MABs in the management of RRMS among the young patient population has shown to be the most effective therapy in comparison to both IFN-based therapy (e.g., Rebif®) and orally administered agents, but with higher cost. Orally administered agents resulted in better outcomes and lower costs in comparison to IFN-based therapy

Interferon

15,068.10 $

-

-

-

Monoclonal antibodies (MABs)

16,421.20 $

-

-

-

Versteegh et al. (2022) [19]

QALY & ICER

PEG-GLA20-OCR-CLA3.5-ALE

672,081.80 $

-

19.59

-

Optimal lifetime health outcomes (20.24 QALYs, 6.11 relapses) were achieved with the sequence peginterferon-dimethyl fumarate-ocrelizumab-natalizumab-alemtuzumab. The most cost-effective sequence (peginterferon-glatiramer acetate-ocrelizumab-cladribine-alemtuzumab) yielded numerically worse health outcomes per patient (19.59 QALYs, 6.64 relapses), but resulted in €98 127 less costs than the most effective treatment sequence

PEG-DIF-OCR-CLA3.5-ALE

676,300.27 $

-

19.65

-

PEG-GLA20-CLA3.5-OCR-ALE

654,324.96 $

-

19.29

-

PEG-TER14-OCR-CLA3.5-ALE

674,927.06 $

-

19.61

-

PEG-DIF-CLA3.5-OCR-ALE

659,500.83 $

-

19.36

-

PEG-TER14-CLA3.5-OCR-ALE

657,541.11 $

-

19.32

-

IFNb250-GLA20-OCR-CLA3.5-ALE

646,464.25 $

-

19.07

-

IFNb250-DIF-OCR-CLA3.5-ALE

482,732.38 $

-

19.13

-

IFNb250-GLA20-CLA3.5-OCR-ALE

628,417.36 $

-

18.78

-

IFNb250-TER14-OCR-CLA3.5-ALE

649,200.42 $

-

19.09

-

Nakhaipour et al. (2020) [59]

QALY & ICER

Fingolimod

58,751.04 $

-

1.500

23,886

Compared with IFN β-1a, fingolimod led to an increase in QALYs with incremental costs and to an ICER of CAD 23,886/QALY over a time horizon of two years

IFN b-1a

56,189.01 $

-

1.376

56,737

Schur et al. (2021) [30]

QALYs, LYs & ICER

Siponimod and BSC

462,785.66 $

18.896

7.495

Dominant

In the base-case analysis, siponimod may be cost-effective for treating Swiss adult patients with SPMS with active disease

Interferon beta-1a and BSC

393,591.69 $

18.412

5.905

-

Albahari et al. (2023) [62]

-

Rituximab

7364.03 $

-

-

Dominant

Rituximab was more effective and less costly than natalizumab in the management of RRMS. Ocrelizumab did not seem to slow the rates of disease progression among patients previously treated with natalizumab

Natalizumab

19,301.91 $

-

-

Rituximab, dominant

Ocrelizumab

35,222.92 $

-

-

-

Gani, et al. (2008) [22]

QALY & ICER

Natalizumab

-

-

-

-

If UK society is willing to pay more than £8200 per QALY, or Health and Social Services are willing to pay more than £26 000 per QALY, this analysis suggests that natalizumab is likely to be a cost-effective treatment for all patients with RRMS

Interferon-β

-

-

-

The ICER for natalizumab compared with interferon-β was £2300 per QALY. From a health and social care cost perspective, the ICERs were £18 700 per QALY

Glatiramer acetate

-

-

-

The ICER for natalizumab compared with glatiramer acetate was £2000 per QALY. From a health and social care cost perspective, the ICERs were £20 400 per QALY

Best supportive care

-

-

-

The ICER for natalizumab compared with best supportive care was £8200 per QALY. From a health and social care cost perspective, the ICERs were £25 500 per QALY,

Chilcott, et al. (2003) [2]

Cost per quality

Interferon betas

The base case cost per quality-adjusted life-year gained by using any of the four treatments ranged from £42 000 ($66 469; &61 630) to £98 000

based on efficacy information in the public domain

-

-

-

Cost-effectiveness varied markedly between the interventions. Uncertainty around point estimates was substantial., Price was the key modifiable determinant of the cost-effectiveness of these treatments

Glatiramer acetate for relapsing–remitting

Increased the cost per QALY gained around 75%

-

-

Interferon betas

The estimates with a 20-year time horizon were markedly lower, ranging from £42 000 to £98 000 per QALY gained

-

-

-

Glatiramer acetate for secondary progressive multiple

Commercial in­confidence estimates of efficacy, the most favorable estimate is £35 000 per QALY and the least favorable is £104 000 per QALY

-

-

-

Chevalier et al., (2016) [17]

QALY & ICER

DMF

$ 1,191,203.33

-

5.271

-

Dimethyl fumarate can be considered a cost-effective option as it is on the efficiency frontier

IFN beta-1a

44mcg

$ 1,185,485.36

-

4.990

-

IFNbeta-1a 30mcg

$ 1,191,212.65

-

4.991

-

IFN beta-1b, 250mcg

$ 1,207,191.61

-

4.819

-

Glatiramer

Acetate

$ 1,208,023.54

-

4.950

-

Teriflunomide

$ 1,192,521.07

-

5.047

-

Fingolimod

$ 1,267,970.65

-

5.021

-

Chanatittarat, et al. (2016) [35]

ICER

BSC

BSC had the lowest cost = $235,000

-

49%

-

Compared with fingolimod and interferon treatments, BSC remains to be the most cost-effective treatment for RRMS in Thailand based on a WTP threshold of $4,500 per QALY gained

fingolimod

the highest cost = $285,000

10.80

5.26 (%18)

$33,000 When compared with BSC

IFNβ − 1b

-

-

%25

$12,000 When compared with BSC

IFNβ − 1a

-

-

-

$42,000 When compared with BSC

Brown, et al. (2000) [52]

1-Disability years avoided (DYA)

2- Cost per exacerbation avoided

3-ICER

Interferon beta-1b

1- Cost per disability year avoided before discounting is $124,892, and $181,395 after discounting at 5%

2- Total healthcare costs for all EDSS scores for Females Per person with MS: $1,976

Total healthcare costs for all EDSS scores for Males Per person with MS:$1,683

-

-

-

Using the Expanded Disability Status Scale, cost per disability year avoided due to interferon beta-1b treatment in RRMS is quite high

Bozkaya, et al. (2017) [23]

ICER & EDSS

Natalizumab (NTZ)

Annual Drug cost: $71,773

-

-

-

Costs ranged from $561,177 (NTZ) to $616,251 (GA). NTZ, DMF, and PEG were dominant (less costly and more effective) compared to FIN, GA, and IFN, respectively, for all ICERs

Fingolimod (FIN)

Annual Drug cost: $77,922

-

-

Incremental cost

NTZ vs FIN

-$35,524

Peginterferon beta-1a (PEG)

Annual Drug cost: $72,072

-

-

-

Subcutaneous interferon beta-1a (IFN, 44 mcg)

Annual Drug cost: $77,797

-

-

Incremental cost

PEG vs IFN-$37,790

Glatiramer acetate

(GA, 20 mg daily

Annual Drug cost: $80,436

-

-

-

Dimethyl fumarate (DMF)

Annual Drug cost: $73,371

-

-

-

Alsaqa’aby et al. (2017) [24]

ICERs and NMB

Interferon 1a (Rebif 44 mcg)

$298 892

-

9.78

-

1-None of the DMDs were found to be cost-effective in the treatment of RRMS at a WTP threshold of

$100,000 in this analysis

2- Monte Carlo simulation results showed that Rebif was the most cost-effective therapy at WTP of $50 000 with 95% probability

3- Avonex reported the lowest ICER value of $337 282/QALY compared to Rebif as a common comparator

4- The NMB of oral DMDs at a WTP of $100,000 (SAR375 000) was lower than the NMB of Rebif, showing that oral DMDs were a costly option

would only be cost-effective at a WTP above

$300 000

Teriflunomide

$360,631

-

9.72

Dominated

Interferon 1a

(Avonex 30 mcg)

$374,502

-

10.01

$337,282

Fingolimod

$391,603

-

10.05

$347,338

Dimethyl Fumarate

(DMF)

$426,030

-

10.02

$531,329

Hernandez et al. (2016) [18]

QALY & ICER

Peginterferon

beta-1a

-

-

Results Over 10 years, peginterferon beta-1a was dominant (i.e., more effective and less costly), with

cost-savings of $22,070 and an additional 0.06 QALYs when compared with interferon beta-1a 44mcg

-

This analysis suggests that long-term treatment with peginterferon beta-1a improves clinical outcomes at reduced costs compared with interferon beta-1a 44 mcg and glatiramer acetate 20 mg and should be a valuable addition to managed care formularies for treating patients with RRMS

interferon beta-1a (44 mcg SC 3 times per week)

-

-

Results Over 10 years

-

glatiramer acetate (20 mg SC once daily)

-

-

Peginterferon beta-1a was dominant (i.e., more effective and less costly), with cost-savings of $19,163 and 0.07, QALYs gained when compared with glatiramer acetate 20 mg.-

-

Hernandez et al. (2017) [25]

QALY & ICER

Peginterferon beta-1a

Total cost: 106,843

-

Total QALYs (patient-caregive): 7.32

-

Long-term treatment with peginterferon beta-1a improves clinical outcomes, while its cost profile makes it either dominant or cost-effective compared with other self-injectable DMTs for the treatment of RRMS in Scotland

Interferon beta-1a 30 mcg

Total cost: 113,257

-

Total QALYs (patient-caregiver): 6.88

-

Interferon beta-1a 22 mcg

Total cost: 115,614

-

Total QALYs (patient-caregiver): 6.99

-

Interferon beta-1a 44 mcg

Total cost: 112,523

-

Total QALYs (patient-caregiver): 7.01

-

Interferon beta-1b

Total cost: 110,657

-

Total QALYs (patient-caregiver): 6.88

-

Glatiramer acetate 20 mg

Total cost: 104,441

-

Total QALYs (patient-caregiver): 6.90

-

Sawad et al. (2017) [63]

QALY & ICER

Strategy 1: SM (symptom management)

US$161,136.60

-

10.49

2,297,141.53 comparing Strategy

2 to Strategy 1

Strategy 1 was the cost-effective strategy for the treatment of relapsing–remitting multiple sclerosis when compared with other strategies

Strategy 2: SM and

IFN-β-1a

US$551,650.66

-

10.66

Strategy 3: SM and natalizumab

US$703,463.60

-

10.69

-1,623,918.00 comparing Strategy 4 to Strategy 3

Strategy 4: SM and alemtuzumab

US$670,985.24

-

10.71

Hashemi-Meshkini A, et al. (2018) [26]

QALY

PEG-interferon

1- total discounted cost PEG-interferon: 68,688

USD

2-In each arm, cost of PEG-interferon 99% total cost

-

5709.88

1- (ICER)

was estimated around 11,111 US dollars (USD) per QALY gained for the

PEG-interferon vs. interferon

2- ICER (USD per QALY): cost discount rate (5%) = 12,080

3- ICER (USD per QALY): Utility discount rate (3%) = 10,208

PEG interferon

beta 1 -a could be considered as a cost-effective treatment for Iranian patients with MS

Interferon

1-total discounted cost in interferon arm:

59,308 USD

2- In each arm, interferon beta 1a were around and 97%total cost

-

4865.61

Else Michels et al. (2019) [32]

QALY& ICER

Cladribine tablets

$ 180.67

-

9.318

Dominant

Cladribine tablets are cost-effective versus alemtuzumab and fingolimod in HAD (high disease activity) patients, and cost-effective versus natalizumab in RES (rapidly evolving severe) patients

Alemtuzumab

$ 1153.24

-

9.219

Dominant

Fingolimod

$ 1397.65

-

8.333

Dominant

Natalizumab

$ 670.29

-

8.794

Dominant

Imani et al., (2012) [36]

QALY/ Incremental cost per QALY gained

Symptom Management

-

-

9.081

Reference

Disease-modifying drugs (DMDs) in relapsing–remitting MS patients were associated with increased benefits compared with symptom management, albeit at higher costs. Because patients receiving Avonex incurred slightly higher QALYs than patients receiving other DMDs, treatment with Avonex dominates other DMDs in Iran

Avonex

$125,280

-

9.285

$607,397

Betaferon

$280,581

-

9.284

$1,374,355

Rebif

$232,740

-

9.279

$1,166,515

CinnoVex

$50,448

-

9.130

$1,010,429

Janković et al., (2009) [31]

QALY/ Incremental cost per QALY gained/ Incremental cost per life years gained

Symptom

management

$ 321,263.12

Life years gained 16.0 ± 7.0

9.2 ± 4.2

Reference

Immunomodulatory therapy of RRMS in a Balkan country in socioeconomic transition is not cost-effective, regardless of the type of the therapy. The moderate gain in relapse-free years does not translate to gain in QALYs, probably due to adverse effects of immunomodulatory therapy

SC GA

$ 566,722.58

16.4 ± 7.0

9.8 ± 4.4

1,240 ± 15,596

SC IFN β-1a

$ 924,082.67

16.4 ± 7.0

9.8 ± 4.3

4,520 ± 61,855

IM IFN β-1a

$ 920,472.98

16.4 ± 7.0

9.8 ± 4.4

4,527 ± 61,854

SC IFN β-1b

$ 855,498.41

16.4 ± 7.0

9.8 ± 4.3

4,022 ± 55,055

Maruszczak et al., (2015) [41]

QALY & ICER

Fingolimod

$ 564,448.36

-

4.70

12,528

Fingolimod remains cost-effective in highly active (HA) RRMS following the introduction of DMF to the UK market, and this model supports the evidence that has led it to be the only oral DMT reimbursed for HA RRMS in England

dimethyl fumarate (DMF

$ 549,139.70

3.93

Mantovani (2019) [42]

QALY, YLG ICER

Dimethyl fumarate

$ 1,396,605.43

19.634

6.526

Reference

This cost-effectiveness analysis confirms that dimethyl fumarate is an optimal first-line treatment for RRMS in Italy, compared with the other first-line alternatives

IFN beta-1a – 22 mcg

$ 1,418,953.20

19.533

5.786

DMF dominates

IFN beta-1a – 44 mcg

$ 1,409,201.85

19.600

6.189

DMF dominates

IFN beta-1b – Betaferon

$ 1,474,840.19

19.440

5.143

DMF dominates

IFN beta-1b – Extavia

$ 1,468,349.53

19.440

5.143

DMF dominates

Glatiramer acetate – 20 mg

$ 1,454,399.37

19.459

5.341

DMF dominates

Teriflunomide – 14 mg

$ 1,421,793.87

19.547

5.953

DMF dominates

Najafi et al., (2014) [50]

Health-related quality of life (HRQoL) & ICER

CinnoVex

Annual per-patient cost: $2410

-

69.5

for physical HRQoL & 63.3 for mental HRQoL

Reference

The results showed that CinnoVex was less expensive and more effective than Avonex over the study period. This implies that CinnoVex is a dominant option and there is no need to calculate the ICER

Avonex

Annual per-patient cost: $4515

-

50.9

for physicalHRQoL &

56.6 for mental HRQoL

CinnoVex dominates

Nuijten et al. (2002) [46]

QALY & ICER

Preventive

treatment with interferon beta

$ 455,373.06

-

Interferon group:

28.2

$ 106,076.04 per QALY

Preventive treatment with interferon beta in patients with multiple sclerosis may not be fully justified from a health-economic perspective, although interferon beta is associated with improved effectiveness compared with no preventive treatment

No preventive treatment

$ 105,319.26

-

no-treatment group:

24.9

Soini et al., (2017) [10]

QALY & ICER

DMF 240 mg PO BID

Total costs/patient, $ 523,140.50

12.098

Total QALY/patient 7.808

$ 51,149.25

$ 114,552.40

Teriflunomide was less costly, with greater QALYs, versus glatiramer acetate and the IFNs. According to Bayesian treatment ranking (BTR), teriflunomide was the first-best among the disease-modifying therapies, with potential willingness-to-pay thresholds of up to €68,000/QALY gained. In the IIA (impact investment assessment), teriflunomide was associated with the longest incremental quality-adjusted survival and time without cane use

Teriflunomide 14 mg once daily

512,918.55

12.096

7.719

$ 36,570.33

vs. teriflunomide

GA 20 mg SC once daily

553,208.02

12.087

7.475

$ 377,612.44

Dominant

IFN-β1a 44 mg SC TIW

521,832.96

12.092

7.595

$ 87,610.24

Dominant

IFN-β1b 250 mg SC EOD

613,172.97

12.074

7.063

Dom

Dominant

IFN-β1a 30 mg IM QW

544,899.55

12.088

7.456

$ 370,707.19

Dominant

Best supportive care (BSC)- placebo

498,725.36

12.084

7.331

vs. BSC

$ 36,570.33

Su et al., (2016) [64]

QALY & ICER, HRQoL

DMF

$243,079

12.124

5.885

-

Reference

DMF can be considered a

cost-effective option compared to other first-line DMTs

Glatiramer

Acetate (GA)

$219,741

12.105

5.357

$44,118

Rebif (Interferon-b 1a SC)

44 mcg

$240,134

12.116

5.610

$10,672

Zhang et al., (2014) [51]

QALY, ICER & incremental net monetary benefit (INMB)

Fingolimod

$239,947

3.69

$ 46,328

$ 36,567

Of the four DMDs, dimethyl fumarate is a dominant strategy to manage RRMS. Dimethyl fumarate dominated all other therapies over the range of willingness-to-pay (WTP) values. After dimethyl fumarate, teriflunomide was the most cost-effective therapy compared with IM IFN-b1a, with an incremental cost-effectiveness ratio of $7,115

Teriflunomide

$226,085

3.68

$7,115

$ 49,780

Dimethyl fumarate

$200,145

3.72

Dominant

$ 80,611

Intramuscular (IM) interferon (IFN)-b1a

$223,606

3.34

ICER vs. IM IFN-b1a

INMB vs. IM IFN-b1a

Zimmermann et al., (2018) [37]

QALYs & ICERs

Ocrelizumab (for first-line treatment for RRMS)

US$1,217,737

-

US$166,338

Dominant

Ocrelizumab was cost effective as a first-line treatment for RRMS. Alemtuzumab dominated other options for second-line treatment of RRMS

Alemtuzumab (for second-line treatment)

US$580,052

-

US$648,799

Dominant

Supportive care

US$341,120

-

US$341,100

-