J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website http://www.jocmr.org

Original Article

Volume 10, Number 2, February 2018, pages 88-105

A Multiple Treatment Comparison of Eleven Disease-Modifying Drugs Used for Multiple Sclerosis

Figure 1. Flowchart of identification and selection of documentation. SR: systematic review; HTA: health technology assessment; RCT: randomized controlled trial.

Figure 4. Cost-effectiveness acceptability curve (all interventions except alemtuzumab). WTP: willingness-to-pay.

Figure 5. Scatter plot for 10,000 Monte-Carlo simulations (all interventions included). Simulations for alemtuzumab show that alemtuzumab was more effective and less costly relative to other treatments.

**Table 1.** Overview of Included Interventions
Interventions	Administration form and recommended dose
mg: milligram; IV: intravenous; h: hour; mL: millilitre; μg: microgram; IU: International Units; IM: intra muscular.
Alemtuzumab (Lemtrada)	12 mg concentrate for solution for infusion 12 mg/day for 5 consecutive days, then after 12 months: 12 mg/day for 3 consecutive days. Diluted and IV over approximately 4 h
Dimethyl fumarate (Tecfidera)	120 or 240 mg gastro-resistant hard capsules 240 mg twice daily
Fingolimod (Gilenya)	0.5 mg hard capsules 0.5 mg once daily
Glatiramer acetat (Copaxone)	20 mg/mL solution for injection, pre-filled syringe 20 mg of glatiramer acetate (one pre-filled syringe), administered as a subcutaneous injection once daily 40 mg of glatiramer acetate administered three times weekly
Interferon beta-1a (Avonex)	30 µg (6 million IU) powder and solvent for solution for injection 30 µg (1 mL solution), by intramuscular (IM) injection once a week
Interferon beta-1a (Rebif)	22 µg (6 million IU) solution for injection in pre-filled syringe 44 µg given three times per week by subcutaneous injection
Peg-interferon beta-1a (Plegridy)	125 µg injected subcutaneously every 2 weeks
Interferon beta-1b (Betaferon)	250 µg (8.0 million IU)/mL, powder and solvent for solution for injection (300 µg (9.6 million IU) per vial) 250 µg (8.0 million IU), contained in 1 mL of the reconstituted solution, to be injected subcutaneously every other day
Interferon beta-1b (Extavia)	See: interferon beta-1b (Betaferon) above
Natalizumab (Tysabri)	300 mg concentrate for solution for infusion 300 mg by IV over approximately 1 h, once every 4 weeks
Teriflunomide (Aubagio)	14 mg film-coated tablets 14 mg once daily, swallowed whole with some water

Table 1. Overview of Included Interventions

Interventions

Administration form and recommended dose

mg: milligram; IV: intravenous; h: hour; mL: millilitre; μg: microgram; IU: International Units; IM: intra muscular.

Alemtuzumab (Lemtrada)

12 mg concentrate for solution for infusion
12 mg/day for 5 consecutive days, then after 12 months: 12 mg/day for 3 consecutive days. Diluted and IV over approximately 4 h

Dimethyl fumarate (Tecfidera)

120 or 240 mg gastro-resistant hard capsules
240 mg twice daily

Fingolimod (Gilenya)

0.5 mg hard capsules
0.5 mg once daily

Glatiramer acetat (Copaxone)

20 mg/mL solution for injection, pre-filled syringe
20 mg of glatiramer acetate (one pre-filled syringe), administered as a subcutaneous injection once daily
40 mg of glatiramer acetate administered three times weekly

Interferon beta-1a (Avonex)

30 µg (6 million IU) powder and solvent for solution for injection
30 µg (1 mL solution), by intramuscular (IM) injection once a week

Interferon beta-1a (Rebif)

22 µg (6 million IU) solution for injection in pre-filled syringe
44 µg given three times per week by subcutaneous injection

Peg-interferon beta-1a (Plegridy)

125 µg injected subcutaneously every 2 weeks

Interferon beta-1b (Betaferon)

250 µg (8.0 million IU)/mL, powder and solvent for solution for injection (300 µg (9.6 million IU) per vial)
250 µg (8.0 million IU), contained in 1 mL of the reconstituted solution, to be injected subcutaneously every other day

Interferon beta-1b (Extavia)

See: interferon beta-1b (Betaferon) above

Natalizumab (Tysabri)

300 mg concentrate for solution for infusion
300 mg by IV over approximately 1 h, once every 4 weeks

Teriflunomide (Aubagio)

14 mg film-coated tablets
14 mg once daily, swallowed whole with some water

**Table 2.** Key Parameters Used in the Base-Case Analysis
	Definition	Value	Source/note
EDSS: expanded disability status scale; SPMS: secondary-progressive multiple sclerosis; RR: relative risk; CI: confidence interval; SE: standard error; PML: progressive multifocal leukoencephalopathy. ^aFor the other probabilities used in the model, see Supplementary materials 4 and 5 (www.jocmr.org). ^bPer person-year. ^cGlatiramer acetate 40 mg RR: 0.66 (0.52 to 0.82). ^dWe did not find any documentation for glatiramer acetate 40 mg. ^eThe majority of patients receiving alemtuzumab would not need new treatment after 5 years treatment. It was assumed that 20% of patients need extra treatment (12 mg/day for 3 days) [29]. ^fGlatiramer acetate 40 mg/mL three times per week: Annual drug cost was estimated to be EUR 9,732. ^gWe used the price for the products (pre-filled syringe and auto-injector pen) that had 85% of Rebif 44- market in the recent years in Norway (2013 - 2015). ^hIt was assumed that the average length of mild or moderate relapse and severe relapse would be 45 and 90 days, respectively [24, 25]. ⁱAll costs were updated to 2015 costs. ^jAssumed fixed utility decrement over the corresponding RRMS EDSS state utility values. ^kIt was estimated based on the data reported by Orme et al [27] and Prosser et al [25].
Transition probabilities^a	EDSS score	Progression rates within RRMS health states^b (variance)	Progression rates from RRMS to SPMS^b (variance)	Progression rates within SPMS health states^b (variance)	[23, 24]
	0	0.144 (0.00007)	0.004 (0.000002)
	1	0.075 (0.00003)	0.002 (0.000001)
	2	0.152 (0.00006)	0.029 (0.000012)	0.370 (0.00370)
	3	0.272 (0.00025)	0.102 (0.000094)	0.385 (0.00129)
	4	0.450 (0.00166)	0.199 (0.000735)	0.594 (0.00280)
	5	0.485 (0.00213)	0.256 (0.001126)	0.349 (0.00088)
	6	0.283 (0.00104)	0.184 (0.000676)	0.241 (0.00029)
	7	0.342 (0.00450)	0.237 (0.000312)	0.186 (0.00024)
	8	0.105 (0.00139)	0.066 (0.000866)	0.107 (0.00015)
	9	0.167 (0.02778)	0.167 (0.027778)	0.093 (0.00038)
Efficacy estimate (Mot placebo)	Interventions	RR of annual relapse rate (95% CI)	RR of disability progression (95% CI)	Based on the results of our systematic review (Table 3)
	Alemtuzumab 12 mg (Lemtrada)	0.29 (0.23 - 0.35)	0.36 (0.16 - 0.74)
	Dimethyl fumarate 240 mg (Tecifidera)	0.50 (0.42 - 0.60)	0.65 (0.49 - 0.85)
	Fingolimod 0.5 mg (Gilenya)	0.46 (0.39 - 0.54)	0.71 (0.55 - 0.90)
	Glatiramer acetate 20 mg (Copaxone)	0.65 (0.59 - 0.73)^c	0.78 (0.63 - 0.96)^d
	Interferon beta-1a 30 µg (Avonex)	0.82 (0.73 - 0.91)	0.80 (0.65 - 0.99)
	Interferon beta-1a 22 µg (Rebif)	0.69 (0.57 - 0.83)	0.84 (0.61 - 1.19)
	Interferon beta-1a 44 µg (Rebif)	0.64 (0.56 - 0.72)	0.77 (0.60 - 1.01)
	Interferon beta-1b 250 µg (Betaferon)	0.66 (0.57 - 0.76)	0.72 (0.54 - 0.92)
	Interferon beta-1b 250 µg (Extavia)	0.66 (0.57 - 0.76)	0.72 (0.54 - 0.92)
	Natalizumab 300 mg (Tysabri)	0.30 (0.24 - 0.36)	0.59 (0.42 - 0.84)
	Peg-interferon beta-1a 125 µg (Plegridy)	0.65 (0.49 - 0.85)	0.61 (0.36 - 0.98)
	Teriflunomide 14 mg (Aubagio)	0.67 (0.58 - 0.77)	0.73 (0.51 - 1.05)
Costs per patients per year in EURⁱ (EUR 1.00 ≈ NOK 8.9530)	Interventions	Annual drug costs	Based on drug procurement cooperation price (LIS)
	Alemtuzumab 12 mg (Lemtrada)^e	35,607 (5 days first year); 21,364 (3 days second year)
	Dimethyl fumarate 240 mg (Tecifidera)	18,839
	Fingolimod 0.5 mg (Gilenya)	22,023
	Glatiramer acetate 20 mg (Copaxone)^f	9,759
	Interferon beta-1a 30 µg (Avonex)	11,648
	Interferon beta-1a 22 µg (Rebif)	10,204
	Interferon beta-1a 44 µg (Rebif)^g	12,929
	Interferon beta-1b 250 µg (Betaferon)	7,407
	Interferon beta-1b 250 µg (Extavia)	6,709
	Natalizumab 300 mg (Tysabri)	21,428
	Peg-interferon beta-1a 125 µg (Plegridy)	12,808
	Teriflunomide 14 mg (Aubagio)	11,769
	Interventions	Monitoring costs	Based on drug procurement cooperation (LIS) and clinical expert opinion
		1 year	2 years	Beyond 2 years
	Alemtuzumab^e (Lemtrada)	2,539	1,628	928 (3 - 5 years) 790 (+5 years)
	Dimethyl fumarate (Tecifidera)	1,290	790	790
	Fingolimod (Gilenya)	2,001	790	790
	Glatiramer acetate (Copaxone)	1,290	790	790
	Interferon beta-1a 30 µg (Avonex)	2,152	1,652	790
	Interferon beta-1a 22 µg (Rebif)	2,152	1,652	790
	Interferon beta-1a 44 µg (Rebif)	2,152	1,652	790
	Interferon beta-1b (Betaferon)	2,152	1,652	790
	Interferon beta-1b (Extavia)	2,152	1,652	790
	Natalizumab (Tysabri)	3,713	3,097	3,097
	Peg-interferon beta-1a (Plegridy)	2,152	1,652	790
	Teriflunomide (Aubagio)	1,440	840	840
	EDSS score	Costs associated to different EDSS states	[26]
	0	2,016
	1	4,122
	2	5,730
	3	14,090
	4	16,481
	5	36,830
	6	63,099
	7	76,982
	8	154,171
	9	155,661
	Costs per relapse^h
	Mild/moderate	2,447
	Severe	4,894
Utility weight	Health state/events	Utility weight (95% CI)	[27] Disability associated with PML: [28]
	EDSS 0	0.870 (0.782 to 0.958)
	EDSS 1	0.799 (0.617 to 0.981)
	EDSS 2	0.705 (0.523 to 0.886)
	EDSS 3	0.574 (0.384 to 0.763)
	EDSS 4	0.610 (0.428 to 0.791)
	EDSS 5	0.518 (0.338 to 0.698)
	EDSS 6	0.460 (0.0277 to 0.641)
	EDSS 7	0.297 (0.112 to 0.481)
	EDSS 8	-0.049 (-0.235 to 0.138)
	EDSS 9	-0.195 (-0.428 to 0.039)
	SPMS^j	-0.045 (-0.079 to -0.014)
	Disutility associated with mild or moderate relapse	-0.071 (-0.096 to -0.046)
	Disutility associated with severe relapse^k	-0.236 (-0.295 to -0.174)
	Disability associated with PML	-0.40 (-0.30 to -0.50)

Table 2. Key Parameters Used in the Base-Case Analysis

Definition

Value

Source/note

EDSS: expanded disability status scale; SPMS: secondary-progressive multiple sclerosis; RR: relative risk; CI: confidence interval; SE: standard error; PML: progressive multifocal leukoencephalopathy. ^aFor the other probabilities used in the model, see Supplementary materials 4 and 5 (www.jocmr.org). ^bPer person-year. ^cGlatiramer acetate 40 mg RR: 0.66 (0.52 to 0.82). ^dWe did not find any documentation for glatiramer acetate 40 mg. ^eThe majority of patients receiving alemtuzumab would not need new treatment after 5 years treatment. It was assumed that 20% of patients need extra treatment (12 mg/day for 3 days) [29]. ^fGlatiramer acetate 40 mg/mL three times per week: Annual drug cost was estimated to be EUR 9,732. ^gWe used the price for the products (pre-filled syringe and auto-injector pen) that had 85% of Rebif 44- market in the recent years in Norway (2013 - 2015). ^hIt was assumed that the average length of mild or moderate relapse and severe relapse would be 45 and 90 days, respectively [24, 25]. ⁱAll costs were updated to 2015 costs. ^jAssumed fixed utility decrement over the corresponding RRMS EDSS state utility values. ^kIt was estimated based on the data reported by Orme et al [27] and Prosser et al [25].

Transition probabilities^a

EDSS score

Progression rates within RRMS health states^b (variance)

Progression rates from RRMS to SPMS^b (variance)

Progression rates within SPMS health states^b (variance)

[23, 24]

0.144 (0.00007)

0.004 (0.000002)

0.075 (0.00003)

0.002 (0.000001)

0.152 (0.00006)

0.029 (0.000012)

0.370 (0.00370)

0.272 (0.00025)

0.102 (0.000094)

0.385 (0.00129)

0.450 (0.00166)

0.199 (0.000735)

0.594 (0.00280)

0.485 (0.00213)

0.256 (0.001126)

0.349 (0.00088)

0.283 (0.00104)

0.184 (0.000676)

0.241 (0.00029)

0.342 (0.00450)

0.237 (0.000312)

0.186 (0.00024)

0.105 (0.00139)

0.066 (0.000866)

0.107 (0.00015)

0.167 (0.02778)

0.167 (0.027778)

0.093 (0.00038)

Efficacy estimate (Mot placebo)

Interventions

RR of annual relapse rate (95% CI)

RR of disability progression (95% CI)

Based on the results of our systematic review (Table 3)

Alemtuzumab 12 mg (Lemtrada)

0.29 (0.23 - 0.35)

0.36 (0.16 - 0.74)

Dimethyl fumarate 240 mg (Tecifidera)

0.50 (0.42 - 0.60)

0.65 (0.49 - 0.85)

Fingolimod 0.5 mg (Gilenya)

0.46 (0.39 - 0.54)

0.71 (0.55 - 0.90)

Glatiramer acetate 20 mg (Copaxone)

0.65 (0.59 - 0.73)^c

0.78 (0.63 - 0.96)^d

Interferon beta-1a 30 µg (Avonex)

0.82 (0.73 - 0.91)

0.80 (0.65 - 0.99)

Interferon beta-1a 22 µg (Rebif)

0.69 (0.57 - 0.83)

0.84 (0.61 - 1.19)

Interferon beta-1a 44 µg (Rebif)

0.64 (0.56 - 0.72)

0.77 (0.60 - 1.01)

Interferon beta-1b 250 µg (Betaferon)

0.66 (0.57 - 0.76)

0.72 (0.54 - 0.92)

Interferon beta-1b 250 µg (Extavia)

0.66 (0.57 - 0.76)

0.72 (0.54 - 0.92)

Natalizumab 300 mg (Tysabri)

0.30 (0.24 - 0.36)

0.59 (0.42 - 0.84)

Peg-interferon beta-1a 125 µg (Plegridy)

0.65 (0.49 - 0.85)

0.61 (0.36 - 0.98)

Teriflunomide 14 mg (Aubagio)

0.67 (0.58 - 0.77)

0.73 (0.51 - 1.05)

Costs per patients per year in EURⁱ (EUR 1.00 ≈ NOK 8.9530)

Interventions

Annual drug costs

Based on drug procurement cooperation price (LIS)

Alemtuzumab 12 mg (Lemtrada)^e

35,607 (5 days first year); 21,364 (3 days second year)

Dimethyl fumarate 240 mg (Tecifidera)

18,839

Fingolimod 0.5 mg (Gilenya)

22,023

Glatiramer acetate 20 mg (Copaxone)^f

9,759

Interferon beta-1a 30 µg (Avonex)

11,648

Interferon beta-1a 22 µg (Rebif)

10,204

Interferon beta-1a 44 µg (Rebif)^g

12,929

Interferon beta-1b 250 µg (Betaferon)

7,407

Interferon beta-1b 250 µg (Extavia)

6,709

Natalizumab 300 mg (Tysabri)

21,428

Peg-interferon beta-1a 125 µg (Plegridy)

12,808

Teriflunomide 14 mg (Aubagio)

11,769

Interventions

Monitoring costs

Based on drug procurement cooperation (LIS) and clinical expert opinion

1 year

2 years

Beyond 2 years

Alemtuzumab^e (Lemtrada)

2,539

1,628

928 (3 - 5 years)
790 (+5 years)

Dimethyl fumarate (Tecifidera)

1,290

790

Fingolimod (Gilenya)

2,001

790

Glatiramer acetate (Copaxone)

1,290

790

Interferon beta-1a 30 µg (Avonex)

2,152

1,652

790

Interferon beta-1a 22 µg (Rebif)

2,152

1,652

790

Interferon beta-1a 44 µg (Rebif)

2,152

1,652

790

Interferon beta-1b (Betaferon)

2,152

1,652

790

Interferon beta-1b (Extavia)

2,152

1,652

790

Natalizumab (Tysabri)

3,713

3,097

Peg-interferon beta-1a (Plegridy)

2,152

1,652

790

Teriflunomide (Aubagio)

1,440

840

EDSS score

Costs associated to different EDSS states

[26]

2,016

4,122

5,730

14,090

16,481

36,830

63,099

76,982

154,171

155,661

Costs per relapse^h

Mild/moderate

2,447

Severe

4,894

Utility weight

Health state/events

Utility weight (95% CI)

[27]
Disability associated with PML: [28]

EDSS 0

0.870 (0.782 to 0.958)

EDSS 1

0.799 (0.617 to 0.981)

EDSS 2

0.705 (0.523 to 0.886)

EDSS 3

0.574 (0.384 to 0.763)

EDSS 4

0.610 (0.428 to 0.791)

EDSS 5

0.518 (0.338 to 0.698)

EDSS 6

0.460 (0.0277 to 0.641)

EDSS 7

0.297 (0.112 to 0.481)

EDSS 8

-0.049 (-0.235 to 0.138)

EDSS 9

-0.195 (-0.428 to 0.039)

SPMS^j

-0.045 (-0.079 to -0.014)

Disutility associated with mild or moderate relapse

-0.071 (-0.096 to -0.046)

Disutility associated with severe relapse^k

-0.236 (-0.295 to -0.174)

Disability associated with PML

-0.40 (-0.30 to -0.50)

**Table 3.** Relative Risk for Annual Relapse and Disability Progression From Network Meta-Analysis
Interventions	Annual relapse	Disability progression
RR: relative ratio; CI: confidence interval; SC: subcutaneous; IM: intra muscular; q.d.: once daily, q.w.: once weekly; t.i.w.: three times weekly; 2.i.d: two times daily; t.i.d: three times daily; 1/2 w: once every 2 weeks; 1/4 w: once every 4 weeks; NA: not available.
Alemtuzumab 24 mg IV q.d.	0.16 (0.1 to 0.25)	Low	0.40 (0.27 to 0.60)	Low
Alemtuzumab 12 mg IV q.d.	0.29 (0.23 to 0.35)	High	0.36 (0.16 to 0.74)	Very low
Natalizumab	0.3 (0.24 to 0.36)	Moderate	0.59 (0.42 to 0.84)	Moderate
Fingolimod oral 1.25 mg	0.45 (0.39 to 0.53)	High	0.71(0.56 to 0.90)	High
Fingolimod oral 0.5 mg	0.46 (0.39 to 0.54)	High	0.71 (0.55 to 0.90	High
Dimethyl fumarate 240 mg 2.i.d.	0.5 (0.42 to 0.6)	High	0.65 (0.49 to 0.85)	High
Dimethyl fumarate 240 mg t.i.d.	0.5 (0.42 to 0.6)	High	0.68 (0.52 to 0.89)	High
Interferon beta-1b 500 µg SC 1/2 d	0.62 (0.51 to 0.74)	Moderate	0.79 (0.56 to 1.10)	Low
Interferon beta-1a 44 µg	0.64 (0.56 to 0.72)	High	0.77 (0.60 to 1.01)	Low
Peg-interferon beta-1a 125 µg 1/2 w	0.65 (0.49 to 0.85)	High	0.61 (0.36 to 0.98)	Low
Glatiramer acetate 20 mg	0.65 (0.59 to 0.73)	High	0.78 (0.63 to 0.96)	Low
Glatiramer acetate 40 mg	0.66 (0.52 to 0.82)	High	NA	NA
Interferon beta-1b 250 µg	0.66 (0.57 to 0.76)	Moderate	0.2 (0.54 to 0.92)	Low
Teriflunomide oral 14 mg	0.67 (0.58 to 0.77)	High	0.73 (0.51 to 1.05)	Low
Interferon beta-1a 22 µg	0.69 (0.57 to 0.83)	Moderate	0.84 (0.61 to 1.19	Low
Peg-interferon beta-1a 125 µg 1/4 w	0.73 (0.56 to 0.95)	High	0.62 (0.38 to 1.01)	Low
Teriflunomide oral 7 mg	0.77 (0.68 to 0.9)	High	0.80 (0.55 to 1.13)	Low
Interferon beta-1a 30 µg	0.82 (0.73 to 0.91)	High	0.80 0.65 to 0.99)	Moderate
Interferon beta-1a 60 µg IM q.w.	0.86 (0.7 to 1.06)	High	NA	NA

Table 3. Relative Risk for Annual Relapse and Disability Progression From Network Meta-Analysis

Interventions

Annual relapse

Disability progression

RR (95% CI)

GRADE

RR (95% CI)

GRADE

RR: relative ratio; CI: confidence interval; SC: subcutaneous; IM: intra muscular; q.d.: once daily, q.w.: once weekly; t.i.w.: three times weekly; 2.i.d: two times daily; t.i.d: three times daily; 1/2 w: once every 2 weeks; 1/4 w: once every 4 weeks; NA: not available.

Alemtuzumab 24 mg IV q.d.

0.16 (0.1 to 0.25)

Low

0.40 (0.27 to 0.60)

Low

Alemtuzumab 12 mg IV q.d.

0.29 (0.23 to 0.35)

High

0.36 (0.16 to 0.74)

Very low

Natalizumab

0.3 (0.24 to 0.36)

Moderate

0.59 (0.42 to 0.84)

Moderate

Fingolimod oral 1.25 mg

0.45 (0.39 to 0.53)

High

0.71(0.56 to 0.90)

High

Fingolimod oral 0.5 mg

0.46 (0.39 to 0.54)

High

0.71 (0.55 to 0.90

High

Dimethyl fumarate 240 mg 2.i.d.

0.5 (0.42 to 0.6)

High

0.65 (0.49 to 0.85)

High

Dimethyl fumarate 240 mg t.i.d.

0.5 (0.42 to 0.6)

High

0.68 (0.52 to 0.89)

High

Interferon beta-1b 500 µg SC 1/2 d

0.62 (0.51 to 0.74)

Moderate

0.79 (0.56 to 1.10)

Low

Interferon beta-1a 44 µg

0.64 (0.56 to 0.72)

High

0.77 (0.60 to 1.01)

Low

Peg-interferon beta-1a 125 µg 1/2 w

0.65 (0.49 to 0.85)

High

0.61 (0.36 to 0.98)

Low

Glatiramer acetate 20 mg

0.65 (0.59 to 0.73)

High

0.78 (0.63 to 0.96)

Low

Glatiramer acetate 40 mg

0.66 (0.52 to 0.82)

High

Interferon beta-1b 250 µg

0.66 (0.57 to 0.76)

Moderate

0.2 (0.54 to 0.92)

Low

Teriflunomide oral 14 mg

0.67 (0.58 to 0.77)

High

0.73 (0.51 to 1.05)

Low

Interferon beta-1a 22 µg

0.69 (0.57 to 0.83)

Moderate

0.84 (0.61 to 1.19

Low

Peg-interferon beta-1a 125 µg 1/4 w

0.73 (0.56 to 0.95)

High

0.62 (0.38 to 1.01)

Low

Teriflunomide oral 7 mg

0.77 (0.68 to 0.9)

High

0.80 (0.55 to 1.13)

Low

Interferon beta-1a 30 µg

0.82 (0.73 to 0.91)

High

0.80 0.65 to 0.99)

Moderate

Interferon beta-1a 60 µg IM q.w.

0.86 (0.7 to 1.06)

High

**Table 4.** Results of the Base-Case Cost-Effectiveness Analysis, Time-Horizon of 20 Years (All Interventions Included; Discounted)^a
Drugs	Total costs (EUR)	Effects (QALYs)	Incremental cost (EUR)	Incremental effect (QALYs)	ICER (EUR/QALY)
QALY: quality-adjusted life year; ICER: incremental cost-effectiveness ratio. ^aThe results are rounded in accordance to the calculations in the probabilistic model, which operates with several decimals. ^bBased on the effect estimates and the annual drug costs, it is highly probable that glatiramer acetate 40 mg three times/week will be as cost-effective as glatiramer acetate 20 mg /day (given all the other parameters are the same).
Alemtuzumab (Lemtrada)	547,068	8.05			Dominant
Interferon beta-1b (Extavia)	673,690	7.40	126,622	-0.64	Dominated by alemtuzumab
Interferon beta-1b (Betaferon)	680,013	7.40	132,945	-0.64	Dominated by alemtuzumab
Glatiramer acetate 20 mg (Copaxone)^b	698,506	7.31	151,438	-0.73	Dominated by alemtuzumab
Peg-interferon beta-1a (Plegridy)	704,857	7.56	157,789	-0.48	Dominated by alemtuzumab
Teriflunomide (Aubagio)	707,862	7.38	160,794	-0.67	Dominated by alemtuzumab
Interferon beta-1a 22 µg (Rebif)	725,854	7.21	178,786	-0.84	Dominated by alemtuzumab
Interferon beta-1a 30 µg (Avonex)	729,802	7.27	182,734	-0.77	Dominated by alemtuzumab
Interferon beta-1a 44 µg (Rebif)	734,347	7.32	187,279	-0.72	Dominated by alemtuzumab
Dimethyl fumarate (Tecifidera)	749,222	7.52	202,154	-0.52	Dominated by alemtuzumab
Natalizumab (Tysabri)	779,977	7.63	232,909	-0.41	Dominated by alemtuzumab
Fingolimod (Gilenya)	786,464	7.43	239,396	-0.62	Dominated by alemtuzumab

Table 4. Results of the Base-Case Cost-Effectiveness Analysis, Time-Horizon of 20 Years (All Interventions Included; Discounted)^a

Drugs

Total costs (EUR)

Effects (QALYs)

Incremental cost (EUR)

Incremental effect (QALYs)

ICER (EUR/QALY)

QALY: quality-adjusted life year; ICER: incremental cost-effectiveness ratio. ^aThe results are rounded in accordance to the calculations in the probabilistic model, which operates with several decimals. ^bBased on the effect estimates and the annual drug costs, it is highly probable that glatiramer acetate 40 mg three times/week will be as cost-effective as glatiramer acetate 20 mg /day (given all the other parameters are the same).

Alemtuzumab (Lemtrada)

547,068

8.05

Dominant

Interferon beta-1b (Extavia)

673,690

7.40

126,622

-0.64

Dominated by alemtuzumab

Interferon beta-1b (Betaferon)

680,013

7.40

132,945

-0.64

Dominated by alemtuzumab

Glatiramer acetate 20 mg (Copaxone)^b

698,506

7.31

151,438

-0.73

Dominated by alemtuzumab

Peg-interferon beta-1a (Plegridy)

704,857

7.56

157,789

-0.48

Dominated by alemtuzumab

Teriflunomide (Aubagio)

707,862

7.38

160,794

-0.67

Dominated by alemtuzumab

Interferon beta-1a 22 µg (Rebif)

725,854

7.21

178,786

-0.84

Dominated by alemtuzumab

Interferon beta-1a 30 µg (Avonex)

729,802

7.27

182,734

-0.77

Dominated by alemtuzumab

Interferon beta-1a 44 µg (Rebif)

734,347

7.32

187,279

-0.72

Dominated by alemtuzumab

Dimethyl fumarate (Tecifidera)

749,222

7.52

202,154

-0.52

Dominated by alemtuzumab

Natalizumab (Tysabri)

779,977

7.63

232,909

-0.41

Dominated by alemtuzumab

Fingolimod (Gilenya)

786,464

7.43

239,396

-0.62

Dominated by alemtuzumab