Cost-effectiveness of delayed-release dimethyl fumarate for the treatment of relapsing forms of multiple sclerosis in the United States

Figures & data

Figure 1. Schematic of model.

Table 1. Cohort characteristics used in the delayed-release dimethyl fumarate cost-effectiveness model (all patients).

Demographic variable	Value	Source
Cohort starting age	37.9	Delayed-release dimethyl fumarate clinical trial data (DEFINE and CONFIRM)
Female/male ratio	3.27	Campbell et al.3 (using the US MEPS database)
EDSS distribution	EDSS 0: 5.05% EDSS 1: 8.52% EDSS 2: 34.08% EDSS 3: 22.94% EDSS 4: 20.64% EDSS 5: 8.65% EDSS 6: 0.12% EDSS 7: 0.00% EDSS 8: 0.00% EDSS 9: 0.00%	Delayed-release dimethyl fumarate clinical trial data, intent-to-treat population (delayed-release dimethyl fumarate twice daily, DEFINE and CONFIRM)

EDSS, Expanded Disability Status Scale; MEPS, Medical Expenditure Panel Survey.

Table 2. Treatment effect parameters for disability progression and relapse rate.

Treatment	Hazard ratio disability progression Mean (95% CI)	Annualized relapse rate relative to placebo Mean (95% CI)
Delayed-release DMF	0.60 (0.43–0.84)	0.53 (0.45–0.62)
Glatiramer acetate*	0.83 (0.64–1.09)	0.65 (0.59–0.72)
Fingolimod	0.80 (0.63–1.01)	0.45 (0.36–0.50)

CI, confidence interval.

*Only studies of glatiramer acetate once a day were included in the MTC. The model assumed the same impact on disability progression and relapse rate for glatiramer acetate 3-times a week.

Source: Estimated using a mixed-treatment comparison analysis28.

Table 3. EDSS state costs used in the cost-effectiveness analysis: excluding costs of disease-modifying therapies.

Cost categories included	EDSS state
	0	1	2	3	4	5	6	7	8	9
Base-case values
Direct care costs  (payer perspective)	$6593	$7405	$8217	$9029	$9840	$10,652	$15,504	$20,357	$25,209	$30,061
Alternative scenarios
Direct + informal care costs	$6593	$8268	$10,196	$12,123	$14,051	$15,978	$24,973	$33,968	$42,963	$51,958
Direct + informal care costs +   productivity losses	$13,085	$19,984	$26,883	$33,782	$40,680	$47,579	$57,013	$63,911	$72,077	$80,243

EDSS, Expanded Disability Status Scale.

Source: Kobelt et al.30 inflated to May 2015 values using linear interpolation from values for EDSS <4, EDSS 4–6, and EDSS >6.

Table 4. Base-case utility scores per EDSS state.

Clinical presentation, disease type	EDSS state
	0	1	2	3	4	5	6	7	8	9
No Relapse
RRMS	0.8752	0.8342	0.7802	0.6946	0.6253	0.5442	0.4555	0.3437	0.0023	−0.1701
SPMS	0.8315	0.7905	0.7365	0.6509	0.5816	0.5005	0.4118	0.3000	−0.0413	−0.2138
Relapse
RRMS	0.8660	0.8250	0.7710	0.6855	0.6161	0.5350	0.4463	0.3346	−0.0068	−0.1793
SPMS	0.8223	0.7814	0.7274	0.6418	0.5725	0.4913	0.4027	0.2909	−0.0505	−0.2229

EDSS, Expanded Disability Status Scale; RRMS, relapsing-remitting multiple sclerosis; SPMS, secondary progressive multiple sclerosis.

Source: Delayed-release dimethyl fumarate clinical trial data (DEFINE and CONFIRM) for RRMS31; Patzold and Pocklington22 for SPMS.

Table 5. Estimates of annual adverse event costs and quality-adjusted life-years lost.

Treatment	Annual AE cost, USD	Annual loss in QALYs from AEs
Dimethyl fumarate	$172	0.0037
Glatiramer acetate	$150	0.0061
Fingolimod	$245	0.0048

AE, adverse event; QALY, quality-adjusted life-year; USD, United States dollars.

All costs reported in 2015 US dollars ($).

Source: see Supplementary Appendix B.

Table 6. Discounted (3.0%) cost-effectiveness model outcomes per patient: 20-year costs and QALYs.

Drug	Total cost (USD)	Total life-years*	Total QALYs	DMF vs Other DMT
				Incremental costs	QALYs gained	ICER (Cost/QALY)
Delayed release DMF	$850,332	14.200	6.856	NA	NA	NA
Glatiramer acetate once daily	$921,142	14.172	6.406	−$70,810	0.450	DMF dominant†
Fingolimod	$883,391	14.176	6.497	−$33,059	0.359	DMF dominant†

DMF, delayed-release dimethyl fumarate; DMT, disease-modifying therapy; ICER, incremental cost-effectiveness ratio; NA, not applicable; QALYs, quality-adjusted life-years; USD, United States dollars.

*20 life-years discounted at 3% is equal to 15.32 discounted life-years.

†DMF is less costly and more effective (lower-right quadrant in the cost-effectiveness plane).

Figure 2. Sensitivity analysis: delayed-release dimethyl fumarate compared with glatiramer acetate.

Table 7. Cost-effectiveness results from sensitivity analyses of a comparison with Fingolimod.

Analysis	Change	Incremental cost	Incremental QALY	ICER (USD)
Baseline results	NA	−$33,059	0.359	DMF dominant*
Delayed-release DMF relapse rate relative risk	Upper 95% CI	−$30,833	0.350	DMF dominant*
	Lower 95% CI	−$35,038	0.368	DMF dominant*
Delayed-release DMF disability progression rate hazard ratio	Upper 95% CI	−$37,332	−0.066	Lower cost, lower efficacy
	Lower 95% CI	−$31,691	0.709	DMF dominant*
EDSS state direct + informal care costs	NA	−$39,896	0.359	DMF dominant*
EDSS state direct + informal care costs + productivity losses	NA	−$48,834	0.359	DMF dominant*
Relapse costs using Goldberg et al.32 ($5447)	NA	−$29,820	0.359	DMF dominant*
Delayed-release DMF acquisition costs	+10%	+$29,207	0.359	$81,274
	−10%	−$157,591	0.359	DMF dominant*
Alternative natural history disease transition rates—no EDSS regression	NA	−$27,905	0.324	DMF dominant*
Alternative natural history disease transition rates—London Ontario values	NA	−$31,949	0.300	DMF dominant*
Alternative natural history relapse rates—Patzold and Pocklington22	NA	−$34,017	0.363	DMF dominant*
Patient utilities using Kobelt et al.30	NA	−$33,059	0.080	DMF dominant*
Discontinue treatment when transition to SPMS	NA	−$1891	0.358	DMF dominant*
Assuming no costs or QALYs lost from adverse events	NA	−$32,419	0.350	DMF dominant*
Assuming 50-year time horizon	NA	−$35,295	0.509	DMF dominant*
Allowing no transition from RRMS to SPMS until EDSS 3	NA	−$33,250	0.395	DMF dominant*

DMF, delayed-release dimethyl fumarate; EDSS, Expanded Disability Status Scale; ICER, incremental cost-effectiveness ratio; NA, not applicable; QALY, quality-adjusted life-year; RRMS, relapsing-remitting multiple sclerosis; SPMS, secondary progressive multiple sclerosis; USD, United States dollars.

*DMF is less costly and more effective (lower right quadrant in the cost-effectiveness plane).

Campbell JD, Ghushchyan V, McQueen B, et al. Burden of multiple sclerosis on direct, indirect costs and quality of life: National US estimates. MS Relat Disord 2014;3:227-36

 PubMed Web of Science ®Google Scholar

Hutchinson M, Fox RJ, Havrdova E, et al. Efficacy and safety of BG-12 (dimethyl fumarate) and other disease-modifying therapies for the treatment of relapsing-remitting multiple sclerosis: a systematic review and mixed treatment comparison. Curr Med Res Opin 2014;30:613-27

 PubMed Web of Science ®Google Scholar

Kobelt G, Berg J, Atherly D, et al. Costs and quality of life in multiple sclerosis: a cross-sectional study in the United States. Neurology 2006;66:1696-702

 PubMed Web of Science ®Google Scholar

Orme M, Lerrigan J, Tyas D, et al. The effect of disease, functional status, and relapses on the utility of people with multiple sclerosis in the UK. Value Health 2007;10:54-60

 PubMed Web of Science ®Google Scholar

Patzold U, Pocklington PR. Course of multiple sclerosis. First results of a prospective study carried out of 102 MS patients from 1976–1980. Acta Neurol Scand 1982;65:248-66

 PubMed Web of Science ®Google Scholar

Goldberg LD, Edwards NC, Fincher C, et al. Comparing the cost-effectiveness of disease-modifying drugs for the first-line treatment of relapsing-remitting multiple sclerosis. J Manag Care Pharm 2009;15:543-55

 PubMed Web of Science ®Google Scholar