Clinical evaluation of dimethyl fumarate for the treatment of relapsing-remitting multiple sclerosis: efficacy, safety, patient experience and adherence

Figures & data

Table 1 Summary of patient-reported outcomes from phase 3 trials

Study	DEFINE^Citation49				CONFIRM^Citation48
	Placebo	BG 12 (240 mg)			Placebo	BG 12 (240 mg)
	BID		TID	BID		TID
SF- 36
Evaluable patients (n)	389	400		400	344	341		328
PCS scale at baseline (Mean, SD)	43.3 (10.2)	42.9 (10.02)		43.7 (10.80)	42.94 (9.90)	43.07 (9.91)		43.02 (10.0)
Improved (%)	16.2	21.8		24.0	19.2	22		26.2
Stable (%)	56.8	59.8		58.8	57	58.7		52.7
Worsened (%)	27.0	18.5		17.3	23.8	19.4		21
OR for improvement		1.47		1.79		1.22		1.6
P-value		0.0498		0.0027		0.3186		0.0188
MCS scale at baseline (mean, SD)	45.7 (11.15)	45.3 (10.93)		45.1 (10.68)	44.8 (10.73)	45.4 (11.7)		44.9 (10.75)
Improved, (%)	20.6	25.8		30	25.9	27.6		30.2
Stable (%)	50.1	50.5		49.8	45.3	44.6		43.3
Worsened (%)	29.3	23.8		20.3	28.8	27.9		26.5
OR for improvement		1.44		1.93		1.20		1.39
P-value		0.0652		0.0008		0.3660		0.1024
	With relapse (n=395)		Without relapse (n=948)		With relapse (n=354)		Without relapse (n=835)
PCS score (mean, SD)
Change from baseline to 2 years	−2.10 (7.45)		0.72 (6.94)		−0.97 (8.07)		0.57 (7.38)
P-value	<0.0001				<0.0001
MCS score (mean, SD)
Change from baseline to 2 years	−0.47 (10.05)		0.31 (9.25)		−0.67 (10.58)		0.52 (9.71)
P-value	0.6635				0.0112
EQ-5D index score (mean, SD)
Change from baseline to 2 years	−0.02 (0.20)		0.01 (0.01)		−0.01 (0.22)		0.01 (0.19)
P-value	0.0004				0.0005
EQ-5D VAS (mean, SD)
Change from baseline to 2 years	−6.03 (17.86)		0.52 (15.99)		−4.04 (19.20)		0.30 (17.52)
P-value	<0.0001				<0.0001

Abbreviations: SF-36, Short Form 36; PCS, Physical Component Summary (physical functioning, role-physical, bodily pain and general health); MCS, Mental Component Summary (vitality, social functioning, role-emotional and mental health); EQ-5D, mobility, self-care, usual activities, pain/discomfort and anxiety/depression; SD, standard deviation; TID, thrice daily; BID, twice daily; OR, odds ratio.

Figure 1 Dimethyl fumarate (DMF) patient adherence data from phase 3 studies.

Abbreviations: D/C, discontinued; BID, twice daily; MS, multiple sclerosis; GI, gastrointestinal; AE, adverse effects; Others, personal reasons or decisions, moving to another geographic area, desire to become pregnant, actual pregnancy, lost to follow-up, investigator decision, perceived lack of efficacy and having previously met the protocol-defined relapse criteria for alternative MS medication.

Table 2 Real-world evidence to dimethyl fumarate adherence

Study name	Miclea et al, 2016^Citation74	Smoot et al, 2017^Citation44	Sejbaek et al, 2018^Citation75
Type of study	Retrospective study	Prospective study	Retrospective study
Number of patients evaluated	644	412	253
Sex ratio M/F	193/451	96/316	77/176
Treatment naïve patients, %	45.2	30	29.2
Discontinuation of DMF, %	28.7	38	27.7
Discontinuation due to AE, %	22.2	28.6	21.3
Gastrointestinal AEs, %	12.7	15	10.9
Lymphopenia, %	5.3	6	2.6
Flushing, %	1.7	2.4	3.2
Other AEs, %	2.5	5.1	4.6
Discontinuation due to relapse/inefficacy/MRI worsening, %	6.5	12.8	6.3

Note: Other AEs include rash, elevated ALT, depression, edema, arthralgia.

Abbreviations: DMF, dimethyl fumarate; M/F, male/female; AE, adverse effects; MRI, magnetic resonance imaging.

Kappos L, Gold R, Arnold DL, et al. Quality of life outcomes with BG-12 (dimethyl fumarate) in patients with relapsing–remitting multiple sclerosis: the DEFINE study. Mult Scler J. 2014;20:243–252. doi:10.1177/1352458513507817

 PubMed Web of Science ®Google Scholar

Kita M, Fox RJ, Phillips JT, et al. Effects of BG-12 (dimethyl fumarate) on health-related quality of life in patients with relapsing–remitting multiple sclerosis: findings from the CONFIRM study. Mult Scler J. 2014;20:253–257. doi:10.1177/1352458513507818

 PubMed Web of Science ®Google Scholar

Miclea A, Leussink VI, Hartung HP, Gold R, Hoepner R. Safety and efficacy of dimethyl fumarate in multiple sclerosis: a multi-center observational study. J Neurol. 2016;263:1626–1632. doi:10.1007/s00415-016-8175-327260297

 PubMed Web of Science ®Google Scholar

Smoot K, Spinelli KJ, Stuchiner T, et al. Three-year clinical outcomes of relapsing multiple sclerosis patients treated with dimethyl fumarate in a United States community health center. Mult Scler J. 2018;24:942–950. doi:10.1177/1352458517709956

 PubMed Web of Science ®Google Scholar

Sejbaek T, Nybo M, Petersen T, Illes Z. Real-life persistence and tolerability with dimethyl fumarate. Mult Scler Relat Disord. 2018;24:42–46. doi:10.1016/j.msard.2018.05.00729906666

 PubMed Web of Science ®Google Scholar