Dimethyl fumarate in the management of multiple sclerosis: appropriate patient selection and special considerations

Figures & data

Table 1 Currently available disease-modifying treatments for relapsing multiple sclerosis

Molecule	Route	Dosage	Schedule	Brand name	Company
IFNβ1b	SC	250 μg	EOD	Betaseron	Bayer
				Betaferon	Bayer
				Extavia	Novartis
IFNβ1a	IM	30 μg	OW	Avonex	Biogen
	SC	22/44 μg	TIW	Rebif	Merck Serono
PEGylated IFNβ1a	SC	125 μg	E2W	Plegridy	Biogen
Glatiramer acetate	SC	20 mg	OD	Copaxone	Teva
	SC	40 mg	TIW	Copaxone 40	Teva
Mitoxantrone	IV	8–12 mg/mq	E1-3M	Novantrone	Wyeth
Natalizumab	IV	300 mg	E4W	Tysabri	Biogen
Alemtuzumab	IV	12 mg	O5D (1st year)	Lemtrada	Genzyme
			O3D (2nd year)
Fingolimod	PO	0.5 mg	OD	Gilenya	Novartis
Teriflunomide	PO	14 mg	OD	Aubagio	Genzyme
Dimethyl fumarate	PO	240 mg	BID	Tecfidera	Biogen

Abbreviations: BID, bis in die (twice daily); E1-3M, every 1–3 months; E2W, every 2 weeks; E4W, every 4 weeks; EOD, every other day; IM, intramuscular; IV, intravenous; O3D, over 3 days; O5D: over 5 days; OD, once daily; OW, once weekly; PO, per os (by mouth); SC, subcutaneous; TIW, ter in week (thrice weekly).

Table 2 Main features of the currently approved oral disease-modifying treatments for relapsing multiple sclerosis (only data relative to currently approved dose presented)

Molecule Trials	Efficacy		Safety	Tolerability
	Relapsea	Disabilitya
Fingolimod Fingolimod Research Evaluating Effects of Daily Oral therapy in Multiple Sclerosis (FREEDOMS)^Citation24	−55%	−26.6%b	Herpes virus and other opportunistic infections,d bradyarrhythmias, macular edema, skin neoplasms	High burden for first-dose administration
TRial Assessing injectable interferoN vs. FTY720 Oral in RRMS (TRANSFORMS)^Citation25	−51.5%b	−25.3%c
Teriflunomide Teriflunomide Multiple Sclerosis Oral (TEMSO)^Citation26	−31.5%	−29.8%	Liver-enzyme increase, neutropenia, pregnancy issues	Hair thinning, gastrointestinal events
Oral teriflunomide for patients with relapsing multiple sclerosis (TOWER)^Citation27	−36.3%	−31.5%
Dimethyl fumarate Determination of the Efficacy and Safety of Oral Fumarate in Relapsing–Remitting MS (DEFINE)^Citation28	−41.3%	−38%	Leukopenia, lymphopeniae	Flushing, gastrointestinal events
Comparator and an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis (CONFIRM)^Citation29	−44.0%	−21%c

Notes:

a Relative reduction in relapse rate (primary end point) and disability worsening (secondary end point) versus placebo;

b versus IFNβ_1a 30 μg once weekly (12-month follow-up);

c not significant;

d including progressive multifocal encephalopathy and cryptococcosis;

e four patients older than 50 years developed progressive multifocal encephalopathy following a prolonged grade 2 or 3 lymphopenia.

Figure 1 Proposed treatment algorithm for treating R-MS with DMF.

Notes: ^aConsider pregnancy desire; ^bconsider anti-VZV serological status, comorbidities, and concomitant non-MS treatments (eg, cardiac illnesses, antihypertensive drugs); cconsider anti-JCV serological status; ^dconsider anti-VZV serological status, latent tuberculosis, and HPV screening. Please note that this algorithm, though based on currently available literature data, represents the authors’ opinion only.
Abbreviations: R-MS, relapsing multiple sclerosis; DMF, dimethyl fumarate; VZV, varicella zoster virus; JCV, John Cunningham virus; HPV, human papillomavirus; DMTs, disease-modifying treatments.

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