Table 1.

Disease Modifying Therapies approved by Health Canada for the treatment of Multiple Sclerosis^a

DMT: Trademark	Indication	Dosage	Clinical Trial	Efficacyb	Safetyc,d	Mechanism of Actione
First line
					Common to all interferonβ	Common to all interferonβ
Interferonβ-1b Betaseron® Extavia®	CIS, RRMS, SPMS w/relapses	250 µg SC; QAD 250 µg SC; QAD	IFNβ MSSG22	34%	– injection site rxn – flu-like symptoms – decreased blood cell counts – increased LFT	– decrease in pro-inflammatory and increase anti-inflammatory cytokine profiles – inhibition of Th1 cell proliferation – downregulation of antigen presentation by B cells and glial cells in CNS – reduce entry of immune cells into the CNS, most likely through inhibition of MMPs – increase expression of neurotrophic factors
Interferonβ-1a Avonex® Rebif®	CIS, RRMS, SPMS w/relapses	30 µg IM; QW 22 µg SC; TIW 44 µg SC; TIW	MSCRG23 PRISMS24 PRISMS24	18% 27% 33%
PEG-Interferonβ Plegridy®	RRMS	125 µg SC; Q2W	ADVANCE25	36%
Glatiramer acetate Copaxone®	CIS, RRMS	20 mg SC; QD	CMSSG26 CONFIRM27	29% 29%	– injection site rxn – post-injection rxn (flushing, chest pain, dyspnea)	– shifts from pro-inflammatory Th1/Th17 to anti-inflammatory Th2 response – regulation of monocytes, dendritic & B cells – increase expression of neurotrophic factors
Teriflunomide Aubagio®	RRMS	14 mg PO; QD	TEMSO30 TOWER29	32% 36%	– GI symptoms – decreased blood cell counts – increased LFT	– dihydroorotate dehydrogenase inhibitor; reduces synthesis of pyrimidine nucleotides – reduced proliferation of activated T cells – shifts from pro-inflammatory Th1/Th17 to anti-inflammatory Th2 response
Dimethyl fumarate Tecfidera®	RRMS	240 mg PO; BD	DEFINE28 CONFIRM27	53% 44%	– flushing – GI symptoms – decreased blood cell counts – strong allergic rxn, including anaphylaxisd – PMLd	– shifts from pro-inflammatory Th1/Th17 to anti-inflammatory Th2 response – cytoprotective effects through Nrf2 – modulation of NF-κB activity
Second line
Fingolimod Gilenya®	RRMS	0.5 mg PO; QD	FREEDOMS40 FREEDOMS-II39	54% 48%	– bradycardia – decreased blood cell counts – infection – skin cancerd – PMLd	– S1P receptor agonist; internalization and degradation – inhibits egress of activated lymphocytes from lymph node – modulate astrocyte function
Natalizumab Tysabri®	RRMS	300 mg IV; Q4W	AFFIRM41	68%	– infusion rxn – PML	– humanized mAb that binds α4 integrin – blocks interaction with VCAM-1 preventing migration of activated lymphocytes into CNS
Alemtuzumab Lemtrada®	RRMS	0.5 mg IV; 5 consecutive days in year 1, then 3 consecutive days in year 2	CARE MS-I42 CARE MS-II42	55% 49% (vs IFNβ-1a)	– infusion rxn – infection – thyroid disorders – secondary autoimmunity	– humanized mAb that binds CD52 – depletion of CD52-expressing lymphocytes through antibody-mediated cytolysis

Notes:

^aan additional DMT, daclizumab (humanized mAb that binds CD25) marketed as Zinbryta^®, was approved by Health Canada for treatment of RRMS in December 2016 while manuscript was in print;

^befficacy reported as % reduction in relapse rate compared to placebo, except for alemtuzumab (compared to IFNβ-1a), in Phase III clinical trials;

^creported in Phase III clinical trials, except indicated as

^drecently reported by Health Canada (http://www.hc-sc.gc.ca; accessed January 14, 2017);⁴²

^eproposed mechanisms based on known pharmacology and/or current evidence from clinical trials and animal models.⁵³

Abbreviations: BD, twice daily; CIS, clinically isolated syndrome; CNS, central nervous system; DMT, disease modifying therapy; GI, gastrointestinal; IFN, interferon; IM intramuscular; IV, intravenous; LFT, liver function tests; mAb; monoclonal antibody; MMP, matrix metalloproteinase; MS, multiple sclerosis; NF-κβ, nuclear factor-kappa β; Nrf2, nuclear factor-erythroid 2-related factor 2; PEG, polyethylene glycol; PO, per oral; PML, progressive multifocal leukoencephalopathy ; QAD, once every other day; QD, once daily; QW, once weekly; Q2W, once every 2 weeks; Q4W, once every 4 weeks; RRMS, relapsing-remitting MS; rxn, reaction; S1P, sphingosine-1-phosphate; SC, subcutaneous; SPMS, secondary progressive MS; TIW, three times weekly; VCAM-1, vascular cell adhesion molecule 1.