Table 1.
Disease modifying treatments used in the management of multiple sclerosis
| Drug (FDA approval year) | Dose | Target group | Mechanism | Intensity/efficacy | Monitoring | Adverse events |
|---|---|---|---|---|---|---|
| IFNβ1α: Avonex (1996), Rebif (1998) PEGylated IFN1α: Plegridy (2014) |
30 μg IM weekly; 22/44 μg SC every other day 125 μg SC every 2–4 weeks | CIS, RMS; CIS, RMS RMS | Inhibition of T-lymphocyte proliferation, shift in cytokine response from inflammatory to anti-inflammatory profile, and reduced migration of inflammatory cells across the blood–brain barrier | Mild | CBC, LFTs | Flu-like symptoms, liver enzyme changes, bone marrow suppression, thyroid dysfunction |
| IFNβ1β: Betaseron (1993), Extavia (2009) | 250 μg SC every other day, as above | CIS, RMS; CIS, RMS | As above | Mild | CBC, LFTs | Flu-like symptoms, liver enzyme changes, bone marrow suppression, thyroid dysfunction |
| Glatiramer acetate: Copaxone (1996) | 20 mg SC daily/40 mg SC three times a week | CIS, RMS/RMS | Promotes TH2 deviation under the development of TH2 glatiramer acetate-reactive CD4+ T cells | Mild | None | Skin irritation, skin lipoatrophy, panic attack-like events |
| Teriflunomide: Aubagio (2012) | 7 or 14 mg PO daily | RMS | Pyrimidine synthesis inhibitor | Mild | Baseline tuberculosis test and pregnancy test, baseline and regular CBC, LFTs | Nausea, headaches, alopecia, liver dysfunction, presumed teratogenicity |
| Dimethyl fumarate: Tecfidera (2013) | 240 mg PO twice daily | RMS | Possible Nrf2-pathway activator and NFκB inhibitor | Moderate | CBC, LFTs | Flushing, gastrointestinal distress, rare lymphopenia, PML (rare) |
| Fingolimod: Gilenya (2010) | 0.5 mg PO daily | RMS | Sphingosine 1 phosphate receptor modulator | Moderate | Pretreatment: ECG, VZV immunity, ophthalmological assessment (macula), skin exam On treatment: CBC, LFTs, ophthalmological assessment, skin examination | Macular edema, bradyarrhythmia, ECG QT-interval prolongation, hypertension, severe varicella-associated complications in nonimmune patients, increased risk of herpes zoster in all patients, mild infections, PML (rare) |
| Mitoxantrone: Novantrone (2000) | 12 mg/m2 IV every 3 months to a maximum of 140 mg/m2 | RMS, SPMS | Anthracenedione antineoplastic | High | Regular echocardiography and CBC during and after treatment ends | Cumulative dose-dependent cardiomyopathy and LVEF reduction, acute leukemia, bone marrow failure |
| Natalizumab: Tysabri (2006) | 300 mg IV monthly | RMS | Monoclonal antibody, binds α4 integrin | High | JCV surveillance, MRI | Nausea, infection, liver dysfunction, PML |
| Alemtuzumab: Lemtrada (2014) | 12 mg/m2 IV: every 5 days (year 1), every 3 days (year 2 and subsequent years if required) | RMS | Monoclonal antibody, anti-CD52 | High | Baseline and on-treatment monitoring of CBC, creatinine, urinalysis (monthly), and thyroid function (quarterly), as well as baseline pap smear in women; continue lab monitoring for 4 years after last infusion | Infusion reactions, mild–moderate infections, thyroid dysfunction, idiopathic thrombocytopenic purpura, antiglomerular basement membrane disease |
| Ocrelizumab:*Ocrevus (2017) | 300 mg IV every 2 weeks×2 induction, then 600 mg IV every 6 months | RMS, PPMS* | Monoclonal antibody, anti-CD20 | High | Pretreatment: hepatitis B testing | Infusion reactions, infections (URTI), undetermined association with malignancy (breast cancer) |
| Cladribine:Mavenclad(EuropeanCommission,Health Canada2017) | 1.75 mg/kg PO annually for 2 years | RRMS | 2-chloro-2′deoxy-β-d-adenosine (also known as 2CdA), a synthetic deoxyadenosine analogue | High | TBA | Lymphopenia, herpes zoster |
Note:
Most effective in a cohort of PPMS patients who had active disease characterized by the presence of gadolinium-enhancing lesions on MRI.8
Abbreviations: CBC, complete blood count; CIS, clinically isolated syndrome; ECG, electrocardiography; FDA, US Food and Drug Administration; IFN, interferon; IM, intramuscularly; IV, intravenously; JCV, John Cunningham virus; LFTs, liver-function tests; LVEF, left-ventricle ejection fraction; MRI, magnetic resonance imaging; PML, progressive multifocal leukoencephalopathy; PO, per os (orally); PPMS, primary progressive MS; RMS, relapsing multiple sclerosis; RRMS, relapsing–remitting MS; SC, subcutaneously; SPMS, secondary progressive MS; TBA, to be announced; URTI, upper respiratory tract infection; VZV, varicella zoster virus.