Table 1.
| Therapeutic Molecule | Commercial Name | Year of Approval | Admin. Route | Admin. Frequency | Mode of Action | Side Effects |
|---|---|---|---|---|---|---|
| IFN-β1a | Avonex® Rebif® |
1993 | i.m. s.c. |
Once a week Three times a week |
Decrease of proinflammatory and increase of anti-inflammatory cytokines; decreased migration of inflammatory cells across the BBB; decrease of Th17 cells; modulation of T and B cells. | Symptoms similar to those of flu; leukopenia; liver damage. |
| pegIFN-β1a | Plegridy® | s.c. | Once per two weeks | Decrease of proinflammatory and increase of anti-inflammatory cytokines; decreased migration of inflammatory cells across the BBB; decrease of Th17 cells; modulation of T and B cells | Symptoms similar to those of flu; leukopenia; liver damage. | |
| IFN-β1b | Betaseron® Extavia® |
1993 | s.c. | Once per two days | Decrease of proinflammatory and increase of anti-inflammatory cytokines; decreased migration of inflammatory cells across the BBB; decrease of Th17 cells; modulation of T and B cells; down regulation of MHC expression on APCs. | Symptoms similar to those of flu; leukopenia; liver damage. |
| Glatiramer acetate | Copaxone® | 1996 | s.c. | - | Decrease of proinflammatory and increase of anti-inflammatory cytokines; decrease of Th17 cells; increase of Th2 cells and Tregs; blocking of pMHC. | Erythema; induration; heart palpitations; dyspnea; tightness of chest; flushes/anxiety. |
| Dimethyl fumarate | Tecfidera® | 2013 | oral | Twice or three times per day | Anti-inflammatory-Increase of Th2 cells; anti-oxidative stress; neuroprotection through activation of Nrf-2 pathway. | Flushes; vomit; diarrhea; nausea; decrease of WBC. |
| Teriflunomide | Aubagio® | 2012 | oral | Once per day | Inhibition of dihydroorotate dehydrogenase; inhibition of T and B cells; | Lymphopenia; nausea; hypertension; fatigue; headache; diarrhea; peripheral neuropathy; acute renal failure; alopecia. |
| Fingolimod | Glenya® | 2010 | oral | Once per day | S1P receptor modulator; preventing the circulation of lymphocytes in non-lymphoid tissues including the CNS. | Weakening of heart rate; hypertension; macular edema; increased liver enzymes; decreased lymphocyte levels. |
| Siponimod [55] | Mayzent® | 2019 | oral | Binding to S1P-1 and S1P-5 | ||
| Ozanimod [56] | Zeposia® | 2020 USA | oral | S1P receptor agonist | ||
| Laquinimod | Oral | Immunomodulation of T cells, DCs and monocytes; neuroprotection of astrocytes; decrease of proinflammatory and increase of anti-inflammatory cytokines; reduced infiltration of cells into the CNS. | No severe cardiac adverse effects were detected during Phase III clinical trials. | |||
| Cladribine [57] | Mavenclad® | 2017 EU 2019 USA |
Reduction of circulating T and B cells. | Risk of cancer | ||
| Mitoxantrone | Novatrone® | 2000 USA | i.v. | Once per three months | Cytotoxic for B and T cells; reduction of Th1 cytokines; inhibition of type II topoisomerase. | Cardiotoxicity; leukemia |
| Methylprednisolone | i.v. | - | Immunosuppression; anti-inflammatory effects. | Risk of infections; retention of sodium; glucose intolerance; mood disturbances. | ||
| Dalfampridine | Ampyra® | oral | Twice per day | Blocking of potassium channel; improvement of motor symptoms. | ||
| Natalizumab | Tysabr® | 2004 | i.v. | Once per 28 days | Targeting α4-integrin | Progressive multifocal leukoencephalopathy. |
| Ofatumumab | Arzerra® | i.v. | Once per two weeks | Targeting CD20 | ||
| Ocrelizumab | Ocrevus® | i.v. | Once per six months | Targeting CD20 | ||
| Alemtuzumab | Lemtrada® | 2013 EU | i.v. | Once a year | Targeting CD52 | High risk of infections Graves’ disease |
| Daclizumab | Zinbryta® | s.c. | Once per month | Targeting CD25 | ||
| Rituximab | Rituxan® | i.v. | - | Targeting CD20 | Chills; nausea; hypotension | |
| Obinutuzumab | Gazyva® | i.v. | - | Direct cell death | Risk of infections; nausea; thrombocytopenia; neutropenia |
IFN: interferon; i.m.: intramuscular; s.c.: subcutaneous; BBB: blood-brain barrier; MHC: major histocompatibility complex; APCs: antigen presenting cells; Nrf-2: nuclear factor erythroid-2; WBC: white blood cell; CNS: central nervous system; i.v.: intravenous.