TABLE 1.
List of drugs approved by the FDA for the treatment of MS.
| Product name | Dosage and Administration | Pharmacological actions and Mechanisms | Adverse reactions | Approved |
|---|---|---|---|---|
| IFN-β-1b (Betaseron) Yu et al. (2015) | 250 µg i.H. every 2 days | Activates the JAK/STAT pathway connected by IFN receptor, resulting in transcriptional changes in immune and anti-proliferative genes, and reduces the migration of lymphocytes across the BBB | Influenza-like syndrome, skin reaction at injection site, headache, leukopenia, etc. | 1993 |
| IFN-β-1a (Avonex) Pavelek et al. (2020) | 30 µg i.m. once a week | Inhibits the proliferation of MBP-specific T cells and their penetrating migration to the BBB, reduces the production of pro-inflammatory factors, and induces the increase of anti-inflammatory factors | Influenza-like syndrome, anemia, fever, myalgia, weakness, etc. | 1994 |
| Glatiramer acetate Song et al. (2020) | 20 mg i.H. once a day | Competitively binds MHC Ⅰ and Ⅱ molecules of APC to block MBP specific T cell receptor, inhibits T cell proliferation, down-regulates the secretion of inflammatory cytokines, and up-regulates the production of brain-derived neurotrophic factor | Skin reaction at the injection site, palpitations, dyspnea, chest pain, vasodilation, etc. | 1996 |
| Mitoxantrone Edan et al. (2004); Burns et al. (2012) | 4–12 mg i.v.gtt every 3 mo | Embeds into DNA base molecules to inhibit DNA synthesis, inhibits the presentation of antigens for T and B cells, reduces the secretion of proinflammatory cytokines, such as TNF-α, and enhances anti-inflammatory response | Intestinal reactions, alopecia, peripheral blood leukopenia, abnormal liver function, etc. | 2000 |
| IFN-β-1a (Rebif) Hupperts et al. (2019) | 44 µg i.H. every 3 wk | Promotes the balance of Th1 and Th2 cells, reduces the secretion of proinflammatory cytokines, enhances the expression of inhibitory cytokines, and reduces the entry of T cells into the CNS through the BBB | Influenza-like syndrome, skin reaction at the injection site, myalgia, abdominal pain, elevated liver enzymes, etc. | 2003 |
| Natalizumab Zhovtis Ryerson et al. (2020) | 300 mg i.v. every 4 wk | Anti-α4 integrin monoclonal antibody; binds and blocks the interaction between α4 integrin and ligand and prevents lymphocytes from entering the CNS through the BBB | Headache, urinary tract infections, abdominal pain, fatigue, joint pain, gastroenteritis, etc. | 2004 |
| Fingolimod Imeri et al. (2021) | 500 µg p.o. once a day | S1P receptor modulator; protects and repairs neurons through the BBB and prevents central memory T cell subsets from migrating to the CNS | Systemic virus infection, headache, influenza, gastrointestinal discomfort, abnormal liver function, angina pectoris | 2010 |
| Teriflunomide Buron et al. (2021) | 7 or 14 mg p.o. once a day | Dihydroorotate dehydrogenase inhibitor; reduces DNA synthesis, inhibits T and B cell proliferation and production of cytokines, and inhibits intercellular adhesion molecule production | Dyspnea, renal failure, hypertension, leukopenia, alopecia, etc. | 2012 |
| Tecfidera Naismith et al. (2020a); Naismith et al. (2020b) | 240 mg p.o. twice a day | Regulates the levels of Nrf2 and glutathione in T cells, activates antioxidant genes, and promotes the transformation of Th1 to Th2 | Abdominal pain, diarrhea, nausea, skin itching, rash, erythema, etc. | 2013 |
| Alemtuzumab Gross et al. (2016); Paterka et al. (2016) | 12 mg i.v. once a day | CD52 monoclonal antibody; induces the clearance of T and B cells and increases the secretion of brain-derived neurotrophic factor | Rash, headache, fever, other autoimmune diseases, etc. | 2014 |
| Peginterferon beta-1a Menge et al. (2021) | 125 µg I.H. every 2 wk | Reduces the expression of adhesion molecules on the surface of T cells, inhibits the activation of T cells, and reduces the infiltration of the CNS | Influenza-like symptoms, injection site reaction, and deterioration of depression | 2014 |
| Daclizumab Cohan (2016); Gold et al. (2016) | 150 mg i.H. once a month | CD25 monoclonal antibody; inhibits IL-2 receptor signal transduction and T cell activation and proliferation | Severe infections and skin reactions, abnormal liver function, etc. | 2016 |
| Ocrelizumab Patel et al. (2021) | 300 mg i.v. every 2 wk | Monoclonal antibodies against CD20 on immature and mature B cells; removes CD20 positive B cells using CDC and ADCC | Skin reaction at the injection site, headache, malignant tumor, etc. | 2017 |
| Cladribine Miravalle et al. (2021) | 10 mg p.o. (3.5 mg/kg cumulative dose over 2 yr) | Nucleoside analogue; inhibits DNA synthesis and DNA chain termination and cytotoxic to lymphocytes and monocytes | Respiratory tract infection, headache, lymphocytopenia, etc. | 2019 |
| Siponimod Spampinato et al. (2021) | 250 μg or 2 mg p.o. once a day | S1P-1 receptor modulator; enters the brain and CNS of MS patients through the BBB, binds to S1P receptor, promotes myelin regeneration, prevents activation of harmful cells, delays disability progression, and preserves cognitive function | Increased blood pressure, decreased heart rate, delayed atrioventricular conduction, macular edema, respiratory and skin infections, etc. | 2019 |
| Ozanimod Lamb (2020); US Food and Drug Administration (2020) | 250 μg p.o. once a day | A novel S1P and dual subtypes of S1P1 and S1P5 receptor modulators; enters the brain and CNS through the BBB and binds to S1P receptors to promote myelin regeneration, prevents activation of harmful cells, delays disability progression, and preserves cognitive function in patients | Respiratory tract infection, urinary tract infection, transient decrease of heart rate and delayed atrioventricular conduction, elevated blood pressure, etc. | 2020 |
i.H., subcutaneous injection; i.m., intramuscular injection; i.v.gtt, intravenous drop infusion; i.v., intravenous injection; p.o., per os; IFN, interferon; BBB, blood-brain barrier; MBP, myelin-basic protein; MHC, major histocompatibility complex; APC, antigen-presenting cells; TNF, tumor necrosis factor; Th, helper T cells; CNS, central nervous system; S1P, sphingosine-1-phosphate; Nrf2, nuclear factor erythroid 2-related factor 2; IL, interleukin; CD, cluster of differentiation; CDC, complement-dependent cytotoxicity; ADCC, antibody dependent cellular cytotoxicity.