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# Multiple sclerosis disease-modifying therapies

Long-term immune-modulating medicines that reduce relapses and new lesions in multiple sclerosis; several raise the risk of serious infections such as PML.

Updated Nov 1, 2026

## What they are

Multiple sclerosis is an immune-mediated demyelinating disease of the central nervous system. Disease-modifying therapies do not cure it but lower relapse rates and slow the build-up of lesions. They include injectables (interferon beta, glatiramer acetate), oral agents (S1P receptor modulators such as fingolimod, fumarates such as dimethyl fumarate, teriflunomide, cladribine) and infused or injected monoclonal antibodies (natalizumab, ocrelizumab, ofatumumab, alemtuzumab). Relapses themselves are treated with short courses of high-dose corticosteroids.

## Mechanism of action

Each family hits a different step of the immune attack: S1P modulators trap lymphocytes in lymph nodes; natalizumab blocks alpha-4 integrin so lymphocytes cannot cross the blood-brain barrier; anti-CD20 antibodies deplete B cells; teriflunomide blocks pyrimidine synthesis in dividing lymphocytes; fumarates activate the Nrf2 antioxidant pathway; glatiramer acetate shifts T cells toward an anti-inflammatory profile.

Target: Immune targets: S1P receptors, alpha-4 integrin, CD20, dihydroorotate dehydrogenase, Nrf2 pathway

## Key points

- Natalizumab carries the highest risk of PML (JC virus): risk rises with anti-JCV antibodies, more than two years of treatment and previous immunosuppressants.
- Fingolimod slows the heart at the first dose: ECG and hourly pulse and blood pressure for six hours; also macular oedema and herpes infections.
- Teriflunomide has a boxed warning for hepatotoxicity and teratogenicity and stays in the body for months unless an accelerated elimination procedure is used.
- Dimethyl fumarate causes flushing and GI upset and can lower lymphocytes (PML has occurred with prolonged lymphopenia).
- Ocrelizumab is the anti-CD20 antibody approved also for primary progressive MS; hepatitis B is a reason to avoid it.

## Drugs in this class

- [**Fingolimod** An oral S1P receptor modulator for relapsing multiple sclerosis that keeps lymphocytes in lymph nodes; the first dose… Sphingosine 1-phosphate receptor 1 (S1P1; also S1P3, S1P4, S1P5)](https://durgical.com/en/pharmacology/fingolimod/)
- [**Glatiramer acetate** A random polymer of four amino acids injected under the skin for relapsing multiple sclerosis; it shifts immune cells… MHC class II molecules and myelin-reactive T cells (immunomodulation)](https://durgical.com/en/pharmacology/glatiramer-acetate/)
- [**Natalizumab** A monthly infused antibody against alpha-4 integrin that keeps lymphocytes out of the brain; its key risk is PML from… Alpha-4 integrin (α4β1 and α4β7)](https://durgical.com/en/pharmacology/natalizumab/)
- [**Dimethyl fumarate** An oral fumarate for relapsing multiple sclerosis that activates the Nrf2 antioxidant pathway; flushing and GI upset… KEAP1, the protein that controls the transcription factor Nrf2](https://durgical.com/en/pharmacology/dimethyl-fumarate/)
- [**Ocrelizumab** An anti-CD20 antibody infused every 6 months that depletes B cells; used in relapsing and primary progressive multiple… CD20 on B lymphocytes](https://durgical.com/en/pharmacology/ocrelizumab/)
- [**Teriflunomide** An oral DHODH inhibitor for relapsing multiple sclerosis; it can injure the liver and harm a fetus, and stays in the… Dihydroorotate dehydrogenase (DHODH)](https://durgical.com/en/pharmacology/teriflunomide/)
- [**Alemtuzumab** An anti-CD52 antibody that wipes out circulating lymphocytes for a long time. Given by IV infusion in yearly courses… CD52, a surface protein of lymphocytes](https://durgical.com/en/pharmacology/alemtuzumab/)
- [**Fampridine** A potassium channel blocker that helps some people with multiple sclerosis walk better. It lowers the seizure threshold. Voltage-gated potassium channels (Kv)](https://durgical.com/en/pharmacology/fampridine/)
- [**Ozanimod** An oral S1P receptor modulator that keeps lymphocytes inside lymph nodes. Used for relapsing MS and ulcerative… Sphingosine-1-phosphate receptor 1 (S1PR1)](https://durgical.com/en/pharmacology/ozanimod/)
- [**Siponimod** An oral S1P receptor modulator for relapsing and active secondary progressive MS. A CYP2C9 gene test decides whether… Sphingosine-1-phosphate receptor 1 (S1PR1)](https://durgical.com/en/pharmacology/siponimod/)

## Others in the class

- Interferon beta
- Siponimod
- Ozanimod
- Ponesimod
- Diroximel fumarate
- Cladribine
- Ofatumumab
- Alemtuzumab

## Test yourself

Think of the answer, then tap the question to see it.

## Which MS drug blocks lymphocyte entry into the CNS through alpha-4 integrin?

Natalizumab.

## Which infection is the key risk of natalizumab?

Progressive multifocal leukoencephalopathy (PML) from the JC virus.

## How does fingolimod reduce MS relapses?

Its phosphate modulates S1P receptors and traps lymphocytes in lymph nodes.

## Which enzyme does teriflunomide inhibit?

Dihydroorotate dehydrogenase (de novo pyrimidine synthesis).

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [DailyMed - FINGOLIMOD capsule](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a545c6fc-7006-52c2-f476-34e9801ac04f) (DailyMed (U.S. National Library of Medicine), 2026); [Natalizumab Injection: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a605006.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=L04AE) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/classes/multiple-sclerosis-disease-modifying-therapies/