Treatment of Multiple Sclerosis
As multiple sclerosis is a chronic disease, all habits related to a healthy lifestyle are important, including a balanced diet, regular physical activity, avoiding obesity, and avoiding harmful substances such as tobacco and recreational drugs.
These measures help prevent the development of other diseases, which may themselves worsen the patient's overall health or aggravate the possible neurological sequelae associated with multiple sclerosis.
There are currently three types of treatment available:
- to treat flare-ups or acute episodes;
- to reduce the activity of the disease and to prevent or delay the disability (drugs that modify the course of the disease);
- to alleviate the symptoms associated with the disease.
However, at present there are no prophylactic therapies—that is, treatments that can be given to people at risk to prevent the disease from developing. Likewise, there are currently no curative therapies or treatments capable of repairing or regenerating neurological damage that has already occurred.
The decision to initiate therapy and the type of therapy will depend on the clinical form, the characteristics of the disease in a particular patient (risk–benefit profile), and taking into consideration personal aspects (lifestyle, work/family situation, and preferences). This will allow treatment to be tailored as individually as possible.
Depending on these characteristics, some patients will be treated with medications that have a high safety profile but moderate efficacy. Based on the course of the disease, it will be decided whether to continue with the same treatment or to escalate to more intensive and more effective therapies. In certain patients, their individual risk–benefit profile will make it necessary to choose a more intensive therapy from the outset.
Corticosteroids. The inflammatory nature of the lesions has led to the use of corticosteroids as treatment for the acute episode. The most commonly used is methylprednisolone at a dose of 1 g/day for 3 to 5 days, administered intravenously or orally. This therapeutic regimen has been shown to shorten the duration of the episode and accelerate recovery.
Plasma exchange. Drawing of all the blood from the body in order to separate the red cells, white cells, and platelets from the plasma. The cells are returned to the patient without the plasma, which the body replaces rapidly. This technique is used in those patients who do not respond to conservative treatment, with no sequelae, or with previous minimal disability.
To date, most of the drugs available are used to treat the relapsing forms of the disease, although some are now available for the progressive forms. More than 20 years have passed since the first drug was approved, and since then more than 17 drugs with different mechanisms of action and different safety/side-effect profiles have been approved.
In general, most are anti-inflammatory drugs; some have immunosuppressive properties, while others are directed against more specific targets (such as monoclonal antibodies). According to their route of administration, they can be classified as self-injectable, oral, and intravenous drugs (the latter being administered in hospital).
It is important to bear in mind that women of childbearing age should use contraception while receiving treatment with any of the available drugs, and that individualized planning is advisable if pregnancy is desired. At present, although no drug is indicated for use during pregnancy, some are not contraindicated if necessary.
Self-injected Drugs
- Beta-interferon was the first approved drug and is a substance that is produced naturally and has anti-inflammatory properties. There are 4 interferons available that differ in the dose and administration route; three are subcutaneous and one is intramuscular.
- Glatiramer acetate. It is a mixture of short polypeptides whose mechanism of action is based on shifting the immune response towards an anti-inflammatory response, and it is administered subcutaneously. It is given as one subcutaneous injection three times a week on non-consecutive days. For example: Mon–Wed–Fri, Tue–Thu–Sat, or Tue–Thu–Sun.
Both beta-interferon and glatiramer acetate are indicated to treat patients with isolated clinical syndrome (ICS) and with relapsing-remitting forms, since they reduce the number of flare-ups and activity observed in the magnetic resonance scan. Both drugs are very safe.
- Ofatumumab. It is a monoclonal antibody specifically directed against B lymphocytes, causing their destruction. It is indicated for the treatment of adult patients with relapsing forms of multiple sclerosis and active disease. It has been shown to be superior to teriflunomide (an oral drug) in its ability to reduce the annualized relapse rate and the number of lesions. The most common adverse effects are reactions related to the first injection, including fever, headache, arthralgia, rhinitis, and others. In the long term, it may increase the risk of infections.
Oral Drugs
- Teriflunomide inhibits an enzyme involved in the proliferation of auto-reactive T and B lymphocytes, and with this, their passage into the central nervous system (CNS) is decreased. This drug is indicated in the relapsing-remitting forms, and has an efficacy similar to high doses of interferon.
- Dimethyl fumarate, through the inhibition of a factor, reduces the release of inflammatory substances and activates another factor that exercises an antioxidant effect. The drug has the same indication as the previous one, and reduces both the clinical and radiological activity of the disease.
- Fingolimod acts against a receptor and triggers the “trapping” of the auto-reactive lymphocytes in the lymphoid organs, without affecting those of the effector memory. The drug is only indicated for the relapsing-remitting forms. It has double the efficacy of a low dose interferon.
Monoclonal antibodies
Natalizumab is an antibody directed against an integrin, which on blocking it makes it difficult for the auto-reactive lymphocytes to pass into the central nervous system. It is administered monthly by the intravenous route. Its effectiveness is very high for reducing flare-ups, the activity as measured by magnetic resonance, as well as delaying the increase in disability. In general, it is well-tolerated, and a hypersensitivity reaction may be produced in only 1-3 cases per 100 patients.
Alemtuzumab is an antibody directed against a protein present on the surface of lymphocytes and monocytes. Its administration (5 consecutive days by the intravenous route) produces the temporary destruction of T and B lymphocytes, which gradually recover. The treatment is repeated one year later for 3 days. The efficacy is very high compared with interferon at high doses, and can persist for one year after a single course of the medication. An infusion reaction is very common during the days that it is administered in the hospital.
Ocrelizumab. It is an antibody directed against a protein located on the surface of certain lymphocytes. It is the first medication to be used for both relapsing-remitting and primary progressive forms of multiple sclerosis. It is administered intravenously every six months. In the clinical trial for relapsing-remitting forms, it showed greater efficacy than a high-dose interferon in terms of relapses, disease progression, and magnetic resonance imaging activity; in the trial for primary progressive forms, it reduced disease progression to a modest but statistically significant extent compared with placebo. It is therefore indicated for two forms of the disease: relapsing-remitting multiple sclerosis and primary progressive multiple sclerosis.
Ublituximab. It is a new monoclonal antibody that acts against a protein located on the surface of certain lymphocytes, like ocrelizumab and ofatumumab. It is indicated for the relapsing-remitting forms of the disease. It is administered intravenously every six months. It offers the advantage of a shorter infusion time than ocrelizumab.
The adverse effects of these drugs are infrequent but serious.
- Changes in cardiac rhythm. The receptors over which fingolimod acts are also distributed in the heart. For this reason, in the first dose, some patients may have a lowering of the heart rate, generally asymptomatic, or even have a block (less than 2 cases per 100 patients), and for this reason the first administration must be monitored in the hospital.
- Progressive multifocal leucoencephalopathy (PML). Is an infection of the central nervous system (CNS) for which there is no treatment. It is produced by the re-activation of a latent virus that is present in approximately 50 out of every 100 healthy subjects. The first cases where described more than 10 years ago in patients treated with natalizumab. Since then, more than 600 cases of PML have been described with its use. The risk depends on the duration of the treatment, if there has been exposure to previous immunosuppressive treatments, and the level of antibodies. The patient’s antibodies help to recognise the individual risk before starting the therapy. Once indicated, continuous analytical controls are performed. Six cases have also been reported in patients treated with fingolimod, although three of them had previously been treated with natalizumab, and four cases in patients treated with dimethyl fumarate. The risk in both cases is very low, probably less than 1 case for every 26,000 patients treated.
- Autoimmune diseases. The appearance of autoimmune diseases has been described in association with alemtuzumab. Up to 30 of every 100 patients treated could develop thyroid autoimmune diseases, or an autoimmune thrombocytopenia in 1-3 of every 100 patients, and more rarely an autoimmune renal disorder. They are diseases that more commonly occur during the second or third year after the first dose administered. A very exhaustive follow-up is required for at least 5 years.
- Tolebrutinib. It is a drug with a new mechanism of action that inhibits an enzyme called Bruton's tyrosine kinase, thereby reducing the activation of B cells. It also penetrates the brain and spinal cord and acts on microglia, the immune cells of the brain that have been linked to the progression of multiple sclerosis. In the clinical trial for relapsing-remitting forms of the disease, tolebrutinib did not reduce relapses compared with teriflunomide. However, it did delay the time to progression compared with placebo in clinical trials involving secondary progressive and primary progressive forms.
- Frexalimab. It is a monoclonal antibody that acts on the CD40–CD40L pathway, regulating the innate and adaptive immune responses involved in the pathogenesis of multiple sclerosis. In a phase 2 trial involving participants with multiple sclerosis, inhibition of CD40L with frexalimab had a greater effect than placebo in reducing the number of new contrast-enhancing lesions after 3 months of treatment. A phase 3 study is currently underway to evaluate its clinical efficacy compared with teriflunomide in relapsing multiple sclerosis.
These are therapies aimed at relieving manifestations or symptoms that may occur during the course of the disease and that have a negative impact on patients' quality of life. Therefore, it is important to identify the symptoms, recognize their causes, and use the appropriate treatments or establish preventive measures.
These include symptoms resulting from spasticity, urinary or sexual dysfunction, as well as pain, which is usually multifactorial in origin, and fatigue. Although in some cases these symptoms can be improved with pharmacological intervention, in others a multidisciplinary approach is required, including rehabilitation treatment, psychological intervention, and social support
Substantiated information by:
Published: 20 February 2018
Updated: 13 July 2026
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