Drugs that modify the course of multiple sclerosis - DMTs. Basic therapy

MTMDs (multiple sclerosis-modifying drugs) are becoming increasingly common and clinically justified in the treatment of multiple sclerosis. In each specific case, DMTs are selected individually, taking into account the nature of the disease, existing symptoms and previously prescribed therapy. To date, doctors have developed an algorithm for the use of DMTs for multiple sclerosis . It provides a reason for prescribing, correcting and discontinuing a drug, as well as a scheme for transferring the patient to another drug of this group. As a rule, DMT drugs are prescribed as soon as the diagnosis is established in order to limit the development of multiple sclerosis.

DPIRS affect the pathological process of demyelination. The use of DMTs can reduce the frequency or completely prevent the occurrence of exacerbations, making them less pronounced, as well as slow down the increase in disability.

For a long period of time, treatment of multiple sclerosis was reduced to hormone therapy and concomitant therapy aimed at reducing the severity of symptoms, improving the metabolism of nervous tissue, strengthening blood vessels and rehabilitation. All these treatment methods brought the patient only temporary relief, sometimes very significant, but not significantly affecting the development of multiple sclerosis.

The use of PMTRS allows the patient to:

• stabilize your condition;
• prevent transition to a progressive form;
• slow down the development of neurological deficits.

But the clinical effect of DMTRS in multiple sclerosis does not develop immediately; the patient may stop taking the drug, judging that he is not experiencing any improvement. It is worth remembering that progress becomes noticeable only in the period from 1 to 6 months from the start of taking the drug.

Doctor's comment

A commentary on the principles of treatment with drugs that modify the course of multiple sclerosis (DMD) and the goals of therapy is given by a leading specialist in the field of multiple sclerosis, Doctor of Medical Sciences, Professor of the Department of Nervous Diseases and Neurosurgery with the Clinic of the First St. Petersburg State Medical University named after Academician I.P. Pavlova Totolyan Natalia Agafonovna

There are first-line and second-line PEDs. First-line DMTs are prescribed as soon as the diagnosis of multiple sclerosis is confirmed. They slow the progression of the disease and reduce symptoms. Second-line DMTs are used when multiple sclerosis becomes active. But first-line drugs are not effective enough.

Main effects of PITRS:

1. slowing down the development of irreversible disorders (disability);
2. reduction in the frequency of exacerbations;
3. reducing the inflammatory response.

Currently developed:

• clear algorithms for treatment with DMT drugs;
• ways to monitor changes in patients' condition;
• recommendations that can significantly reduce the severity of adverse reactions or completely eliminate them.

However, there are cases that may require a change in DMT drugs.

These include:

• severe adverse reactions that cannot be corrected;
• pregnancy (including planned);
• lack of effectiveness of therapy.

In any case, the decision to prescribe or cancel DMTs is made by the attending physician and depends on the patient’s condition.

The international medical community has accepted that DMTs are the first-priority and most effective drugs for the treatment of multiple sclerosis.

Symptomatic treatment

The goal of symptomatic therapy is to eliminate or alleviate existing neurological symptoms. Symptomatic therapy has no effect on the course of MS itself, but can improve the patient’s quality of life. For this purpose, drugs of various groups are used. Often, the same remedy simultaneously eliminates several manifestations of multiple sclerosis.

Synthetic analogues of GABA

Gamma-aminobutyric acid is one of the so-called. inhibitory mediators in the central nervous system. Damage to brain structures in multiple sclerosis is accompanied by the elimination of inhibitory impulses with the development of muscle spasms and spastic pain. Such symptoms are eliminated with the help of Baclofen. This synthetic analogue of GABA restores inhibitory impulses and inhibits spasm. Baclofen relaxes not only skeletal but also smooth muscles. Therefore, it can be used for spastic constipation and difficulty emptying the bladder.

Benzodiazepines

Benzodiazepine derivatives (Diazepam, Clonazepam) are similar in properties to GABA. They enhance the effect of Baclofen and also have tranquilizer properties. Therefore, they are used to eliminate anxiety and fear in patients with multiple sclerosis. In addition, benzodiazepines have analgesic properties - they can eliminate pain.

Anticholinergics

These drugs normalize muscle tone by influencing central and peripheral cholinergic receptors. "Mydocalm", "Hyoscyamine", "Oxybutynin" are used to relieve spasms of skeletal muscles, smooth muscles of the intestines and bladder.

Antiepileptic drugs

They can also be useful for multiple sclerosis. “Carbamazepine”, “Phenytoin” prevent the development of seizures, normalize sensitivity, and are effective for neuritis accompanied by pain, impaired swallowing and speech.

Tricyclic antidepressants

Eliminates feelings of depression and fatigue, improves mood and performance. These drugs also normalize muscle tone and eliminate pain.

Vitamins

The importance of these biologically active substances in multiple sclerosis is difficult to overestimate. B vitamins normalize sensitivity and movement, ascorbic acid improves immunity, vitamin E strengthens blood vessels, and vitamin D prevents the development of osteoporosis, a frequent companion of multiple sclerosis. All drugs for the symptomatic treatment of multiple sclerosis are used only as prescribed by a doctor and under his supervision.

Commentary by doctor E.V. Popova about PED

Ekaterina Valerievna will talk about what types of DEDs exist, how different DEDs differ, and what influences a doctor’s choice in prescribing a particular drug for the treatment of multiple sclerosis. Let's consider the indications for prescribing DMTRS for various types of MS.

The role of PITRS

The clinical effect of DMTs in multiple sclerosis develops, as a rule, from 1 month to six months from the start of use. To assess the effectiveness of the drug, treatment results are reviewed over a period of 6 months to 1 year.

Patients who have been prescribed DMT for the first time often ask the following questions:

Why take the drug if I don't feel better?

The mechanisms of action of DMTRS are such that a noticeable effect from therapy usually occurs within 1-6 months. The duration of this period is individual and depends on a number of factors, such as the nature of the disease, the patient’s condition before the prescription of drugs, concomitant therapy, individual reactions to the drug, etc. In addition, it is worth remembering that the effect of treatment for PED is not manifested by any specific sensations, but by a long-term absence of exacerbations.

Do I need PEDs if I have never had an exacerbation?

There are cases when the diagnosis of multiple sclerosis is made to a patient who has never had any manifestations of the disease. This most often occurs when lesions are detected by MRI before symptoms appear. The patient is then diagnosed with radiologically isolated syndrome (RIS). On the other hand, the patient could only experience one clinical episode—clinically isolated syndrome (CIS). And, since the symptoms of MS are nonspecific and can occur in various neurological diseases, the patient may not realize that he has had an exacerbation. In both cases, according to the decision of the attending physician, the patient may be prescribed DMT therapy. This approach is justified.

Can it get worse while taking DED?

As a rule, DMT therapy stops the development of exacerbations of MS. More often, during treatment, various side effects of the drug may appear. Subjectively, these sensations may be regarded by the patient as a deterioration of the condition. Over time, these reactions may become less pronounced and no longer bring such pronounced concern to the patient. In each case, it is necessary to discuss the occurrence of side effects of the drug and options for their correction with your doctor.

I felt the effect of therapy/I felt better, when can I stop taking the drug?

If a good result is obtained from the prescribed therapy and exacerbations do not occur, treatment with DMT should not be stopped. Some patients stop treatment for MS on their own, and most typically experience a return of MS symptoms within two years or less of stopping treatment. Long-term drug treatment often causes anxiety among patients. You can compare DMTs with drugs to lower blood pressure or normalize blood sugar, which are also taken for a long time. This treatment should be regarded as helping the body with what it cannot cope with on its own. In any case, you should consult your doctor.

What are the risks of long-term use of DMTs?

With long-term use of prescribed drugs of the DMT group, mandatory monitoring of clinical blood parameters is carried out, the function of the liver, kidneys and other vital organs is assessed. If serious deviations in any of the indicators are determined, the drug may be temporarily discontinued or replaced by the attending physician. If no changes are detected during regular monitoring, there is no risk to the body.

Side effects interfere with my daily life, is it possible to stop the drug?

The criteria for changing treatment for DMT are:

• planned pregnancy;
• poor tolerability of therapy;
• change in the type of course of multiple sclerosis;
• low effectiveness of therapy.

The listed situations are quite rare, with the exception of possible pregnancy and adverse reactions. As a rule, adverse reactions are more likely to bother the patient at the beginning of therapy. Over time, they become less pronounced or disappear completely. If the attending physician confirms the severity of side effects, and the therapy prescribed to reduce their severity does not help, the drug should be changed.

What are the treatment tactics for PED during a planned pregnancy?

During pregnancy and childbirth, as well as during breastfeeding, taking DMT drugs is not recommended. Continuation of therapy should definitely be discussed with your doctor, who will assess the benefits and possible risks of therapy. After breastfeeding ends, the patient usually returns to her previous therapy. The drug for each patient must be selected individually, taking into account the form of multiple sclerosis and the characteristics of the course of the disease. The choice should also depend on the presence of certain symptoms and tolerability of certain medications. PEDs can preserve the health of the patient and prolong the period of working capacity and activity of patients with multiple sclerosis

Pathogenetic therapy of multiple sclerosis

Multiple sclerosis (MS) is a chronic, autoimmune disease of the central nervous system (CNS), characterized by inflammation of the white matter of the central nervous system, demyelination and destruction of axons, which is the most common cause of neurological disability among young people.

The average age of MS patients is 30 years. The main peak incidence of MS occurs between the ages of 20 and 40 years. The incidence in children under 16 years of age is 2.7% of cases. MS is rare in patients over 60 years of age. Women are twice as likely to get MS. The incidence of MS varies significantly around the world. Thus, the number of MS cases increases with distance from the equator; the disease is most common in Northern Europe, South Australia and central North America. It is believed that there are about 2 million patients in the world, including approximately 150,000 in Russia.

In recent years, significant advances have been made in understanding the pathogenesis and development of new pathogenetic treatments for MS. The generally accepted theory is that the etiology of MS is multifactorial, based on the interaction of environmental factors (virus and/or other pathogen and geographic factors) and hereditary predisposition.

Currently, the concept of the pathogenesis of MS includes the identification of an initial inflammatory phase, accompanied by a demyelination phase, and then a phase of neurodegeneration [5; 7]. The initiation of immunopathological mechanisms, namely the activation of anergic, inactive CD4+ T cells, occurs outside the CNS through the interaction of the corresponding T cell receptor and autoantigen bound to class II molecules of the major histocompatibility complex on antigen-presenting dendritic cells, which promotes the proliferation of T cells. Subpopulations of T cells with their different functional differentiation and regulatory interactions play an important role in the immunopathogenesis of MS. After antigen presentation, T-lymphocytes differentiate into two types of effector cells - T-helper cells type 1 and 2, secreting pro- and anti-inflammatory cytokines, respectively. The type of T helper cells is determined by the influence of the antigen, co-stimulation, as well as the cytokine profile in the environment [5]. The secretion of pro-inflammatory cytokines promotes the activation of other immune cells - B-lymphocytes, macrophages and other T-cells, which enhances the immune response [1; 7]. In addition, cytokines of this profile induce the expression of adhesion molecules.

In addition to the activation, differentiation and proliferation of T cells, the imbalance of different T cell subsets is also important. The role of CD4+CD25+FoxP3 regulatory T cells has recently been defined. These studies support dysregulation of regulatory T cells, which plays an important role in the pathogenesis of MS. These cells participate in the maintenance of immunological tolerance and have the ability to suppress antigen-specific proliferation and effector functions of autoreactive lymphocytes. Patients with MS are characterized by a decrease in the total number and hypofunction of regulatory T cells. Data have also been obtained indicating different functions and expression of CD4+CD25+FoxP3 T cells depending on the course of MS (remitting and secondary progressive).

The penetration of activated CD4+ T cells through the blood-brain barrier (BBB) ​​into the central nervous system is carried out with the participation of chemokines, adhesion molecules, proteases and occurs in several stages [7]. At the initial stages, chemokines are of greater importance, while later the interaction of various types of adhesion molecules expressed both on the surface of T lymphocytes and on endothelial cells promotes cell migration across the BBB with the participation of matrix metalloproteinases [5].

In the CNS, T cells are reactivated by antigen-presenting cells, which are macrophages and microglia. Autoreactive T cells and secondary activated macrophages and microglia that have penetrated into the CNS also secrete pro-inflammatory cytokines (interferon-gamma, tumor necrosis factor-alpha (TNF-alpha), lymphotoxin, etc.), which further induces and maintains inflammatory reactions and increases disruption of the BBB permeability. Activation of immune reactions, including macrophages, B-lymphocytes with the production of antibodies, leads to the destruction of the myelin sheath. Phagocytosis of damaged areas of myelin by macrophages is carried out with the participation of cytotoxic mediators, such as TNF-alpha, reactive oxygen species, and nitric oxide metabolites.

Immunoinflammatory changes and demyelinating lesions are accompanied by neurodegenerative damage with axonal death, which is observed already in the early stages of the disease and plays a key role in the progression of MS and the development of irreversible disability in patients [5; 8]. The probable cause of direct destruction of axons in MS is considered to be the expression of the class I molecule of the major histocompatibility complex on them, which makes them vulnerable to the cytotoxic influence of CD8+ T lymphocytes [1]. Axonal damage may be associated with inflammatory reactions, namely increased extracellular pressure with edema; excitotoxic damage resulting from exposure to the excitatory amino acid glutamate; degenerative changes when exposed to nitric oxide. However, axonal damage is also possible due to disturbances in trophic support, including changes in the expression of trophic factors, as well as in the chronic demyelinating process due to disruption of the trophic influence of oligodendrogliocytes and myelin-axonal interactions [6; 8].

In the formation of neurological deficits in MS, much attention is paid to the balance between destructive and reparative processes [3]. Reduction of the severity of acute inflammatory reactions, remyelination and improvement of conduction due to the redistribution of sodium channels in demyelinated axons are considered as mechanisms for regression of clinical symptoms. Another factor that determines the restoration of certain functions in the event of irreversible damage to myelin and axons in MS is considered to be cortical reorganization [2; 5]. Thus, the well-known phenomenon of brain plasticity is driven by multiple substrates (including increased axonal expression of sodium channels, synaptic changes, recruitment of parallel pathways or “latent” connections, reorganization of distant regions such as subcortical nuclei projecting to the cortex) , may have an adaptive value in limiting the functional manifestations of axonal damage in MS [1; 5].

The above ideas define approaches to the pathogenetic treatment of MS, which consist of two main directions: 1) treatment of exacerbations and periods of sharp increase in disease activity, 2) prevention of exacerbations and progression of disability.

Data from studying the natural history of MS and the results of clinical trials have shown that the sooner adequate treatment begins, the less frequent and milder the exacerbations of MS are, the less pronounced are the subsequent atrophic processes that determine persistent neurological disorders, i.e., the severity of the disease.

Modern assessment of the effectiveness of MS treatment methods is based on the mandatory use of a number of criteria that objectify changes in the clinical condition of patients in three areas:

• influence on the frequency and severity of exacerbations, duration of remission;
• influence on the increase in disability indicators on one of the neurological scales (EDSS, MSFC, etc.);
• influence on magnetic resonance imaging (MRI) data, which allows one to judge both the activity of the inflammatory and demyelinating process (total volume of lesions, the number of “active” lesions accumulating paramagnetic contrast), and the severity of neurodegenerative changes associated with the progression of disability (degree of local degeneration - “black holes” and diffuse atrophy).

The main principle of treating exacerbations of MS is glucocorticosteroid therapy, which has an anti-inflammatory and immunosuppressive effect. The immunological effects of glucocorticoids include inhibition of T-cell activation and production of proinflammatory cytokines (interleukin-2, interferon-gamma); increased production of pro-inflammatory cytokines; decreased expression of major histocompatibility complex type II molecules on macrophages, induced by interferon-gamma; inhibition of the synthesis of proinflammatory cytokines, prostaglandins and leukotrienes by macrophages; preventing the adhesion of neutrophils to endothelial cells; inhibition of activation of endothelial cells and adhesion molecules. The above mechanisms determine the effects of steroids at the level of the BBB, which prevents the penetration of immune cells and molecules into the nervous system. In addition, glucocorticosteroids inhibit nuclear factor kappa B, which influences immunoinflammatory reactions, and can also induce apoptosis of autoreactive T cells, which can help suppress the acute attack of MS. Thus, glucocorticoids stabilize the state of the BBB, limit inflammatory and autoimmune processes and the degree of myelin destruction, i.e., reduce the severity and duration of exacerbation and prevent the development of persistent neurological consequences. The greatest effectiveness of glucocorticosteroids is achieved by using them in a short period of time during the most acute stage of exacerbation of MS. The concentration of the hormone in the body during an attack of MS must reach a fairly high level, so the most widely used regimens are those administering the drug in pulse doses (intravenous pulse therapy with methylprednisolone in a total dose of 3000–7000 mg). The advantage of intravenous pulse therapy over tablet administration of corticosteroids is its greater effectiveness in the absence of a whole range of side effects characteristic of long-term oral administration.

Plasmapheresis (2–3 sessions) can be used to relieve severe exacerbations of MS. The high effectiveness of its use is also shown in combination with intravenous administration of methylprednisolone, after each manipulation, 500–1000 mg.

In some cases, to reduce the frequency and severity of exacerbations, slow down the frequency and severity of disability, intravenous administration of immunoglobulin G is used. Several possible mechanisms of its influence are assumed: binding and activation of pathogenic antibodies to immunoglobulins; blockade of the Fc receptor on mononuclear phagocytes, modulation of endogenous production of immunoglobulins, weakening of complement-mediated effects; neutralization of molecules involved in inflammatory reactions; induction of anti-inflammatory cytokines and apoptosis [7]. However, at present, the lack of large controlled clinical studies, limited MRI data, and the lack of a clearly established dosage regimen at the high cost of the drug are the main problems in the use of immunoglobulin in MS.

Currently, the main direction of pathogenetic preventive therapy for MS is the use of drugs that modify the course of MS, which include immunomodulators and immunosuppressants.

Immunomodulatory agents are the first line of this therapy for MS and include: beta interferons - Betaferon (interferon beta-1b), Rebif (interferon beta-1a) for subcutaneous administration and Avonex (interferon beta-1a) for intramuscular administration, as well as glatiramer acetate (Copaxone-Teva).

All three drugs based on interferon beta are obtained using genetic engineering methods using recombinant DNA. Copaxone-Teva is a synthetic analogue of one of the immunomodulatory zones of human myelin.

All three interferon beta drugs are indicated for the treatment of relapsing-remitting MS. Betaferon is used at a dose of 250 mcg (8 MME) subcutaneously every other day. It should be noted that, unlike Rebif and Avonex, Betaferon is produced by Escherichia coli and is different from a natural molecule. Rebif is the only drug with two registered doses (22 mcg and 44 mcg). The recommended dose of Rebif is 44 mcg subcutaneously three times a week. Rebif 22 mcg is recommended in patients who cannot tolerate a higher dose for dose titration during the first month of therapy and in patients aged 12–18 years for the treatment of juvenile MS. Avonex is administered intramuscularly once a week at a dose of 30 mcg (6 MME). For the treatment of secondary progressive MS, only two drugs are used - Betaferon and Rebif at a dose of 44 mcg. Glatiramer acetate is indicated for the treatment of patients with relapsing-remitting MS only and is administered subcutaneously daily at a dose of 20 mg.

The results of randomized clinical trials that met all modern requirements of evidence-based medicine showed that regular treatment with these immunomodulatory drugs in patients with relapsing-remitting MS is safe, can significantly reduce the frequency and severity of exacerbations (on average by 25–33% compared to placebo), and also significantly slow down the rate of progression of disability. The positive effect is stable over at least 5–10 years of follow-up, especially when treatment is started early. Similar results were obtained when using Betaferon in patients with secondary progressive MS. For the treatment of patients with clinically isolated syndrome, the effectiveness of two drugs, Avonex and Betaferon, has been proven in terms of slowing down the development of reliable MS.

These drugs have different mechanisms of action. Thus, the therapeutic effects of beta interferons are associated with an effect on the presentation of antigens and inhibition of the proliferation and activation of inflammatory cells; inhibition of the production of pro-inflammatory cytokines and a change in the cytokine profile towards an anti-inflammatory phenotype; as well as a decrease in the entry of leukocytes into the central nervous system through the blood-brain barrier due to the effect on adhesion molecules, chemokines and matrix metalloproteinases, which leads to a decrease in neuronal damage. In addition, interferon beta induces the synthesis of nerve growth factor by astrocytes and enhances the secretion of neurotrophin by endothelial cells during their interaction with T lymphocytes [4].

In turn, drugs that modulate the course of MS include glatiramer acetate, which has several mechanisms of action: competitive binding with myelin basic protein to the class II molecule of the major histocompatibility complex, which is involved in the presentation of antigens, as well as activation of the Th2 phenotype of CD4+ T cells , crossing the blood-brain barrier and secreting anti-inflammatory cytokines (interleukin-4, interleukin-10, interleukin-13, transforming growth factor-beta), which leads to suppression of the autoimmune response to multiple myelin antigens [7]. In addition, glatiramer acetate-specific T cells have been shown to express brain-derived neurotrophic factor and transforming growth factor-beta.

In addition to effectiveness, the safety of drug administration is no less important. Side effects during treatment with interferons include flu-like (fever, headaches, muscle and joint pain), local (hyperemia, soreness), cardiovascular (hypotension, tachycardia and arrhythmias) and hematological (leukopenia, thrombocytopenia) reactions, as well as neurological symptoms ( increase in the severity of spasticity, less often - aggravation of other neurological symptoms against the background of influenza-like phenomena). An uncommon but serious side effect is depression with suicidal ideation. However, it is currently assumed that treatment with beta interferons does not increase the risk of developing depressive disorders and may induce or exacerbate pre-existing psychiatric symptoms.

The most common side effects of glatiramer acetate include local reactions, but general systemic reactions may also develop, including vasodilation, chest pain, shortness of breath, rapid heartbeat, and anxiety.

Second-line drugs that modify the course of MS include drugs with an immunosuppressive effect: natalizumab (Tysabri); non-selective drugs - mitoxantrone (Novantron), alemtuzumab; selective drugs - rituximab, cladribine. These drugs are indicated for significant worsening of the course of relapsing-remitting and secondary progressive MS, provided that interferon beta or glatiramer acetate are ineffective.

Only mitoxantrone is registered in Russia. In this regard, only this drug is used in our country. Mitoxantrone has an immunosuppressive effect on T and B lymphocytes, reduces the production of proinflammatory cytokines, and has also been shown in vitro to induce apoptosis of antigen-presenting cells and deactivate macrophages. The mechanism of action of mitoxantrone is that it causes DNA damage and also disrupts DNA repair by inhibiting topoisomerase-II. Several regimens for using the drug are suggested - 12 mg/m2 intravenously every 3 or 6 months, also preferably in combination with methylprednisolone. For the treatment of patients with a malignant course of the disease, it is advisable to administer monthly intravenous drips of mitoxantrone with premedication with 1 g of methylprednisolone intravenously for 6 months. The total dose should not exceed 100 mg/m2. The use of mitoxantrone in both men and women requires special caution due to the possibility of cumulative cardiotoxicity, hematopoietic suppression and gonadal dysfunction. In this regard, the duration of the course of treatment is no more than two years and includes no more than 8 infusions, always under the control of echocardiography.

One of the new directions in MS therapy that is actively being developed is the use of monoclonal antibodies aimed at specific antigens. Thus, antibodies to adhesion molecules can inhibit one of the main stages of MS pathogenesis—interaction with endothelial cells and migration of lymphocytes across the BBB. One such drug that has undergone clinical trials for MS is natalizumab, which binds to the alpha4 subunit of alpha4beta1 and alpha4beta7 integrin [10]. Natalizumab is indicated as monotherapy for the treatment of patients with relapsing-remitting MS who have had at least one exacerbation during previous interferon beta therapy, or patients with rapidly progressive severe relapsing-remitting MS who have had at least two exacerbations in the previous year and have demonstrated negative changes in the disease. MRI (new lesions accumulating contrast agent, or an increase in the total volume of focal brain lesions by the number of T2 lesions). The drug is administered every 4 weeks intravenously by drip over 1 hour at a dose of 300 mg. The course of treatment is usually designed for 2 years. However, it is necessary to take into account the increased risk of developing progressive multifocal leukoencephalopathy and the possible increased risk of other opportunistic infections [4].

Various oral drugs are currently being studied, including the immunosuppressive agents cladribine and laquinimod. Inhibition of activated lymphocytes under the influence of fingolimod was also revealed, and the immunomodulatory and immunosuppressive activity of dimethyl fumarate was shown. These drugs have demonstrated effectiveness in MS, at least according to neuroimaging data [5]. In particular, the possibility of prescribing statins for MS is being studied, which, in addition to their lipid-lowering effect, also have immunomodulatory activity [6; 9].

Since the leading mechanism of increasing disability in patients with primary progressive MS is considered to be predominant degenerative changes in the nervous tissue, all of the above drugs turned out to be ineffective in the treatment of primary progressive MS. Currently, drugs with neuroprotective properties are being developed.

Thus, there are a large number of therapeutic options for MS, most of which are likely to be used in treatment practice in the near future. In this case, preference will be given to drugs aimed at specific pathogenetic mechanisms of the demyelinating process in MS.

Literature

1. Zavalishin I. A., Peresedova A. V., Stoyda N. I. et al. Comparative analysis of the effectiveness of immunomodulatory therapy for multiple sclerosis with Rebif 22 mcg, betaferon and Copaxone (results of 3 years of treatment) // Journal of Neurology and Psychiatry named after. S. S. Korsakova 2007, issue 4 “Multiple sclerosis.” pp. 99–105.
2. Arnold D.L., Campagnolo D., Panitch H. et al. Glatiramer acetate after mitoxantrone induction improves MRI markers of lesion volume and permanent tissue injury in MS.//J.Neurol. 2008; 255(10):1473–1478.
3. Capobianco M., Rizzo A., Malucchi S. et al. Glatiramer acetate is a treatment option in neutralizing antibodies to interferon-beta-positive patients // Neurol. Sci. 2008; 29 Suppl. 2:S227–229.
4. Comi G. Induction vs. Escalating therapy in multiple sclerosis: practical implications // Neurol. Sci. 2008; 29 Suppl. 2:S253–255.
5. Confavreux C., Vukusic S. Multiple sclerosis: a degenerative disease? // Bull. Acad. Natl. Med. 2008; 192(3):483–491.
6. Coyle PK Early treatment of multiple sclerosis to prevent neurologic damage // Neurology 2008; 71 (24 Suppl. 3): S3–7.
7. Dong C., Flavell RA Cell fate decision: T-helper 1 and 2 subsets in immune responses // Arthritis Res. 2000; 2: 179–188.
8. Fong JS, Rae-Grant A., Huang D. Neurodegeneration and neuroprotective agents in multiple sclerosis // Recent Pat. CNS Drug Disco. 2008; 3 (3): 153–165.
9. Freedman MS Induction vs. Escalation of therapy for relapsing multiple sclerosis: the evidence // Neurol. Sci. 2008; 29 Suppl. 2:S250–252.
10. Goodin DS, Cohen BA, O'Connor P. et al. Assessment: the use of natalizumab (Tysabri) for the treatment of multiple sclerosis (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology // Neurology 2008; 71(10):766–773.

I. A. Zavalishin, Doctor of Medical Sciences, Professor D. D. Eliseeva NCN RAMS, Moscow

Pathogenetic treatment

The goal of pathogenetic treatment of MS is to quickly relieve symptoms caused by exacerbations, as well as to prevent exacerbations and increase the period of remission. In addition, one should strive to change the course of the disease and slow its progression. Medicines used to treat MS can be divided into two groups. The first group is drugs that are used during periods of exacerbation. The second group is drugs that change the course of the disease by suppressing the pathologically active immune system. These include immunomodulators, immunosuppressants, cytostatics and monoclonal antibodies. Of course, the most effective type of treatment for multiple sclerosis would be etiological, aimed at eliminating the cause. But since the etiology of the disease is still poorly understood, treatment begins with influencing the pathogenesis, the mechanism of development of the disease.

Pathogenetic treatment is aimed at:

• preventing axonal demyelination;
• acceleration of remyelination;
• immunosuppression - a decrease in the pathological activity of the immune system;
• immunomodulation – change, modulation of the immune response;
• inhibition of local inflammatory and autoimmune processes;
• strengthening, reducing the permeability of the vascular wall and the BBB (blood-brain barrier).

With properly selected pathogenetic treatment, recovery processes begin to prevail over the processes of damage to the axons of the myelin sheath of nerve fibers. As a result, the severity of exacerbations is reduced, and remissions, on the contrary, are lengthened. In this case, the transition of a relapsing course into a secondary progressive course with disability occurs as late as possible or does not occur at all.

Drugs

Glucocorticoids

These are synthetic analogues of adrenal hormones - Prednisolone, Methylprednisolone, Dexamethasone. These drugs for multiple sclerosis block certain biologically active substances of the cytokine class and reduce the production of T-lymphocytes. Thus, glucocorticoids inhibit inflammatory and autoimmune processes. In addition, these drugs reduce the permeability of vascular walls and the BBB. Glucocorticoids for multiple sclerosis are used in pulse therapy mode - in large doses over short periods of time.

ACTH

Adrenocorticotropic hormone is secreted by the anterior pituitary gland and stimulates the production of its own glucocorticoids by the adrenal cortex. Thus, the effect of ACTH and its synthetic analogues (Synacten, Tetracosactide) is similar to the drug of the previous group, but has less risk of side effects (ulceration, hypercortisolism). Although in this case, disturbances in water-salt metabolism and increased blood pressure are possible.

Synthetic beta interferons

(“Avonex”, “Rebif”, “Betaferon”) have an immunomodulatory effect, inhibit autoimmune processes, reduce the activity of T-lymphocytes, and prevent the penetration of cytokines through the BBB. In addition, beta interferons are effective in the initial stages of viral infections, one of the causes of multiple sclerosis.

Copaxone

This drug has immunomodulatory properties and is specially designed for the treatment of multiple sclerosis. It is a sequence of amino acids glutamine, lysine, alanine, tyrosine. Its chemical structure is similar to myelin.

Angioprotectors and antiplatelet agents

These drugs (“Curantil”, “Pentoxifylline”) prevent red blood cells from sticking together, improve blood flow and strengthen the vascular wall.

Proteolytic enzyme inhibitors

When administered intravenously, Contrikal and Gordox inhibit enzymes of the protease class, which destroy protein structures and participate in inflammatory processes. Plasmapheresis, a method of hardware extracorporeal (outside the body) blood purification, gives good results. During plasmapheresis, antigenic complexes, biologically active substances that trigger autoimmune processes, are removed along with plasma. Not so long ago, the drug Anti-LINGO-1 was developed in the USA, which accelerates remyelination. Now this drug is in the clinical trial phase, but perhaps it will still say a new word in the treatment of multiple sclerosis.

Treatment of exacerbations

During exacerbations, therapy is carried out using potent anti-inflammatory drugs and corticosteroid hormones. The regimens and doses of administration of these drugs are individually determined by the doctor depending on the patient’s condition. Along with corticosteroids, during an exacerbation, drugs that improve the functions of nervous tissue (so-called neuroprotectors), drugs that strengthen the vascular wall, and drugs that improve the rheological properties of the blood are usually prescribed. In the absence of contraindications, physical therapy and physiotherapeutic procedures are indicated.