Multiple sclerosis-related fatigue and possibilities of its correction

Multiple sclerosis (MS)-related fatigue is encountered in 75–92% of patients and it is one of the key symptoms that affect quality of life. Physicians and patients' relatives frequently underestimate MS-related fatigue; the latter may occur at any disease stage, its degree is inadequate to physical exercise and reduces after a short-term daytime rest. Fatigue due to MS is not directly related to the degree of paresis; however, it is more common in patients with pyramidal insufficiency. Overfatigue may be the first symptom of an MS exacerbation. The genesis of fatigue in MS is not known with certainty. The development of this symptom is associated with impairments in neuroimmune responses and biochemical processes and with the administration of some drugs. Special tests and scales are used to objectify the degree of fatigue. The most commonly used questionnaires are the Fatigue Severity Scores to rate physical and mental fatigue, as well as the Modified Fatigue Impact Scale in patients having MS. When a patient with MS complains about fatigue, it is necessary to rule out its other possible causes and to specify its relation to MS and the necessity of fatigue correction. Аmantadine is one of the drugs used for the symptomatic therapy of MS. This paper presents the data of randomized clinical trials evaluating the efficacy and safety of this drug for the symptomatic treatment of MS. Correction of MS-related fatigue requires a multidisciplinary approach that involves a combination of drug therapy, therapeutic exercises, active lifestyle, and relatives' understanding

Monoclonal antibodies in the treatment of multiple sclerosis: from clinical research to practical application

Multiple sclerosis (MS) is a chronic autoimmune inflammatory demyelinating and neurodegenerative disease with a multifactorial etiology of development. MS in most cases has a wave-like course (periods of exacerbations and remissions), over time, the disease becomes progressive, which worsens the quality of life of patients. The drugs disease-modifying therapies (DMT) has been actively used in clinical practice for more than 30 years to prevent exacerbations and progression of MS. In patients with MS, in which the disease occurs with frequent exacerbations and signs of radiological activity of the demyelinating process, according to magnetic resonance imaging (MRI) of the brain and spinal cord, it is recommended to use monoclonal antibody preparations. The only drug registered for the treatment of primary progressive MS is ocrelizumab. In addition, ocrelizumab is indicated for patients with remitting and secondary progressive MS. Ocrelizumab is a humanized monoclonal antibody that selectively depletes a population of CD20+ B cells. The article presents data from clinical studies of OPERA I and OPERA II and describes a clinical case from the practice of a neurologist. Depletion of the B cell population is achieved by several mechanisms, including antibody-dependent cell-mediated phagocytosis, antibody-dependent T cell-mediated cytotoxicity, complement-dependent cytotoxicity, and apoptosis induction. The issues of efficacy and safety of ocrelizumab therapy in patients with MS are considered

Use of monoclonal antibodies in patients with multiple sclerosis in the practice of a neurologist

Multiple sclerosis (MS) ranks first for prevalence among diseases affecting the CNS white matter with 2.5 million cases estimated globally. InRussia, the number of cases is about 200 thousand. MS in most cases has a wavy course (periods of exacerbations and remissions), over time the progression of disease worses the quality of life of patients. The “gold standard” at the beginning of MS is first-line drugs disease-modifying therapies (DMT). If they are ineffective, it is necessary to strengthen the effect on the immune processes and the patient is prescribed second-line drugs (escalation of therapy). There is a method of induction therapy, when high activity of MS is recommended to start with drugs that have a strong immunosuppressive effect with a possible subsequent transition to soft supportive treatment. In patients with frequent exacerbations and signs of radiological activity of the disease, according to magnetic resonance imaging (MRI) of the brain and spinal cord, monoclonal antibody preparations are effectively used. Except of escalation and induction, it is also used the method of immune system reconstruction, which leads to a decrease in autoagression in MS. This article discusses a clinical case of using a drug of monoclonal antibodies that selectively bind to CD 52 on the surface of lymphocytes. The issues of efficacy and safety of alemtuzumab therapy in patients with MS are considered

Relevance of first-line drugs for treatment of multiple sclerosis in present-day conditions

Multiple sclerosis (MS) is a chronic demyelinating disease of young employable people. Demyelination develops as a result of the autoimmune mechanisms of the damage to nerve fibers, while the neurodegenerative changes in the brain matter begin from the first days of the disease. MS in most cases has a wavy course (periods of exacerbations and remissions), over time the progression of disease worses the quality of life of patients. Usually, there are remitting, secondary progressive, and primary progressive MS. The «gold standard» of treatment after the diagnosis of MS is first-line drugs disease-modifying therapies (DMT) of the first line -glatiramer acetate and в—interferons. These drugs have been used for more than 20 years and have proven their effectiveness, safety and good tolerability in long-term continuous observational clinical studies. It is important to note that therapy should be started as early as possible, from the moment of diagnosis, since in most patients, even with a stable clinical picture and no symptoms, the disease progresses. Over time, this can lead to persistent, irreversible neurological deficits and disability. The use of active immune -modulating drugs requires constant monitoring of the patient’s condition by qualified neurologists. This article presents the results of clinical trials of Timexon® (glatiramer acetate) and Teberif ® (interferon beta- 1а) in patients with remitting multiple sclerosis and discusses the issues of prescribing first-line drugs, switching from one therapy to another within the first-line, monitoring the effectiveness and safety of treatment

Glatiramer acetate 40 mg/ml: A review of the results of GALA and GLACIER clinical studies

Multiple sclerosis (MS) is a demyelinating disease of the CNS, which affects mainly young able-bodied people; in this connection the problem of MS treatment assumes particular relevance. The paper reviews the main GALA (Glatiramer Acetate Low-frequency Administration) and GLACIER (Glatiramer Acetate low frequenCy safety and patient ExpeRience) clinical studies of subcutaneous glatiramer acetate (GA) 40 mg/ml three times per week (TIW).The results of the Phase III GALA multicenter randomized placebo-controlled parallel-group study of GA 40 mg injections administered less frequently (TIW) were published in 2013. The study involved 142 centers from 17 countries, including 17 Russian centers. The GALA study proved the efficacy, safety, and good tolerability of GA 40 mg TIW in patients with relapsing-remitting MS (RRMS). The safety profile of GA 40 mg was completely consistent with the well-known profile of GA 20 mg.The new GLACIER study was initiated to evaluate the efficiency and tolerability of treatment with GA 40 mg TIW versus GA 20 mg every day. This study confirmed that the tolerability profile of therapy with GA 40 mg TIW was better than that of GA 20 mg every day in patients with RRMS. GA 40 mg/ml TIW was approved for use in the USA, the United Kingdom, and a number of European countries for the treatment of patients with RRMS. In the Russian Federation, GA 40 mg was approved for use in September 2015

New drugs for anti-B-cell therapy of multiple sclerosis

The review presents the data characterizing the mechanism of action of anti-B-cell therapy for multiple sclerosis (MS) and the results of clinical trials of ocrelizumab, the first drug of this group, which has been approved for use in MS. Multicenter randomized controlled studies have shown that this drug is effective in treating both MS with exacerbations and primary progressive MS. Currently ocrelizumab is the only drug that can be used as a pathogenetic treatment for this MS course type

Experience with anti-B-cell therapy in the pathogenetic treatment of multiple sclerosis

One of the promising areas in the pathogenetic treatment of multiple sclerosis (MS) is anti-B-cell therapy using ocrelizumab, an anti-CD20 monoclonal antibody. The drug is indicated for primary progressive MS (PPMS), secondary progressive MS (SPMS) and exacerbations, and highly active MS.Objective: to analyze the use of the drug in 32 patients with different types of MS in everyday neurological practice.Patients and methods. The investigation included 32 patients diagnosed with MS using the 2017 McDonald criteria: 12 patients with PPMS, 12 with highly active MS and 8 with SPMS and exacerbations. The median Expanded Disability Status Scale (EDSS) score was 4.0; the most severe course of the disease was observed in patients with SPMS. All the patients received a treatment cycle of 600-mg intravenous ocrelizumab injections (with an infusion pump) every 6 months; the initial dose was by 300 mg every 2 weeks. The follow-up period was 6 to 18 months.Results and discussion. During ocrelizumab therapy, the patients with PPMS showed stabilization of EDSS score; and 6 (50%) had even its slight decrease by 0.5–1.0 scores, which may be caused by compensation for the existing symptoms due to pathogenetic treatment. In highly active MS, only 1 of the 12 ocrelizumab-treated patients had an ongoing exacerbation of the disease. During a subsequent 6–18-month follow-up, magnetic resonance imaging revealed that none of the patients had manifestations of MS activity; the EDSS score decreased in all the patients, indicating their achievement of stable remission. Six (75%) of the 8 patients with SPMS and exacerbations also displayed a decrease in EDSS score in the absence of exacerbations. No adverse events, including infusion reactions, were recorded during drug administration. The drug has a good tolerance and safety profile and ease-to-use.Conclusion. Ocrelizumab therapy with will be able to improve the quality of treatment in patients with different types of MS, which is of great medical and social importanc