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The article provides an analysis of modern methods of treatment of secondary progressive multiple sclerosis (SPMS). The only drug that has proven its effectiveness in all types of SPMS (with exacerbations and without exacerbations) is siponimod. Clinical trials of this drug have proven its efficacy and safety in this type of MS. If the drug is included in the list of high-cost technologies, this modern method of treating SPMS can be made available to all patients who need it.

Siponimod (Kajendra) is a sphingosine-1-phosphate receptor modulator type 1 and 5 (S1P1,5), the first targeted agent for the treatment of patients with secondary progressive multiple sclerosis, both with and without exacerbations and/or activity according to magnetic resonance imaging. The drug was approved in Russia at the end of December 2020. The efficacy of siponimod was confirmed in EXPAND study, a large, randomized, double-blind phase III clinical study. This article presents three clinical cases of patients with secondary progressive multiple sclerosis from the practice of specialists of the Novosibirsk Center for Multiple Sclerosis and Other Autoimmune Diseases of the Nervous System with an analysis of patients selection for siponimod treatment and an assessment of the therapy effectiveness.

The process of neurodegeneration in multiple sclerosis (MS) remains an urgent problem of modern neurology; from the point of view of its therapy, it is especially important to identify this condition during the transition to secondary progression. This paper reflects the opinion of the Council of Leading MS Experts on the early detection of secondary progressive MS and its diagnostic tools, including the use of new online questionnaires. Special attention is paid to the concept of clinical progression verification using the indicator of the confirmed progression of disability and to the prospect for introducing siponimod (Kiendra® ) into clinical practice for the treatment of patients with secondary progressive MS.

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.

The meeting of experts discussed the clinical and pathophysiological features of secondary progressive multiple sclerosis (MS) (SPMS), clinical trials, and promising treatments for the progressive MS stage, as well as proposals contributing to the improvement of the current state of the problem of SPMS. In particular, the definition of and criteria for SPMS are formulated; the earliest period, when its confirmed progression can be recorded, is stated to be 3 months. The exacerbation-unaffected disability progression confirmed 6 months later may be considered to be more convincing. The introduction of tools for the early assessment of disability progression into routine practice will be able to identify the signs of progression at an earlier stage in order to timely change treatment policy. It is also noted that therapeutic possibilities in establishing secondary progression, especially in the absence of exacerbations, but in maintaining progression, are still insufficient. Certain hopes for slowing the progression in patients with SPMS are associated with the advent of siponimod, a new molecular class of S1P receptor modulators. The confirmed efficiency of siponimod in a large population of patients with SPMS allows the latter to be recommended for its treatment with both persistent disease activity (SPMS with exacerbations) and disability progression without exacerbations (SPMS without exacerbations).

Aim: To analyze the efficacy, safety and pharmacoeconomic aspects of using ocrelizumab in adult patients with relapsing/remitting multiple sclerosis (R/R MS).Materials and Methods. We used the commonly accepted PICo(S) questionnaire with the following specifics: the population – patients with R/R MS; the intervention – ocrelizumab; the comparators – all disease-modifying treatments for MS; the outcomes – the annualized relapse rate, confirmed disability progression, MRI results, quality-adjusted years of survival (QALYs), adverse events, and other clinical outcomes. The search for the relevant information was conducted in 2018 by using the embase, PubMed, Cochrane and eLibrary.ru databases and the «ocrelizumab» AND «multiple sclerosis» keywords. The levels of evidence and conclusiveness of the cited studies were also assessed.Results. Treatments with ocrelizumab resulted in a lower rate of disease progression as compared with interferon β -1a. As evidenced by a randomized clinical trial, the annualized relapse rate estimated after 96 weeks was lower with ocrelizumab than that with interferon β-1a (0.16 vs. 0.29, 47% decrease, p

Despite significant success in the treatment of multiple sclerosis achieved in the recent years, the issues of therapy for progressive forms of the disease are far from being resolved. The first medication with proven efficiency at SPMS is the oral selective sphingosine 1 phosphate (S1P) receptor modulator siponimod. Before the registration of siponimod in Russia, Novartis company organized a «Managed access program to enable siponimod in patients with secondary progressive multiple sclerosis without satisfactory alternative therapy». For the period from September 2020 to May 2021, 10 patients with SPMS with exacerbations were included in the programme by RAS. The results of the treatment of the patients under the programme were similar to the results of previously controlled studies. The medication was well tolerated and the expected side effects (mainly lymphopenia and Elevated transaminases) were not more severe than moderate and were stopped by temporary cancel of the current treatment or concomitant therapy. During 1 year of therapy, the stabilization of condition of all patients and positive dynamics was noticed, including a decrease in the EDSS score in 44% of patients. Despite the limited number of patients and time of observation, the safety and efficacy of siponimod in patients with SPMS are quite high. The use of the medication in routine clinical practice does not require extraordinary methods of observation and control, but nevertheless includes genetic examination before the prescription of therapy, regular monitoring of clinical blood and biochemical parameters.

Siponimod is a selective modulator of sphingosine-1-phosphate (S1P) receptors of types 1 and 5, registered in the Russian Federation for the treatment of patients with secondary progressive multiple sclerosis (SPMS), regardless of the presence or absence of exacerbations. The effectiveness of the drug in comparison with placebo was demonstrated in patients with SPMS in the international clinical trial EXPAND (phase III). This review devotes actual problems in the treatment of patients with SPMS, discusses the pathophysiology of multiple sclerosis progression, describes the peripheral and central mechanisms of siponimod action and its differences from fingolimod. According to analysis of scientific literature experimental, clinical and neuroimaging data are presented, which could explain the reasons for the successful use of siponimod in patients with SPMS, taking into account the pathophysiological mechanisms of the development of progression and the mechanisms of drug action.

Aim: To study the efficacy and safety of siponimod in patients with secondary progressive multiple sclerosis (SPMS) in the Russian population of the EXPAND study., Material and Methods: Ninety-four patients with SPMS from Russia were included in the analysis. Sixty-three patients received siponimod and 31 patients received placebo. The primary endpoint of the study was time to 3-month confirmed disability progression (3m-CDP) events, other clinical and radiological endpoints were also evaluated., Results: The siponimod group showed a 54% reduction in the risk of 3m-CDP compared with the placebo group (p=0.0334). Secondary endpoints also showed the advantage of the drug over placebo. In the siponimod group, mild adverse events associated with impaired liver function, as well as arterial hypertension, were more common. No patient left the study due to an adverse event., Conclusion: The use of siponimod in patients with SPMS in the Russian population reduced the risk of disability progression. Siponimod showed a favorable safety profile.