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1.
Artigo em Russo | MEDLINE | ID: mdl-38676683

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of the anti-CD20 monoclonal antibody divozilimab (DIV) used as an intravenous infusion at a dose of 500 mg every 24 weeks during 100 weeks for the treatment of patients with multiple sclerosis (MS), including relapsing-remitting multiple sclerosis (RRMS) and secondary progressive MS (SPMS) with relapses. MATERIAL AND METHODS: The multicenter, randomized, double-blind and double-masked phase III clinical trial (CT) BCD-132-4/MIRANTIBUS (NCT05385744) included 338 adult patients with MS distributed in a 1:1 ratio into two groups: DIV 500 mg and teriflunomide (TRF) 14 mg. After screening, subjects were included in the main CT period, which consisted of two cycles of therapy over 48 weeks, then entered an additional period from weeks 49 to 100, which included three cycles of therapy. The efficacy was assessed based on the results of brain MRI and registration of data on relapses. RESULTS: 308 subjects completed 5 therapy cycles according to the study protocol. An analysis of the effectiveness of DIV therapy over 2 years showed a persistent suppression of MRI and clinical activity of the disease in comparison with TRF, which was confirmed by all the studied MRI indicators (including CUA; total number of gadolinium-enhancing (GdE) lesions on T1-weighted scans ; number of new or enlarged lesions on T2-weighted scans; lesions volume change on T2-weighted scans; change in the volume of hypointense lesions on T1-weighted scans). The use of DIV was associated with a statistically significant decrease in ARR compared to TRF (p=0.0001). The ARR in the DIV group was 0.057, in the TRF group - 0.164 with 95% confidential interval for the frequency ratio [0.202; 0.593]. The incidence of GdE lesions on T1-weighted scans in the DIV group was significantly lower than in the TRF group. The average number of such lesions was 0.0±0.08 and 1.0±4.46 in the DIV and TRF groups, respectively (p<0.0001). Progression of EDSS was detected in 18 (10.7%) and 36 (21.3%) patients in the DIV and TRF groups, respectively (p=0.0075). The proportion of patients with relapses was 11.2% (n=19) in the DIV group and 23.1% (n=39) in the TRF group (p=0.0039). In the subpopulation of patients with SPMS, no cases of increase in EDSS were detected, and not a single case of exacerbation was recorded over 2 years of using DIV. Also, DIV has shown a favorable safety profile. Among the adverse reactions (AR), infusion reactions and laboratory abnormalities, such as a decrease in the number of leukocytes, neutrophils, and lymphocytes, were most often recorded. Identified AR were expected, had mild to moderate severity, and resolved without any negative consequences. CONCLUSION: The results of the BCD-132-4/MIRANTIBUS CT indicate a high sustained efficacy and safety of long-term use of DIV in comparison with TRF during 2 years of therapy.


Assuntos
Esclerose Múltipla Recidivante-Remitente , Nitrilas , Humanos , Masculino , Feminino , Método Duplo-Cego , Adulto , Resultado do Tratamento , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla/tratamento farmacológico , Imageamento por Ressonância Magnética , Crotonatos/uso terapêutico , Crotonatos/efeitos adversos , Hidroxibutiratos , Toluidinas/uso terapêutico , Toluidinas/efeitos adversos
2.
Artigo em Russo | MEDLINE | ID: mdl-38529866

RESUMO

OBJECTIVE: To evaluate the effectiveness of telerehabilitation (TELEREBT) of patients with multiple sclerosis (MS) in the context of the coronavirus pandemic 2020-2021. MATERIAL AND METHODS: The study included 37 patients with MS who underwent a course of teleRBT. The course included 10 classes of 60 minutes for 10 days with a two-day break. Various questionnaires and scales were used to assess the effectiveness, as well as an assessment of the neurological status. RESULTS: 19 patients refused to participate in the program. The level of disability on the EDSS scale decreased from 4.86±1.19 at the initial level to 4.73±1.12 after the course of teleRBT, while no statistically significant changes were found. CONCLUSION: TeleRPT in patients can be an effective way to correct existing disorders. Further research is required to establish the effectiveness of teleRBT.


Assuntos
COVID-19 , Esclerose Múltipla , Telerreabilitação , Humanos , Esclerose Múltipla/reabilitação , Pandemias , Avaliação da Deficiência
3.
Zh Nevrol Psikhiatr Im S S Korsakova ; 123(10): 123-128, 2023.
Artigo em Russo | MEDLINE | ID: mdl-37966451

RESUMO

Multiple sclerosis (MS) is a chronic autoimmune progressive demyelinating disease of the central nervous system, mainly in young people. The clinical picture of MS has a variety of neurological symptoms, which manifests itself during periods of exacerbation or progression and stabilizes at the moments of remission. The widespread introduction of new drugs with immunosuppressive and immunomodulatory mechanisms of action has led to the development of special risk management plans for monitoring patients during therapy and preventing adverse events and new comorbid conditions. This article presents a review of the literature and a case report on the combination of MS and melanoma in patients. Melanoma can rarely develop in patients treated with DMD, so it is necessary to introduce such a specialist in dermatology and venereology into a multidisciplinary team.


Assuntos
Melanoma , Esclerose Múltipla , Humanos , Adolescente , Esclerose Múltipla/complicações , Esclerose Múltipla/tratamento farmacológico , Melanoma/induzido quimicamente , Melanoma/tratamento farmacológico , Imunossupressores/uso terapêutico
4.
Artigo em Russo | MEDLINE | ID: mdl-37994888

RESUMO

Demyelinating disease of the central nervous system associated with antibodies to myelin oligodendrocyte glycoprotein (MOGAD) has been proposed to be distinguished from neuromyelitis optica spectrum disorders (NMOSD) into a separate nosological form. The basis for the recognition of nosological independence was the presence of clinical features of this disease and the detection of a specific biomarker in the blood serum of patients - IgG class antibodies to MOG. The article summarizes the current data on the clinical and radiological phenotypes of MOGAD in children and adults and the features of the course of the disease. The requirements for the laboratory diagnosis of the disease and diagnostic criteria for MOGAD proposed by an international group of experts in 2023 are given.


Assuntos
Sistema Nervoso Central , Neuromielite Óptica , Adulto , Criança , Humanos , Glicoproteína Mielina-Oligodendrócito , Imunoglobulina G , Neuromielite Óptica/diagnóstico por imagem , Fenótipo
5.
Artigo em Russo | MEDLINE | ID: mdl-37796063

RESUMO

Multiple sclerosis (MS) is a common neurological disease among young people of working age, which tends to increase the number of cases registered in the world and in the Russian Federation. However, with improved diagnostics and the emergence of new drugs that change the course of MS (disease-modifying therapy), people's life expectancy increases and the percentage of patients in the older age group increases as well. In this article, we consider the possibility of developing MS among people over 50 years of age, features of the course, diagnosis and treatment.


Assuntos
Esclerose Múltipla , Humanos , Pessoa de Meia-Idade , Idoso , Adolescente , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/terapia , Expectativa de Vida , Federação Russa/epidemiologia
6.
Artigo em Russo | MEDLINE | ID: mdl-37796071

RESUMO

OBJECTIVE: To evaluate the severity and frequency of infusion reactions (IR) in patients with highly active relapsing-remitting multiple sclerosis (MS) In Russian population receiving alemtuzumab therapy. MATERIAL AND METHODS: In retrospective study, we analyzed data from 50 patients with highly active relapsing-remitting multiple sclerosis (MS) from six Regional MS Centers in the Russian Federation who received two courses of alemtuzumab between 2018 and 2022. RESULTS: Among all IRs, the most frequently reported were hives-like rashes, which were registered in 27 people, mostly of mild severity (70.6%). Headaches were the second most common IR, observed in 17 patients (34%). When comparing the group of patients who underwent music therapy (MT) with those who received alemtuzumab therapy without MT, no statistically significant difference was found in the frequency and severity of IRs. CONCLUSION: All patients experienced IRs of varying degrees of severity. A decrease in the score on the EDSS disability scale was noted. MT did not affect the occurrence or severity of IRs.


Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Alemtuzumab/efeitos adversos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Estudos Retrospectivos , Federação Russa
7.
Artigo em Russo | MEDLINE | ID: mdl-37796076

RESUMO

The coexistence of optic neuritis and Guillain-Barré syndrome is a rare combination of neurological diseases. The trigger of an autoimmune inflammatory process is often a respiratory mycoplasma infection. Ignorance of such combination can lead to diagnostic and therapy mistakes. This article describes the case of a rare combination of overlapping optic neuritis and Guillain-Barré syndrome, associated with Mycoplasma pneumoniae and provides the short literature review. Further studies are required to identify common pathogenetic mechanisms of combined inflammatory lesions of the optic nerves and peripheral nervous system.


Assuntos
Síndrome de Guillain-Barré , Neurite Óptica , Humanos , Síndrome de Guillain-Barré/complicações , Síndrome de Guillain-Barré/diagnóstico , Mycoplasma pneumoniae , Nervo Óptico , Neurite Óptica/diagnóstico , Neurite Óptica/tratamento farmacológico , Neurite Óptica/etiologia
8.
Mol Biol (Mosk) ; 57(5): 819-826, 2023.
Artigo em Russo | MEDLINE | ID: mdl-37752647

RESUMO

Multiple sclerosis (MS) is a chronic autoimmune inflammatory and neurodegenerative disease of the central nervous system, which is characterized by significant clinical heterogeneity. Primary progressive MS (PPMS) develops in 10-15% of patients. Unlike the most common relapsing-remitting form of MS, PPMS involves steady progress of neurodegeneration and, as a consequence, a persistent gradual increase in neurological symptoms. The peculiarities of epigenetic regulation of gene expression may be one of the reasons for the differences in the pathogenesis of the two MS forms. DNA methylation is one of the key epigenetic mechanisms, which remains almost unexplored in different cell populations of PPMS patients. The goal of this work was to identify differential methylation profiles of the CpG sites in the CD14+ monocyte DNA, which characterize PPMS. A genome-wide analysis of DNA methylation in PPMS patients and healthy individuals has identified 169 differentially methylated positions (DMPs), 90.5% of which were hypermethylated in PPMS patients. More than half of all DMPs are located in/near known genes and within CpG islands and their neighboring regions, which indicates their high functional significance. We have found six differentially methylated regions (DMRs) in the OR2L13, CAT, LCLAT1, HOXA5, RNF39, and CRTAC1 genes involved in inflammation and neurodegeneration, which indicates active epigenetic regulation of their expression.


Assuntos
Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Doenças Neurodegenerativas , Humanos , Esclerose Múltipla/genética , Esclerose Múltipla Crônica Progressiva/genética , Esclerose Múltipla Recidivante-Remitente/genética , Epigênese Genética , Metilação de DNA , Monócitos , Doenças Neurodegenerativas/genética , Proteínas de Ligação ao Cálcio/genética
9.
Zh Nevrol Psikhiatr Im S S Korsakova ; 123(7. Vyp. 2): 8-14, 2023.
Artigo em Russo | MEDLINE | ID: mdl-37560828

RESUMO

The review presents current data on the use of positron emission tomography and single-photon emission computed tomography in multiple sclerosis (MS) to assess the activity of the pathological process, including neuroinflammation, demyelination, activation of microglia, neurodegeneration and local blood flow disorders. These methodologies are a new approach for studying the mechanisms of action and evaluating the clinical effect of disease modifying therapy of MS, especially those capable of penetrating into brain tissue. Among them, the most attention is attracted by cladribine tablets acting on the mechanism of immune reconstitution therapy, most likely with the modulation of immune reactions directly in the brain tissue.


Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Esclerose Múltipla/tratamento farmacológico , Doenças Neuroinflamatórias , Cladribina/uso terapêutico , Neuroimagem , Encéfalo/diagnóstico por imagem , Comprimidos/uso terapêutico , Imunossupressores/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico
10.
Zh Nevrol Psikhiatr Im S S Korsakova ; 123(7. Vyp. 2): 43-52, 2023.
Artigo em Russo | MEDLINE | ID: mdl-37560833

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of the anti-CD20 monoclonal antibody divozilimab (DIV) used as an intravenous infusion at a dose of 500 mg for the treatment of patients with relapsing-remitting multiple sclerosis (RRMS) in comparison with the teriflunomide (TRF). The study of the efficacy and safety of the use of the drug DIV was carried out for 48 weeks of therapy. MATERIAL AND METHODS: The multicenter, randomized, double-blind and double-masked phase III clinical trial (CT) BCD-132-4/MIRANTIBUS included 338 adult patients with RRMS distributed in a 1:1 ratio into two groups: DIV 500 mg and TRF 14 mg. After screening, subjects were included in the main CT period, which consisted of two cycles of therapy over 48 weeks. The primary end point was «Mean annualized relapse rate 48 weeks after the last patient is randomized in the study¼. RESULTS: 321 subjects completed 48 weeks of therapy according to the study protocol. The analysis of the of efficacy data for the primary endpoint successively proved the hypothesis of superiority of the test drug DIV at a dose of 500 mg over the reference drug TRF. A rapid suppression of acute disease activity according to the brain MRI and clinical manifestations of the disease was shown after the first infusion of DIV in patients with RRMS. Thus, after 48 weeks of therapy in patients treated with DIV, there were no T1 gadolinium-enhancing lesions, while in the TRF group such lesions were observed in 20.7% (35/169) of subjects. Evaluation of the CUA per scan showed that the mean values for the estimated period were statistically significantly lower in the DIV drug group compared to the TRF group: the ratio of the adjusted per scan rates (DIV/TRF) was 0.125 [95% CI: 0.089; 0.177]. Over the 48 weeks of therapy, the proportion of subjects with relapses was 9.5% (n=16/169) in the DIV group and 19.5% (33/169) in the TRF group (p=0.0086). DIV has shown a favorable safety profile. Among the adverse reactions (AR), infusion reactions and deviations of laboratory data, such as a decrease in the number of leukocytes, neutrophils, and lymphocytes, were most often recorded. Identified AR were expected, had mild to moderate severity, and resolved without any negative consequences. CONCLUSION: The results of the clinical study indicate the high efficacy and safety of DIV in comparison with TRF.


Assuntos
Antineoplásicos , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Adulto , Humanos , Esclerose Múltipla/tratamento farmacológico , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Método Duplo-Cego , Resultado do Tratamento
11.
Zh Nevrol Psikhiatr Im S S Korsakova ; 123(7. Vyp. 2): 60-64, 2023.
Artigo em Russo | MEDLINE | ID: mdl-37560835

RESUMO

OBJECTIVE: To study the whole-genome DNA methylation profiles of peripheral blood mononuclear blood cells (PBMCs) of patients with relapsing-remitting multiple sclerosis (RRMS) in remission and relapse in order to assess the contribution of this epigenetic mechanism of gene expression regulation to the activity of the pathological process. MATERIAL AND METHODS: Eight patients with RRMS in remission and 6 patients in relapse were included in the study. Methylation levels of DNA CpG sites in PBMCs were analyzed using Infinium HumanMethylation450 BeadChip DNA microarrays. RESULTS: Seven differentially methylated positions (DMPs) were identified, of which 3 were hypermethylated (cg02981003, cg18486102, cg19533582) and 4 were hypomethylated (cg16814680, cg1964802, cg18584440, cg08291996) during RRMS relapse. Five DMPs are located in protein-coding genes (GPR123, FAIM2, BTNL2, ZNF8, ASAP2), one in microRNA gene (MIR548N), and one in an intergenic region. For all identified DMPs, we observed a change in DNA methylation levels of more than 20% (range 20.2-57.5%). Hierarchical clustering of DNA samples on the heatmap shows their clear aggregation into separate clusters corresponding to RRMS patients in the stages of relapse and remission. CONCLUSION: For the first time it was shown that during relapse and remission of RRMS there are differences in the DNA methylation profile that allow discrimination between these clinical stages. These data indicate the involvement of the epigenetic mechanism of DNA methylation in the activation of the pathological process in RRMS.


Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Esclerose Múltipla/genética , Metilação de DNA , Leucócitos Mononucleares/patologia , Esclerose Múltipla Recidivante-Remitente/genética , Doença Crônica , DNA , Recidiva , Butirofilinas/genética , Proteínas Ativadoras de GTPase/genética , Fatores de Transcrição Kruppel-Like/genética
12.
Zh Nevrol Psikhiatr Im S S Korsakova ; 123(7. Vyp. 2): 65-71, 2023.
Artigo em Russo | MEDLINE | ID: mdl-37560836

RESUMO

OBJECTIVE: To study the effect of fluoxetine on Th17- and Th1-immune response, which plays an important role in the pathogenesis of multiple sclerosis (MS). MATERIAL AND METHODS: Ten patients with relapsing-remitting MS and ten healthy subjects were examined. The functions of Th17- and Th1-immune responses were assessed by the production of cytokines interleukin-17 (IL-17) and interferon-gamma (IFN-γ) by CD4+ T cells stimulated with macrophages or microbeads coated with anti-CD3 and anti-CD28-antibodies. To assess the effect of fluoxetine on the macrophages-induced Th17- and Th1-immune response, macrophages were pre-incubated in the presence of fluoxetine and co-cultured with autologous CD4+ T-cells. In the case of stimulation of CD4+ T-cells with anti-CD3/CD28-microbeads, fluoxetine was added directly to the T-helper cells before adding of microbeads. In addition, we evaluated the effect of fluoxetine on the production of the factors of differentiation of Th17-cells cytokines IL-6 and IL-1ß by macrophages. The levels of cytokines in the cell culture supernatants were measured by ELISA. RESULTS: The production of IL-17 and IFN-γ by CD4+ T-cells stimulated with macrophages or anti-CD3/CD28-microbeads was comparable between the groups. Fluoxetine suppressed the production of IL-17 and IFN-γ by anti-CD/CD28-stimulated CD4+ T-cells in both groups. Fluoxetine also suppressed the production of IL-6 and IL-1ß by macrophages as well as their ability to induce IL-17 and IFN-γ production by CD4+ T-cells in both groups. CONCLUSIONS: Fluoxetine may have an anti-inflammatory effect in MS that could be mediated by suppression of Th17- and Th1-cells or macrophage-induced Th17- and Th1-immune response.


Assuntos
Esclerose Múltipla , Humanos , Esclerose Múltipla/tratamento farmacológico , Interleucina-17 , Fluoxetina/farmacologia , Fluoxetina/uso terapêutico , Interleucina-6 , Neuroimunomodulação , Células Th1 , Citocinas , Interferon gama
13.
Zh Nevrol Psikhiatr Im S S Korsakova ; 123(7. Vyp. 2): 84-87, 2023.
Artigo em Russo | MEDLINE | ID: mdl-37560839

RESUMO

OBJECTIVE: To measure the knee range of motion (ROM) in the sagittal plane by video analysis in patients with multiple sclerosis (MS) after a course of medical rehabilitation and determine the minimal clinically important differences (MCID). MATERIAL AND METHODS: We examined 45 patients (37 women, 8 men) with relapsing-remitting (n=38) and secondary-progressive MS before and after a course of medical rehabilitation. Gait parameters were recorded on video analysis system Physiomed Smart («Physiomed¼, Germany, the Davis protocol). RESULTS: The course of complex medical rehabilitation contributes to an increase knee ROM in MS patients in a wide range of disability (EDSS <6.5 points). MCID is estimated as 7.14° in mild (EDSS ≤4.0) and as 7.67° in moderate (EDSS=4.5-5.5) gait impairment. CONCLUSION: The results will assist clinicians and researchers in interpreting the significance of observed kinematic changes in the knee joint in MS patients after medical intervention.


Assuntos
Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Masculino , Humanos , Feminino , Articulação do Joelho , Marcha , Amplitude de Movimento Articular
14.
Zh Nevrol Psikhiatr Im S S Korsakova ; 123(7. Vyp. 2): 96-102, 2023.
Artigo em Russo | MEDLINE | ID: mdl-37560841

RESUMO

OBJECTIVE: To assess the level of microbiota markers in the blood and cerebrospinal fluid (CSF) of patients with different types of multiple sclerosis (MS), people with radiologically isolated syndrome (RIS) and control subjects. MATERIAL AND METHODS: We used gas chromatography-mass spectrometry (GC-MS) to evaluate the levels of microbiota markers in 69 patients with different types of MS (27 patients in the acute stage, 35 patients with MS in remission, 7 patients with primary-progressive MS), 10 people with RIS, and 47 control subjects (different diseases of the nervous system of a non-autoimmune or inflammatory nature). RESULTS: We showed a statistically significant increase in the content of various microbiota markers in the CSF of patients with MS compared with the control group. We found no change in the content of these markers in blood of patients with MS. This suggests a change of markers of microbial load at the level of the central nervous system, but not at the level of the whole organism. The greatest number of statistically significant differences with the control group was found in the content of markers in CSF of patients with MS in remission. In the acute stage, on the contrary, we found no statistically significant differences compared to the control group. In particular, in CSF of patients with MS in remission, a statistically significant increase in the content of bacterial plasmalogen (4.5 times), and increase in the level of microbial markers specific to Peptostreptococcus anaerobius, Pseudomonas aeruginosa, Eubacterium, Bifidobacterium, Butirivibrio, Moraxella, Acinetobacter, Propionibacterium acnes, as well as an increase of markers of the Epstein-Barr virus were found. In addition, there was an increase of campesterol, the likely source of which is campesterol-producing microfungi. In the CSF of subjects with RIS there were a statistically significant increase in the level of markers of the Epstein-Barr virus, Propionibacterium acnes, as well as Pseudomonas, Moraxella, and Acinetobacter. CONCLUSION: An association of MS with polymicrobial infection is possible. It is also likely that there is a certain pattern of increase of microbiota markers in the CSF of patients with MS, but not in blood.


Assuntos
Infecções por Vírus Epstein-Barr , Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla , Humanos , Herpesvirus Humano 4 , Sistema Nervoso Central
15.
Zh Nevrol Psikhiatr Im S S Korsakova ; 123(7. Vyp. 2): 133-135, 2023.
Artigo em Russo | MEDLINE | ID: mdl-37560845

RESUMO

The article discusses the possibility and expediency of validating translations into Russian of objective and subjective neurological scales, the advantages and disadvantages of such translations, which is extremely relevant at the present time. As an example, the expediency of «validating¼ the translation into Russian of the objective neurological scale for assessing the severity of symptoms of the Expanded Disability Status Scale, which is widely used in patients with multiple sclerosis is discussed. The results of assessing the severity of neurological disorders according to these neurological scales do not depend on translation into other languages and therefore do not need validation.


Assuntos
Esclerose Múltipla , Humanos , Síndrome , Inquéritos e Questionários , Esclerose Múltipla/diagnóstico , Idioma , Federação Russa , Avaliação da Deficiência
16.
Artigo em Russo | MEDLINE | ID: mdl-37084363

RESUMO

OBJECTIVE: To find the optimal therapeutic dose of the anti-B cell mAb divozilimab (DIV) based on the efficacy and safety data of intravenous administration at a dose of 125 mg or 500 mg in patients with relapsing remitting multiple sclerosis (RRMS) compared to placebo (PBO) and teriflunomide (TRF). To study the efficacy and safety of DIV within 24 weeks of treatment. MATERIAL AND METHODS: A multicenter, randomized, double-blind and double-masked, placebo-controlled phase 2 clinical trial (CT) BCD-132-2 involved 271 adult patients with RRMS from 25 centres In Russia. Patients were randomly assigned (2:2:2:1) into 4 groups: TRF, DIV 125 mg, DIV 500 mg and PBO. After screening patients entered to the main period, which consisted of one cycle of therapy for 24 weeks. The primary endpoint was the total number of gadolinium-enhancing T1 lesions (Gd+) observed on brain MRI scans after 24 weeks (per scan - involves estimating the mean value of the score from all the MRI assessments performed for each participant in the study). RESULTS: 263 patients completed 24 weeks of treatment. Most of the patients in the DIV groups had no lesions on T1-weighted MRI after 24 weeks of treatment (94.44% on 125 mg and 93.06% on 500 mg). In the TRF and PBO groups the values were significantly lower: 68.06% and 56.36% respectively (both p<0.05). The proportions of relapse-free patients in the DIV groups were 93.06% and 97.22% (125 mg and 500 mg, respectively). As expected, DIV reduced the CD19+ B-cells. However, the repopulation rate of CD19+ B-cells in the 125 mg group was more pronounced (mainly due to the recovering pool of CD27-naive B-cells) compared to the 500 mg group. DIV showed a favorable safety profile at both doses. CONCLUSION: Thus, the assessment of 24 weeks treatment demonstrated that DIV is a highly effective, safe and convenient option for the treatment of RRMS patients, both naive and previously treated with disease modifying therapy. A dose of 500 mg is recommended for further efficacy and safety evaluation during phase 3 CT.


Assuntos
Antineoplásicos , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Adulto , Humanos , Esclerose Múltipla/tratamento farmacológico , Anticorpos Monoclonais , Antineoplásicos/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Infusões Intravenosas , Método Duplo-Cego , Imageamento por Ressonância Magnética , Resultado do Tratamento
17.
Artigo em Russo | MEDLINE | ID: mdl-36843459

RESUMO

OBJECTIVE: To assess the efficacy and safety of sampeginterferon-ß1a (samPEG-IFN-ß1a) 180 µg and 240 µg administered once every 2 weeks compared to placebo and low dose interferon beta-1a (LIB) 30 µg administered once weekly. MATERIAL AND METHODS: Patients with relapsing-remitting multiple sclerosis aged 18-60 years, with Expanded Disability Status Scale score ≤5.5 were randomized at a ratio of 2:2:2:1 to the following groups: samPEG-IFN-ß1a 180 µg, samPEG-IFN-ß1a 240 µg, LIB, placebo. After 20 weeks, the placebo group completed the study. After week 52, the final analysis was performed, which included the primary endpoint analysis, the LIB group patients completed their participation in the study. The patients in samPEG-IFN-ß1a groups continued to receive therapy with samPEG-IFN-ß1a 240 µg until week 100 inclusive. The results of the final analysis after 52 weeks have been previously published. The current article presents a long-term efficacy and safety of samPEG-IFN-ß1a after 104 weeks of the trial. RESULTS: The annualized relapse rate over the second year was 0.16 in the samPEG-IFN-ß1a 180 µg group and 0.09 in the samPEG-IFN-ß1a 240 µg group. By week 104, the proportion of relapse-free patients was 77.0% (87/113) and 83.3% (95/114) in the samPEG-IFN-ß1a 180 µg and 240 µg groups, respectively. There were no negative dynamics of MRI markers, neurological deficit parameters and cognitive functions by scales and tests. The safety profile of samPEG-IFN-ß1a was consistent with the known safety profile of IFN-ß therapy. CONCLUSION: Treatment with samPEG-IFN-ß1a is an effective and safe first-line therapy for relapsing-remitting multiple sclerosis patients.


Assuntos
Interferon beta-1a , Esclerose Múltipla Recidivante-Remitente , Humanos , Método Duplo-Cego , Interferon beta-1a/administração & dosagem , Interferon beta-1a/efeitos adversos , Interferon beta-1a/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Recidiva , Resultado do Tratamento , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade
18.
Klin Lab Diagn ; 67(10): 600-606, 2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36315176

RESUMO

The relationship between multiple sclerosis and the state of the human microbiome was studied, namely, the change in the representation of microbiota phylotypes, the proportion of coccal flora, the proportion of anaerobic, gram-negative, proteolytically active microflora, as well as the concentration of markers of bacterial plasmalogen and endotoxin in the blood. Microbiome studies were carried out by gas chromatography - mass spectrometry of microbial markers in the blood. A statistically significant increase in blood concentrations of the total level of microbial markers of bacterial plasmalogen and endotoxin was determined in multiple sclerosis, which may be associated with an increase in the permeability of the intestinal wall. In multiple sclerosis, the proportion of coccal, gram-negative, anaerobic microflora with a proteolytic type of metabolic activity increases. The correlations of the representation of microbiota phylotypes change due to the switching of the direct relationship Proteobacteria-Bacteroides to Proteobacteria-Firmicutes. In multiple sclerosis, Actinobacteria and Proteobacteria increase and Firmicutes decrease. Conclusion. The multiple sclerosis disease may be associated with pathological changes in the structure of the microbiome and the growth of endotoxemia, which may be one of the factors in the pathogenesis of the disease. New laboratory markers for diagnosing and predicting the course of MS have been proposed.


Assuntos
Microbiota , Esclerose Múltipla , Humanos , Plasmalogênios , Bactérias/genética , Endotoxinas/análise , Biomarcadores
19.
Zh Nevrol Psikhiatr Im S S Korsakova ; 122(7. Vyp. 2): 14-18, 2022.
Artigo em Russo | MEDLINE | ID: mdl-35912551

RESUMO

The most common and important consequence of multiple sclerosis (MS) is impaired walking, which limits daily activities and increases the risk of falling. This article provides an overview of the main non-pharmacological methods of medical rehabilitation of gait disorders in people with MS (aerobic and strength training, robotic technologies, orthotics and functional electrical stimulation), which have an evidence base on systematic reviews and meta-analyses. Special attention is paid to the approach to rehabilitation in people with severe disabilities. Methods for determining gait parameters using tests and high-tech devices are considered, which serve as the basis for the routine assessment of the domains of the International Classification of Functioning (ICF) and the effectiveness of interventions.


Assuntos
Transtornos Neurológicos da Marcha , Transtornos dos Movimentos , Esclerose Múltipla , Marcha , Transtornos Neurológicos da Marcha/etiologia , Humanos , Caminhada/fisiologia
20.
Zh Nevrol Psikhiatr Im S S Korsakova ; 122(7. Vyp. 2): 19-26, 2022.
Artigo em Russo | MEDLINE | ID: mdl-35912552

RESUMO

This article reviews the literature concerning the possibility of using magnetic resonance imaging (MRI) with different field strengths to detect the central vein sign (CVS). CVS is a relatively new and promising symptom of multiple sclerosis (MS). This symptom is a parenchymal vein visualized with the help of special MRI modes, which is localized in the focus of demyelination. Studies show that CVS has a high sensitivity and specificity in the diagnosis of MS, allowing the differentiation from other demyelinating, vascular, systemic diseases. However, most studies in this direction have been done using different MR-sequences and on tomographs with different field strengths, so the purpose of this review is to summarize and compare the results of various studies, which may be of practical benefit to clinicians.


Assuntos
Imageamento por Ressonância Magnética , Esclerose Múltipla , Encéfalo/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia , Literatura de Revisão como Assunto , Veias
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