[Provision of alemtuzumab safety is one of the main components of pharmacovigilance]. / Obespechenie bezopasnosti terapii alemtuzumabom - odna iz glavnykh sostavliaiushchikh farmakonadzora.

Modern multiple sclerosis therapy with disease-modifying drugs is characterized by the risks of dangerous infectious complications. In the last 5 years, there have been several reports of severe, sometimes lethal, listeriosis infection in patients treated with alemtuzumab. This article presents a clinical case of lethal listeriosis meningoencephalitis, which developed within 7 days after the completion of the first cycle of alemtuzumab therapy. In January 2018, a meeting of the expert Council was held, at which the clinical recommendations published in 2017 were revised and updated.

[The first experience of the use the Russian Β-interferon-1b biosimilar (infibeta) in the daily practice of the Moscow Center of Multiple Sclerosis].

We summarized the 1-year experience of using the Russian Β-interferon-1b biosimilar (infibeta) in 123 patients including 65 patients with relapsing-remitting multiple sclerosis (RMS) and 58 patients with secondary progressive multiple sclerosis (SPMS). The significant decrease in the frequency of exacerbations per year was seen during the first year of treatment. We also noted the stabilization of the process of disability without the rise in EDSS scores in more than 50% of patients. Good tolerability comparable to that of the original drug was observed during the first year of treatment. There was no refusal from therapy with infibeta, which indicated sufficiently strong adherence to this type of treatment.

[Natalizumab in the treatment of patients with relapsing-remitting multiple sclerosis: the preliminary results of the observational program "Sovet"].

The post marketing observational program "Sovet" has been launched in 2011. Sixty-nine patients with relapsing-remitting multiple sclerosis (MS) treated with natalizumab (NZ), a second generation DMD, have been examined. NZ infusions were carried out during 1h every 4 weeks for 12 months. After treatment, there were a significant reduction in the frequency of relapses from 2.22±0.98 to 0.18±0.42 per year and a trend towards the decrease in EDSS scores from 3.69±1.00 to 3.37±1.17. Adverse effects were noted in 11 patients, with each patient having no more than one side-effect. One patient discontinued treatment due to a generalized allergic reaction. These findings are in line with literature results on the positive effect of NZ on the course and symptoms of MS. It has been concluded, that the strict selection of patients and their correct management during the treatment with NZ may provide the positive balance between advantages and potential risks.

[Neurodegenerative process in multiple sclerosis and a possible neuroprotective effect of ß-interferon 1a (avonex)].

To evaluate clinical perspectives of proton multi-voxel magnetic-resonance spectroscopy (PMMRS) for monitoring the severity of multiple sclerosis (MS) and neurodegenerative process, we studied the changes of the NAA/Cr ratio in the brain tissue of patients with MS and calculated the correlations between this parameter and the clinical state of patients. Based on these results, we studied the potential neuroprotective effect of ß-interferon 1a (avonex) for intramuscular injection in patients with remitting MS. Twenty-six patients with remitting MS were enrolled in the study. The study of anamnesis, neurological examination using EDSS, neuropsychological testing and dynamic MRI using PMMRS were performed. The NAA/Cr ratio was decreased in patients compared to controls. An analysis of the NAA/Cr ratio after one year revealed the significant decrease of this parameter. The negative correlation between the NAA/Cr ratio in the brain tissue and the level of neurological and cognitive deficits was noted. The analysis of existing treatment of MS with ß-interferon 1a for intramuscular injection revealed the neuroprotective stabilizing effect during one year of treatment that is probably associated with the effect of this drug on the neurodegenerative process in MS.

[The neurodegenerative process in multiple sclerosis and the possible neuroprotective effect of treatment with Β-interferon 1a (avonex)].

The aim of the study was to investigate the change of NAA/Cr ratio in the brain parenchyma in patients with MS with the help of protonic multivoxel magnetic resonance spectroscopy (PMMRS) and to detect the correlation between this factor and clinical status of the patients. The study was also performed in order to investigate whether this method can be potentially used for monitoring of the severity of the disease and severity of the neurodegenerative process. On the basis of this knowledge potential neuroprotective effect of the interferon beta 1a (IFN Β1а) i.m. (avonex) was investigated. Twenty six patients with relapsing-remitting multiple sclerosis (RRMS) were included in the study. The procedures included examination of the history of the disease, neurological examination, EDSS, neuropsychological tests, dynamic MRI with PMMRS. The decrease of the NAA/Cr ratio in patients with RRMS compared to healthy controls was detected. The dynamic control in a year revealed the decrease NAA/Cr in patients with MS. Negative association was revealed between NAA/Cr in the brain and the level of neurological and cognitive deficit. The analysis of the 1 year therapy with IFN Β1а i.m. revealed neuroprotective effect which can be related to the possible positive effect of the drug on the neurodegenaration process.

[Results of a comparative clinical trial of the Russian Β - interferon-1b bioanalogue (infibeta)].

Results of annual comparative clinical research of the Russian biosimilar of beta-IFN - 1в at 122 patients with multiple sclerosis are presented. There were positive dynamics on EDSS scores in both groups (in the main group and group of control) in a year of treatment. There were positive dynamics in frequency of relapses in the main group (with 1.5 to 0.4 in a year) and in group of control (with 1.4 to 0.37 in a year). Positive dynamics according to MRI was also fixed in both groups. In both groups, good tolerability of the treatment was noted. This research didn't reveal essential distinctions on efficiency and safety parameters in both groups.

[The role of dopamine in the regulation of the interaction between nervous and immune systems in multiple sclerosis].

A complex neurological and neuropsychological examination, including the detection of depression, was conducted in 71 patients with multiple sclerosis aged from 23 to 62 years (mean age 43 ± 9 years). An immunobiochemical study included the analysis of expression of CD80 and CD86 on monocytes and B-cells, expression of TLR2 and TLR4 on monocytes, expression of D3 and D5 dopamine receptors on monocytes and B-cells, using flow cytometry, and the determination of Il-6, Il-10, IL-12p40 and dopamine plasma levels as well as vanillylmandelic acid (VMA, dopamine metabolite) urine levels measured with immunoenzyme assay. The results suggest the involvement of dopamine in the pathogenesis of depression in MS as assessed by dopamine and its metabolites levels. The role of dopamine and monocyte activation (by TLR2) in the pathogenesis of cognitive disturbances was specified as well.

[Damage of macular ganglion cell complex and peripapillary retinal nerve fiber layer in multiple sclerosis].

The aim of this study was to evaluate macular ganglion cell complex (GCC) characteristics and peripapillary retinal nerve fiber layer (RNFL) thickness in patients with multiple sclerosis (MS) and to investigate the associations between these parameters and clinical characteristics of patients for evaluation perspectives of using this method for monitoring of disability and neurodegenerative processes. We examined a total of 113 participants (analysis of 211 eyes), divided into three groups: 1. 48 MS patients (66 eyes) with a history of optic neuritis (ON); 2. 35 MS patients (70 eyes) without a history of ON; 3. 30 disease-free control subjects (45 eyes). The estudy included anamnesis collection, neurological examination with assessment of EDSS scores. Refracted visual acuity prior to optical coherence tomography (OCT) was tested. RTVue-100 ОСТ system was used to assess peripapillary RNFL thickness and macular inner parameter (protocol GCC). The strongly correlated decline of the most RNFL and GCC indices was characteristic of all groups of MS patients with and without ON compared to controls. The damage of GCC was greater in patients with ON. The inverse correlation was found between the indices studied and the level of patient's disability. The study of GCC and RNFL thickness can be used to describe and characterize the level of axonal damage in MS and for objectification of neurodegenerative process in studies on neuroprotection and neuroreparation.

[Efficacy and tolerability of long-term using of glatimer acetate (copaxone): a 10 year-study in the Moscow Municipal Multiple Sclerosis center].

Experience of 10-year administration of glatimer acetate (copaxone) in 74 patients with active remitting multiple sclerosis is summarized. The significant decrease in the frequency of exacerbations was seen over these ten years. Disease severity on the EDSS was stable and decreased only to the end of the 10-year period. The positive stable clinical dynamics did not depend on the disease severity at baseline. The drug was well-tolerated that allowed to control the course of multiple sclerosis: 64.8% of patients had no more than one exacerbation over 10 years and in 71.6% patients, the disease progression was absent or minimal (less than one score on EDSS). It has been concluded, that the long-term 10-year treatment with copaxone enables to control the development of disease in many patients.

[The comparative study of efficacy and tolerability of intramuscular introduction of beta-interferon-1a in adults and adolescents with remitting multiple sclerosis].

The experience of the treatment of patients with remitting multiple sclerosis (MS) with intramuscular introduction of beta-interferon-1a (avonex) is presented. Seventeen children and adolescents, aged from 11 to 18 years, and 55 adults, aged over 55 years, were treated for at least one-year period. Results revealed a significant reduction of exacerbations in both groups (from 1.35 to 0.06 in average in adolescents and from 0.86 to 0.17 in adults). The changes were accompanied by the stabilization of MS severity index: EDSS scores have decreased in 23.6% of adults and in 17.6% of adolescents. In both groups, good tolerability of the treatment was noted. There was a low probability of side-effects with the exception of increased frequency of a flu-like syndrome (47% cases) in patients younger than 18 years that demands special attention from children neurologists. The high efficacy and good tolerability and safety profile of beta-interferon-1a give grounds for administering this drug to children and adolescents with MS.

[Neurodegeneration and neuroprotection in multiple sclerosis].

Multiple sclerosis (MS) has neurodegenerative features including neuronal and axonal loss in demyelination lesions and widespread atrophy of the brain. The cause of this neurodegeneration has been largely attributed to inflammation but other mechanisms, including those associated with classic neurodegenerative disease, might also be involved in the MS pathogenesis. Certain noninvasive tests such as magnetization transfer imaging, diffusion weighted imaging and proton magnetic resonance spectroscopy might be superior in early detection of axonal loss. In the current review, the authors discuss the current understanding of the neurodegenerative mechanisms in MS, agents with neuroprotective properties and their possible application in the treatment of MS.

[Elimination of NSE and MBP into cerebrospinal fluid and blood in acute experimental autoimmune encephalomyelitis].

An immuno-enzyme assay of NSE and MBP in the cerebrospinal fluid (CFS) and blood serum of rats during the development of acute experimental autoimmune encephalomyelitis revealed the increase of NSE, a neuronal marker, and MBP, a marker for myelin. The investigation has shown that the increased level of NSE in CSF was prior to the increased concentration of MBP. The changes of these neurospecific proteins (NSP) in the serum were not the same as in the CSF. The analysis of the ratio between NSP concentrations in CSF to serum revealed the initial marked decrease of BBB permeability to MBP but not to NSE.

[Elimination of neurospecific proteins from CNS: pathogenetic and methodical aspects].

Appearance of neurospecific proteins (NSP) outside the brain plays a certain pathogenetic role in the development of autosensitization occurring in many kinds of CNS injuries and diseases. Analysis of modern views of cerebrospinal fluid (CSF) exchange allows us to suppose that NSP are eliminated from the brain tissue within CSF, moving from the subarachnoid space into cranial veins, and by lymphatic way, into deep cervical lymph nodes. Elevation of NSP level in CSF indicates an actual neudegenerative process. Serum levels of NSP are determined by the balance between the elimination of NSP from the brain, on the one hand, and their metabolism and the response of the immune system to the appearance of these autoantigenes in the blood stream, on the other. Basing on their own data on the dynamics of NSP (NSE, GFAR, and MBP) concentrations and the proportions of these proteins in CSF and serum (coefficient of elimination) in rats after ischemic, hypoxic, and autoimmune cerebral lesions, the authors offer an algorithm of pathogenetic evaluation, including, on the one part, a conclusion on the presence or absence of a neurodegenerative process, and, on the other, a conclusion on a normal or lowered rate of NSP elimination (metabolism). The results of such an analysis may have a clinical significance in terms of the development of a pathogenetic therapy, including, in every individual case, not only neuroprotectors, but also pharmaceuticals directed towards correction of the functional condition of the immune system.

[The interferon beta therapy after the first clinical episode of demyelination in multiple sclerosis].

The currently available treatment of definite multiple sclerosis (MS) includes different preparations of interferon beta. Recently reported data of pathomorphological, MRI, MR-spectroscopy and immunohistochemical studies suggest that axonal damage secondary to inflammation appears at the very early stage of MS. Early pathological events can predict a future course of the disease. Inflammatory activity in relapsing MS does not confine to episodes of clinical impairment but often develops before the first episode and generally continues during remissions. Patients with clinically isolated syndrome (CIS) and an abnormal brain MRI scan are at high risk of developing clinically definite MS (CDMS). If the presence of lesions predisposes to MS, the number of lesions determines when disability will develop. The results of interferon beta trials in patients with CIS showed significant benefit of the treatment in decreasing risk of CDMS development.