[Long-term efficacy and safety of divozilimab during 2-year treatment of multiple sclerosis patients in randomized double-blind placebo-controlled clinical trial BCD-132-4/MIRANTIBUS]. / Effektivnost' i bezopasnost' dvukhletnei terapii divozilimabom u patsientov s rasseyannym sklerozom v ramkakh randomizirovannogo dvoinogo slepogo platsebo-kontroliruemogo klinicheskogo issledovaniya BCD-132-4/MIRANTIBUS.

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.

[Efficacy and safety of antiCD20 monoclonal antibody divozilimab during 48-week treatment of multiple sclerosis patients in randomized double-blind placebo-controlled clinical trial BCD-132-4/MIRANTIBUS]. / Effektivnost' i bezopasnost' 48 nedel'nogo primeneniya monoklonal'nogo antitela protiv CD20 divozilimaba u patsientov s rasseyannym sklerozom: rezul'taty randomizirovannogo dvoinogo slepogo platsebo-kontroliruemogo klinicheskogo issledovaniya BCD-132-4/MIRANTIBUS.

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.

[Characteristics and dynamics of pathological changes in visual evoked potentials in multiple sclerosis]. / Kharakteristika i dinamika patologicheskikh izmenenii zritel'nykh vyzvannykh potentsialov pri rasseyannom skleroze.

OBJECTIVE: Clarification of the characteristics and dynamics of changes in the main indicators of visual evoked potentials (VEP) for a reverse chess pattern in patients with multiple sclerosis (MS) at various stages of the disease and severity of disability. MATERIAL AND METHODS: The study of VEP was carried out on 477 subjects, 120 of which were healthy volunteers and 357 patients with MS, including those with clinically isolated syndrome (CIS; 22.7%), remitting course (RT; 55.7%), primary progressive course (PPT; 8.4%), secondary progressive course (VPT; 13.2%). Disability was assessed using the Expanded Disability Status Scale (EDSS). RESULTS: A high sensitivity of VEP in the detection of demyelinating damage to the visual pathways, including subclinical, was noted already at the initial stages of MS, which increases with the progression of the disease from 77.8 to 97.8%. There was a significant increase in latency (r=0.42, p<0.05) and a decrease in amplitude (r= -0.26, p<0.05) of the P100 peak as the EDSS score increased. In patients with MS, 5 patterns of VEP were identified depending on the level and severity of damage to the visual pathways, where pattern 1 is normative VEP, pattern 5 is the absence of VEP recording in case of a pronounced axonal-demyelinating lesion of the visual pathways (prechiasmal/postchiasmal levels). Patterns 1 and 2 are most typical for CIS (22.2 and 53.1%) or RT (20.1 and 26.6%). Patterns 3 and 4 are typical for APT (70 and 20%) and VPT (48.9 and 21.3%), pattern 5 - for VPT (19.1%). Patterns 3-5 predominated in patients with higher EDSS (r=0.54, p<0.05). CONCLUSION: The classification of VEP changes into patterns makes it possible to identify the dissemination of a focal lesion in the projections of the visual pathways, which increases the diagnostic efficiency of the study and makes it possible to assess the severity of MS.

[Efficacy and safety of divozilimab during 24-week treatment of multiple sclerosis patients in randomized double-blind placebo-controlled clinical trial BCD-132-2]. / Effektivnost' i bezopasnost' 24 nedel' primeneniya divozilimaba sredi patsientov s rasseyannym sklerozom v ramkakh randomizirovannogo dvoinogo slepogo platsebo-kontroliruemogo klinicheskogo issledovaniya BCD-132-2.

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.

[Long-term Efficacy and Safety of Sampeginterferon-ß1a in the Treatment of Relapsing Remitting Multiple Sclerosis: a Randomized, Double-Blind Clinical Trial 104-Week Results]. / Dolgosrochnye dannye po effektivnosti i bezopasnosti preparata sampeginterferon-ß1a u patsientov s remittiruyushchim rasseyannym sklerozom: rezul'taty 104-nedel'nogo randomizirovannogo dvoinogo slepogo klinicheskogo issledovaniya.

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.

[Differential diagnosis of multiple sclerosis in children]. / Differentsial'naya diagnostika rasseyannogo skleroza u patsientov detskogo vozrasta.

At the onset, multiple sclerosis (MS) in children is characterized by a phase of active inflammation with extensive demyelination of the white matter of the CNS, which often mimics this nosology with a whole spectrum of inflammatory demyelinating diseases such as ADEM, anti-MOG encephalitis, ONMSD. In order to formalize the diagnostic process, the International Pediatric Multiple Sclerosis Study Group (IPMSSG) proposed diagnostic criteria for the main immune-mediated demyelinating diseases of the CNS in children, which, in theory, should simplify the diagnostic search. However, in practice, the range of nosologies in the course of differential diagnosis is much wider and often it is not possible to establish an unambiguous diagnosis in the early stages. The authors analyze their own clinical observations based on a sample of 100 pediatric patients with a referral diagnosis of «MS?¼ and describe a clinical case of the onset of highly active MS with an assessment of the dynamics of the clinical and paraclinical course of the disease.

[New opportunities in the treatment of patients with multiple sclerosis (Resolution of the Council of Experts on April 23, 2022, Moscow, JSC «BIOCAD¼)]. / Novye vozmozhnosti v terapii patsientov s rasseyannym sklerozom¼ (Rezolyutsiya soveta ekspertov 23 aprelya 2022 goda, Moskva, AO «BIOKAD¼).

One of the target areas for the development of the Russian pharmaceutical industry at present is the development of next-in-class drugs medicines. These are original, patent-protected drugs that act on known biological targets, improved or modified in structure and mechanism of action compared to existing, successfully proven medicine. The article presents the results of an expert council on the management of patients with multiple sclerosis and the place of new original medicines of the JSC BIOCAD company (SamPEG-IFN-ß1a and divozilimab) in multiple sclerosis therapy algorithm.

[Efficacy and safety of sampeginterferon ß-1a in the treatment of relapsing remitting multiple sclerosis: results of 52 weeks of therapy in a randomized, double-blind clinical trial]. / Effektivnost' i bezopasnost' sampeginterferona ß-1a dlya lecheniya remittiruyushchego rasseyannogo skleroza: rezul'taty 52-nedel'nogo randomizirovannogo dvoinogo slepogo klinicheskogo issledovaniya.

OBJECTIVE: To evaluate the efficacy and safety of samPEG-IFN-ß1a 180 µg and 240 µg administered once every 2 weeks for the treatment of relapsing remitting multiple sclerosis (RRMS) compared to placebo and low dose interferon beta-1a (LIB) 30 µg administered once weekly. The primary endpoint after 52 weeks of therapy was the time to first relapse, the hypotheses of non-inferiority and superiority to LIB were tested. MATERIAL AND METHODS: This international, multicenter, double blind, comparative, placebo-controlled clinical study enrolled 399 patients with the diagnosis of RRMS, randomized in 4 groups: samPEG-IFN-ß1a180 µg (n=114), samPEG-IFN-ß1a 240 µg (n=114), LIB (n=114) and placebo (n=57). Placebo group patients participated in the study for 20 weeks. After 52 weeks of therapy and 4 weeks of follow-up, LIB group patients completed their participation in the study, patients from PEG-IFN-ß1a groups continued to receive therapy until week 100 inclusive. The article presents the results of an analysis conducted after the end of 52 weeks of a double-blind, comparative, randomized, placebo-controlled clinical trial. RESULTS: Final analysis of the efficacy and safety was performed after 52 weeks of study. Main statistical hypothesis testing proved that both doses of samPEG-IFN-ß1a were equally effective when compared to LIB by the primary endpoint - «Time to first relapse¼. Due to detection of statistically significant differences in the primary endpoint between the study drug and the reference drug, indicating a greater efficacy of the study drug, an additional testing was carried out and the hypothesis of superiority of samPEG-IFN-ß1a at a dose of 240 µg over the reference LIB was proved. Evaluation of the dynamics of certain key parameters of magnetic resonance imaging (MRI) of the brain and clinical outcomes demonstrated a positive effect of samPEG-IFN-ß1a therapy in the form of decreased activity of the demyelinating process in the brain and reduce the number of relapses. The proportion of patients without new T2 lesions after 52 weeks was 87.6% and 90.4% in 180 µg and 240 µg samPEG-IFN-ß1a groups, versus 72.6% in the LIB group (p=0.0199 and p=0.0033). No progression of multiple sclerosis was shown based on EDSS scale evaluation. During the study, the most common adverse reactions were flu-like symptoms and injection site reactions. CONCLUSION: The new drug samPEG-IFN-ß1a is an effective and safe agent for relapsing remitting multiple sclerosis treatment, while having an advantage over other low-dose interferons in the form of reduced frequency of intramuscular injections.

[Updated recommendations of the Council of Experts on the use and safety of alemtuzumab (Lemtrada)]. / Obnovlennye rekomendatsii soveta ekspertov po primeneniyu i obespecheniyu bezopasnosti terapii preparatom alemtuzumab (Lemtrada).

Alemtuzumab (Lemtrada) is a recombinant humanized IgG1 kappa monoclonal antibody to the surface cell glycoprotein, a CD52 differentiation cluster. The drug is approved for use in more than 65 countries, including the Russian Federation. The drug is one of the most effective methods of treating patients with aggressive multiple sclerosis, but the risk management plan should be followed. The safety profile of the drug includes infusion-associated reactions, thyroid dysfunction, immune cytopenia, acute cardiovascular events, infections, and other autoimmune diseases. This publication provides updated practical recommendations for the use of the drug and ensuring the safety of patients treated with alemtuzumab.

[Comparison of the efficacy of Cellex and Cortexin in patients in the early recovery period of ischemic stroke]. / Sravnenie effektivnosti preparatov Tselleks i Korteksin u patsientov v rannem vosstanovitel'nom periode ishemicheskogo insul'ta.

OBJECTIVE: To compare the efficacy of Cellex and Cortexin in patients in the early recovery period of ischemic stroke (ERPIS) receiving basic therapy (BT). MATERIAL AND METHODS: Forty patients were randomized into the cellex group (n=20) and the cortexin group 2 (n=20). Cellex was administered in a dose of 0.1 mg daily SC for 10 days and cortexin in a dose of 10 mg per 2 ml of 0.9% NaCl solution IM daily for 10 days. The efficacy of treatment was assessed with NIHSS, Bartel's index (BI), MMSE, the Rivermead Mobility Index (RMI), the Frontal Assessment Battery (FAB), Beck's depression scale (BDS). RESULTS: A more pronounced positive dynamics of NIHSS: 3 [2; 4.5] vs. 5 [2; 7] (p=0.03) and MMSE scores: 24 [21.5; 25] vs. 22 [20; 23] (p=0.04) was noted in the cellex group. Also, in this group, a more significant trend towards regression of depressive disorders (BDS) was revealed: 17.5 [14.5; 21] vs. 14 [13; 16] (p=0.064). The dynamics of RMI and FAB scores did not differ significantly between the groups. CONCLUSION: The use of cellex in comparison with cortexin is more effective in terms of the dynamics of regression of neurological and neurocognitive dysfunctions in patients with ERPIS.

[Efficacy, tolerability and safety of the treatment with teberif: the results of a 2-year randomized clinical trial of treatment naïve patients with remitting multiple sclerosis, who have not received DMT, after switching from other interferon ß-1a]. / Éffektivnost', perenosimost' i bezopasnost' terapii preparatom teberif: rezul'taty dvukhletnego klinicheskogo issledovaniia u patsientov s remittiruiushchim rasseiannym sklerozom, ranee ne poluchavshikh PITRS, i pri perekliuchenii s drugogo interferona ß-1a.

OBJECTIVES: To evaluate efficacy, safety, and tolerability of the treatment with teberif/interferon ß-1a, to analyze safety, tolerability and dynamics of key efficacy variables after switching from referent drug rebif to biosimilar teberif in patients with remitting multiple sclerosis (RMS). MATERIAL AND METHODS: During the main period of the international multicenter randomized study patients were randomized to receive treatment with teberif for 52 weeks, or rebif for 52 weeks, or placebo for 16 weeks to evaluate efficacy and safety of treatment. After the main study period, patients were group-independently switched to take open-label teberif treatment during the next 48 weeks. RESULTS AND CONCLUSION: The analysis of multiple evaluation parameters of the efficiency during the 1st study period (blinded) and the 2nd study period (open-label) has shown that teberif and rebif demonstrate equivalent efficacy and stable 2-year efficacy of teberif was proven. There were no significant differences between teberif and rebif for all safety, and tolerability parameters. Switching from rebif to teberif didn't influence treatment efficacy. The 2-year study results confirmed a biosimilar teberif's benign tolerability and expected safety profile to other interferons ß-1a in patients with RMS.

[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 results of an open comparative retrospective trial of the course of multiple sclerosis during treatment with infibeta and other interferon-beta bioanalogues and glatiramer acetate]. / Rezul'taty otkrytogo sravnitel'nogo retrospektivnogo issledovaniia osobennostei rasseiannogo skleroza na fone terapii preparatom infibeta i drugimi bioanalogami interferonov beta i glatiramera atsetatom.

AIM: To evaluate the efficacy and safety of the interferon beta-1b bioanalogue 'infibeta' in the treatment of multiple sclerosis (MS) in comparison with other interferon beta bioanalogues and the generic drug glatiramer acetate. MATERIAL AND METHODS: The data of 500 patients with MS treated with different disease-modifying drugs were analyzed. Patients of group 1 (n=95) received infibeta; group 2 (n=108) interferon beta-1b; group 3 (n=83) genfaxon-44; group 4 (n=109) sinnovex; group 5 (n=105) aksoglatiran FS. RESULTS: In all groups, there was a significant decrease in the AARR and an increase in the EDSS score (p<0,05) after 12 and 24 months of treatment (p<0,05) with the best indicators in groups 1-3. After 12 months of treatment, the number of patients without signs of MRI activity was higher in groups 1-3 (48-61%) than in groups 4 and 5 (47, 43%, respectively) (p>0,05). After 24 months of treatment, the number of patients without signs of MRI activity decreased to 41-46% in groups 1-3, and more significantly in group 4 (27%). The percentage of NEDA-3 achieving patients did not significantly differ in the groups (23-32%) after 12 months of treatment. After 24 months of treatment the NEDA-3 declined more in group 4 (19%), least of all in groups 1 and 2 (27, 25%, respectively) (p>0,05). In most cases, the observed adverse events were mild or moderate. Flu-like syndrome was observed rarely in groups 1 and 4 (p<0,05). Injection reactions were observed most commonly in groups 3 and 5 (p<0,05). CONCLUSION: Infibeta, while retaining all the advantages of high-dose interferon beta, has the best tolerability profile, which makes it one of the optimal first line disease-modifying therapy for treatment of patients with MS.

[Evaluation of efficiency and safety of adding neuromultivit to basic therapy of vertebrogenic radiculopathy]. / Éffektivnost' i bezopasnost' neiromul'tivita pri vertebrogennykh radikulopatiiakh.

AIM: To evaluate the efficacy and safety of neuromultivit (valiant, Russia) as add-on to the basic therapy of vertebrogenic radiculopathy (VR) L5-S1. MATERIAL AND METHODS: The open clinical trial included 100 patients with VR L5-S1 randomized into 2 groups. In group 1, patients received neuromultivit and basic therapy; in group 2 only basic therapy. Treatment efficacy was assessed by the dynamics of regression of pain intensity on the visual analogue scale (VAS), McGill pain questionnaire (MGPQ), Aberdeen back pain scale (ABPS), the Quebec Back Pain Disability Scale (QBPDS), the dynamics of neurologic symptoms, the need for additional treatment with NSAID. Safety was assessed by evaluation of vital functions, laboratory tests, ECG, registration of adverse events (AE). RESULTS: In both groups, a significant positive changes on VAS, MGPQ, ABPS, QBPDS were observed. Nevertheless, the positive effect of therapy was more pronounced in group 1 p<0.05). The AE spectrum between two groups did not differ significantly (p<0.05). CONCLUSION: Addition of neuromultivit to basic therapy increased the efficacy of treatment of VR L5-S1.

[A comparative placebo-controlled clinical study on the efficacy and safety of interferon beta-1a for subcutaneous injections in patients with remitting multiple sclerosis: results of the first year of observations]. / Sravnitel'noe platsebo-kontroliruemoe klinicheskoe issledovanie éffektivnosti i bezopasnosti preparatov interferona beta-1a dlia podkozhnogo vvedeniia u patsientov s remittiruiushchim rasseiannym sklerozom: rezul'taty pervogo goda nabliudeniia.

AIM: To prove the equivalent efficacy of teberif (BCD-033, interferon beta-1) and rebif (interferon beta-1a) in patients with remitting multiple sclerosis (RMS). MATERIAL AND METHODS: A multicenter double blind placebo-controlled comparative randomized III phase study included 163 patients with RMS. Patients were randomized into three equal groups (teberif, rebif or placebo). RESULTS AND CONCLUSION: After 52 weeks, the equivalent efficacy of teberif and the brand drug rebif was shown. The result of assessment of the primary endpoint, which was combined unique active (CUA) lesion (the total of MRI T1-weighted lesions and new or newly enlarging T2-weighted lesions, without double counting of lesions with both activities), showed no significant differences (0.727±1.042 and 0.652±1.059 (p=0.7354, t-Student test) in the teberif and rebif groups, respectively. No between-group differences were found for other MRI indices and clinical parameters related with relapses. Teberif was shown to have a favorable safety and tolerability profile comparable to that of rebif. The results suggest the therapeutic equivalency of the drugs and form the basis for using the bioanalogue of interferon-beta 1 in patients with RMS.

[Primary progressive multiple sclerosis: current issues of timely diagnosis]. / Pervichno-progressiruiushchii rasseiannyi skleroz: sovremennoe sostoianie problemy svoevremennoi postanovki diagnoza.

This article presents a review of international data on primary progressive multiple sclerosis (PPMS) and an analysis of factors influencing timely diagnosis of PPMS in a number of regions of the Russian Federation.

[Comparative, placebo-controlled clinical study of efficacy and safety of glatiramer acetate 20 mg in patients with relapsing-remitting multiple sclerosis: results of the first year of the study]. / Sravnitel'noe platsebo-kontroliruemoe klinicheskoe issledovanie effektivnosti i bezopasnosti preparatov glatiramera atsetata 20 mg u patsientov s remittiruyushchim rasseyannym sklerozom: rezul'taty pervogo goda nablyudeniya.

The article presents the results of international multicenter randomized double-blind, active and placebo-controlled, comparative phase 3 trial. The goal of the study was to demonstrate non-inferiority of BCD-063 (glatiramer acetate, manufactured by JSC «BIOCAD¼, Russia) to copaxone-Teva (Teva Pharmaceutical Enterprise Co., Ltd., Israel) in patients with relapsing-remitting multiple sclerosis. METHODS: 158 patients with relapsing-remitting multiple sclerosis were randomly assigned into 3 groups: BCD-063, copaxone-Teva and placebo, at a ratio of 2:2:1, respectively. RESULTS AND CONCLUSION: Efficacy analysis after 48 weeks of therapy demonstrated no differences between BCD-063 group and copaxone-Teva group in both MRI parameters and frequency of relapses. The mean (SD) of number of MRI-confirmed relapses per patient per year (the primary endpoint) in BCD-063 group was 0.098361 (0.351422), in copaxone-Teva group - 0.098361 (0, 351 422) and in placebo group - 0.178571 (0.390021). There were also no differences between the groups for all other efficacy parameters (EDSS and MSFC). Both investigational BCD-063 and copaxone-Teva demonstrated a favorable safety profile. The data obtained from the present study confirm the therapeutic equivalence of BCD-063 (CJSC BIOCAD, Russia) and copaxone-Teva, that is important for further implementation of glatiramer acetate generic in the clinical practice of multiple sclerosis therapy.

[Effect of cerebrolysin on remyelination processes in multiple sclerosis patients in stage of relapse regression]. / Primenenie tserebrolizina u bol'nykh rasseyannym sklerozom v stadii regressa obostreniya.

AIM: To evaluate the efficacy and safety of Cerebrolysin (EVER Neuro Pharma GmbH, Austria) in the treatment of patients with multiple sclerosis (MS) in stage of relapse regression. MATERIAL AND METHODS: The study involved 40 patients with remitting MS (McDonald criteria 2010) in stage of MS relapse regression after pulse therapy with methylprednisolone 1000 mg/day 5. Patients randomized into 2 groups: group 1 (G1, n=20) received cerebrolysin 20 ml per 200 ml of 0.9% NaCl solution 1 times per day 10; Group 2 (G2, n=20) - only 200 ml 0.9% NaCl solution on analogical scheme. All patients before and 3-4 weeks after the treatment were carried out assessment of vital signs, routine laboratory tests, tests of cognitive-motor functions (SDMT), visual acuity (LCAT), a comprehensive neurophysiological examinations (CNE). 4 patients in the G1 with presence of previously identified G+ lesions (G+L) were conducted MRI of brain after 3-4 weeks after treatment. RESULTS: In G1 the average age of the patients was 27.35 (5.65) years, the ratio of M/F - 40/60%, the duration of the disease 29.9 (11.01) months, the EDSS in relapse stage - 3.5 [2.0; 4.5] points. The average age of patients in G2 was 26.65 (4.93) years, the ratio of M/F - 35/65%, the duration of the disease - 30.25 (11.98) months, the EDSS in relapse stage - 3.0 [1.5; 4.5] points. Clinical relapse of MS was categorized into groups as follows: optic neuritis (15% vs. 30%; p=0.26), stem dysfunction (15% vs. 25%; p=0.43), hemispheric dysfunction (50% vs. 35%; p=0.34), transverse myelitis (20% vs. 10%; p=0.38). 17 patients (85%) in G1 and 18 patients (90%) in G2 completed a full course of treatment. In both groups showed significant regression estimation EDSS (2.0 [1.75; 2.5] vs. 2.5 [1.75; 2.5]), while significant intergroup differences were not found (p=0.665). In G1 was noted more pronounced dynamics of performance improved in testing MSFC and SDMT (p=0.038 and p=0.026, respectively). Significant intergroup differences in the dynamics of improvement VCAT values were not found (p=0.658). Also in G1 was revealed greater regression of total variance in the CNE than G2 (70.59% vs. 27.78%, p=0.028), while in almost all cases the previously identified neurophysiological abnormalities are not completely regressed. In addition to G1 was marked a tendency to reduce of progressive deterioration of CNE indicators (10% vs. 30%; p=0.228). On MRI cerebrolysin treatment was not associated with an increase of G+L (G+L number before treatment in 4 patients - 14, after treatment - 12), which indicates a potential anti-inducing effect of the drug on the intrathecal inflammation in MS. CONCLUSION: Cerebrolysin positive role in the stimulation of remyelination process in MS has been confirmed by CNE and the selected treatment regimen has demonstrated its safety. Effect of the drug appear to be due to its composition: so according to a group of authors found that investigated the drug contained fragments of tubulin, actin and myelin basic protein, all of which is necessary to ensure non-specific trophic regenerated CNS myelin sheath.

[Clinical, neurophysiological and neuroimaging study of tremor in multiple sclerosis]. / Klinicheskoe, neirofiziologicheskoe i neirovizualizatsionnoe izuchenie tremora pri rasseiannom skleroze.

OBJECTIVE: To identify clinical types of tremor in multiple sclerosis (MS) and clarify their pathophysiological mechanisms. MATERIAL AND METHODS: We examined 124 patients with MS, including 58 patients with tremor, using clinical (digital spiralography), neurophysiological (tremor electromyography, visual and sensory evoked potentials, transcranial magnetic stimulation with tremor resetting, long latency reflexes, electroencephalography) and neuroimaging (MRI, morphometry) methods. RESULTS AND CONCLUSION: Five main variants of tremor were identified: distal postural and postural-intention (variant 1), distal intention (variant 2), proximal and distal intention and postural-intention (variant 3), Holmes (variant 4), axial (variant 5). Postural tremor (variants 1, 3) and rest tremor (variant 4) are caused by the central oscillators. Intention tremor (variants 2, 3), postural-intention tremor (variant 4), axial (variant 5) are caused by the pathology of cerebellar feedback loops. Clarification of mechanisms for the development of tremor in MS allowed to develop a scheme of differential treatment.