[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.

[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.

[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.

[Frequency of antibodies against surface and nuclear antigens of hepatitis B virus in population of St. Petersburg in 2013].

AIM: Determine the frequency of antibodies to surface (anti-HBs) and core (anti-HBc) antigens of hepatitis B in population of St. Petersburg of various age for evaluation of protective herd immunity against hepatitis B virus (HB). MATERIALS AND METHODS: Blood sera of 970 individuals (491 males, 479 females) of 10 age groups from 0 to 50 years and older were examined for the presence of anti-HBs and anti-HBc IgG by enzyme immunoassay using commercial diagnostic test-systems. RESULTS: In general anti-HBs at the level of 5 mIU/ml and above were detected in 603 of the examined individuals (62.2%). Anti-HBs at the level of 10 mIU/ml and above were detected in 53.9%. The frequency of anti-HBs in protective titers in males and females in general turned out to be similar (52.6% and 55.2%, respectively). Juxtaposition of age-specific parameters of seroprotection and acute HB morbidity in St. Petersburg revealed an inverse correlation of medium strength (r = - 0.54). CONCLUSION: Results of the study confirm high effectiveness of the program of HB vaccine prophylaxis in St. Petersburg and emphasize the necessity of further implementation of broad measures of population immunization against HB.