[Efficacy of dupilumab in real practice in the treatment of severe forms of asthma and atopic dermatitis (comparative retrospective study)].

BACKGROUND: Dupilumab, a fully human monoclonal antibody directed against the common α-subunit of interleukin (IL)-4 receptors and blocking signaling from both IL-4 and IL-13, may be recommended for the treatment of moderate to severe atopic dermatitis (AD) and bronchial asthma (BA). AIM: To perform a comparative assessment of the effectiveness of maintenance therapy with dupilumab in patients with severe BA as the main indication for genetically engineered biological drugs and in patients with severe asthma with concomitant severe AD as the indication for targeted therapy. MATERIALS AND METHODS: A 6-month retrospective comparative study was performed at the specialized reference center for allergology and immunology. The study included 115 adult patients of both sexes treated with dupilumab for uncontrolled severe asthma as the main indication for targeted therapy (BA group; n=65) or for a combination of severe uncontrolled asthma and severe AD (BAAD; n=50). Dupilumab was administered subcutaneously for 6 months. The first dose was 600 mg once and then 300 mg Q2W. Evaluation of the effectiveness of dupilumab therapy at 6 months of treatment in both groups included achieving asthma control (ACT, ACQ5), improving pulmonary function test, reducing the risk of exacerbations and the need for systemic glucocorticosteroids (SGCS), improving quality of life (AQLQ), change of biomarkers (FeNO, eosinophil count) and the course of comorbid diseases, including improvement in the AD (SCORAD, EASI) and rhinosinusitis polyposa (SNOT-22). RESULTS AND CONCLUSION: During dupilumab therapy, in a significant proportion of patients, regardless of the presence or absence of other T2-associated diseases (e.g., AD or rhinosinusitis polyposa), an improvement in asthma was demonstrated as early as in the first 6 months of treatment with dupilumab in all recommended domains for assessing the response to targeted therapy: improving asthma control and respiratory function, reducing the frequency of moderate and severe exacerbations associated with the use of SGCS and/or hospitalization, a positive effect on the quality of life and the comorbid diseases, as well as a cumulative reduction in the need for SGCS.

[Pre-exposure prophylaxis of new COVID-19 coronavirus infection with tixagevimab/cilgavimab in adult Moscow patients with primary immunodeficiencies].

BACKGROUND: Primary immunodeficiencies (PIDs), now known as inborn errors of immunity, are a group of inherited diseases caused by defects in the genes that control the immune response. Patients with PIDs have risks of developing a severe course and/or death in COVID-19. Passive immunization with long-acting monoclonal antibodies (MABs) to SARS-CoV-2 should be considered as pre-exposure prophylaxis in patients with PIDs. Tixagevimab/cilgavimab is a combination of MABs that bind to the SARS-CoV-2 spike protein. AIM: To evaluate the efficacy and safety of pre-exposure prophylaxis of new SARS-CoV-2 infection in PIDs with the combination of tixagevimab/cilgavimab. MATERIALS AND METHODS: Forty eight patients diagnosed with PIDs were included in the study. Median follow-up after drug administration was 174 days. The total number of confirmed coronavirus infections in patients with PIDs as well as 6 months before and after administration of MAT were assessed. RESULTS: In the analyzed cohort, the overall incidence of COVID-19 from pandemic onset to MABs administration was 75% (36/48), with 31% (11/36) of over-infected patients having had the infection more than once. The incidence of COVID-19 immediately 6 months before the introduction of tixagevimab/cilgavimab was 40%. All patients who had COVID-19 after pre-exposure prophylaxis had a mild infection. The incidence of COVID-19 6 months after tixagevimab/cilgavimab administration significantly decreased compared to the incidence 6 months before administration (7 and 40%, respectively; p<0.001). CONCLUSION: The use of tixagevimab/cilgavimab in patients with PIDs is effective as pre-exposure prophylaxis and reduces the risk of severe COVID-19.

[Analysis of predictors of response to anti-IgE therapy in patients with severe atopic bronchial asthma in real clinical practice].

INTRODUCTION: Guidelines on Biological Therapy for Bronchial Asthma of the European Academy of Allergy and Clinical Immunology (EAACI) identified a number of controversial issues for additional outcome analysis using randomized clinical trials and data from routine clinical practice. In particular, there is unmet need to clarify algorithms for prescribing biologicals using predictors of response and its timing, taking into account risk factors and multimorbidity. Omalizumab is a recombinant humanized monoclonal anti-IgE antibody of IgG1 class used for the treatment of severe refractory atopic bronchial asthma (BA) and a variety of IgE-mediated diseases. Among biological agents, this "pioneer molecule" has the greatest experience in the "allergology and immunology" profile. Detailed description of the "nonresponders" portraits will allow to perform the therapy response assessment on time and facilitate rational planning of individual therapy, which is a prerequisite for biologicals era. Using only routine methods, it is possible to perform initial and dynamic screening to phenotype a heterogeneous cohort of patients with severe asthma and chose the optimal strategy. AIM: To identify predictors of nonresponse to omalizumab anti-IgE therapy in patients with severe atopic BA and to establish optimal timing of efficacy assessment using retrospective analysis of data from the Biologic Therapy Registry of Allergology and Immunology in routine clinical practice. MATERIALS AND METHODS: A retrospective single-center registry study was conducted at the Allergy and Immunology Reference Center from June 2017 to August 2021. 135 patients with severe BA, with confirmed perennial sensitization, who received omalizumab according to the recommendations of the current version of GINA, were selected from the clinical and dynamic observational system (registry). Dosing regimen and administration frequency of omalizumab were determined in accordance with the instructions for the drug. Assessment of therapy efficacy was performed at the time point 4, 6 and 12 months. Patients were subgrouped into "responders" and "non-responders" according to the following criteria: ACT score less than 19 and/or difference between initial ACT score in dynamics less than 3 points; forced expiratory volume in the first second less than 80%; combination of these two criteria. Nonparametric methods of descriptive statistics were used in data processing: median, interquartile range. Differences were considered significant at p0.05. MannWhitney U-test, KruskalWallis one-way analysis of variance, and Fisher's 2 test were used to compare quantitative characteristics. RESULTS: Heterogeneous subgroups of patients differing in reaching the criteria of "non-responders" to treatment were identified; the informativity of modifiable and unmodifiable factors differed at time-points of dynamic observation. In the differential analysis, two profiles of "nonresponders" were defined in combination with the most significant predictors of "nonrsponse" to omalizumab. According to the data obtained, one of the clinical phenotypes, namely the combination of severe asthma with the Samters triad, corresponded to the characteristics of the patient "nonresponders": age of onset is about 30 years, females, severe exacerbations of BA while taking non-steroidal anti-inflammatory drugs, accompanied with high levels of eosinophilia. CONCLUSION: The data obtained illustrates the hypothesis of pathogenetic heterogeneity of severe BA with the phenomenon of overlapping phenotypes and can serve as an additional orienteer for creating the individual plan of anti-IgE therapy in real clinical practice.

[Hypoglycemic activity of bicyclic diterpenoids of the clerodane series as compared to adebit and maninil]. / Izuchenie gipoglikemicheskoi aktivnosti bitsiklicheskikh diterpenoidov klerodanovogo riada v sravnenii s adebitom i maninilom.

Biocyclic diterpenoids--salvin, salvicin and salvifolin, administered per os to rats at a dose of 50 mg/kg show marked hypoglycemic activity in intact animals as well as in animals with experimental hyperglycemia developing against a background of GTT (3000 mg/kg intraperitoneally) or alloxan (150 mg/kg subcutaneously). They are superior to adebit but inferior to maninil. Prophylactic and therapeutic administration of these compounds ensure the preservation of islet beta-cells in animals with alloxan diabetes.

[Changes in the chromatin structure of the thyroid cells related to the expression of the thyroglobulin gene]. / Izmeneniia struktury khromatina tireoidnykh kletok, sviazannye s ékspressiei gena tireoglobulina.

A highly purified thyroglobulin mRNA was isolated from human nodal euthyroid goiter. A full-length cDNA was synthesized from 33S RNA by using reverse transcriptase in the presence of human placenta ribonuclease inhibitor. A DNA complementary to human Tg mRNA was used in liquid hybridization experiments to quantify Tg mRNA. The amount of Tg mRNA in euthyroid nodal and congenital goiter was reduced. In thyroid cancer Tg specific mRNA was absent. Direct correlation between Tg gene expression in thyroid cells and DNAase-I hypersensitivity of chromatin from the thyroid gland nucleus was revealed.