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AIM: To evaluate the efficacy and safety of a combination of virus-neutralizing monoclonal antibodies - MAB (casirivimab and imdevimab) in patients with mild to moderate COVID-19 with risk factors in real word settings. MATERIALS AND METHODS: A non-interventional non-comparative observational study with primary prospective data collection included 108 patients with mild to moderate COVID-19 (mean age 61 years), who had risk factors for developing severe disease. All patients (n=108) were treated with a combination of MAB casirivimab and imdevimab intravenous single infusion 1200 mg (600 mg of each component). The efficacy and safety of MAB were assessed at 7, 14, and 28 days after infusion. RESULTS: Efficacy. Indications for hospitalization by day 7 from the moment of MAB administration were in 0.9% (n=1), by day 14 - in 1.9% (n=2), by day 28 - in 0.9% of patients; to stay in the intensive care units by the 7th day - in 4.6% (n=5), by the 14th day - in 0.9% (n=1), by the 28th day - in 0.9% (n=1) patients. During 28 days of follow up, the need for mechanical ventilation and extracorporeal membrane oxygenation was registered in 2/108 (1.8%) patients. There were no deaths directly related to COVID-19 in the assessed cohort of patients. Safety. By the 28th day of the follow up, no adverse effects due to MAB therapy were registered. CONCLUSION: An analysis of the results of a non-interventional observational study summarized in this article showed the high efficacy and safety of virus-neutralizing MAB combination (casirivimab and imdevimab) in patients with mild to moderate COVID-19 with of risk factors for severe COVID-19 in real word settings.
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COVID-19 , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Pessoa de Meia-Idade , Anticorpos Neutralizantes , HospitalizaçãoRESUMO
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.
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Asma , Dermatite Atópica , Adulto , Masculino , Feminino , Humanos , Dermatite Atópica/tratamento farmacológico , Estudos Retrospectivos , Qualidade de Vida , Método Duplo-Cego , Asma/diagnóstico , Asma/tratamento farmacológico , Resultado do Tratamento , Índice de Gravidade de DoençaRESUMO
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.
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COVID-19 , Profilaxia Pré-Exposição , Humanos , Adulto , COVID-19/prevenção & controle , Moscou/epidemiologia , SARS-CoV-2 , Anticorpos MonoclonaisRESUMO
On July 3, 2023, an interdisciplinary Council of Experts "The burden of COVID-19 in a heterogeneous population of immunocompromised patients - post-pandemic realities" was held in Moscow with leading experts in pulmonology, rheumatology, hematology, oncology, nephrology, allergology-immunology, transplantation, and infectious diseases. The aim of the meeting was to discuss the current clinical and epidemiologic situation related to COVID-19, the relevance of disease prevention strategies for high-risk patients. The experts addressed the following issues: 1) the disease burden of COVID-19 in 2023 for patients with immunodeficiency in different therapeutic areas; 2) the place of passive immunization with monoclonal antibodies as a method of COVID-19 prophylaxis among immunocompromised patients; 3) prerequisites for the inclusion of passive immunization of immunocompromised patients into routine clinical practice.
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COVID-19 , Reumatologia , Humanos , COVID-19/epidemiologia , Imunização Passiva , Hospedeiro Imunocomprometido , Atenção à SaúdeRESUMO
Postoperative pulmonary complications in cardiac surgery patients occur in 10-35% of cases, depending on differences in their definition, patient characteristics and type of surgical intervention, most of them are associated with ineffective coughing and evacuation of bronchial secretions. OBJECTIVE: To determine the effectiveness of stimulating the evacuation of bronchial secretions with the help of oscillating PEP therapy carried out during the first three days. MATERIAL AND METHODS: A randomized prospective study of 60 adult patients after elective cardiac surgery was performed (Clinical Trials.gov. protocol number NCT05159401). Oscillatory PEP-therapy was performed in 30 patients using Acapella DHGreen device (SmithMedicalASD, USA) 10-12 hours after tracheal extubation 3 times a day for 3 days after surgery. The control group (30 patients). The inclusion criteria: age over 18 years, spontaneous breathing after tracheal extubation, clear consciousness and productive contact with the patient, the ability to maintain adequate gas exchange on the low-flow oxygen inhalation, adequate analgesia (<2 points of VAS). Exclusion criteria: the need for re-intubation and mechanical ventilation, non-invasive mask ventilation, high-flow oxygen therapy, acute cerebrovascular accident, ongoing bleeding, cardiac insufficiency (inotropic index >10), shocks syndrome of various etiologies, the use of any extracorporeal support, any neuromuscular disorders, pneumothorax, hydro-or hemothorax. Before each session and 20 minutes after its end, when breathing air, blood oxygen saturation was recorded using a pulse oximeter (SpO2), the maximum inspiratory capacity (MIC) was measured using a Coach-2 incentive spirometer from SmithsMedical and spirometry with a portable ultrasonic spirometer Spiro Scout (Schiller, Switzerland). For the purposes of this work, the total index of the spirometry maximum inspiratory capacity (SMIC) was used - the sum of the respiratory volume and the reserve volume of inspiration in ml. RESULTS: Difficulties in evacuation of sputum were noted in 90% of patients. Three-day sessions of oscillating PEP- therapy are accompanied by a significant improvement in the passage of sputum, as evidenced by a 3-fold increase in the number of patients with productive cough. The increase in MIC in the main group was 46.9% and 21.3%, respectively (p=0.042), and the number of patients with values greater than MICo. 1500 ml increased from 23.3% to 7.6% (p<0.001). The effectiveness of oscillatory PEP-therapy is confirmed by a 7-fold decrease in the frequency of radiological changes in the lungs at the end of sessions (p<0.001), while in the control group the frequency of their occurrence practically did not change and remained at a high level. The total number of patients with respiratory insufficiency (SpO2≤92%) decreased by 8.6 times after completion of all PEP- therapy sessions (p=0.001), however, without statistically significant difference with the control group. CONCLUSIONS: Oscillatory PEP- therapy in cardiac surgery patients has a positive effect on sputum passage, ventilation parameters and oxygenating lung function. The procedure was well tolerated and there were no complications associated with it.
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Procedimentos Cirúrgicos Cardíacos , Adulto , Humanos , Adolescente , Estudos Prospectivos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Oxigênio , Terapia Respiratória , PulmãoRESUMO
BACKGROUND: Clinical and laboratory signs of hyperinflammatory response in COVID-19 may serve as prognostic markers of the disease scenario. In real-world practice, there is an unmet need to determine the optimal timing of identifying predictors of SARS-CoV-2 adverse outcomes in the context of patient stratification to improve the effectiveness of anti-IL-6R therapy. Lymphopenia has a high informative value for the adverse prognosis of the COVID-19 course; however, the informative value of CD3+CD4+, CD3+CD8+ T-cell count remains questionable. In addition to lymphocyte phenotyping, a six-criterion additive scale (cHIS) was used in the study. AIM: To study the informative value of CD3+CD4+, CD3+CD8+ T-cell phenotyping and cHIS scale as predictors of severe COVID-19 when using IL-6R blockers. MATERIALS AND METHODS: A single-center, bi-directional study included 179 patients with SARS-CoV-2-induced community-acquired pneumonia with severe acute inflammation and progressing respiratory failure. Data were obtained from electronic patient records. Anti-IL-6R was administered in addition to standard therapy in the cohorts. The following disease outcomes were used to determine the informative value of the studied parameters: mortality and hospital discharge. Inflammatory markers were measured before and after administering anti-IL-6R, followed by monitoring. Statistical analysis was performed using SPSS (version 25.0). The quantitative indices were described using the median and interquartile range. Quantitative indices were compared using nonparametric methods: Mann-Whitney U-test, Kruskal-Wallis test. The groups were compared by qualitative characteristics using Pearson's chi-square test. Correlation analysis of quantitative indicators was performed using Spearman rank correlation. For additional analysis of the cHIS scale, odds ratio and decision tree methods were used. Differences were considered statistically significant at Ñ≤0,05. RESULTS: Immunophenotyping of lymphocytes as a predictor of the severe SARS-CoV-2 requires further research. The cHIS scale may be implemented in routine clinical practice due to its high predictive value. A cHIS score of ≥2 on the first day of admission is a critical threshold for intensification and revision of therapy. The prognosis with cHIS is logically relevant in the first three days of hospitalization. CONCLUSION: The main result of the study is the definition of target groups of patients with community-acquired SARS-CoV-2 pneumonia for the IL-6R-blockers, considering the timing of their effective use in real clinical practice.
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COVID-19 , Receptores de Interleucina-6 , Humanos , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , COVID-19/diagnóstico , Hospitais , Receptores de Interleucina-6/antagonistas & inibidores , SARS-CoV-2 , Contagem de LinfócitosRESUMO
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.
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Antiasmáticos , Asma , Hipersensibilidade , Feminino , Humanos , Omalizumab/farmacologia , Omalizumab/uso terapêutico , Antiasmáticos/farmacologia , Antiasmáticos/uso terapêutico , Estudos Retrospectivos , Anticorpos Monoclonais , Asma/diagnóstico , Asma/tratamento farmacológico , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Imunossupressores/uso terapêutico , Fatores Biológicos/uso terapêutico , Imunoglobulina G , Anti-Inflamatórios/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: The use of virus-neutralizing monoclonal antibodies is an effective method of etiotropic therapy for SARS-CoV-2 in patients of high-risk groups of severe COVID-19. Regdanvimab is a single-component monoclonal antibodies immunoglobulin G1, whose mechanism of action is aimed at binding SARS-CoV-2 virus at the RBD site of the spike protein S1 domain. In the Russian Federation, regdanvimab is approved for emergency administration in COVID-19 for adult patients not requiring respiratory therapy who are at high risk of developing a severe course of the disease. AIM: To evaluate the efficacy and safety of therapy with regdanvimab in patients with mild/moderate COVID-19 in a short-term hospital unit. MATERIALS AND METHODS: Virus-neutralizing therapy with regdanvimab was performed at the short-term hospital unit of the Moscow City Clinic. An open retrospective observational single-center study included 92 adult patients with mild/moderate coronavirus infection. All patients had comorbid chronic diseases and belonged to the high-risk group for the development of a severe COVID-19. INCLUSION CRITERIA: age 18 to 75 years; presence of a verified diagnosis of COVID-19 of mild/moderate COVID-19, polymerase chain reaction (PCR) confirmed; one or more chronic diseases; first 7 days from the onset of the first symptoms of COVID-19 (including day 7). EXCLUSION CRITERIA: need for oxygen support. Clinical efficacy was assessed according to the World Health Organization Сlinical Progression Scale and supplemented with laboratory markers at baseline and in dynamics, as well as with monitoring of virus elimination by PCR. STATISTICS: Calculations were performed using the statistical computing environment R 4.1.3 (R Foundation for Statistical Computing, Austria). For quantitative indices the median (1; 3 quartiles) was indicated. For binomial signs we calculated 95% confidence intervals according to Wilson's method. Time interval analysis was performed according to the KaplanMeier method. The significance level was determined at p0.05. RESULTS: A significant decrease in the severity of clinical manifestations according to the World Health Organization Clinical Progression Scale was noted by patients by day 4 after regdanvimab administration. All 92 patients in the cohort were discharged from the hospital l on average on day 5 after regdanvimab administration and on day 9 of the disease. On day 4 after drug administration 82% of patients was being PCR negative. No adverse events related to the administration of regdanvimab were reported during the study. CONCLUSION: In real clinical practice, the efficacy and safety of regdanvimab in patients at high risk of severe COVID-19 was confirmed once again, with a positive clinical result observed in a mixed cohort by the causative agent omicron and delta strain.
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Tratamento Farmacológico da COVID-19 , COVID-19 , Adulto , Humanos , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , COVID-19/epidemiologia , SARS-CoV-2 , Estudos Retrospectivos , Glicoproteína da Espícula de Coronavírus , Fatores de Tempo , Anticorpos Monoclonais Humanizados/efeitos adversos , Resultado do Tratamento , OxigênioRESUMO
Asthma and chronic obstructive pulmonary disease remain major problems of medicine, and still there is need to improve the level and quality of diagnosis of these diseases. Primary care physicians (general practitioners, therapists) should be involved widely and actively in this process. To simplify the diagnosis, special questionnaires have been developed, they can be used in a real clinical practice. Only this approach will bring statistical data closer to the true prevalence of these diseases and improve quality of their treatment.
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Asma , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/terapia , Asma/diagnóstico , Asma/epidemiologia , Asma/terapia , Inquéritos e Questionários , Prevalência , Federação Russa/epidemiologiaRESUMO
AIM: To study the effect of levilimab or baricitinib in combination with standard therapy (ST) on the incidence of severe viral pneumonia associated with a new coronavirus infection COVID-19. MATERIALS AND METHODS: A multicenter, open-label observational study of the efficacy and safety of levilimab in combination with ST (group 1, n=100), baricitinib in combination with ST (group 2, n=139), or in comparison with ST (group 3, n=200) in outpatients with verified CT-1 pneumonia. RESULTS: According to the results of laboratory tests, patients treated with levilimab in combination with ST had the best dynamics of changes in CRP from reliably the highest level (mg/L) to the lowest in comparison with other groups. In the group of patients with ST, in contrast to the other groups, no dynamics of CRP was observed by day 5 of therapy. In group of hospitalized patients initially receiving levilimab in addition to ST, the rate of transfer to the intensive care unit (2 patients, 9.52%) and length of stay (4 days) was significantly lower compared to the values in patients in both the baricitinib group in combination with ST (7 patients, 15.56%; 5 days [interquartile range 36.5]) and in patients receiving ST alone (7 patients, 15.56%; 5 days [interquartile range 36.5]). Also in hospitalized patients we observed no statistically significant intergroup differences in the incidence of infectious complications and thromboembolic events, which confirms the safety of including levilimab or baricitinib in COVID-19 pathogenetic therapy regimens. Observational results support the hypothesis that the initial inclusion of levilimab or baricitinib in addition to ST is accompanied by a reduced risk of viral pneumonia progression. CONCLUSION: The addition of levilimab or baricitinib to the therapy regimen for coronavirus infection during the outpatient phase has demonstrated a preemptive anti-inflammatory effect and reduced the probability of lung tissue damage progression.
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Tratamento Farmacológico da COVID-19 , Pneumonia Viral , Humanos , Pacientes Ambulatoriais , SARS-CoV-2 , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Resultado do TratamentoRESUMO
Chronic urticaria (CU) affects about 1% of the world population of all ages, mostly young and middle-aged women. It usually lasts for several years (> 1 year in 25-75% of patients) and often takes > 1 year before effective management is implemented. It presents as chronic spontaneous urticaria (CSU), chronic inducible urticaria (CIndU) or both in the same person. More than 25% of cases are resistant to H1 -antihistamines, even at higher doses, and third- and fourth-line therapies (omalizumab and ciclosporin) control the disease only in two-thirds of H1 -antihistamine-resistant patients. Here we review the impact of CU on different aspects of patients' quality of life and the burden of this chronic disease for the patient and society. CU may have a strong impact on health-related quality of life (HRQoL), particularly when CSU is associated with angio-oedema and/or CIndU (Dermatology Life Quality Index > 10 in 30% of patients). Comorbidities, such as anxiety and depression, which are present in more than 30% of patients with CSU, compound HRQoL impairment. Severe pruritus and the unpredictable occurrence of weals and angio-oedema are responsible for sleep disorders; sexual dysfunction; limitations on daily life, work and sports activities; interfering with life within the family and in society; and patients' performance at school and work (6% absenteeism and 25% presenteeism). Apart from treatment costs, with annual values between 900 and 2400 purchasing power parity dollars (PPP$) in Europe and the USA, CU is associated with a high consumption of medical resources and other indirect costs, which may reach a total annual cost of PPP$ 15 550.
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Urticária Crônica , Urticária , Doença Crônica , Europa (Continente) , Feminino , Humanos , Pessoa de Meia-Idade , Omalizumab/uso terapêutico , Qualidade de Vida , Urticária/tratamento farmacológico , Urticária/epidemiologiaRESUMO
BACKGROUND: Several anti-cytokine therapies were tested in the randomized trials in hospitalized patients with severe acute respiratory syndrome coronavirus 2 infection (COVID-19). Previously, dexamethasone demonstrated a reduction of case-fatality rate in hospitalized patients with respiratory failure. In this matched control study we compared dexamethasone to a Janus kinase inhibitor, ruxolitinib. METHODS: The matched cohort study included 146 hospitalized patients with COVID-19 and oxygen support requirement. The control group was selected 1:1 from 1355 dexamethasone-treated patients and was matched by main clinical and laboratory parameters predicting survival. Recruitment period was April 7, 2020 through September 9, 2020. RESULTS: Ruxolitinib treatment in the general cohort of patients was associated with case-fatality rate similar to dexamethasone treatment: 9.6% (95% CI [4.6-14.6%]) vs 13.0% (95% CI [7.5-18.5%]) respectively (p = 0.35, OR = 0.71, 95% CI [0.31-1.57]). Median time to discharge without oxygen support requirement was also not different between these groups: 13 vs. 11 days (p = 0.13). Subgroup analysis without adjustment for multiple comparisons demonstrated a reduced case-fatality rate in ruxolitnib-treated patients with a high fever (≥ 38.5 °C) (OR 0.33, 95% CI [0.11-1.00]). Except higher incidence of grade 1 thrombocytopenia (37% vs 23%, p = 0.042), ruxolitinib therapy was associated with a better safety profile due to a reduced rate of severe cardiovascular adverse events (6.8% vs 15%, p = 0.025). For 32 patients from ruxolitinib group (21.9%) with ongoing progression of respiratory failure after 72 h of treatment, additional anti-cytokine therapy was prescribed (8-16 mg dexamethasone). CONCLUSIONS: Ruxolitinib may be an alternative initial anti-cytokine therapy with comparable effectiveness in patients with potential risks of steroid administration. Patients with a high fever (≥ 38.5 °C) at admission may potentially benefit from ruxolitinib administration. Trial registration The Ruxolitinib Managed Access Program (MAP) for Patients Diagnosed With Severe/Very Severe COVID-19 Illness NCT04337359, CINC424A2001M, registered April, 7, 2020. First participant was recruited after registration date.
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Tratamento Farmacológico da COVID-19 , Adulto , Estudos de Coortes , Dexametasona/uso terapêutico , Humanos , Nitrilas , Pirazóis , Pirimidinas , SARS-CoV-2 , Resultado do TratamentoRESUMO
AIM: To determine the criteria for the optimal use of IL-6 receptor blockers in patients with COVID-19 community-acquired pneumonia based on predictors of adverse outcomes. MATERIALS AND METHODS: The single-center, non-randomized prospective study included 190 patients with community-acquired pneumonia caused by coronavirus 2 between the beginning of March and the end of May 2020. Of these, 89 patients received tocilizumab and 101 patients received sarilumab. The study inclusion criterion for the patient was indications for initiating therapy with one of the inhibitors of IL-6 receptors (anti-IL-6R) according to the Interim guidelines (versions 4 and 5). The exclusion criterion was the need to re-prescribe genetically engineered biological therapy (GEBT). The severity of the patient's condition was assessed according to the early warning score (NEWS2), the volume of lung tissue lesions was assessed according to computed tomography (CT). Laboratory monitoring included counting the absolute (abs) number of lymphocytes, serum levels of C-reactive protein (CRP), interleukin 6 (IL-6), D-dimer, lactate dehydrogenase, fibrinogen. Statistical data processing was conducted by nonparametric methods using the IBM SPSS Statistics V-22 software. RESULTS: The phenotype of a patient with a negative outcome prognosis was described: a male patient over 50 years of age with aggravated premorbid background (with cardiovascular diseases, obesity and/or chronic renal disease), lung lesion CT 34, saturation less than 93% upon inhalation of atmospheric air, persisting for 2448 hours after GEBT. According to the blood test, lymphopenia was below 1000 U/L and CRP levels were above 50 mg/L. The laboratory parameters and clinical picture of the patient progressively worsened after 911 days of illness, regardless of the use of Anti-IL-6R. The features of patients monitoring when administering IL-6 receptor blockers have been determined. CONCLUSION: IL-6 receptor blockers should be administered to patients hospitalized with severe COVID-19 before the development of hyperinflammatory reactions. The optimal "therapeutic window" is 78 days of illness.
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Tratamento Farmacológico da COVID-19 , Humanos , Masculino , SARS-CoV-2 , Interleucina-6 , Estudos Prospectivos , Proteína C-Reativa , Receptores de Interleucina-6 , Fibrinogênio , Lactato DesidrogenasesRESUMO
During last few years, the approaches to the management of patients with severe asthma have been revised. Monoclonal antibodies (MABs), inhibitors of interleukin-5 (reslizumab, mepolizumab, benralizumab) have been recently introduced for the treatment of severe eosinophilic asthma. The mentioned drugs were approved in Russia and included into the list of Vitally Essential Drugs. AIM: The aim of this study was to compare the clinical and economic consequences of the use of biological agents that antagonize IL-5 in the treatment of severe eosinophilic asthma in adults. MATERIALS AND METHODS: Two methods of clinical and economic research were used: assessment of the cost-effectiveness ratio and analysis of the budget impact. The effectiveness of the drugs was assessed using indirect comparison; special attention was paid to comparability of the patient groups in the studies chosen for such an assessment. Two approaches were used for calculation of the cost of therapy for severe asthma: using DRGs (applicable to most regions of Russia), and without the use of DRGs, which is relevant only for few Russian regions. RESULTS: Basing on the data obtained from a budget impact study without the use of DRG, it was shown that reslizumab was dominating for patients with body mass of up to 70 kg, while for the patients with body mass of 70 to 110 kg, mepolizumab was dominating, while utilization of reslizumab appeared to be somewhat more expensive. In the group of patients with body mass over 110 kg, mepolizumab also was dominating. The calculation of the cost-effectiveness ratio (CER) showed that reslizumab appeared to be dominating over two other MABs, The results of the study using the DRG demonstrated that the cost of an annual course of benralizumab in most cases in Russia would exceed the amount that can be compensated by Territorial Funds for Mandatory Medical Insurance to a healthcare institution for therapy of bronchial asthma in one adult patient with genetically engineered drugs. Therefore, further comparisons were made for reslizumab and mepolizumab only. Analysis of the impact on the budget demonstrated that treatment with reslizumab and mepolizumab would represent a similar burden for the budget. When applying cost-effectiveness analysis, reslizumab was more cost-effective than mepolizumab (regardless of patient body mass). CONCLUSION: Thus, the results of the clinical and economic study suggested that, basing on the cost-effectiveness analysis, reslizumab appeared to be the dominant IL-5 antagonist (regardless of body mass if DRG approach was used and in patients with body mass up to 110 kg, if such an approach was not used). Basing on budget impact analysis, calculations without use of DRG approach showed superiority of reslizumab over mepolizumab and benralizumab for the patients with body mass up to 70 kg and the DRG-based approach showed equal burden for the budget for reslizumab and mepolizumab for the patients with any body mass.
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Antiasmáticos , Asma , Adulto , Antiasmáticos/uso terapêutico , Anticorpos Monoclonais Humanizados , Asma/tratamento farmacológico , Humanos , Federação RussaRESUMO
Common variable immune deficiency is the most common form of a group of primary immunodeficiencies in adult patients. Pulmonary complications occupy leading positions. It is the development of recurrent bronchopulmonary inflammatory diseases that is considered to be one of the main causes of death and disability in patients with this disease. By presenting two clinical cases with long diagnostic delays, the authors try to attract the attention of specialists of related professions, which will minimize the development of irreversible complications in the patients.
Assuntos
Imunodeficiência de Variável Comum , Adulto , Imunodeficiência de Variável Comum/complicações , Imunodeficiência de Variável Comum/diagnóstico , HumanosRESUMO
OBJECTIVE: To unite within the framework of a single clinical entity (based on the model of hypochondriacal paranoia) phenomena of the somatopsychotic and hypochondriacal range, which, in accordance with modern systematics, are classified as various categories of psychosomatic, affective disorders and personality disorders. MATERIAL AND METHODS: The sample for analysis consisted of 29 patients (with the diagnosis of delusional disorder (ICD-10; F22.0 in ICD-10), 10 men (34.5%) and 19 women (64.5%), the average age was 42.9±19.9 years; men - 10 nab. (34.5%), women - 19 nab. (64.5%). The average duration of the disease iswas 9.4±8.5 years. The psychopathological method was used as the main one. RESULTS: The article forms an alternative concept of somatic paranoia based on the model of hypochondriacal paranoia. The fundamental difference between the construct of somatic paranoia is an obligate connection between somatopsychic and ideational disorders. Somatopsychic (coenesthesiopathic) symptoms do not exist as an independent (equivalent to the structure of somatic clinical syndromes) dimensions and are formed exclusively with the participation of ideational phenomena. CONCLUSION: In accordance with the presented concept, coenesthesiopathic symptoms within the framework of somatic paranoia act as a somatic equivalent of delusional disorders.