ABSTRACT
As numerous scientific data show, despite the fact that patients with severe psoriasis have a high risk of coronavirus infection, COVID-19 in this group proceeds quite easily. However, many specialists have encountered an unusual exacerbation of the pso-riatic process already after the infection, the reasons for which may be several. On the one hand, the skin is one of the target organs for SARS-CoV-2, on the other hand, exacerbations may be caused by the immune system response to the infection. The influence of specific therapy on the course of the psoriatic process is also not excluded. But interleukin status of patients with psoriasis is of the greatest interest. It is known that interleukin-6 (IL-6) plays an active role in pathogenesis of COVID-19 and cytokine storm arising at infection. It is also regarded as an indicator of inflammatory activity in psoriasis. In addition, IL-6 is involved in lipid and hepatobiliary disorders in this group of patients. It is also associated with IL-17, the role of which has been well studied in psoriasis and autoimmune hepatitis. Patients with psoriasis often have changes in biochemical blood parameters, similar to those seen with COVID-19. Combinations of all these factors can lead to exacerbation of psoriasis with predominance of erythroderma and toxic component. In our opinion, in such cases it is necessary to include in the therapy a systemic hepato-protective drug containing glycyrrhizic acid. It has a pronounced anti-inflammatory effect, inhibits IL-6 production and allows to achieve significant improvement of psoriatic process in a short time. © 2022, Remedium Group Ltd. All rights reserved.
ABSTRACT
A new SARS-CoV-2-associated coronavirus infection pandemic began in late 2019. The present article is devoted to the analysis of the mechanisms of COVID-19 impact on the course of psoriasis and its consequences. According to the scientific literature, patients with psoriasis are somewhat more likely to be infected with coronavirus infection than the healthy population, but tolerate it in a milder form. At the same time, cases of psoriatic process exacerbation during the active phase of the disease and after COVID-19 have been described. The negative effect of infection on skin disease can be explained by the common genome of the two nosologies, the «cytokine storm» and the prescription of COVID-19 drugs. In addition, both COVID-19 and psoriasis can cause liver dysfunction related to the specific pathogenesis of the diseases as well as the prescribed therapy. The article describes our own experience of monitoring patients with exacerbation of psoriasis against the background of coronavirus infection with pathological changes in liver tests. Inclusion of a fixed combination of glycyrrhizic acid and essential phospholipids in the complex treatment allowed to stop the exacerbation of the psoriatic process more effectively, to reduce the activity of liver enzymes without worsening the clinical conditions associated with COVID-19. Thus, in particular, a clinically significant improvement of the skin condition was recorded. In patient B., alanine aminotransferase activity decreased to 44.4 U/L and aspartate aminotransferase activity to 18.2 U/L. In turn, in patient M. the activity of liver enzymes decreased to 37.8 U/L and 34.7 U/L, respectively. The prescription of this drug can be considered pathogenetically justified, given the effect of glycyrrhizic acid on the production of key cytokines involved in the inflammatory process in psoriasis, coronavirus infection and liver pathology. In addition, the hypothesis of the ability of glycyrrhizic acid to prevent the entry of SARS-CoV-2 into the cell by reducing the expression of angiotensin-converting enzyme 2 is of interest. © Katkova K.V., Plieva K.T., Denisova E.V., Zhukova O.V., Volnukhin A.V., Korsunskaya I.M. 2021.
ABSTRACT
Severe and critical forms of COVID-19 are beset by the development of "a cytokine storm", which is characterized by an increased secretion of proinflammatory cytokines. Therefore, one of the leading strategies for treating patients with severe forms of COVID-19 is the reduction of concentration of proinflammatory cytokines and leveling out their effect on the patient. Among the drugs aimed at reducing the concentration of proinflammatory cytokines, IL-6 inhibitors, IL-1 inhibitors, JAK inhibitors and systemic glucocorticosteroids have been found useful in COVID-19. All of these drugs are currently prescribed off-label. The aim of the work is a comparative analysis of the data from the literature sources in the PubMed system, devoted to the clinical efficacy and safety of IL-6, IL-1, JAK inhibitors and systemic glucocorticosteroids in the treatment for severe forms of COVID-19. Materials and methods. In the treatment for severe forms of COVID-19, materials for the comparative analysis were the data from the literature sources in the PubMed system, on the studies devoted to the use of the systemic glucocorticosteroid dexamethasone, IL-6 inhibitor tocilizumab, IL-1 inhibitor anakinra, and JAK inhibitor ruxolitinib. The analysis was performed by statistical evaluation of the drugs effect within the 28-day survival rate among the patients with severe COVID-19. Attributive statistics was used as a statistical tool. The safety of the drug use was assessed by analyzing potential drug interactions. The information about potential drug interactions, was obtained from a specialized website - Drugs.com. Knowmore. Besure (https://www.drugs.com/interaction/list/). Results. As a result of the analysis, it has been established that tocilizumab has the highest efficacy rates. In this respect, it is followed by dexamethasone. The attributive efficacy rates and 95% confidence interval values for the both drugs were statistically significant. The indices of relative and population attributive kinds of efficacy, were also higher for tocilizumab, but a 95% confidence interval of these indices, get into the range of statistically insignificant values, requiring additional evidence of their efficacy. According to the data obtained, tocilizumab efficacy is higher than that of the other drugs compared: NNT (dexamethasone) - 32;NNT (tocilizumab) - 4, NNT (ruxolitinib) - 7;NNT (anakinra) - 35. Conclusion. The choice of a drug should be based on the patient's condition, comorbidities, and medications used in therapy to minimize the risk of undesirable drug interactions. Against the background of the lowest efficacy among the compared drugs, a high efficacy for the patients with concomitant hepatobiliary disorders and DIC syndrome, has been established for the inhibitor IL-1 anakinra, which makes it the drug of choice among the patients with these diseases and under these conditions in the development of "a cytokine storm".
ABSTRACT
Background. Severe forms of COVID-19 are associated with the development of a cytokine storm that is characterized by an increased secretion of anti-inflammatory cytokines. Thus, one of the leading strategies of treatment for patients with severe forms of COVID-19 is a decrease in the concentration of anti-inflammatory cytokines and inhibition of their effect on the organism. Objective: to perform a comparative analysis of clinical and economic constituents of the application of an IL-6 inhibitor tocilizumab and systemic glucocorticosteroid dexamethasone for the therapy of severe conditions in patients with COVID-19 based on the published data review. Material and methods. The authors analyzed the data obtained from PubMed/MEDLINE databases on the study dedicated to the application of tocilizumab and dexamethasone for the therapy of severe conditions in patients with COVID-19. A statistical evaluation of the influence of these drugs on the 28-day survival rate of patients with a severe form of COVID-19 was performed. The statistical tools included methods of the attribute-based statistic (attribute-based efficiency, relative efficiency (RE), populational attributive efficiency (PAE)). For the visualization of the clinical efficiency of the compared drugs, the authors applied beta-distribution. Markov's model was used for modeling of the mortality rate. The modeling included the study of a hypothetical cohort of patients (1,000 patients with COVID-19). Besides, the authors evaluated the economic constitutive of the therapy with tocilizumab and dexamethasone. The cost-effectiveness analysis was performed. Results. The indication of dexamethasone statistically significantly increases the survival rate by 3.1% and tocilizumab - by 22.5%. RE was 1.04 (95% CI 0.040-2.042) for dexamethasone and 1.66 (95% CI 0.400-2.917) for tocilizumab. The lower border of 95% CI for both drugs was within the range of values <1, which was statistically significant. PAE for dexamethasone was 1.0% (95% CI -0.6-2.6), for tocilizumab - 16.5% (95% CI -0.7-33.7). Lower borders of 95% CI for both drugs ranged within negative values, which was not statistically significant. NNT (dexamethasone) was 32;NNT (tocilizumab) was 4. Markov's modeling showed that the mortality rate among patients who received these drugs was 36 out of 1000 patients with COVID-19 for dexamethasone (initially distributed by the degree of severity according to the official statistical data) and 30 out of 1000 patients for tocilizumab, respectively. The cost of the treatment course with dexamethasone was 107.45 rub., tocilizumab - 78,827.20 rub. Clinical efficiency by the rate of cured patients obtained as a result of Markov's modeling among patients with severe forms of COVID-19 for both drugs was comparable (0.964 for dexamethasone and 0.970 for tocilizumab) with slightly higher values for tocilizumab. Conclusion. Despite relatively comparable clinical efficiency of dexamethasone and tocilizumab and a significantly higher cost the later, it is not impossible to replace tocilizumab with dexamethasone because of a great number of side effects and potential inter-drug interactions during the treatment of severe forms of COVID-19. In particular, dexamethasone therapy should be performed with caution in patients with diabetes mellitus. Procurement planning should be made taking account the reserves of tocilizumab for the stabilization of patients with cytokine storm when dexamethasone application is not safe.
ABSTRACT
Introduction. With the onset of the COVID-19 pandemic the dermatological manifestations of the infection are widely discussed along with the correct management tactics for patients with severe chronic dermatoses, primarily those on immunosuppressive therapy. Immunocompromised patients are overly vulnerable to infections, which is especially important in the context of the pandemic. The article provides up-to-date literature information regarding the general risks of infection in patients receiving systemic immunomodulatory agents for the treatment of psoriasis, as well as evidence based treatment recommendations, including the example of our own clinical experience of using targeted therapy during the COVID-19 pandemic. Purpose of the study. The aim of the study was to analyze the therapeutic efficacy and safety of the systemic immunomodulatory drugs therapy in the context of the global COVID-19 pandemic. Materials and methods. The study included 142 patients with psoriasis receiving GEBD and small molecules therapy at the Department of Anti-Cytokine Therapy and Efferent Methods of Treatment of MNPCDK DZM. All patients were examined to deter-mine their level of IgM and IgG antibodies to the SARS-CoV-2 virus strain in the blood serum. All patients continued to receive therapy according to their individual dosing regimen. The study was conducted at a time of high morbidity in the city of Moscow. Results. The overall morbidity among the studied patients was 13.4% of which the majority were patients with an asymptomatic course of the disease. It should be noted that there was a low incidence rate among patients receiving therapy with IL-17 inhibitors (secukinumab, netakimab). Conclusion. Our study confirms worldwide records that there is no evidence of an increased risk of COVID-19 among patients receiving targeted therapy for psoriasis. In our opinion, the discuntinuation of the current treatment can lead to unjustified risks, such as a relapse of psoriasis, including with severe manifestations and subsequent possible ineffectiveness when resuming therapy. Potentially, the termination of therapy that suppresses the production of proinflammatory cytokines will lead to an increase in the “cytokine storm” and a worsening of the course of viral infection when it occurs. © 2020, Remedium Group Ltd. All rights reserved.
ABSTRACT
The objective was to evaluate the effect of tocilizumab on the mortality indexes in patients with severe COVID-19 by using linear graph modeling and a state transition probability matrix to describe the COVID-19 course. Materials and Methods. Official statistical data on the absolute and relative numbers of COVID-19 cases were used. Linear graphs of states were used to model the COVID-19 course. Sensitivity analysis was performed to determine how the model output (the fatality rate) changes as a result of simultaneous changes in p34 (a transition from severe to critical disease), p35 (a transition from severe disease to death), and p45 (a transition from critical disease to death). Results. The input was a model group of 1000 patients, which were initially distributed by disease severity according to the statistical data. The model yields an absolute mortality of 54 patients;the fatality rate is 5.4% at the given state transition probabilities. Tocilizumab administration is intended only in severe and critical cases, where cytokine storm occurs. With this input, the model yields an absolute mortality of 48 patients (fatality rate is 4.8%). The probabilities in sensitive analysis were varied in a range of ±50% with an increment of 10%. Calculations showed that 10% decreases in probabilities p34, p35, and p45 decrease the fatality rate to the same extent, by 10.39%. Conclusion. A decrease in the rate of transition to critical disease reduces the fatality rate in COVID-19 to the same extent. Promising results have been obtained with tocilizumab, demonstrating a decrease in the frequency of critical cases and, therefore, the fatality rate. The safety profile and efficacy of the drug need additional verification.
ABSTRACT
Currently, information on the epidemiology, clinical features, prevention and treatment of a novel coronavirus infection COVID-19 caused by SARS-CoV-2 is constantly updated. The new SARS-CoV-2 coronavirus is a single-stranded RNA virus of the Coronaviridae family, Beta-CoV line B. SARS-CoV-2 is included in the pathogenicity group II along with other viruses of this family (SARS-CoV virus, MERS-CoV virus). Case definition and diagnosis of COVID-19 is carried out in accordance with the interim guidelines “Prevention, diagnosis and treatment of novel coronavirus infection (COVID-19)” of the Ministry of Health of the Russian Federation (ver. 6, 04/28/2020). The most common clinical manifestation of COVID-19 is bilateral pneumonia, with 3-4% of patients developing acute respiratory distress syndrome (ARDS). In connec-tion with the ongoing COVID-19 pandemic, new symptoms of multiple organ lesions, including skin lesions, appear in the clinical symptoms of the disease. Clinical symptoms of COVID-19 characterized by skin lesions may be the first symptoms of the disease. The article presents materials on a brief description of the novel coronavirus infection COVID-19, as well as the clinical characteristics of skin lesions in this infection according to foreign researchers and based on personal observations of patients in hospitals of medical organizations of the Moscow Department of Health.