Search

Metastatic renal cell carcinoma accounts for almost 85% of all cases of malignant neoplasms of the kidney. Sunitinib is an anti-angiogenic tyrosine kinase inhibitor, one of the indications is the treatment of mRCC in adults. Sunitinib is an oral tyrosine kinase inhibitor that includes the vascular endothelial growth factor receptor (VEGFR) and the platelet-derived growth factor receptor (PDGFR). Sunitinib is primarily used as a first-line drug at an initial dose of 50 mg. 1 time per day for 4 weeks followed by a 2-week break. Recommendations, if dose modification is necessary, indicate a dose reduction to 37.5 mg per day and, if necessary, a further dose reduction to 25 mg per day. Another promising regimen is to continue the daily dose of 50 mg with more frequent breaks: 2 weeks of treatment followed by a pause of 1 week. The analysis presented in the article shows that patients with mRCC who switched to sunitinib 2/1 regimen due to adverse events from the standard 4/2 regimen do show an improved safety profile. There is evidence of a significant reduction in overall grade 3-4 toxicity, as well as a reduction in the incidence of specific drug toxicity such as fatigue, hypertension, hand and foot syndrome, and thrombocytopenia. The article presents a clinical observation of a patient with advanced renal cell carcinoma who has a contraindication for immunotherapy. The patient underwent cytoreductive laparoscopic resection of the left kidney. Taking into account the existing contraindications to immunotherapy, the patient was prescribed sunitinib monotherapy at the standard dosage in the first line. After two courses of therapy, due to adverse events, the therapy regimen was changed from 4/2 to 2/1. The ongoing therapy in the 2/1 regimen demonstrated a satisfactory safety profile with adequate clinical efficacy.

Hepatocellular carcinoma is a common type of liver malignancy and one of the leading causes of cancer death worldwide. In the Russian Federation, according to statistical reports, there is also an increase in the incidence. For over 10 years, the tyrosine kinase inhibitor sorafenib has been the only approved treatment for advanced hepatocellular carcinoma. Lenvatinib was registered as the second drug for the treatment of advanced hepatocellular carcinoma in the first line. In the era of checkpoint inhibitors, the possibility of such therapy in the first and subsequent lines of advanced hepatocellular carcinoma remains relevant. The combination of atezolizumab with bevacizumab in a phase III study (IMbrave150) improved treatment outcomes such as overall survival and progression-free survival. The results of the phase III randomized trial IMbrave 150 showed undoubtedly better efficacy of the atezolizumab + bevacizumab combination compared to sorafenib in terms of a median progression-free survival of 6.8 vs 4.3 months. The above clinical observation demonstrates the result of treatment of a patient with advanced hepatocellular carcinoma with a combination of atezolizumab and bevacizumab. After verification of the diagnosis, since January 2021, therapy with a combination of atezolizumab 1200 mg, bevacizumab 15 mg/kg was started with an interval of 21 days.At present, 20 courses of therapy have been carried out in this regimen, and the stabilization of the disease is maintained. Against the background of the ongoing therapy, no adverse events were noted, including immune-mediated ones that required the abolition or reduction of doses of drugs. In the above clinical observation, a patient with severe comorbidity achieved stabilization of the disease in the first three months of therapy. Combination therapy showed a favorable tolerability profile.

The need to review the guidelines for the management of patients with multiple sclerosis using multiple sclerosis disease modifying drugs has become acute enough since the beginning of 2020 following the outbreak of the COVID-19 pandemic caused by a novel coronavirus SARS-CoV-2. Immunosuppressive drugs were also specifically addressed, as it is during administration of these drugs that the more severe course of COVID-19 disease was expected. Both the Russian and foreign teams published results of their research works. This article presents a retrospective analysis of the incidence rates of COVID-19 in patients with multiple sclerosis after selective immunosuppressive therapy with alemtuzumab and a clinical case when a patient was infected with coronavirus in the first days following the last infusion of the therapy course without clinical manifestations of the infectious disease. The author discusses the mechanisms underlying such a favourable outcome due to the CD52 lymphocyte depletion leading to the reduction of risks of developing hyperimmune reactions that underlie severe complications of COVID-19, and analyses previously published works of our foreign colleagues on the same theme. The review of the accumulated works and personal experience suggest that it is the CD52 lymphocyte depletion that makes it possible to avoid the cytokine storm and, as a result, the more severe course of COVID-19. Amidst the COVID-19 pandemic, during the prescription of multiple sclerosis disease modifying drugs, it should be borne in mind that patients should have access to all types of modern therapy and that the benefits should outweigh the sum of possible risks.

The COVID-19 pandemic was announced in 2020, and many professional medical societies had to review their algorithms for the management of high-risk patients. In addition to risk factors such as overweight, age over 65 years, cardiovascular disease, diabetes mellitus, and bronchial asthma, other chronic diseases should also be emphasized, taking into account possible immunosuppressive therapy. This publication presents two clinical cases of COVID-19 infection in patients with multiple sclerosis treated with ocrelizumab. During the course of the disease, both patients developed a cytokine storm and were treated with IL-6 blockers. Both cases ended with recovery and a subsequent return to anti-B-cell therapy. Given the mechanism of action of ocrelizumab, there are higher risks of infectious complications, including with COVID-19, but mortality is not higher than the population average. The information published to date may serve as a reason to consider the use of extended dosing intervals to minimize the possible risks of COVID-19 infection, which are probably highest in the first months after infusion.

Introduction. The routine use of highly effective drugs that alter the course of multiple sclerosis requires careful patient selection in order to minimize the risks of possible adverse events. At present, drugs modifying the course of multiple sclerosis have been registered with different mechanisms of action. This makes it possible to implement individual selection of therapy taking into account the multifaceted pathogenesis of the disease. However, the presence of a burdened somatic anamnesis in the patient may significantly limit the choice of drugs by the attending physician. Aim: to gain experience in using ocrelizumab to treat patients with multiple sclerosis. Materials and methods. From 2018 ocrelizumab therapy was started in 52 MS patients: 32 patients with recurrent multiple sclerosis (MS) (23 with remitting multiple sclerosis (RMS) and 9 with secondary progressive MS with exacerbations) and 20 patients with primary progressive multiple sclerosis (PPMS). The drug was administered intravenously in drops with infusion in a dose of 600 mg every 6 months in a daytime regimen with an approved protocol of premedication and symptomatic therapy to prevent possible risks of adverse events. The initial dose was divided into 2 infusions of 300 mg at intervals of 2 weeks [5]. Before each infusion, detailed clinical blood analysis, biochemical blood tests, serological tests (HIV, hepatitis B and C, syphilis), and screening for tuberculosis (once a year) were necessarily repeated.The results. The achieved results clearly demonstrate high efficacy of ocrelizumab in the form of reduction of exacerbations frequency, disease activity according to MRI data and slower progression, which is compared with the data from previous OPERA I, OPERA II and ORATORIO clinical trials. After analysis of the data of dynamics of disability index according to EDSS scale there was observed stabilization in PPMS patients and a slight decrease in RMS patients. No exacerbations were registered in patients with RMS during the period of treatment, as well as no objective data on progression in patients with PPMS were noted.There is also good tolerance of therapy. However, the question remains as to how long the therapy should take into account the safety spectrum.

Acetaminophen (AAP) is one of the most common and widely used antipyretic drugs, but its overdose is the leading cause of fulminant hepatic insufficiency in the world. Mechanisms of liver damage at the use of toxic doses of AAP are caused by the transformation of the isoform of cytochrome P450 (CYP2E1, CYP2A6) into a reactive metabolite, N-acetyl-parabenzoquinonimine (NAPQI), which plays a major role in hepatotoxicity. Another mechanism of hepatotoxicity includes the formation of peroxynitrite – a toxic free radical produced in the mitochondria, which causes oxidative damage. In addition to liver damage in case of acetaminophen poisoning, nephrotoxic effect can occur. Potential mechanisms of nephrotoxicity in overdose of AAP are presented, caused by cytochrome P450, as well as prostaglandin synthetase and enzyme N-deacetylase are described. In the clinical case described by us, the development of fulminant hepatic insufficiency against the background of acetaminophen administration led to the development of a coma along with the kidney damage, however, a stable positive dynamics, was achieved during treatment. In the catamnesis 2.5 years later, there were no signs of fibrosis or cirrhosis of the liver.

This article presents a clinical case of suboptimal response to multiple sclerosis therapy and an algorithm for treatment, taking into account the existing performance criteria.

This article presents the results of the immunological profile of CD4+ T cells and Th17 cells and production of interleukin-17 (IL-17) in two groups of patients receiving treatment natalizumab and fingolimod. The results can underpin the justification for the preferred transfer of patients with relapsing-remitting multiple sclerosis after treatment by natalizumab to fingolimod.

This article presents a review of the efficacy and safety of three oral drugs for multiple sclerosis, which are registered in the Russian Federation: teriflunomide, dimethylfumarate, fingolimod.

Monoclonal antibodies are widely used in various fields of modern medicine, for example, in oncology, rheumatology, gastroenterology, transplantation. Since beginning of this century monoclonal antibodies began to be explored for the treatment of multiple sclerosis (MS). From this period monoclonal antibody also actively introduced in pathogenetic therapy of MS. In this review, we discuss the findings of clinical trials already registered monoclonal antibodies in the Russian Federation, such as Natalizumab and Alemtuzumab.

There was a whole series of drugs that change the course of multiple sclerosis over the past 20 years. However, a single algorithm of patients of childbearing age has yet been developed. There are new drugs more efficiently, but at the same time with high risk of pathological effects on the fetus, which requires more detail to provide algorithm of this category of patients.

This review includes results of experimental and clinical studies of new oral drug teriflunomide for pathogenetic treatment of multiple sclerosis (MS). Given the mechanism of action, clinical data of the studies II and III phases of clinical efficacy, tolerability and safety. Discusses the place of teriflunomide in pathogenetic treatment of MS.

Multiple sclerosis (MS) is an immune-mediated chronic inflammatory disorder of the central nervous system (CNS) often causing disability in young adults. As is the case with the majority of autoimmune diseases, multiple sclerosis patients are predominantly women - 2.5 times more often than men. [1-4, 13] Considering the fact that the disease onset mainly occurs in childbearing age, it becomes clear why so much attention has been recently given to the possibility of pregnancy for patients with multiple sclerosis.

Dimethyl fumarate (DMF) is dimethyl ester of fumaric acid, a naturally occurring molecule that plays a key role in redox processes of tissue respiration. Results of studies on animal models demonstrate that the drug has an anti-inflammatory and cytoprotective action. Anti-inflammatory effects of DMF could be mediated by several mechanisms, including inhibition of nuclear factor-kappaB-dependent transcription and suppression of cytokine production and cell adhesion molecule expression. 2 years after start of treatment DMF significantly increased the relative number of patients without active disease by clinical, radiological and general criteria in comparison with the placebo group. According to the DEFINE trial, the proportion of patients without active disease in twice daily DMF group was 28% (vs placebo, p = 0,012), and 18% (vs placebo, p < 0, 0001) according to the CONFIRM trial. DMF demonstrated similar efficacy in various subgroups of patients classified according to baseline characteristics of the disease, including frequency of relapses in the past, pre-treatment, level of disability, as well as type and extent of the lesions. In terms of safety profile, DMF was similar to GA and placebo. Adverse effects on the gastrointestinal tract against the background of DMF were mild or moderate, transient and treatable. Administration of DMF did not increase the risk of infections and malignancies.

13 patients from the Moscow Multiple Sclerosis Center with remitting MS and not responsive to treatment with 1st line DMD were given Fingolimod (Gilenya) starting from January 2012. After one year of therapy, the group demonstrated a significant decrease in the frequency of exacerbations from 2,54 ± 0,97 to 0,15 ± 0,38 (p ≤ 0,0001) per year, and showed no disability progression according to EDSS. Other results were good tolerability and safety of therapy, no clinically relevant deviations in hematological state, no ophthalmic complications. In view of the possible risk of transient bradycardia, before starting fingolimid therapy MS patients were examined, and their heart was monitored for 6 hours after they were given first dose. The monitoring registered a decrease in heart rate within permissible range (not requiring medical intervention) in 30.76% of cases at 34th hour, and by 6th hour the heart rate returned to the baseline value.

A definite progress has been achieved in the treatment of patients with multiple sclerosis so far. However, first-line MS disease-modifying medications (MSDMM) do not always contribute to the stabilization of the autoimmune process. Second-line medications, including natalizumab, are successfully used for aggressive, hard-to-treat forms of multiple sclerosis. Given the potential risks of opportunistic infection in natalizumab therapy, a risk stratification scheme for progressive multifocal encephalopathy (PME) was developed. Strict adherence to the algorithm of MS treatment allows to minimize the risk of complications and successfully manage the hard-to-treat manifestations.

82 patients diagnosed with remitting multiple sclerosis, (MS) undergoing treatment with fingolimod were followed up for minimum 12 months at the Moscow Multiple Sclerosis Centre. The purpose of the follow-up was to evaluate the effects of fingolimod. 9 of 12 patients were subject to a comprehensive immunological examination to identify subpopulations of circulating T-cells. All patients were in clinical remission at the time of recruitment. All patients showed a significant decrease in the frequency of exacerbations during therapy with fingolimod. The disability status on the EDSS scale did not progress during the whole year of the follow-up. The therapy showed significant decrease in the production of IL-17 and the amount of TH17 cells in comparison with the control group, thus demonstrating a relevant decrease in the the autoimmune process activity. Withdrawal of fingolimod in 6-8 weeks was associated with normalization of the lymphocyte level in the peripheral blood due to drug elimination and wash-out of S1P receptors. However, given that wash-out of S1P receptors results in increased production of IL-17 and, consequently, higher BBB permeability, it is appropriate to name the disease reactivation as "rebound syndrome" which is primarily associated with a sharp increase in IL-17. This raises questions about management of patients who for various reasons need withdrawal of fingolimod therapy.

This article presents the review of results of clinical trials of drugs for pathogenetic therapy of primary progressive multiple sclerosis, including ocrelizumab.