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Graft failure (GF) is an extremely rare complication of autologous hematopoietic stem cell transplantation (auto-HSCT) with a frequency not exceeding 3–5 % of all cases of this technology. Primary graft failure is distinguished when restoration of hematopoiesis has not occurred by day +28 after hematopoietic stem cell transfusion, and secondary GF, implying the occurrence of neutropenia

Nowadays, the problems caused by polypharmacy are recognised and widely discussed in the medical community. Multimorbidity, which is not uncommon in paediatric practice, comes with an increase in the number of prescriptions and necessitates an active search for tools to reduce the potential risk and frequency of adverse drug–drug interactions in paediatric patients.The aim of the study was to use a clinical case to illustrate the need for monitoring, including laboratory monitoring of pharmacokinetic parameters, during concomitant therapy in paediatric practice.Materials and methods: the study consisted in a retrospective analysis of the archived medical records of an 11-year-old child with nephrotic syndrome associated with a concomitant tuberculous process who had been receiving inpatient treatment with immunosuppressants at the Russian Children’s Clinical Hospital from May to July 2018.Results: the prescription of cyclosporine for nephrotic syndrome entailed monitoring of plasma drug levels for potential pharmacokinetic interactions with the medicinal products used to treat the concomitant disease. The monitoring revealed an interaction between cyclosporine and rifampicin at the level of biotransformation. An adjustment of the concomitant therapy (discontinuation of rifampicin) allowed for achieving the target blood cyclosporine concentration, decreasing proteinuria and hypercholesterolemia, and increasing the blood total protein level in the child, which indicated the effectiveness of the ongoing treatment for the chief complaint.Conclusions: the data obtained suggest that laboratory monitoring of pharmacokinetic parameters in paediatric polypharmacy can increase the effectiveness of therapy and prevent adverse reactions and irrational combination of medicinal products.

Aim. То evaluate the effectiveness of a novel multi-targeted treatment approach including rituximab (RTX), cyclophosphamide (CPH) and steroids (S) to the induction of remission in patients with primary membranous nephropathy (PMN) compared to standard immunosuppression (IST). Materials and methods. An open-label prospective comparative study included 56 PMN patients (pts) with nephrotic syndrome (NS) and high serum level of antibodies to the phospholipase A2 receptor anti-PLA2R (mean age 5112 years, men 70%). We recorded demographic and clinical parameters at the time of kidney biopsy, data from light-optical and immunomorphological studies. All pts were on stable doses of the renin-angiotensin systems blockers. We compared the effectiveness of different treatments in the inductions of clinical and immunological remissions in pts who received experimental treatment with RTX, CPH and S (RTX+CPH+S group, n=14) and two control groups: high-dose RTX therapy (group RTX, n=12), cyclosporine and steroids (group CsA+S, n=30). Results. In the RTX+CPH+S group, remission was achieved in 100% of cases (of which complete remissions CR in 21.4%). The median time-to-remission (2.5 [1.0; 3.5] months) was significantly lower compared to both control groups: RTX (8.7 [6.6; 14.0] months, p=0.005) and CsA+S (12.4 [6.5; 19.9] months, p0.001). The cumulative incidence of clinical and immunological remissions was also significantly higher in the RTX+CPH+S group than in the control groups. These results were confirmed in comparative analyzes in the same treatment groups after propensity score matching. The cumulative incidence of clinical and immunological remissions in the RTX+CPH+S group was higher than in the combined group of patients who received other therapies (p0.001). The incidence of serious adverse events was low and did not differ between groups. Conclusion. The use of multi-targeted therapy with rituximab, cyclophosphamide, and steroids seems to be an effective approach for the rapid induction of PMN remission and prevention of NS complications.

In order to be registered, generic drugs with a narrow therapeutic range have to undergo bioequivalence or therapeutic equivalence studies. In most cases, comparative pharmacokinetic studies and demonstration of bioequivalence between the test and the reference products are sufficient for this group of drugs. However, there is no established official definition in Russia for the group of drugs that are regarded as having a narrow therapeutic range. Evaluation of bioequivalence of such drugs has to be performed providing for narrower confidence intervals, which entails certain problems at the stage of bioequivalence study planning. Finding solutions to the problems stated above is of great importance. The aim of the study was to develop approaches to planning bioequivalence studies of drugs with a narrow therapeutic range. Materials and methods: the paper analyses the results of 33 bioequivalence studies of drugs with a narrow therapeutic range, in which Cmax, AUC0-t, and tmax were calculated. Intra-individual variation and weighted mean intra-individual variation of Cmax and AUC0-t were estimated in the study. Statistical processing was performed using IBM SSPS Statistics v.25. and Microsoft Office Excel 2016. Results: the paper summarises criteria for categorising drugs as having a narrow therapeutic range and describes general requirements for assessing their bioequivalence. A number of bioequivalence studies of generic valproic acid, carbamazepine, levothyroxine, tacrolimus, and cyclosporine products which meet the criteria for drugs with a narrow therapeutic range, were analysed retrospectively. The data on their pharmacokinetics and intra-individual variation were calculated. It also summarises requirements for bioequivalence evaluation of drugs with a narrow therapeutic range. The paper gives product-specific recommendations for performing bioequivalence studies. Conclusion: the study helped to formulate approaches to the planning of bioequivalence studies of generic drugs with a narrow therapeutic range using the examples of valproic acid, carbamazepine, levothyroxine, tacrolimus, and cyclosporine.

Aim: to develop the emulsion transdermal therapeutic system (TTS) of cyclosporine and the research of its diffusion from TTS.Materials and methods. The quantitative evaluation of cyclosporine in model media was performed on liquid chromatograph Agilent 1100 G1311 with spectrophotometric detector G1315B (Germany). For the production of the emulsion matrix, the Heidolph DIAX900 disperser (Germany) and the ultrasonic homogenizer Hielscher UIS250V (Germany) were used. The cyclosporine diffusion from TTS through Strat-M membrane (25 mm in diameter, Merck Millipore) was studied using Copley diffusion analyser (Great Britain).Results. Using the developed method of micro-HPLC, it was established that the amount of cyclosporine passed through the Strat-M membrane over 24 hours from 10 sm2 TTS, containing 173 mg of the substance, was 5.9 mg. The estimated blood concentration is ~ 50 ng/ml which corresponds to the therapeutic maintenance blood concentration during organ transplantation (50–75 ng/ml).Conclusion. The model studies demonstrate the possibility of the cyclosporine transdermal transfer.

Currently, patients after kidney transplantation can receive mycophenolate mofetil (MPM), mycophenolic acid (MPA), cyclosporine (CSA) and tacrolimus (TAC) through the Federal High-cost Nosologies Program (VZN) in Russia. Use of everolimus (EVL) in combination with a reduced dose of calcineurin inhibitors has some advantages over the current practice of immunosuppressive therapy that is financed through VZN.Aim: to conduct a comprehensive pharmacoeconomic research of using EVL for immunosuppressive therapy of adult de novokidney transplantation recipients in comparison with the current immunosuppressive therapy practice that is covered by the VZN Program in the Russian Federation.Materials and methods. According to the latest clinical data, effectiveness of immunosuppressive therapy schemes based on EVL and MPA is comparable, which allows to use ‘cost minimization’ method for pharmacoeconomic research. We also performed budget impact analysis of the VZN Program expenditures for a period of 2020–2022.Results. The three-year medication costs of using EVL-based immunosuppressive scheme were 502,785 RUB, which was 508,493 RUB (50.3%) less than medication costs of using MPA-based schemes that are covered by the VZN Program in current practice. The inclusion of EVL to the VZN Program will reduce its costs by 90 million RUB during the first year (2020), by 181 million RUB – during the second year (2021), and by 262 million RUB during the third year (2022). In three years VZN Program costs could be reduced by 533 million RUB (48.6%).Conclusion. Use of EVL is a cost-saving approach for immunosuppressive therapy of adult de novo kidney transplant recipients, compared to MPA-based schemes, that are covered by the VZN Program in current practice in Russia.

A natural variant of cyclosporine A, cyclosporine D, has been studied using high-resolution NMR spectroscopy in a non-polar solution (chloroform). A complete assignment of the 1H and 13C NMR signals has been made. A comparative analysis of the obtained spectra with the data on cyclosporine A has revealed certain differences between these two peptides, which are most noticeable in the chemical shifts of the atoms of the main chain of residues 5, 8 and the appearance of the hydrogen bond in residue 1. Cyclosporine D is slightly different from CsA in its spectral parameters, but it shows practically no immunological activity. The presented results fill in the gap in the NMR data for cyclosporine variants other than CsA and provide more details about the differences between the peptide variants that may be responsible for their different biological activity.

Autoimmune hepatitis is a progressive immune-mediated liver disease of unknown etiology. Its key characteristics include hyper-gammaglobulinemia, circulating autoantibodies, and periportal inflammation seen in a liver biopsy sample. It is not infrequent that the lack of unified diagnostic tests makes the verification of the disease very challenging. Most patients respond well to standard immunosuppressive therapy; however, a significant proportion of them demonstrate side effects and disease relapses after treatment withdrawal. A wide range of side effects of systemic steroids and eventual disruptions with azathioprine (the agent of choice in the treatment algorithms for autoimmune hepatitis) supplies to the Russian market make it relevant to use alternative treatment regimens. In the real world practice, alternative treatment regimens are rarely used in such patients due to the absence of hard evidence of their efficacy. Low prevalence of autoimmune hepatitis, multiplicity of its clinical types, as well as a lack of understanding of its pathogeneticmechanisms hinder the synthesis of new agents and performing trials with already known immunosuppressants with a statistical power necessary to obtain persuasive data. One of solutions of the problem could be the accumulation of clinical data into registries for further systematization of the knowledge and formulation of new clinical guidelines.

The review discusses whether antiviral therapy for recurrent hepatitis C virus (HCV) infection may be used following liver transplantation. It analyzes the concepts of pre-emptive therapy initiated within the first weeks after the transplantation, as well as therapy for histologically verified active hepatitis and/or liver fibrosis. Capabilities and limits in the use of pegylated interferons and ribavirin as monotherapy or combination therapy are considered. Particular emphasis is placed on the role of viral kinetics in the determination of the duration of further therapy, including the possibility of its prolongation up to > 12 months. There are arguments in favor of a better course of recurrent HCV infection in patients receiving cyclosporine versus those taking tacrolimus.

Chronic nephrotoxicity of calcineurin inhibitors (CNI-nephrotoxicity) is one of the most common causes of kidney graft dysfunction requiring correction of maintenance immunosuppressive therapy.The aim of the study was to compare the efficacy and safety of the two possible approaches to dose adjustment of cyclosporine in patients with dysfunction of the transplanted kidney due to CNI-nephrotoxicity. It was established that the main cause of the abolition of Everolimus was proteinuria of nephrotic levels, developed in 19% of patients.

Clinical laboratory results were analyzed in patients on one- and two-component suppression in the late period after liver transplantation.Objective: to study the impact of one-component immunosuppression with calcineurin inhibitors on clinical laboratory parameters in the late period after liver transplantation.Subjects and methods. Examinations were made in 3 groups of patients receiving various immunosuppressive therapy regimens: 1) 15 took cyclosporine; 2) 10 had tacrolimus; 3) 8 received a calcineurin inhibitor and a mycophenolic acid preparation. Their peripheral blood samples were biochemically and immunologically studied.Results. Hyperglycemia was detected in 5 (38.5%) patients receiving tacrolimus and 3 (15%) patients taking cyclosporine. Hypertension was observed in 11 (55%) patients on cyclosporine and in 3 (23%) on tacrolimus. The above complications were seen in 50% of the patients on two-component immunosuppression. Two cases of acute rejection were noted in Groups 1 (6.7%) and 3 (12.5%). The most pronounced biochemical and immunological changes were observed in the two-component immunosuppression group.Conclusion. The use of one-component immunosuppression with calcineurin inhibitors in patients after liver transplantation is effective and adequate; however, the etiology of liver cirrhosis should be taken into account on switching to one-component suppression.

Calcineurin inhibitors, cyclosporine and tacrolimus, are the main immunosuppressants used in solid organ transplantation, but the peculiarities of their pharmacokinetics allow to classify them to a group of medicines with a narrow therapeutic range. Currently in Russia more than 10 generic drugs of cyclosporine and tacrolimus are used. In this review the problem of interchangeability of cyclosporine and tacrolimus is discussed. The pharmacokinetic and technological factors that affect the bioequivalence of calcineurin inhibitors are presented.

We include a review of modern methods of systemic therapy of psoriasis in children, indications for which are moderate and severe forms of psoriasis with PASI > 10, skin pathological process that is uncontrollable with topical drugs, skin lesions with functional localization (lesions of genitals, palms and soles, facial skin), erythrodermic psoriasis, pustular psoriasis, psoriatic arthritis. We provide information on the techniques of narrow-band phototherapy (UVB 311 nm) that are used in the treatment of psoriasis in children. We provide data on efficacy, safety, necessary monitoring of clinical and laboratory indicators, peculiarities of vaccination during treatment of children with acitretin, methotrexate, cyclosporine.

The article presents a review of randomized studies involving patients with severe psoriasis, which showed that after 10-12 weeks of monotherapy with cyclosporine there was a decline of the Index of prevalence and severity of psoriasis (PASI). After achieving clinical remission must be decided on a gradual reduction of the dose of cyclosporine to the lowest effective dose, or the complete abolition of the medication. Simultaneous use of cyclosporine and UVB at the moment is not widely studied. Combined use of methotrexate and cyclosporine has been used successfully in the treatment of rheumatoid and psoriatic arthritis. The combined intake of cyclosporine and systemic biological agents should be used in exceptional cases of severe forms of psoriasis, not amenable to other treatments, and only for a limited period of time.

The authors provide current data related to the etiology, pathogenesis, classification, clinical picture, differential diagnostics and treatment methods of pyoderma gangrenosum.

Purpose. To estimate a possibility of therapeutic management of conjunctiva lesion without mechanical destruc tion of follicles.Material and methods. The article performs an analysis of literature showing an algorithm of the up-to-dated diagnosis and treatment of patient with vernal keratoconjunctivitis.Results. Treatment with antiallergic drugs, glyco-corticosteroids in a low concentration, 0.05% Cyclosporine A in combination with the artificial tears therapy enabled to obtain a regression of symptoms.Conclusion. On the basis of modern concepts of local immunomodulatory therapy the choice was made in favor of the therapeutic management of severe pathology of the conjunctiva.

Introduction. Kidney transplant (KTx) with reduced functional reserve is more sensitive to the toxic effects of calcineurin inhibitors (CNI). Immunosuppressive therapy (IST) approach with m-TOR inhibitors in case of KTx from expanded criteria donors (ECD) leads to decreasing levels of cyclosporine (CsA) in the blood. Despite the presence of international pilot studies we do not have yet clear recommendation as to combination of CsA and Everolimus. In this article, we presented 5-year results of the fi rst Russian experience of systematic administration of Everolimus as a basic IST in KTx from ECDs.Materials and methods. The group of recipients (n = 41) having received bilateral kidney transplants from the same ECDs was analyzed. Comparison group (n = 19) received standard IST consisting of CsA, MMF and steroids. Study group included 22 recipients who received kidneys from the same ECDs and IST based on early (starting from the 90th day after transplantation) conversion from MMF to Everolimus – 1.5 mg/day (target concentration – 3–6 ng/mL). Simultaneously with the administration of Everolimus, dosing of Neoral dropped immediately by 50%, and then, in accordance with the target concentration (C0 30–50 ng/mL). Dosage of steroids in patients of the study group was gradually minimized.Results. Both groups were comparable in terms of serum creatinine level and glomerular fi ltration rate (GFR) up to 3 months after transplantation. As a result of the introduction of a new IST scheme in the study group, serum creatinine level in 60 months after KTx was 149.27 ± 42.68 μmol/L, in the comparison group – 209.87 ± 39.56 μmol/L; р < 0.05. In the control group GFR reduced to 27.50 ± 7.39 mL/min/1.73 m2, in the study group it was 46.21 ± 15.17 mL/min/1.73 m2, p < 0.05.Conclusion. Early administration of Everolimus is strongly recommended in all cases of ECD KTx. This approach helps minimize CNI nephrotoxicity, provides the prevention of chronic allograft nephropathy, enables the stable renal function, and contributes to the survival of renal transplant recipients.

The emergence of new immunosuppressants, such as the macrolide drug tacrolimus (prograf), has recently become one of the most important advances in transplantology. Tacrolimus belongs to calcineurin inhibitors and differs from cyclosporine in a rapider and uniform bile acid-independent absorption, causing a reduction in the individual variability of the blood concentration of the active ingredient. On renal transplantation in sensitized patients and/or repeated allografting, the use of tacrolimus makes it possible to reduce the percentage of hormone-resistant crises by more than twice and to prevent intractable acute rejection crisis.

We’ve analyzed results of the therapeutic drug monitoring (TDM). TDM is a routine investigation into the compulsory health insurance system and more than 3 000 TDM-tests are performed annually. The most demanded TDM was the monitoring of antiepileptic drugs, cyclosporin, tacrolimus; rarely were monitored digoxin and antibacterial agents. It turned out that more than % of patients with the application of standard doses of antiepileptic drugs do not reach the therapeutic concentrations of these drugs in the blood of patients. In some patients were observed excess of the therapeutic concentration range: for valproate in 15% of cases, for carbamazepine in 7% of cases. Patients treated with cyclosporine in 9%, and tacrolimus in 17% of cases required a dose adjustment. It is found that the application of various drugs containing the same drug substance in the blood concentration may vary considerably.

Purpose. To study topical 0.05% cyclosporine A as an adjunct to LASIK in patients with a high percentage of altered (corneal) tissue (PAT) and, consequently, with a high susceptibility risk to the post-LASIK dry eye syndrome.Material and methods. This study included 23 patients (48 eyes) with PTA≥0.4 (40%) ((PTA=(PFT+CAD)/PCT, PFT – predicted flap thickness, CAD – calculated ablation depth, PCT – preoperative corneal thickness). The patients were divided into 2 study groups: (1) standard postoperative treatment and an additional topical 0.05% cyclosporine A (3 months preoperatively and within 1 month postoperatively) and (2) standard postoperative treatment. Instability of surface regularity index (ISRI), tear production and corneal sensitivity were estimated 90±10 days preoperatively and 30±3 days postoperatively.Results. There was no statistically significant difference in ISRI, tear production and corneal sensitivity between the study groups at initial control point of investigation 90±10 days preoperatively. In the follow-up period of 30±3 days postoperatively the dynamics to an ISRI increase, a reduction of tear production and corneal sensitivity compared to preoperative values was detected in both groups. The ISRI was significantly higher in the group 2 compared to the group 1 (0.37±0.06 and 0.28±0.07, respectively, p=0.017), the tear production was significantly lower in the group 2 compared to group 1 (11.4±2.7mm and 13.8±3.6mm, respectively, p=0.021), the corneal sensitivity was significantly lower in the group 2 compared to the group 1 (34.9±5.7mm and 48.2±6.6mm,respectively, p=0.003).Conclusion. The topical application of 0.05% cyclosporine A as an pre- and post-operative adjunct to LASIK in the patients with the high PAT value (≥0.4 (40%)) reduces a severity of symptoms of post-LASIK dry eye syndrome.

Adenovirus disease is one of the most common eye infections. There are 5 stages for adenovirus keratoconjunctivitis (AVKC): I – acute conjunctival manifestations, II – corneal involvement, III – recovery, IV – stage of secondary dry eye syndrome, V – recurrence of corneal infiltrates. The application of topical corticosteroids is a main method of therapy at the final stage of the disease, including recurrent corneal infiltrates. But they have side effects such as the IOP elevation, the development of cataracts and glaucoma. In this regard, the actual problem consists in a search of effective therapy without side effects of corticosteroids. One of the promising anti-inflammatory drugs in ophthalmology is 0.05% Cyclosporine A (Restasis).Purpose. To study an effect of the therapy 0,05% Cyclosporine A on the condition of recurrent subepithelial corneal infltrates after avkc . Material and methods. The study was performed in 87 eyes of 49 patients who had corneal infiltrates following the AVKC 3 months and more after the acute period: 19 male and 30 female, aged 19-65 years. All patients had a negative result of adenoviral PCR definition in conjunctival smear before the treatment. All patients were divided into 2 equal groups. The therapy of the first group (25 patients – 45 eyes) included Corticosteroids (Dexamethasone 0.1%, 0.02%, 0.01% eye drops) descending for 12 weeks. Topical 0.05% Cyclosporine (Restasis) was additionally included in the second group of the therapy for 6 months. Biomicroscopy, non-contact IOP measurements, visual acuity test were carried out in all patients, the comfort status of patients and the degree of corneal damage were evaluated according to the developed schemes (0 points: no infiltrates, 1: 1-10, 2: 1120, 3: 21-30, 4: more than 31 infiltrates).Results. Before the treatment the best corrected visual acuity (BCVA) was 0.6±0.15. The main complaints were a blurred vision (100%), foreign body sensations (87%), a light aberration (56%), objects distortions (53%). The condition of the cornea was: 4 points – 8 patients, 3 points – 23 patients, 2 points – 12 patients and 1 point – 6 patients. The IOP data was in the normal range in 97.9% of patients during the whole follow-up. Only 1 person had short-term hypertension, which was stopped by a temporary application of 0.25% Timolol 2 times daily. At 3 months after beginning of the therapy the visual acuity was 0.95±0.05. Only 3 patients had a blurred vision. The condition of the cornea was: 0 points – 47 patients, 1 point – 1 patient in each group. At 6 months after the therapy start there were complaints for the blurred vision (88%), the distortion of objects (52%), halo-effects (32%). The condition of the cornea was: 3 points – 3 patients, 2 – 7 patients, 1 point – 13 patients and 0 point – 2 patients. The BCVA among 23 patients with infiltrates averaged 0.75±0.1. The patients’ condition remained stable in the second group. New corneal infiltrates (number of infiltrates from 3 to 6) appeared after the dexamethasone cancellation in 3 patients (12.5%). The average BCVA was 0.9±0.05.Conclusions. Application of 0.05% Cyclosporine (Restasis) in patients with recurrent post-adenoviral corneal infiltrates is justified not only because of the presence of the secondary dry eye syndrome, but also because of the presence of a certain control of the local inflammatory reaction, which leads to a reduction of the corneal infiltrate recurrence risk in these patients.

Objective: to calculate cost difference between two approaches for immunosuppressive therapy after renal transplantation: everolimus plus reducedexposure cyclosporine and mycophenolic acid plus standard-exposure cyclosporine. Methods. We calculated the two-year difference in costs that resulted from effectiveness and safety differences of alternatives employing the probability-statistical model. Data on safety and efficiency were taken from D. Cibrik et al. (2013) randomized control trial. We also estimated the budget impact for everolimus inclusion into 7 expensive diseases program (7EDP). 7 EDP is the special federal program of drug provision for patients suffering from 7 certain diseases and health states including organ posttransplantation period. Results. Everolimus plus reduced-exposure cyclosporine leads to cost reduction by 161 RUB thousands (17%) per patient in a two-year period. The reduction mainly results from cheaper medication in everolimus plus reduced-exposure cyclosporine approach compared to mycophenolic acid plus standard-exposure cyclosporine. Everolimus inclusion into 7 expensive diseases program leads to reduction in federal budget spending starting from the first year; the total five-year budget savings are 275 RUB millions.

The aim of the study was the evaluation of pharmacokinetic parameters and clinical efficacy of generic cyclosporine (Ecoral) and Sandimmune Neoral. Materials and methods’. The pharmacokinetic parameters of different cyclosporine formulations. In 197 kidney graft recipients 319 comprehensive pharmacokinetic studies were performed. In 42 patients received in consecutive order original and generic Cyclosporine in the same dosage the complete pharmacokinetic study was perforfomed. AUC calculations based on dosing interval concentration values were fulfilled using linear trapezoidal rule. To evaluate clinical efficacy 235 short pharmacokinetic studies with concentration examination at 0, 1, 2 and 3 hours after taking Cyclosporine (Co, C1 C2 and C3) were performed in patients treated with Neoral (n = 75) or generic cyclosporine (n = 160). Clinical efficacy of generic cyclosporine was estimated by the prevalence of allograft dysfunction and biopsy proved acute rejection episodes as well as by one-years graft survival and events-free survival. The graft survival rate was calculated by Kaplan–Meyer method. Results. At 100–200 ng/ml maintenance concentration (estimated by C0 concentration) pharmacokinetic parameters did not significantly differ according to Cyclosporine formulation in both complete or short pharmacokinetic studies: AUC-4265 vs. 4204 and 3834 vs. 3670 ng/ml/h respectively; (p > 0.05), Cmax (1036 vs 931 and 813 vs 741 ng/ml respectively; (p > 0.05). Allograft dysfunction occurred in 5% of patients subjected to Neoral immunosuppression and in 8% of Equoral recipients (p > 0.05). However biopsy-proven acute rejection as a cause of graft dysfunction was seen only in patients receiving Ecoral (7% vs 0; p < 0.05). One-years graft survival rate did not differ between groups (99% and 94% in generic CyA and Neoral respectively; p > 0.05), whereas events-free graft survival was significantly lower in patients, receiving generic CyA than in Neoral group (88 vs 94% respectively; p = 0,03). Conclusion. Pharmacokinetic studies have shown the absorption profile of generic formulations Equoral do not differ significantly from that of Neoral. Prospective pilot trial demonstrated no difference between one-year graft survival or graft dysfunction rate, but lower eventsfree one-year graft survival as well as the tendency to higher acute rejection rate in patients treated with generics in comparison with those receiving Neoral should be noted. This issue is to be studied further.

Objective: Comparative economic evaluation of clinical application of various alternatives to anti-allergic therapy. The total budget for the treatment of severe chronic idiopathic urticaria for the 12 weeks of the study (4 weeks of therapy and 8 weeks of observation) was assessed according to treatment: Group 1 -cyclosporine2.5 mg/kg/day, Group 2-cetirizine 20 mg and ranitidine 300 mg/day, Group 3 - cetirizine 20 mg. These groups were evaluated by direct medical, direct nonmedical and indirect costs. It was found that the lowest overall cost of treating 100 patients with severe CIU, within 12 weeks of the study were recorded in the group, where a combined therapy of cetirizine 10 mg ranitidine 300 mg. The greatest costs were associated with the appointment of therapy cetirizine 20 mg

The purpose of the research is to evaluate the clinical effectiveness of cyclosporine and other antihistamines in patients with chronic forms of urticaria resistant to basic first-line therapy. Open randomized controlled study has been performed in parallel groups. 53 patients with chronic idiopathic urticaria ages 18-50 years have been examined. In case of ineffectiveness of previous therapy, patients have been randomized into 2 groups: group I receiving cyclosporine (Sandimmune Neoral ®) 2,5 mg/kg/day, group II receiving cetirizine (Zyrtec ®) 10 mg/day and ranitidine (Zantac ®) 300 mg/day orally. It has been found that the administration of cyclosporine in patients with severe chronic idiopathic urticaria provides a more rapid achievement of clinical effect than the therapy with H1/H2 histamine antagonists. It is confirmed by a significant decrease of total index of severity of illness and major symptoms of skin lesions. This tendency towards normalization of quality of life of patients taking cyclosporine remains during 8 weeks after the medication. Thus administration of cyclosporine can be considered as therapy of choice in patients with chronic idio-pathic urticaria with a severe course and ineffective long-term therapy with antihistamines / systemic corticosteroids

In recent years, anti-inflammatory therapy has become a significant part of the complex approach to treatment of patients with dry eye syndrome (DES), with cyclosporine preparations becoming increasingly important in the structure of the therapy. Taking into account the immunosuppressive effect of cyclosporine A, which is realized through hindering the activation of T-lymphocytes in the tissues of the ocular surface, its topical application in DES has a pronounced pathogenetic focus. Numerous clinical studies have shown that instillations of cyclosporine into the conjunctival cavity contribute to an increase in total tear production, as well as recovery of the density of goblet cells in the conjunctiva of DES patients. The positive effect of cyclosporine A instillations has been convincingly demonstrated in the complex therapy of patients with vernal and atopic corneal conjunctivitis, Thygeson's superficial punctate keratitis, autoimmune keratitis, meibomian gland dysfunction, etc. However, one significant problem associated with cyclosporine A instillations is the irritating effect of the drug. That prompted the development of a drug that is safe and tolerable during instillations into the conjunctival cavity - preservative-free 0.1% cyclosporine A labelled Ikervis (Santen, Japan). The drug carrier is artificial tear Cationorm (Santen), which has an advantage of stabilizing the tear film and protecting the ocular surface from the irritating effect of cyclosporine. According to numerous clinical studies, Ikervis instillations can improve the effectiveness of complex therapy in patients with DES (especially secondary to Sjögren syndrome, Stevens-Johnson syndrome, graft-versus-host disease), with allergic diseases of the cornea and conjunctiva (spring, atopic corneal conjunctivitis), with corneal transplant disease, and other similar conditions. The high efficacy and safety of Ikervis constitute the reason to recommend it for wide clinical use.

The review discusses approaches to treatment of acquired thrombotic thrombocytopenic purpuгa (aTTP). In patients with aTTP plasma exchanges, glucocorticosteroids allow to stop an acute attack of TTP, and use of rituximab allows to achieve remission. In recent years, caplacizumab has been used. Treatment options such as cyclosporin A, bortezomib, splenectomy, N-acetylcysteine, recombinant ADAMTS13 are also described. Separately discussed issues of management of patients with TTP during pregnancy, and pediatric patients with TTP.

Aim: То evaluate the effectiveness of a novel multi-targeted treatment approach including rituximab (RTX), cyclophosphamide (CPH) and steroids (S) to the induction of remission in patients with primary membranous nephropathy (PMN) compared to standard immunosuppression (IST)., Materials and Methods: An open-label prospective comparative study included 56 PMN patients (pts) with nephrotic syndrome (NS) and high serum level of antibodies to the phospholipase A2 receptor anti-PLA2R (mean age 5112 years, men 70%). We recorded demographic and clinical parameters at the time of kidney biopsy, data from light-optical and immunomorphological studies. All pts were on stable doses of the renin-angiotensin systems blockers. We compared the effectiveness of different treatments in the inductions of clinical and immunological remissions in pts who received experimental treatment with RTX, CPH and S (RTX+CPH+S group, n=14) and two control groups: high-dose RTX therapy (group RTX, n=12), cyclosporine and steroids (group CsA+S, n=30)., Results: In the RTX+CPH+S group, remission was achieved in 100% of cases (of which complete remissions CR in 21.4%). The median time-to-remission (2.5 [1.0; 3.5] months) was significantly lower compared to both control groups: RTX (8.7 [6.6; 14.0] months, p=0.005) and CsA+S (12.4 [6.5; 19.9] months, p0.001). The cumulative incidence of clinical and immunological remissions was also significantly higher in the RTX+CPH+S group than in the control groups. These results were confirmed in comparative analyzes in the same treatment groups after propensity score matching. The cumulative incidence of clinical and immunological remissions in the RTX+CPH+S group was higher than in the combined group of patients who received other therapies (p0.001). The incidence of serious adverse events was low and did not differ between groups., Conclusion: The use of multi-targeted therapy with rituximab, cyclophosphamide, and steroids seems to be an effective approach for the rapid induction of PMN remission and prevention of NS complications.

Treatment programs for patients with acquired aplastic anemia include two main therapeutic options: allogeneic bone marrow transplantation and combined immunosuppressive therapy (IST). However, combined IST remains the method of choice for most adult AA patients. This study included 120 AA patients who received IST at the National Research Center for Hematology in 20072016. The analysis was applied to 120 patients. Median age was 25 (1765) years, M/F: 66/54, SAA/NSAA: 66%/34%. Effectiveness of IST was carried out in 120 patients with AA. This group did not include 8 SAA patients who died during the first 3 months from the start of treatment from severe infectious complications (early deaths 6.2%) and 2 AA patients who dropped out of surveillance. The observation time was 55 (6120) months. Paroxysmal nocturnal hemoglobinuria (PNH clone) was detected in 67% of AA patients. The median PNH clone size (granulocytes) was 2.5 (0.0199.5)%. The treatment was according to the classical protocol of combined IST: horse antithymocytic globulin and cyclosporin A. Most of patients (87%) responded to combined immunosuppressive therapy. To achieve a positive response, it was sufficient to conduct one course of ATG to 64% of patients, two courses of ATG 24% of patients and 2% of patients responded only after the third course of ATG. A positive response after the first course was obtained in 64% of patients included in the analysis. Most of the responding patients (93%) achieve a positive response after 36 months from the start of treatment. Therefore, the 3rd6th months after the first course of ATG in the absence of an answer to the first line of therapy can be considered the optimal time for the second course of ATG. This tactic allows to get an answer in another 58% of patients who did not respond to the first course of ATG. The probability of an overall 10-year survival rate was 90% (95% confidence interval 83.696.2).

We present a case with a rare variant of glomerulonephritis, IgM nephropathy, which occurs mainly with nephrotic syndrome. The clinical features of this variant of kidney damage are characterized; the pathogenetic and the transformation of this form of nephritis into focal segmental glomerulosclerosis are discussed. The development of severe nephrotic syndrome at the beginning of the disease, the formation of secondary steroid resistance have confirmed this hypothesis and have justified the treatment with cyclosporin A aimed at the recovery of the function of the podocyte with remission of nephritis.

Introduction: The problems of controlling inflammatory and proliferative response of the retina and correcting tear production in the post-operative period after photorefractive keratectomy (PRK) have not been fully solved yet. Patients intolerable to local steroids require an alternative. One drug that covers those needs is Cyclosporine 0.05%., Purpose: To analyze clinical effectiveness of Restasis eye drops in solving inflammatory-degenerative response and tear production insufficiency (dry eye syndrome) for post-PRK patients with steroid eye drops intolerance accompanied with increasing intraocular pressure (IOP)., Patients and Methods: Retrospective analysis of 14 myopic patients (28 eyes) was conducted; mean patient age was 25.9±6 years; myopia was (-)5.65±1.5 Diopters of spherical equivalent (SE); corneal-compensated IOP was 16.98±3.68 mm Hg before the surgery. All patients underwent excimer laser correction (PRK or Trans-PRK) with Schwind Amaris (SCHWIND eye-tech-solutions). After epithelization, all patients were prescribed 0.1% Dexamethasone solution 4 times a day (with decreasing dosing frequency) for 2 months, as well as local lubricants. The article also describes a separate clinical case of subepithelial fibroplasia that occurred post-PRK and was successfully stopped., Results: All patients had transitory IOP increase caused by local steroid therapy. Mean IOP at 1-month post-op was 20.5±7 mm Hg. At that point local steroids were replaced with 'Restasis' 0.05% (Cyclosporine) eye drops prescribed 2 times per day for 2 months. As the result, IOP values decreased to 16.2±3.21 mm Hg (without any additional therapy); at 6 months mean uncorrected visual acuity reached 0.98±0.05, best corrected visual acuity achieved 1.03±0.06 and SE was 0.04±0.12 Diopters., Conclusion: Local Cyclosporine ('Restasis') is the method of choice for regulation of inflammatory and degenerative response and tear production insufficiency (dry eye syndrome) for post-PRK patients with intolerance to steroid eye drops.

Aim: To analyze the clinical and morphological manifestations of membranous nephropathy (MN) and to evaluate the efficiency of its therapy., Material and Methods: MN cases in 2009 to 2016 were retrospectively detected with a subsequent analysis of patients with primary MN (PMN). The titer of IgG-autoantibodies to phospholipase A2 receptor (anti-PLA2R Ab) was determined by an indirect immunofluorescence assay. Treatment outcomes, such as the time course of changes in proteinuria, nephrotic syndrome (NS), and the development of complete and partial remissions (CR and PR), were assessed., Results: MN was detected in 201 cases; the secondary etiology of the disease was established in 24.9%. The prevalence of MN among morphologically confirmed glomerulopathies was 14%; that of PMN was 10.4%. The median period to diagnosis PMN was 8 (5; 19) months. 150 patients with PMN (66.7% were men; age was 50±15 years) were distributed according to the following morphological stages: Stages I (23.9%), II (48.5%), III (26.1%), and IV (1.5%). Elevated anti-PLA2R Ab levels were found in 51.6% of cases; NS in the presence of proteinuria was detected in 85.6% of patients. An estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73 m2 was seen in 25% of cases. Treatment outcomes were evaluated in 80 cases; the median follow-up period was 19 (8; 40) months. 68% of cases had CR (32%) or PR (36%) with a median follow-up of 26 (13; 44) months. Spontaneous CRs or PRs were observed in 7.5% of the patients. Multivariate analysis showed that the probability of CR or PR increased 3.2-fold in the use of cyclophosphamide and/or cyclosporine and decreased as eGFR dropped., Conclusion: In Russia, PMN is a common type of glomerulopathy, the specific features of which should include the low rates of spontaneous remissions and detection of anti-PLA2R Abs. For renal protection, the majority of patients with PMN require timely diagnosis and treatment; individualization of the choice of treatment and its enhanced efficiency call for further investigations.

Corneal transplantation is the most common and successful type of allotransplantation surgery. Post-transplant immune response in keratoplasty is less pronounced than that in other transplantation procedures, which is accounted for by anatomical features of the cornea and, also, its low antigenic potential and active immunosuppression. However, the immune privilege of the cornea can be violated by neovascularization, inflammation, or trauma. Patients who require keratoplasty to restore their sight and whose immune privilege is disturbed, fall into a high-risk group and are likely to demonstrate tissue incompatibility and non-transparent engraftment. Two approaches exist as to how graft rejection can be prevented. One of them involves induction of donor-specific tolerance, the other - non-specific suppression of the recipient's immune response. To avoid tissue incompatibility, measures can be taken to restore the immune privilege of the cornea as well as to induce antigen-specific tolerance, which is considered a promising, thought yet experimental, area of modern transplantology. In clinical practice, one pays most attention to improvement of non-specific immune suppression methods based on interfering in the metabolism of immunocompetent cells. Thus, timely prescriptions and proper immunosuppressive tactics with account to possible risk factors determine the outcome in high-risk patients undergoing corneal transplantation surgery.

Cyclosporin A (CA) was used in the treatment of 2 patients with acquired aplastic anemia. Upon reaching hematological remission these children had recurrence consequent to dose lowering or discontinuation of CA. The remission occurred again when full-dose CA treatment was resumed. Slow 2-year decrease in CA dose led to uneventful end of CA treatment without deterioration of blood picture.