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Libman–Sachs endocarditis (nonbacterial thrombotic endocarditis, NBTE) may be one of the cardiac manifestations of systemic lupus erythematosus (SLE). It is characterized by the presence of sterile platelet thrombi on previously normal heart valves. The diagnosis of NBTE is difficult as it is often asymptomatic until complications such as systemic emboli or valvular dysfunction occur. Patients with Libman–Sachs endocarditis and SLE are treated with immunosuppressive and anticoagulant therapy and, if it is ineffective, surgical treatment.A clinical case of SLE and Libman–Sachs endocarditis is presented. The clinical manifestations, diagnostic methods and treatment of NBTE in SLE are discussed. The difficulties in differential diagnosis and selection of optimal treatment tactics faced by physicians are highlighted.

The aim of the study was to evaluate the clinical manifestations and survival of patients with giant cell arteritis (GCA).Methods. A retrospective study included 166 patients with newly diagnosed GCA. Clinical, laboratory and instrumental data, three sets of classification criteria were used to confirm the diagnosis: the American College of Rheumatology (ACR) 1990, the revised ACR criteria of 2016 and/or the new ACR and European Alliance of Associations for Rheumatology (EULAR) 2022 criteria. Some of the patients underwent instrumental investigations: temporal artery ultrasound Doppler (n=61), contrast-enhanced computed tomography (CT) (n=5), CT angiography (n=6), magnetic resonance imaging (n=4), magnetic resonance angiography (n=3) and 18F-FDG positron emission tomography/CT (n=47). Overall and recurrence-free survival were analyzed using survival tables, Kaplan – Meier method.Results. The most frequent first manifestations of GCA were headache (81.8%), weakness (64%), fever (63.8%) and symptoms of rheumatic polymyalgia (56.6%). Changes of temporal arteries in color duplex scanning were detected in 44 out of 61 patients. GCs therapy was performed in all patients who agreed to be treated (n=158), methotrexate was used in 49 out of 158 patients, leflunomide – in 9 patients. In 45 (28.5%) out of 158 patients a stable remission was achieved as a result of GCs monotherapy, in 120 (75.9%) patients long-term maintenance therapy with GCs was required to prevent exacerbations, including 71 (44.9%) patients – in combination with methotrexate or other immunosuppressive drugs. The follow-up period of patients with a history of relapses was 21.0 (8.0–54.0) months. Relapses developed in 73 (46.2%) patients. The overall one-year survival rate was 97.1% [95% confidence interval (CI): 94.3; 99.9], and the five-year survival rate of patients was 94.6% [95% CI: 90.2; 99.0]. The one-year relapse-free survival rate was 86.4% [95% CI: 80.5; 92.3], and the five-year relapse-free survival rate was 52.4% [95% CI: 42.0; 62.8]. 12 (7.2%) of 166 patients died. The cause of death was myocardial infarction in two patients, stroke in two patients, and breast cancer in one patient; in the remaining seven cases, the cause of death was not determined.Conclusion. Given the high frequency of disease exacerbation, patients with GCA require long-term follow-up, especially during the first year after diagnosis.

The aim of the study was to assess the incidence of arterial lesions of various localizations in patients with giant cell arteritis (GCA) according to positron emission and computed tomography (PET/CT) with 18F-fluorodeoxyglucose (18F-FDG).Methods. Patients over 50 years of age diagnosed with GCA (with or without polymyalgia rheumatica) were included in a retrospective study. Damage to extracranial arteries was assessed based on the accumulation of 18F-FDG in the walls of large vessels according to PET/CT data.Results. The study included 47 patients, 14 (30%) men and 33 (70%) women, with a median age of 65 [57; 68] years. In 32 (68%) patients, 18F-FDG-PET/CT was performed before the start of therapy with glucocorticosteroids (GCS), in 15 (32%) after the start of treatment. In 40 (91%) patients, signs of damage to extracranial vessels of various localization were revealed, most often in the thoracic and abdominal aorta (72% and 64%, respectively).Conclusions. According to 18F-FDG-PET/CT data, in most patients with GCA, not only the arteries of the head and neck, but also vessels of other localization are involved in the pathological process.

Aim of the work – to compare the frequency of upper respiratory tract (URT) involvement in patients with ANCAassociated vasculitides (AAV), to reveal its main clinical and radiological patterns and to estimate their association with the serological profile (ANCA presence and type).Material and methods. This retrospective study evaluated 369 patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). The enrolled patients were diagnosed with AAV according to the ACR criteria, CHCC classification (2012) and EMA algorithm. Patients with URT manifestations underwent standard ENT assessment and X-ray/CT. Serum ANCA levels were measured by ELISA.Results. URT involvement was diagnosed in 280 (75.9%) patients with AAV. It was significantly more common amongthe patients with GPA (86.4%) and EGPA (85.5%) compared with the MPA group (29.2%) (p

Liver involvement in systemic lupus erythematosus is common and in most cases clinical course is asymptomatic, that makes diagnosis difficult. Determination of the cause of the liver involvement is important to select treatment and to evaluate the prognosis of the disease.The aim of the research was to characterize the clinical features of liver involvement in patients with systemic lupus erythematosus and identify the most significant clinical and laboratory parameters for the differential diagnosis of lupus hepatitis.Materials and methods. The study included 313 patients with systemic lupus erythematosus observed in the E.M. Tareev Clinic of Rheumatology, Internal Medicine and Occupational Diseases of I.M. Sechenov First Moscow State Medical University (Sechenov University) in the period from 2001 to 2019. The verification of diagnosis of systemic lupus erythematosus was based on the criteria of the American College of Rheumatology (1997). Patients examination included complete blood count, biochemical and immunological blood tests and an abdominal ultrasonography. In 13 cases hepatic autoantibodies (ASMA, anti-LKM-1, LC-1, SLA-LP, AMA-M2) were analyzed, in 4 – magnetic resonance cholangiopancreatography and in 6 – liver biopsy were made.Results. Liver involvement were represented by an increase of liver enzymes in 58 (18.5%) cases. Chronic viral hepatitis C was diagnosed in 4 (1.3%) patients. Drug-induced hepatitis was found in 17 (5.4%) patients. Autoimmune liver diseases occured in 2 (0.6%) patients. In 2 (0.6%) patients, liver damage was associated with thrombotic microangiopathy (atypical hemolytic uremic syndrome, hereditary thrombophilia). In 15 (4.8%) cases, the most likely diagnosis was NAFLD. Lupus hepatitis was the most likely cause in 18 (5.7%) patients. Differential diagnosis in cases of liver involvement in patients with systemic lupus erythematosus requires assessment of risk factors for various liver diseases, age of the patients, level of liver enzymes, lupus activity, ultrasound signs of liver steatosis and secondary antiphospholipid syndrome.Determining the cause of the liver involvement for the patients with the systemic lupus erythematosus allows establishing better treatment tactic and improvement of the prognosis.

Recent studies have shown a high risk of chronic kidney disease and associated cardiovascular complications in patients with rheumatoid arthritis (RA), which determines the prognosis. However, the prevalence of chronic kidney disease (CKD) in RA has not been established in the Russians. Aim. Study was to examine the prevalence, risk factors and histological variants of CKD in RA. Materials and methods. 180 patients with rheumatoid arthritis were observed in the Tareev clinic of nephrology, for the period from 2014 to 2019 years. Age, gender, duration of RA, drug therapy, ESR, CRP, DAS28, renal function, proteinuria, histological variants were analyzed. Of the common population risk factors for CKD arterial hypertension, weight index, serum lipids and glucose levels were also assessed. Results. The prevalence of CKD in RA was 19.7%. Age, presence and stage of arterial hypertension, an increase in body mass index, as well as high rates of disease activity ESR, CRP, DAS28 score and duration of RA were risk factors of CKD in RA. Age, duration of the disease, stage of AH and hypercholesterolemia were risk factors in multifactorial regression analysis. Amyloidosis was the most common histologic pattern (50.0%), followed by chronic glomerulonephritis (30.4%) and tubulo-interstitial nephritis (19.6%). Among chronic glomerulonephritis mesangial glomerulonephritis was the most frequent. Renal amyloidosis was associated with a duration of RA, presence of systemic symptoms and CRP level. An isolated decrease in GFR of less than 60 ml/min was detected in 31 (36.0%) out of 86 patients. Сonclusion. The risk factors for CKD in patients with RA are activity and duration of the disease In addition to common population factors. Amyloidosis was the most common histologic pattern associated with duration of RA and inflammatory proteins levels.

Neuromyelitis optica ((NMO), Devic's syndrome) is an immune-mediated inflammatory demyelinating disease characterized by transverse myelitis and optic neuritis. Determination of the level of antibodies to aquaporin 4 (NMO-IgG) is presently one of the key methods for the diagnosis and assessment of the activity of ONM, which allows this disease to be differentiated from multiple sclerosis and other demyelinating CNS lesions. ONM can occur not only as an independent disease, but also as a syndrome in different systemic diseases, such as: systemic lupus erythematosus (SLE), antineutrophilic cytoplasmic antibody-associated vasculitides, Sjögren's disease, etc. (up to 50–70%). In such situations, the clinician is always confronted with a question as whether the patient can have two rare autoimmune diseases or develop ONM as a systemic manifestation of rheumatic disease.The paper describes a clinical case of a young female patient with SLE concurrent with a CNS lesion, the manifestations of which corresponded to ONM. The patient had focal changes in the substance of the brain and spinal cord, as evidenced by magnetic resonance imaging, as well as high NMO-IgG titers. The development of ONM worsens SLE prognosis and requires active immunosuppressive therapy. The patient received three plasmapheresis sessions, ultrahigh-dose glucocorticoid and cyclophosphamide therapy, followed by replacement with azathioprine, causing a stable clinical and laboratory disease remission to be achieved.

Certolizumab pegol (CZP) is the only pegylated biological agent (BA) that does not contain an Fc fragment, which minimizes its transplacental transfer. Takayasu arteritis mostly occurs in reproductive-aged women.Objective: to evaluate the efficacy and safety of CZP used to treat standard immunosuppressive therapy-resistant Takayasu arteritis.Subjects and methods. The retrospective study enrolled 6 female patients aged 18 to 35 years with Takayasu arteritis who received CZP. The median disease duration before BA usage was 66 months (24 to 204 months). The median duration of immunosuppressive therapy prior to CZP treatment was 92 months (14 to 132 months). All the female patients had taken glucocorticoids and methotrexate before and during CZP therapy. Only four patients had received two to five immunosuppressive drugs at different times prior to BA administration. Three patients had previously used other BAs. The disease activity was determined by the National Institute of Health (NIH) criteria. The Indian Takayasu Clinical Activity Score (ITAS2010) was used. The disease activity was recorded in all the patients prior to CZP therapy.Results and discussion. The median duration of CZP treatment was 17 months (6 to 24 months). The median erythrocyte sedimentation rate after CZP usage decreased from 22.5 to 10.5 mm/h; the median C-reactive protein level dropped from 7.8 to 0.39 mg/dl (p

Objective. To compare the frequency, clinical features and outcomes of renal involvement in ANCA-associated vasculitides (AAV) in patients with antibodies against proteinase-3 (pr3-ANCA) and myeloperoxidase (MPO-ANCA). Materials and methods. In our retrospective study we enrolled 264 patients, 94 males and 170 females, median age 53 [36; 62] years. Among them 157 were pr3-ANCA positive and 107 were MPO-ANCA positive. AAV was diagnosed according to ACR criteria and Chapel Hill consensus conference definition (2012). Median follow up was 44 [18; 93] months. We assessed baseline BVAS and VDI by the end of the follow up. Serum creatinine (sCr), estimated glomerular filtration rate (eGFR), hematuria and daily proteinuria were estimated. Diagnosis and stage of chronic kidney disease (CKD) and acute kidney injury (AKI) were established according to KDIGO guidelines (2012) and Scientific Society of Russian Nephrologists (2016). Results. Renal involvement was present in 181 (68.6%) patients, and its frequency was similar in pr3-ANCA and MPO-ANCA subgroups. Patients with MPO-ANCA developed rapidly progressive glomerulonephritis and hypertension significantly more often than patients with pr3-ANCA: 50.7% vs 35.6% (p=0.049) and 46.1% vs 29.8% (p=0.029) respectively. At disease onset, median sCr was significantly higher and eGFR was significantly lower in patients with MPO-ANCA (p

Aim. To evaluate clinical features and outcomes of renal involvement in patients with microscopic polyangiitis (MPA). Materials and methods: We enrolled 99 patients with MPA, diagnosed in accordance with the algorithm of the European Medicines Evaluation Agency (EMEA) and the Chapel Hill consensus conference definition (2012). Serum creatinine (sCr), estimated glomerular filtration rate (eGFR), hematuria and proteinuria were estimated. Frequency of rapidly progressive renal failure (a twofold increase in the sCr level in ≤3 months) was regarded as the clinical equivalent of rapidly progressive glomerulonephritis (RPGN). Results and discussion. Renal involvement was present in 92 (92.9%) patients. RPGN developed in 51 (55,4%) patients. The most common features of kidney involvement were hematuria and subnephrotic proteinuria. Arterial hypertension was revealed in 32 (34.7%) patients and was associated with RPGN (p

Systemic vasculitis is a heterogeneous group of inflammatory diseases, which are classified according to the diameter of the affected vessels. The treatment of systemic vasculitis is no longer empirical, because of increasing number of randomized clinical trials in this field. In recent years, there was a trend to limit the cumulative dose of glucocorticosteroids and immunosuppressive drugs, partially through biological drugs usage. However, biologic therapy is not always superior to combination of glucocorticosteroids and cytotoxic drugs. The efficacy of different biologic drugs varies in patients with different forms of systemic vasculitis, which creates the ground forpersonalized therapy of these diseases. Another serious problem is the absence of strict criteria to immunosuppressive therapy intensification, especially in vasculitis, affecting large vessels, due to the lack of reliable laboratory markers of disease activity. The article reviews modern approaches to the treatment of some types of systemic vasculitis, including ANCA-associated vasculitides, giant cell arteritis, Takayasu`s arteritis and cryoglobulinemic vasculitis.

The paper describes clinical cases in 2 patients (brothers) with giant cell arteritis. It analyzes the genetic and epigenetic aspects of the disease. The data available in the Russian and foreign literature are given.

Study Objective . To evaluate the correlation between cytokine synthesis and organ involvement in patients with granulomatosis with polyangiitis (GPA). Methods. The study involved 60 patients with GPA diagnosed following the ACR criteria and the CHCC-2012 definition. Cytokines genes expression was studied in blood samples from 57 patients with reverse transcription polymerase chain reaction. We evaluated mRNA for the following cytokines: interferon (IFN)-α, IFN-γ, interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18, tumor necrosis factor (TNF)-α production. Also, we investigated the serum concentration of IFN-α, IL-1β, IL-8 IL-18 and TNF-α by ELISA in 40 patients with GPA. Results . Markers for granulomatous disease were detected in 45 (75,0%) GPA patients, markers for vasculitis - in 23 (38,3%) patients. GPA affected eyes in 33 patients (55,0%), ears in 29 (48,3%), nose and sinuses in 57 (95,0%), lungs in 35 (58,3%) and kidneys in 28 (46,7%). There was total positive correlation between eye disease and IL4 and IL12 genes expression ( r =1,00). Total negative correlations were between ear disease and IL-12 gene expression; glomerular filtration rate reduction more than 50% and serum IFN-α ( r =-1,00). Conclusion. Cytokines may upregulate the direct immune response in organ damage in GPA patients. Markers for granulomatous disease correlated with cytokines, that suppressed Th2 type immune response and promoted Th1 type immune response. Correlation between vasculitis markers and cytokines showed that IFN-α, TNF-α, IL-1β and IL-6 participated in vascular damage in GPA patients.

Aim. To summarize the experience of a multidisciplinary therapy hospital in treating patients with hepatitis C virus (HCV)-associated cryoglobulinemic vasculitis (CV). Subjects and methods. Seventy-two patients (mean age, 49.4±10.3 years) with HCV-associated CV were examined and followed up for an average period of 2.8±3.6 years. The efficiency of traditional (corticosteroids ± cyclophosphamide) and selective (rituximab) immunosuppressive therapy (IST) was estimated in 31 and 15 observations, respectively, and that of antiviral therapy (AVT) in 25. Vasculitis activity was assessed using the Birmingham vasculitis activity score (BVAS). The patients’ survival was studied; multivariate logistic regression analysis was carried out. Results. 24 (33.4%) of the 72 patients had a stage of liver cirrhosis (LC). The pretreatment mean BVAS was 11.9±7.2 (range 2 to 36). Severe CV (BVAS ≥15) was present in 30.6% of the patients. AVT was accompanied by achievement of sustained virologic response in 48% of the patients, clinical remission in 68% and had an advantage over IST in relation to long-term treatment results. Rituximab was significantly more effective than traditional immunosuppressants (remission rates of 73 and 13%, respectively). Combined therapy (rituximab and AVT) was most effective in patients with severe forms of vasculitis. Sixteen patients died from complications of vasculitis (37.5%), infection (37.5%), and LC (25%). The factors adversely affecting prognosis were age >55 years (odds ratio (OR), 4.49), the presence of LC (OR, 3.68), renal failure (OR, 4.66) and the use of glucocorticosteroids (OR, 3.91). Conclusion. HCV-associated CV can determine the prognosis of chronic HСV infection. AVT is the treatment of choice in all patients with HСV-associated CV. AVT must be combined with rituximab therapy in patients with severe forms of vasculitis.

Aim. To estimate the frequency of lesions in the organ of vision in granulomatosis with polyangiitis (GPA) (Wegener’s) and to determine their relationship to systemic diseases. Subjects and methods. The retrospective study enrolled 218 patients followed up at the E.M. Tareyev Clinic of Nephrology, Internal and Occupational Diseases, with a diagnosis of GPA. The frequency and association of ophthalmic manifestations with systemic involvement were statistically analyzed using PASW Statistics 18. Results. The organ of vision was impaired in 48.1% of the patients with GPA. The most common manifestations were orbital space-occupying lesion (22.9%), conjunctivitis/episcleritis (14.7%), dacryocystitis (6.0%), and scleritis (4.6%). Orbital space-occupying lesions occurred more frequently in the local type of the disease (p=0.0003), and, on the contrary, the involvement of the conjunctiva and eyeball was seen in patients with the systemic types of GPA (p=0.02). Conclusion. The findings may suggest that the orbital lesion is an independent manifestation of GPA, which develops more commonly in its local type. Conjunctivitis/episcleritis is, on the contrary, more frequently seen in the active phase of the disease and generally in the involvement of other organs and systems.

Granulomatosis with polyangiitis (GPA), formerly earlier known as Wegener’s granulomatosis, is primary systemic necrotizing vasculitis of small and medium-sized vessels, which is characterized by the formation of foci of granulomatous inflammation. One of the target organs in GPA is the organ of vision. Its affection may not only reduce quality of life, but also may lead to the severest complications even to a fatal outcome. The affection varies in severity from slight inflammation of the ocular superficial structures to severe involvement of all orbital and ocular structures to develop complete blindness, including bilateral one. GPA can affect any portion of the organ of vision. The changes are low specific, which makes early diagnosis and timely adequate therapy difficult. Overall, all ophthalmologic manifestations can be divided into 4 groups: 1) lesions of the orbit and appendages; 2) those of the conjunctiva and fibrous tunic of the eyeball; 3) those of the retina; 4) those of the optic nerve. Orbital affection is characterized by the development of granulomas, dacryoadenitis with marked inflammatory infiltration of the surrounding tissues, including oculomotor muscles, and destruction of orbital bony walls. Nonspecific conjunctivitis and episcleritis are commonly encountered. Affection of the fibrous tunic of the eyeball is characterized by the development of necrotizing scleritis, peripheral ulcerative or stromal keratitis. The retina is rarely involved and mainly described as sporadic cases in the literature. The optic nerve is most commonly damaged due to the compression of the orbit by inflamed tissue; the lesion is more infrequently ischemic.

Aim. To assess the relationship of the carriage of IL-10 -1080 G/A and IL-28 rs8099917 C/T polymorphisms to the course of lupus nephritis (LN). Subjects and methods. Ninety-nine patients with systemic lupus erythematosus (SLE), including 68 with LN, were examined. Gene polymorphisms were analyzed using standard molecular genetic techniques. The frequency of the clinical manifestations of LN was analyzed; renal survival (RS) was estimated by the Kaplan-Meier method. Results. Ten-year RS rates were 80 and 86% of the patients with and without the mutant IL-10 allele, respectively (p=0.78). The 10-year RS was lower (75%) in carriers of the mutant IL-28 rs12979860 allele than in patients without this mutant allele (83%; p=0.049) and in those of the mutant IL28 rs8099917 allele than in patients without the above mutant allele (67 and 88%, respectively; p=0.047). LN patients, carriers of the mutant IL-10 -1028 G/A allele, were observed to have higher-grade proteinuria in the presence of nephritic syndrome (mean 6.1 g/l) than those without the mutant allele of this gene (mean 2.9 g/l; p=0.034). However, the mutant allele carriers responded to treatment better (p=0.050). The mutant IL-10 and IL-28 alleles were unassociated with the development of rapidly progressive nephritis, the activity of a renal lupus process, and the rate of onset of SLE and LN. Conclusion. In the LN patients, the carriage of the mutant IL-10 allele A is associated with a better response to treatment and that of the mutant IL-28 allele is linked to the severe course of the disease.

The paper describes a case of giant cell arteritis whose leading clinical sign is long-term fever. It discusses current approaches to diagnosing giant cell arteritis.

AIM. To study the rate and types of cardiac involvement, the patterns of cardiovascular events (CVE) and to determine the importance of risk factors for atherosclerosis and the role of noninvasive methods in the diagnosis of cardiovascular diseases in patients with systemic vasculitides (SV). MATERIALS AND METHODS. Three hundred and twenty-one patients with SV, including 138 (42.8%) with granulomatosis and polyangiitis (Wegener's granulomatosis) (GPA), 79 (24.7%) with Takayasu's arteritis (TA), 55 (17.2%) with polyarteritis nodosa (PAN), and 49 (15.3%) with eosinophilic granulomasis and polyangiitis (EGPA) (Churg-Strauss syndrome), were examined in 1989 to 2011. The clinical manifestations of the disease were studied retrospectively in 153 (47.6%) patients examined in 1989 to 2004 and prospectively in 168 (52.4%) patients examined in 2005 to 2011. The investigators performed EchoCG in the examinees prospectively, myocardial perfusion scintigraphy (PSG) in 92 patients, and multislice spiral computed tomography (MSCT) of coronary vessels in 32. The SCORE scale was employed to study risk factors for CVE. The data of cardiac and vascular morphological examinations were analyzed in 55 patients. RESULTS. Heart damage as a major visceral injury in SV was detected in 63.3% of the cases with TA, in 70.9% of those with PAN, in 67.3% of those with EGPA, and in 48.5% of those with GPA. CVEs were diagnosed in 51 (15.9%) of the 321 patients. The rate of CVEs turned out to be higher in the patients with EGPA (22.3%) and PAN (18.2%) and slightly below in those with GPA (14.5%) and TA (12.6%). Echocardiography revealed aortic regurgitation in 28.5% of the patients with TA, left ventricular hypertrophy in 47% and diastolic dysfunction in 55% of those with PAN, pericarditis in 16 and 8% of those with EGPA and GPA, respectively; the signs of myocardial dilatation were diagnosed more frequently in EGPA (18.3%) than in other SVs. PSG diagnosed various myocardial perfusion disorders in 59% of the patients with SV; at the same time, focal changes prevailed over diffuse ones in the patients with PAN (45.8%) and EGPA (50%), diffuse ones in those with GPA (42.3%); these disorders being approximately equally frequently found in TA. MSCT revealed coronary calcification in 66% of the patients with GPA, 62.5% of those with EGPA, in 50% of those with PAN, and in 14.3% of those with TA. Postmortem examination displayed atherosclerotic changes in one or more great arteries in 28 (50.9%) of 55 dead patients. Deaths from cardiovascular causes were noted in 18 (30.9%) patients with SV. The causes of death were stated to be an acute cerebrovascular accident in 14.5% of the patients, myocardial infarction in 9.1%, and chronic heart failure in 7.3%. CONCLUSION. The cardiac manifestations of SV are associated with immune inflammation and concomitant hypertension and atherosclerosis. The combination of traditional RFs for atherosclerosis and SV in the same patient allows the latter to be assigned to a very high CVE risk group. Early heart damage diagnosis using non-invasive methods provides a way of optimizing the further management tactics in patients with SV.

AIM: To assess the risk of severe adverse events (AEs) within 6 months after treatment with biological agents in patients with rheumatic diseases (RD)/MATERIAL AND METHODS: The 6-month open-label trial included 107 patients with rheumatoid arthritis, antineutrophil cytoplasmic antibody-associated vasculitides, systemic lupus erythematosus, and other RDs who received genetically engineered biological agents (GEBAs), primarily rituximab (n=66) and infliximab (n=31)/RESULTS: The majority of patients were noted to have improvements, including complete and partial remission in 62 (57.9%) and 42 (39.3%), respectively. There were mild or moderate AEs in 22 (20.6%) of the 107 patients, severe AEs in 6 (5.6%): grade IV neutropenia in 2 patients (after the use of rituximab), severe infusion reactions in 2 (after the administration of infliximab and rituximab), and systemic infections in 2 (fatal nocardial sepsis after rituximab treatment and unspecified sepsis after infliximab treatment)/CONCLUSION: The rate of serious AEs, mainly infusion AEs and infections during treatment with infliximab, rituximab, and other GEBAs proved to be relatively low in patients with different RDs. At the same time, the use of biological agents could lower RD activity in the presence of severe visceral injuries refractory to conventional immunosuppressive therapy.

There has been a substantial expansion in the possibilities of current therapy for rheumatic diseases (RD) primarily due to the use of genetically engineered biological agents (GEBA). Objective: to evaluate the short-term efficacy and safety of GEBA in patients with different RD. Subjects and methods. The trial included all RD patients receiving GEBA: rituximab (RTM), infliximab (INF), adalimumab, etanercept, tocilizumab, abatacept in 2009-2012. Therapeutic efficiency and safety were evaluated 6 months later. The effect of GEBA was determined as “remission”, “improvement”, and “no response”, by using the parameters peculiar to specific diseases (such as BVAS, DAS28, BASDAI). Results. The trial enrolled 107 patients (49 men and 58 women; mean age 41.5 years) with rheumatoid arthritis (n=34), ANCA-associated vasculitis (n = 34), systemic lupus erythematosus (n=16), cryoglobulinemic vasculitis (n=11), ankylosing spondyloarthritis (n = 8), systemic vasculitis with large artery involvement (n=6), and other RD. All the cases showed severe systemic autoimmune disease refractory to standard immunosuppressive therapy. RTM (n=66) and INF (n = 31) were most frequently used. The high rate of RTM prescription was due to the fact that this drug was given to all patients with ANCA-associated vasculitis, systemic lupus erythematosus, and cryoglobulinemic vasculitis who totaled more than half of the patients included into the trial. The vast majority of them received GEBA for the first time. After the treatment, there was remission in 62 (57.9%) and improvement in 42 (39.3%) cases. Mild or moderate adverse reactions were observed in 22 (20.6%) patients and severe ones were seen in 6 (5.6%). Conclusion. GEBA therapy ensures a significant improvement in a substantial proportion of patients with different RD refractory to standard immunosuppressive therapy.

Aim. To assess efficacy of rituximab in patients suffering from Wegener's granulematosis (WG) with renal disease. Material and methods. We analysed clinical laboratory data from 9 WG patients with renal disease treated with rituximab in E.M. Tareev clinic. Results. The treatment led to a complete remission in 7 (77.8%) patients, a partial remission - in 2 (22.2%) patients. Vasculitis activity regressed including renal damage (a decrease of 24 h proteinurea, enhanced glomerular filtration rate). A prednisolone dose decreased from 38.3 to 10 mg/day (to month 6) and to 7.5 mg/day (to month 12). Non-selective cytostatic drugs were discontinued in all the patients. Recurrences occurred in 3 (33.3%) patients, one with lethal outcome after 6 months of rituximab administration, in two cases one more course of rituximab produced another complete remission. Serious side effects were absent. Conclusion. Rituximab demonstrated high efficacy in the treatment of WG with renal affection resistant to standard therapy, in multiple side effects of standard immunosuppressive therapy and recurrent course. Rituximab help overcome steroid dependence even at late stages of the disease.

The paper discusses the problems of the diagnosis and treatment of Wegener's granulomatosis, the most common anti-neutrophil cytoplasmic antibody-associated systemic vasculitis. It describes a clinical case in which the administration of rituximab could achieve remission of severe Wegener's granulomatosis in a young man having numerous adverse reactions associated with the long-term use of high- and average-dose glucocorticoids and nonselective immunosuppressive agents. A place of rituximab in current drug therapy for Wegener's granulomatosis is shown.