Genetically engineered biological agents in therapy for systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a prototype for chronic autoimmune disease. Its prevalence is 20 to 70 cases per 100,000 women and varies by race and ethnicity. Despite considerable progress in traditional therapy, many problems associated with the management of these patients need to be immediately solved: thus, 50-80% are found to have activity signs and/or frequent exacerbations and about 30% of the patients have to stop work; Class IV lupus nephritis increases the risk of terminalrenal failure. In the past 20 years great progress has been made in studying the pathogenesis of SLE: biological targets to affect drugs have been sought and fundamentally new therapeutic goals defined. Belimumab is the first genetically biological agent specially designed to treat SLE, which is rightly regarded as one of the most important achievements of rheumatology in the past 50 years

Redistribution of sediment and sediment-associated contaminants in the River Chern basin during the last 50 years

A detailed study was undertaken in the upper part of the River Chern basin (126 km2). An integrated approach was used to investigate the redistribution of sediment and sediment-associated contaminants within the upper part of the basin, upstream from the reservoir located in the middle reach of the main valley. It was found that maximum sheet, rill and gully erosion rates were observed during the 1960s. This led to increased erosion rates in all parts of the fluvial system. The intensity of erosion decreased considerably after 1991 for a number of reasons. The commencement of mining activity and the sharp increase in the application of chemical fertilizers caused detectable heavy metal pollution within the basin during the late 1950s and early 1960s, when the Mikhailovsky iron ore mining development started. As a result, concentrations of Zn and As in floodplain sediment increased and exceeded the maximum permissible levels, according to Russian human health standards. Copyright © 2012 IAHS Press

Значение качества жизни, связанного со здоровьем, у больных системной красной волчанкой и современные инструменты его оценки

The paper presents an overview of studies assessing health-related quality of life (HRQoL) in patients with systemic lupus erythematosus (SLE). It describes the HRQoL concept and prerequisites for its creation. The classification of questionnaires used in patients with SLE is considered in relation to the study objectives. The main key triad (fatigue, pain, and depression), which causes a reduction in HRQoL in SLE patients, is derived on the basis of many studies. The paper provides brief comparative characteristics of eight specific HRQoL questionnaires in SLE patients: Symptom checklist (SSC), SLEQol, LupusQol, L-QoL, LupusPRO, and Lupus Impact Tracker (LIT), LUP-QoL, and SMILEY. Special attention is paid to HRQoL assessment in patients receiving different treatment options: glucocorticoids, cytostatic and anti-B-cell therapy. Представлен обзор исследований, посвященных оценке качества жизни, связанного со здоровьем (КЖСЗ), у больных системной красной волчанкой (СКВ). Описаны концепция КЖСЗ, а также предпосылки ее создания. Рассмотрена классификация опросников, применяемых у пациентов СКВ, в зависимости от задач, поставленных в исследовании. У больных СКВ на основании многих исследований выведена основная ключевая триада проблем (усталость, боль и депрессия), вызывающая ухудшение КЖСЗ. Приведена краткая сравнительная характеристика восьми специфических опросников для оценки КЖСЗ у больных СКВ: SLE Symptom checklist (SSC), SLEQol, LupusQol, L-Qol, LupusPRO и Lupus Impact Traker (LIT), LUP-QoL, SMILEY. Отдельное внимание уделено оценке КЖСЗ у больных, получающих разные виды лечения: глюкокортикоиды, цитостатическую, анти-В-клеточную терапию.

Results of therapy of chronic urticaria in patients with IgE-dependent and IgE-independent disease profile

The main mechanism for the occurrence of urticaria is the degranulation of mast cells. It has been proven that, regardless of the activation pathway, clinical manifestations will not differ. According to the literature, up to half of cases of chronic spontaneous urticaria are autoimmune in nature, can be combined with autoimmune thyroid disease, SLE, etc., and have a more severe course.In therapy, antihistamines are traditionally used. However, some patients do not respond to the treatment, even with a multiple increase in doses. In the treatment of urticaria resistant to traditional antihistamines, the use of Omalizumab is recommended. The purpose of the study: to determine the profile of patients with chronic urticaria, as well as to evaluate the effectiveness of treatment with Omalizumab in patients with IgE- dependent and IgE-independent chronic urticaria.Eight-one patients with chronic urticaria (60 adults, 21 children) were examined. Patients before the start of therapy had a long history of CU: from 1 to 20 years. Patients before the start of therapy were treated with antihistamines, but no control was obtained. An increase in the level of serum IgE was detected in 51.7% of cases in adults and 42% in children. Concomitant sensitization was determined in 48.3% of adults and 76.2% of children. In children, food, epidermal and pollen sensitization was the most common. Pollen and epidermal sensitization were more common in adults. The level of eosinophilia in the group with IgE-dependent was more pronounced than in other group (p = 0.0097). After 6 months, the group with IgE-dependent showed an improvement in the symptom score (UCT) from 3.1 CI (1.5-4.6) to 12.2 CI (10.8-13.7), (p = 0.0001). In other group, symptoms improved from 0.63 CI (0.36-1.6) to 8.1 CI (5-11.2) after 6 months (no control). After 6 months of genetically engineered biological therapy (GIBT), complete control over the symptoms of CU in group 1 was obtained in 66.7% of patients, partial — in 33.7%. In the second group, in 33.3% of cases, positive treatment results could not be achieved. Thus, genetically engineered biological therapy with Omalizumab increases the control over the course of CU. Treatment outcomes are higher in patients with an IgE-dependent disease profile

Рупус – сочетание системной красной волчанки и ревматоидного артрита как отдельный фенотип болезни (описание клинического случая)

Rhupus is a rare combination of systemic lupus erythematosus (SLE) and rheumatoid arthritis, one of the characteristic features of which is the development of erosive polyarthritis on the background of the main immunological signs of SLE. The article presents a clinical observation in which, along with the typical immunological picture of SLE, the patient was diagnosed with erosive polyarthritis with “swan neck” type deformities of the hand joints, which required administration of anti-B-cell therapy.Рупус (Rhupus) – редкое сочетание системной красной волчанки (СКВ) и ревматоидного артрита, одной из характерных особенностей которого является развитие эрозивного полиартрита на фоне основных иммунологических признаков СКВ. В статье представлено клиническое наблюдение, в котором у пациентки наряду с типичной иммунологической картиной СКВ выявлен эрозивный полиартрит с деформациями суставов кистей по типу «шеи лебедя», что потребовало назначение анти-Вклеточной терапии

Терапия с последовательным применением ритуксимаба и белимумаба у пациентов с системной красной волчанкой

Objective: to determine the efficiency of sequential (combined) therapy with rituximab (RTM) and belimumab (BLM) in patients with active systemic lupus erythematosus (SLE).Patients and methods. Twelve patients with true SLE having moderate-to-high activity were followed up. Six of them were noted to have skin and articular manifestations and 6 had kidney damage, vasculitis. The patients took RTM at 500–2000-mg doses, with 6-methylprednisolone as premedication, whereupon they were prescribed BLM according to the standard regimen of 10 mg/kg once monthly. The follow-up period was 1 year. At baseline and every three months after RTM administration, the efficiency and tolerability of therapy were evaluated, the concentrations of autoantibodies and complement components was estimated, and the dose of oral glucocorticoids (GCs) was recorded.Results and discussion. During combined therapy with the biological agents (BAs), there was a considerable clinical and laboratory improvement: reductions in disease activity (median (Me) SLEDAI-2K scores were 12 [9.5; 17] at baseline and 2 [2; 6] at Visit 4), the Me concentrations of anti-double-stranded DNA (anti-ds-DNA) antibodies, 101 [39; 250] and 28 [6; 112] U/ml, respectively; those of complement component 3 (C3), 0.44 [0.39; 0.59] and 0.83 [0.81; 0.87] g/L, respectively; and those of complement C4, 0.06 [0.031; 0.1] and 0.16 [0.15; 0.18] g/l, respectively). Most patients received the medium and low doses of oral GCs as initiating therapy. During the year, the dose of GCs was reduced by more than a quarter and they could be completely discontinued.evaluated, the concentrations of autoantibodies and complement components was estimated, and the dose of oral glucocorticoids (GCs) was recorded. Results and discussion. During combined therapy with the biological agents (BAs), there was a considerable clinical and laboratory improvement: reductions in disease activity (median (Me) SLEDAI-2K scores were 12 [9.5; 17] at baseline and 2 [2; 6] at Visit 4), the Me concentrations of anti-double-stranded DNA (anti-ds-DNA) antibodies, 101 [39; 250] and 28 [6; 112] U/ml, respectively; those of complement component 3 (C3), 0.44 [0.39; 0.59] and 0.83 [0.81; 0.87] g/L, respectively; and those of complement C4, 0.06 [0.031; 0.1] and 0.16 [0.15; 0.18] g/l, respectively). Most patients received the medium and low doses of oral GCs as initiating therapy. During the year, the dose of GCs was reduced by more than a quarter and they could be completely discontinued. Conclusion. Combined biological therapy with RTM and BLM is a promising treatment for active SLE. The use of this regimen promotes a rapid and effective reduction in disease activity, normalization of laboratory markers of SLE (anti-ds-DNA antibody and complement C3 and C4 levels), and decreases in the dose of oral GCs and, as a consequence, in the risk of irreversible organ damages.. Combined biological therapy with RTM and BLM is a promising treatment for active SLE. The use of this regimen promotes a rapid and effective reduction in disease activity, normalization of laboratory markers of SLE (anti-ds-DNA antibody and complement C3 and C4 levels), and decreases in the dose of oral GCs and, as a consequence, in the risk of irreversible organ damages.Цель исследования – определение эффективности последовательной (комбинированной) терапии с применением ритукисмаба (РТМ) и белимумаба (БЛМ) у пациентов с активной системной красной волчанкой (СКВ).Пациенты и методы. Под наблюдением находилось 12 пациентов с достоверной СКВ высокой и средней степени активности. У 6 из них отмечались кожно-суставные проявления, у 6 – поражение почек, васкулит. Пациенты получали РТМ в дозе 500–2000 мг с премедикацией 6-метилпреднизолоном, после чего им назначали БЛМ по стандартной схеме 10 мг/кг 1 раз в месяц. Срок наблюдения – 1 год. Исходно после введения РТМ и затем каждые 3 мес оценивали эффективность и переносимость терапии, определяли концентрацию аутоантител и компонентов комплемента, регистрировали дозу пероральных глюкокортикоидов (ГК).Результаты и обсуждение. На фоне комбинированной терапии генно-инженерными биологическими препаратами (ГИБП) наблюдалось значительное клинико-лабораторное улучшение: снижение активности заболевания (медиана, Ме SLEDAI-2K исходно – 12 [9,5; 17] баллов, на момент визита 4 – 2 [2; 6] балла), Ме концентрации антител к двуспиральной ДНК – АТ к дс-ДНК (101 [39; 250] и 28 [6; 112] Ед/мл соответственно), С3-компонента комплемента (0,44 [0,39; 0,59] и 0,83 [0,81; 0,87] г/л соответственно), С4-компонента комплемента (0,06 [0,031; 0,1] и 0,16 [0,15; 0,18] г/л соответственно). Большинство пациентов получали средние и низкие дозы пероральных ГК в качестве инициирующей терапии. За год доза ГК была уменьшена более чем на четверть, а у части больных удалось полностью их отменить.Заключение. Комбинированная терапия ГИБП с применением РТМ и БЛМ является перспективным методом лечения активной СКВ. Использование такой схемы способствует быстрому и эффективному снижению активности заболевания, нормализации лабораторных маркеров СКВ (уровня АТ к дс-ДНК, С3-, С4-компонентов комплемента), уменьшению дозы пероральных ГК и как следствие – риска развития необратимых органных повреждений

Перспективы применения белимумаба при волчаночном нефрите

Over the past 50 years the survival rate of patients with systemic lupus erythematosus (SLE) significantly improved, however, it is necessary to develop a new generation of drugs for the treatment of lupus nephritis (LN), the development of which is one of the main factors of high mortality risk in at least 50% of SLE patients. The international clinical trial BLISS-LN has demonstrated a high rate of achievement and maintenance of renal response (RR), confirmed by a higher rate of achievement of RR primary efficacy and complete renal response when using belimumab (BLM) in addition to standard therapy (ST) compared to ST alone in patients with LN. When using BLM, there was a statistically significant reduction in the risk of developing adverse renal events (in particular, deterioration of renal function) or death within 104 weeks compared with placebo. Improvement in LN outcomes was achieved in the setting of long-term reduction in glucocorticoids use after the induction phase. With BLM therapy, there was also a decrease in the total activity of SLE, a decrease in the number of severe exacerbations, and an improvement in serological markers. The benefit/risk ratio of BLM in combination with ST for LN treatment was favorable. BLM can be recommended for LN therapy in combination with standard treatment methods in order to achieve and maintain remission.За последние 50 лет удалось существенно улучшить выживаемость больных системной красной волчанкой (СКВ), однако необходимо создание нового поколения препаратов для терапии волчаночного нефрита (ВН), развитие которого не менее чем у 50% больных СКВ является одним из основных факторов высокого риска летальности. Международное клиническое исследование BLISS-LN продемонстрировало высокую частоту достижения и сохранения почечного ответа (ПО), подтвержденную более высокой частотой достижения ПО первичной эффективности и полного почечного ответа при применении белимумаба (БЛМ) в дополнение к стандартной терапии (СТ) по сравнению с одной СТ у пациентов с волчаночным нефритом (ВН). При применении БЛМ наблюдалось статистически значимое снижение риска развития нежелательных явлений со стороны почек (в частности, ухудшения функции почек) или смертельного исхода в течение 104 нед по сравнению с плацебо. Улучшение исходов ВН было достигнуто в условиях долгосрочного уменьшения применения глюкокортикоидов после индукционной фазы. При терапии БЛМ отмечалось также снижение общей активности СКВ, уменьшение числа тяжелых обострений и улучшение показателей серологических маркеров. Соотношение «польза/риск» при использовании БЛМ в сочетании со СТ для лечения ВН было благоприятным. БЛМ может быть рекомендован для терапии ВН в комбинации со стандартными методами лечения с целью достижения и поддержания ремиссии

Генно-инженерные биологические препараты в терапии системной красной волчанки

Systemic lupus erythematosus (SLE) is a prototype for chronic autoimmune disease. Its prevalence is 20 to 70 cases per 100,000 women and varies by race and ethnicity. Despite considerable progress in traditional therapy, many problems associated with the management of these patients need to be immediately solved: thus, 50-80% are found to have activity signs and/or frequent exacerbations and about 30% of the patients have to stop work; Class IV lupus nephritis increases the risk of terminalrenal failure. In the past 20 years great progress has been made in studying the pathogenesis of SLE: biological targets to affect drugs have been sought and fundamentally new therapeutic goals defined. Belimumab is the first genetically biological agent specially designed to treat SLE, which is rightly regarded as one of the most important achievements of rheumatology in the past 50 years.Системная красная волчанка (СКВ) является прототипом хронического аутоиммунного заболевания. Распространенность СКВ составляет от 20 до 70 случаев на 100 тыс. женщин и варьирует в зависимости от расовой и этнической принадлежности. Несмотря на значительные успехи традиционной терапии, многие проблемы, связанные с ведением этих больных, требуют незамедлительного решения: так у 50-80% больных СКВ выявляются признаки активности и/или частые обострения, около 30% вынуждены прекратить работу, наличие IV класса волчаночного нефрита увеличивает риск развития терминальной почечной недостаточности. За последние 20 лет достигнут огромный прогресс в изучении патогенеза СКВ: найдены биологические мишени для воздействия лекарственных средств и определены принципиально новые терапевтические задачи. Белимумаб – первый генно-инженерный биологический препарат, созданный специально для лечения СКВ, что по праву рассматривается как одно из наиболее крупных достижений ревматологии за последние 50 лет