Анти-В-клеточная терапия у больных системной красной волчанкой

The paper presents an analytical literature review of the use of rituximab (RTM) in patients with systemic lupus erythematosus (SLE). It considers current views on the mechanisms of action of RTM, its efficacy in different organ damages in patients with SLE, particularly in those with lupus nephritis and central nervous system involvement. There is evidence suggesting that it is expedient to use RTM in patients with high activity of SLE, especially when the latter is refractory to standard therapy with glucocorticoids and cytostatics. Attention is paid to the steroidsparing effect of RTM and to the reduction of the risk of irreversible organ damages associated with high-dose prednisone. The paper discusses the possibility of using a RTM biosimilar (Acellbia) and prospects of RTM therapy for early SLE. В статье представлен аналитический обзор литературы, посвященной вопросам применения ритуксимаба (РТМ) у больных системной красной волчанкой (СКВ). Рассмотрены современные взгляды на механизмы действия РТМ, его эффективность при различных органных повреждениях у больных с СКВ, в частности при волчаночном нефрите и поражении центральной нервной системы. Представлены данные, свидетельствующие о целесообразности применения РТМ у больных с высокой активностью СКВ, особенно при развитии рефрактерности к стандартной терапии глюкокортикоидами и цитостатиками. Уделено внимание стероид-сберегающему эффекту РТМ и снижению риска развития необратимых органных повреждений, ассоциированных с высокими дозами преднизолона. Обсуждаются возможность применения биоаналога РТМ (ацеллбия), а также перспективы терапии РТМ при ранней СКВ.

Узловатая эритема: васкулит или панникулит?

Erythema nodosum (EN) as an individual entity has been known for more than 200 years. The long-term study of the disease by rheumatologists, pulmonologists, dermatologists, and other specialists has allowed them to state a variety of etiotropic factors and polymorphism of its clinical symptomatology. Up to now, the discussion of the histopathomorphological nature of EN (vasculitis or panniculitis?) has been continued. The described case makes it possible to regard EN as a manifestation of vasculitis to a greater extent. Further clinical studies are needed depending on the stage of the disease and etiotropic factors.Узловатая эритема (УЭ) как отдельная нозологическая форма известна более 200 лет. Длительное изучение заболевания ревматологами, пульмонологами, дерматологами и другими специалистами позволило констатировать разнообразие этиотропных факторов и полиморфность его клинической симптоматики. До настоящего времени продолжается обсуждение гистопатоморфологической природы УЭ: васкулит или панникулит? Описанное наблюдение позволяет расценивать УЭ в большей степени как проявление васкулита. Необходимы дальнейшие клинические исследования в зависимости от стадии заболевания и этиотропных факторов

Anti-B cell therapy in patients with systemic lupus erythematosus

The paper presents an analytical literature review of the use of rituximab (RTM) in patients with systemic lupus erythematosus (SLE). It considers current views on the mechanisms of action of RTM, its efficacy in different organ damages in patients with SLE, particularly in those with lupus nephritis and central nervous system involvement. There is evidence suggesting that it is expedient to use RTM in patients with high activity of SLE, especially when the latter is refractory to standard therapy with glucocorticoids and cytostatics. Attention is paid to the steroidsparing effect of RTM and to the reduction of the risk of irreversible organ damages associated with high-dose prednisone. The paper discusses the possibility of using a RTM biosimilar (Acellbia) and prospects of RTM therapy for early SLE

EXPERIENCE WITH BELIMUMAB IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Objective: to investigate the efficacy of an anti-BlyS drug (belimumab) for the treatment of systemic lupus erythematous (SLE).Subjects and methods. Belimumab (BLM) was administered to three patients with SLE (two women and one man were aged 24, 28, and 39 years, respectively). SLE activity was estimated according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K, the values of which were 8, 12, and 14 scores, respectively, due to high immunological activity, skin, joint, and mucosal lesions. The high Systemic Lupus International Collaborating Clinics (SLICC) Damage Index score of 3 was found in 2 of the 3 patients. All patients received glucocorticoids (GC) 20–25 mg/day; two – hydroxychloroquine and one – mycophenolate mofetil 1000 mg/day. Therapy with BLM was performed using a standard scheme: three 10 mg/kg infusions during the first month, then one infusion every month.Results. Positive clinical changes were noted 2 months after therapy initiation; symptoms completely disappeared 3 and 6 months later. Anti-DNA antibodies and complement fractions, the levels of which were partially normalized at 2 to 9 months of treatment, were most refractory to BLM therapy. During the follow-up, there were no SLE exacerbations; the dose of GC could be halved in two cases. Glomerular filtration normalized in one patient with inactive lupus nephritis.Conclusion. BLM treatment is justified in patients with moderate SLE activity in the presence of polyarthritis, serositis, skin and mucosal lesions and with high immunological activity. The use of BLM is not contraindicated in patients with inactive lupus nephritis without obvious kidney dysfunction. The additional motivation to use BLM may be an inadequately high GC dose, a recurrent disease course, insufficient therapeutic efficiency, and a risk for irreversibleorgan damage

ERYTHEMA NODOSUM: VASCULITIS OR PANNICULITIS?

Erythema nodosum (EN) as an individual entity has been known for more than 200 years. The long-term study of the disease by rheumatologists, pulmonologists, dermatologists, and other specialists has allowed them to state a variety of etiotropic factors and polymorphism of its clinical symptomatology. Up to now, the discussion of the histopathomorphological nature of EN (vasculitis or panniculitis?) has been continued. The described case makes it possible to regard EN as a manifestation of vasculitis to a greater extent. Further clinical studies are needed depending on the stage of the disease and etiotropic factors

RITUXIMAB TREATMENT EFFICACY IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS REFRACTORY TO STANDARD THERAPY IN THE LONG-TERM FOLLOW-UP

Objective. To evaluate the efficacy and safety of rituximab (RTM) treatment in the long-term follow-up of patients with systemic lupus erythematosus (SLE) refractory to standard therapy. Material and methods. RTM therapy was prescribed to 97 SLE patients with high disease activity and insufficient effica- cy of using high doses of glucocorticoids (GC) and cytostatics. The median follow-up time (25th; 75th percentiles) was 18 [12; 36] months. The most common clinical manifestations of SLE included nephritis (62%), skin lesion (33%), and lesion of the nervous system (22.7%). The clinical assessment of the SLE activity was carried out using the SLEDAI-2K activity index. In assessing the therapy efficacy, the following concepts were used: the partial response (PR), complete response (CR), and flare. Flare was classified as moderate (MF) and severe (SF) using the SLE flare index (SFI). Results. Immediately after RTM therapy, depletion of B-cells was determined in 78% of the patients with SLE. During the 6-year follow-up, the effect of RTM therapy was achieved in 84% of the patients after repeated courses of RTM (CR – 56%, PR – 28%). In total, flares were observed in 24 (24.7%) patients; the median interval from RTM administration to flare was 12 [12; 24] months. In the long-term follow-up, the decline in the SLEDAI-2K index, normalization of laboratory test values, and the decrease in the daily GC dose were noted. Most patients tolerated well both the first and repeated courses of RTM therapy. Conclusion. According to the results of the long-term follow-up, RTM therapy is a highly effective method to treat SLE patients with the ineffectiveness of previously conducted standard therapy with GC and cytostatics. Good tolerance of RTM treatment has been noted; no increase in risk of infectious complications or adverse reactions has been found

TREAT-TO-TARGET SLE RECOMMENDATIONS FROM THE INTERNATIONAL TASK FORCE AND RUSSIAN EXPERTS’ COMMENTARIES

The start of the new millennium is marked by a substantial progress in the development of rheumatology: pathogenesis of many rheumatic diseases (RDs) was more deeply studied; their diagnostic criteria validated; disease activity indices worked out; the concepts of remission and exacerbation introduced; much attention has been given to the investigations of quality of life in patients. The possibility of pharmacotherapy for immunoinflammatory RDs was extended by the advent of biological agents (BA). The treatment strategy for RDs was also changed. The treat-to-target concept was put forth for rheumatoid arthritis in 2010 and for ankylosing spondylitis later. The project of treat-to-target concept in systemic lupus erythematous (SLE) was launched on the initiative of the world’s leading rheumatologists in January 2013. The result of their work is the treat-to-target-in-SLE recommendations published in 2014 and formulated as 4 basic principles and 11 general recommendations. The purpose of this publication is to provide general characteristics of the basic provisions of the principles and recommendations with commentaries of leading experts discussing characteristics of SLE in the Russian Federation and some debatable and unsolved problems

Irreversible organ damages in a cohort of patients with systemic lupus erythematosus (RENAISSANCE)

Objective: to reveal irreversible organ damages and to establish factors that influence their development in a RENAISSANCE cohort of patients with systemic lupus erythematosus (SLE) admitted to the clinic of the V.A. Nasonova Research Institute of Rheumatology in the period 2012 to 2014.Subjects and methods. The investigation enrolled 231 young (mean age, 34.91±11.10 years) patients (209 women and 22 men) with a mean SLE duration of 107.65±97.36 months. On admission of the patients, the investigators collected history data (disease duration, the number of exacerbations and hospitalizations during the follow-up period), assessed current disease activity by SLEDAI-2K, irreversible organ damages by SLICC damage index (DI), and the therapy performed.Results and discussion. Irreversible organ damages were absent in 95 (41%) patients; one or more damages associated with both disease itself and the therapy were observed in the other (59%) patients. There were low (1), mean (2–4), and high (>4) SLICC DI values in 64 (28%), 62 (27%), and 11 (5%) patients, respectively. Ocular lesions were most common (35%); a significant proportion of patients were found to have damages to the cardiovascular (22%), musculoskeletal (19%), and nervous (10%) systems. Lung disease, diabetes mellitus, and cancer were less prevalent (6.0, 3.4, and 1.3%, respectively). The patients with damages were significantly older (p = 0.02), had a longer disease duration (p = 0.0005) and more frequent SLE exacerbations and hospitalizations (p = 0.0003 and p = 0.001, respectively). The patients with DI ≥1 received glucocorticoids (GCs) longer (p = 0.001). At the onset of SLE they had significantly higher doses of GCs (mean 44.06±18.97 mg) than those without damages (35.91±20.12 mg; р = 0.002). DI correlated with GC doses at the onset of the disease, duration of GC use, number of hospitalizations and exacerbations. There was also a statistically significant correlation of overall SLICC DI with the duration of disease (r = 0.23) and the total dose of cyclophosphamide (CP) (r = 0.19).Conclusion. Irreversible organ damages are present in 59 patients in the RENAISSANCE cohort. Older individuals develop a larger number of damages, with higher frequency of exacerbations and hospitalizations, longer use of GCs, and higher cumulative dose of CP. DI correlates with the dose of GC and does not depend on the activity and clinical manifestations of SLE at its onset

THE REGISTRY OF SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS, A EURASIAN COHORT (RENAISSANCE)

<p class="MsoNormal"><span lang="EN-US">The article presents the data of international registries and cohort studies of systemic lupus erythematosus (SLE). It justifies the purpose and objectives of the international registry of SLE patients, a Eurasian cohort (RENAISSANCE), which was launched in 2012 and amalgamated the leading rheumatology centers of the Russian Federation (V.A. Nasonova Research Institute of Rheumatology; Department of Rheumatology,  Pacific State Medical University), Kazakhstan (Department of Rheumatology,  S.D. Asfendiyarov Kazakh National  Medical University), and Kyrgyzstan (Academician M. Mirrakhimov  National  Center for Cardiology and Therapy), which mainly concentrate patients with the acute course of this disease. The first data of the registry are given.</span></p

ANTI-B-CELL THERAPY AT IMMUNE INFLAMMATORY RHEUMATIC DISEASES: EFFICACY AND TOLERABILITY IN 229 PATIENTS

Objective: to assess the efficacy and tolerability of Rituximab treatment in patients with serious immune inflammatory rheumatic diseases (IRD) like systemic lupus erythematosus (SLE), systemic sclerosis (SS), systemic vasculitis (SV), Sjogren syndrome (SjS), dermatomyositis/polymyositis (DM/PM).Subjects and methods. The clinical efficacy has been analyzed in 229 patients with IRD: SLE (n=97), SV (n=50), SS (n=40), SjS (n=23) and DM/PM (n=19). Rituximab treatment was accompanied by administration of glucocorticoids and/or immunosuppressive drugs. Most patients demonstrated resistance to or low tolerability of standard therapy. Efficacy of treatment was analyzed in each group with the criteria relevant for each disease. To compare clinical response to the treatment between the groups we used gradations accepted by international registries: complete (good) response, partial response, no response. Average duration of monitoring comprised 72 (1–288) weeks after the first introduction of Rituximab. Average Rituximab dose administered to patients over the period of monitoring was low and varied from 1.6±0.84 in DM/PM to 3.1±1.75 in SV. About 80% of patients received one or two courses of Rituximab except for patients with SS (half of them received three and more courses).Results. «Complete response» was observed in 50.6%, «partial response» – in 35% of patients. Rituximab courses provided positive dynamics in clinical scores and allowed to reduce supportive dose of glucocorticoids and to lower the dose or withdraw of immune-stimulating drugs. Multiple Rituximab courses provided stable and longlasting effect. Recurrences were observed less frequently, whereas efficacy of the therapy increased during a year and longer. Occurrence of adverse events and mortality rate were comparable to data of other national Rituximab registries.Conclusion. The results of the study may prove administration of Rituximab in patients with resistance to standard therap