Treatment of severe juvenile idiopathic arthritis (JIA) represents a serious challenge. This study investigates the efficacy and safety of repeat courses of rituximab in patients with different forms of JIA refractory to infliximab and standard immunosuppressive therapy. Patients (n = 55; age 2.3-17.0 years) with severe polyarticular and systemic JIA (International League of Association for Rheumatology diagnostic criteria) received rituximab (one intravenous infusion/week for 4 weeks, 375 mg/m(2) per dose). Efficacy was assessed using the American College of Rheumatology Pediatric (ACR Pedi) criteria. The primary endpoint was an ACR Pedi 30 response at week 24. At week 24, ACR Pedi 30, 50, and 70 responses were achieved by 98%, 50%, and 40% of patients, respectively. By week 96, ACR Pedi 30, 50, and 70 responses were achieved by 98%, 93%, and 93% of 25 patients, respectively. Remission was recorded in 25%, 52%, 75%, and 98% of patients following the first (24 weeks), second (48 weeks), third (72 weeks), and fourth (96 weeks) courses of rituximab, respectively. Rituximab treatment significantly reduced the number of systemic manifestations at week 12 and also enabled 52% of patients to achieve remission of arthritis by week 48. This study supports the efficacy of rituximab in patients with severe forms of JIA, refractory to several prior agents.

BackgroundThe aim of this study was to investigate the efficacy of etanercept treatment and to identify predictors of response to therapy within 12 months in patients with juvenile idiopathic arthritis (JIA) without systemic manifestations.MethodsA total of 197 juvenile patients were enrolled in this study. Response to therapy was assessed using the ACRPedi 30/50/70/90 criteria, the Wallace criteria, and the Juvenile Arthritis Disease Activity Score 71 (JADAS-71). Univariate and multivariate logistic regression analyses were performed to identify potential baseline factors associated with treatment response in different JIA categories.ResultsOne year after treatment initiation, 179 (90.9%) patients achieved ACRPedi30; 177 (89.8%) patients achieved ACRPedi50; 168 (85.3%) patients achieved ACRPedi70; and 135 (68.5%) patients achieved ACRPedi90 response. A total of 132 (67.0%) and 92 (46.7%) patients achieved inactive disease according to the Wallace criteria and the JADAS-71 cut-off point, respectively. Excellent response (achieving ACRPedi90 and clinically inactive disease according both to the Wallace criteria and the JADAS71 cut-off point) was associated with persistent oligoarticular JIA category, shorter disease duration before the start of etanercept, a lower number of DMARDs used before the introduction of etanercept, a lower number of joints with limited motion, and lower C-reactive protein at baseline. Poor response (failure to achieve ACR 70 or active disease according to both the Wallace criteria and JADAS71 even when ACR 70 was achieved) was associated with the polyarticular or enthesitis-related JIA categories, higher disease duration before the start of etanercept, and older age at disease onset.ConclusionAlmost half (45.7%) of the patients who initiated etanercept treatment achieved an excellent response (inactive disease and ACRPedi90) after 1 year. What may be novel is our finding that the response to etanercept therapy was strongly associated with the JIA category. The response to etanercept therapy was also associated with the disease duration before the start of etanercept treatment.

(p < 0,001),5 (1,0;5,0) до 1,0 (0,0; 3,0) (p = 0,024), концентрация С4-компонента комплемента повысилась с 0,13 (0,04; 0,19) до 0,43 (0,18; 0,50) г/л (p = 0,017), число антител к двуспиральной ДНК снизилось с 73,5 (11,5; 245,0) до 1,9 (0,0;40,0) МЕ/мл (p = 0,004). Деплеция в В лимфоцитах была зарегистрирована у всех пациентов через 24 и 48 нед терапии ритукси-мабом. Доза преднизолона была снижена с исходной 0,80 (0,43; 1,00) мг/кг в сут до 0,20 (0,17; 0,30) через 48 нед (p = 0,025 ОБОСНОВАНИЕСистемная красная волчанка (СКВ) -аутоиммунное заболевание, при котором наблюдается генерализо-ванное воспаление сосудов и соединительной ткани. Рас пространенность СКВ у детей зависит от их этниче-ской принадлежности и составляет от 10 до 20 случаев на 100 тыс. педиатрической популяции [1,2]. До 20% слу-чаев СКВ манифестируют в детском возрасте, при этом отличаются более тяжелым и агрессивным началом по сравнению с дебютом болезни у взрослых [3][4][5].В этиопатогенезе СКВ играют роль генетические, гормональные, иммунные факторы, а также факторы внешней среды. У пациентов с СКВ выявляют высокую концентрацию аутоантител и иммунных комплексов, что может быть результатом гиперпродукции В лимфоцитов [6,7], увеличения продолжительности их жизни и дли-тельной активации [8,9].Ритуксимаб -это моноклональное химерное анти-тело к CD20 антигену, который экспрессируется как на зрелых В лимфоцитах, так и на их предшественни-ках, но отсутствует на гемопоэтических и нормальных плазматических клетках. В результате антителозависи-мой клеточной цитотоксичности, комплементсвязанно-го лизиса, апоптоза, ингибирования клеточного роста происходит деструкция В лимфоцитов [10]. Хороший клинический ответ на терапию ритуксимабом у больных СКВ обусловлен длительной деплецией В лимфоцитов в периферической крови [11][12][13][14]. В связи с рефрактер-ностью к стандартной терапии ритуксимаб успешно при-меняется для лечения как лимфопролиферативных, так 498Оригинальная статья и аутоиммунных заболеваний у детей, например, таких как синдром Эванса, аутоиммунная гемолитическая ане-мия, идиопатическая тромбоцитопеническая пурпура, СКВ, ювенильный идиопатический артрит, ювенильный дерматомиозит, васкулит [15,16].Целью настоящего исследования было оценить эф-фективность и безопасность терапии ритуксимабом у детей с тяжелым течением СКВ, рефрактерной к глюко-кортикостероидам и иммунодепрессантам. МЕТОДЫ Дизайн исследования Оценка результатов леченияКлинические и лабораторные параметры оценивали в период госпитализации, перед инфузией ритуксимаба, и далее каждые 6 мес. Индексы активности СКВКлиническая активность болезни оценивалась по индексу SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) в модификации SELENA (Safety of Estrogen in Lupus Erythematosus National Assessment, Национальная оценка безопасности эстрогенов при красной волчанке) [19]. Индекс рассчитывался с учетом 24 показателей (16 клинических и 8 лабораторных), при этом каждый признак оценивался в баллах от 1 до 8. По индексу SLEDAI выделяют следующие степени активности СКВ:• 0 балл...

The results of the retrospective study evaluating efficacy and safety of tocilizumab treatment in 75 patients with severe systemic-onset juvenile idiopathic arthritis refractory to standard immunosuppressive therapy are presented in the paper. Inactive disease was documented in 64% of patients after 6 months of treatment and in 73% of patients after 12 months. Adverse events manifested as mild and moderate infections as well as laboratory abnormalities: leukopenia, neutropenia, and elevated aminotransferase levels.

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Background: Addition of genetically engineered biological agents in the paradigm of juvenile idiopathic arthritis (JIA) treatment significantly increased the efficacy of the antirheumatic therapy in patients with

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Background Systemic Juvenile Idiopathic Arthritis (sJIA) is classified as an acquired autoinflammatory disease. The interleukin-1 and interleukin-6 play a pivotal role in pathogenesis of this disease. The systemic manifestations as well as arthritis in sJIA are related to interleukin-6 action. Tocilizumab is promising drug for the treatment of systemic arthritis refractory to immunosuppressive drugs. Objectives To evaluate safety and efficacy of tocilizumab treatment in children with systemic juvenile idiopathic arthritis. Methods An open observational study in patients with sJIA taking tocilizumab. 75 patients were included into the study. Analysis of efficacy and safety tocilizumab therapy was performed in 75 patients. Median age was 7,5 years (range; 0,9 to 15 years) and median disease duration was 2,5 years (range; 0.3 to 12 years). Tocilizumab was administrated intravenously at a dose of 8-12 mg/kg every 2 weeks during 2 months then every 4 weeks. All patients received DMARDs. Efficacy end points included the American College of Rheumatology (ACR) Pediatric criteria for improvement 30 (ACR30), ACR50, ACR70, ACR90 and criteria of inactive disease and remission. During the follow-up period, significant side-effects were sought and the reduction in oral prednisolone was recorded too. Results The ACR Pedi 30, 50, 70 and 90 improvement were achieved by 100%, 90%, 80% and 55% of patients at Week 24 (n=72) and by 100%, 100%, 95% and 70% of patients at Week 52 (n=60), respectively. Inactive disease was achieved by 60% of patients at week 24 (n=72) and by 73% of patients at week 52 (n=61). Remission was achieved by 72% of patients (n=61). The mean dose of oral glucocorticoid was decreased at week 52. The frequently observed non-severe adverse events were nasopharyngitis, upper respiratory tract infections and gastroenteritis. No cases of opportunistic infections, malignancies or death were reported. There were three cases of pneumonia and cellulitis. 30 patients had incidences of neutropenia. Tocilizumab treatment was discontinued in 14 patients during the follow-up 52 weeks period. The causes for cancellation were relapse of disease (n=7), lack of efficacy (n=3), remission (n=1), parent’s refusal (n=1), infusion reaction (n=1) and Crohn’s disease (n=1). Dynamics in systemic features Conclusions The results of the annual prospective observational study have shown the high efficacy of tocilizumab in patients with the severe sJIA. Drug induced remission of extra-articular manifestations, arthritis and normalized laboratory parameters of the disease activity without initiation of treatment with oral prednisolone and increase its dose, thus avoiding severe irreversible complications of glucocorticoid therapy. Tocilizumab induced disease remission in 72 % of patients at Week 52. Disclosure of Interest None Declared