Long-term follow-up of patients with refractory systemic lupus erythematosus during rituximab treatment


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AIM: To evaluate the impact of anti-B-cell therapy on the clinical and immunological parameters of systemic lupus erythematosus (SLE) activity, on the time course of changes in these parameters during long-term follow-up, and on the tolerability of repeated rituximab (RTM) therapy cycles/MATERIAL AND METHODS: RTM was given to 97 patients with high activity of SLE refractory to treatment with glucocorticosteroids (GCS) and cytostatics. The follow-up lasted 18 (12-36) months. The most common clinical manifestations of SLE were lupus nephritis (LN) (62%) and skin (33%) and nervous system (22.7%) involvements. Clinical SLE activity was assessed applying the SLE disease activity index 2000 (SLEDAI2K); therapeutic effectiveness was evaluated using indicators, such as partial response (PR), complete response (CR) and exacerbation. The exacerbation was classified as moderate and severe using the Selena-Sledai Flare index (SFI)/RESULTS: Depletion was identified in 78% of the patients with SLE immediately after RTM therapy. During 3.5 years of follow-up, the effect of RTM was seen in 82% of the patients after repeated RMT therapy cycles (CR 56% and PR 28%). Exacerbations were observed in a total of 24 (24.7%) patients; the exacerbation lasted 12 (12-24) months after RTM therapy: of them 17.5% with LN and 7.2% with extrahepatic manifestations of SLE (exacerbations occurred 12 (12-24) and 18 (6-48) months after RMT therapy). In 24 exacerbated patients, B cells recovered at 6 (3-12) months. A year after RMT therapy, a group of 35 patients who were observed to have complete B cell depletion achieved CR statistically significantly more frequently than a group of 20 patients who had B-cell recovery (65.7 and 30% respectively, p=0.03). CR was observed significantly more often in patients after repeated RTM therapy cycles than those who had received only one RTM therapy cycle (p=0.02). The long-term follow-up showed a reduction in SLEDAI2K, normalization of laboratory values, and a decrease in the daily dose of GCS. Most patients tolerated well both the first and repeated RTM therapy cycles/CONCLUSION: According to the results of the long-term follow-up, RTM therapy is a highly effective treatment option for SLE patients in whom the previous standard therapy with GCS and cytostatics was previously ineffective. The 3.5-year follow-up showed a good tolerability of RTM and revealed no increase in the risk of infectious complications or adverse reactions.

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Длительное наблюдение больных с рефрактерной системной красной волчанкой на фоне лечения ритуксимабом. - Резюме. Цель исследования. Оценить влияние анти-В-клеточной терапии на клинические и иммунологические показатели активности системной красной волчанки (СКВ), динамику данных показателей при длительном наблюдении и переносимость повторных курсов терапии ритуксимабом (РТМ). Материалы и методы. РТМ назначен 97 больным СКВ с высокой активностью и рефрактерностью к лечению глюкокортикостероидами (ГКС) и цитостатиками. Длительность наблюдения составила 18 (12-36) мес. Наиболее распространенными клиническими проявлениями СКВ были нефрит (62%), поражение кожи (33%) и нервной системы (22,7%). Клиническая активность СКВ оценена с использованием индекса активности СКВ (SLEDAI2K), эффективность лечения - с помощью таких показателей, как частичный ответ (ЧО), полный ответ (ПО), обострение. Обострение классифицировали как умеренное обострение (УО) и тяжелое обострение (ТО) с использованием индекса обострения СКВ (SFI). Результаты. Сразу после терапии РТМ деплеция определялась у 78% больных СКВ. В течение 3,5 года наблюдения эффект РТМ получен у 82% пациентов после повторных курсов РТМ (ПО 56%, ЧО 28%). В общей сложности обострения наблюдались у 24 (24,7%) больных, срок обострения составил 12 (12-24) мес после проведения терапии РТМ. Из них 17,5% больные с люпус-нефритом (срок обострения 12 [12-24] мес после терапии РТМ), а 7,2% - с внепочечными проявлениями СКВ (срок обострения 18 (6-48) мес после терапии РТМ). У 24 пациентов с обострением восстановление В-клеток происходило на сроке 6 (3-12) мес. Через 1 год после терапии РТМ в группе из 35 больных, у которых отмечалась полная деплеция В-лимфоцитов, ПО достигался статистически значимо чаще, чем в группе из 20 больных, у которых наблюдалось восстановление В-клеток (65,7 и 30% соответственно; р=0,03). ПО у больных СКВ на фоне повторных курсов РТМ наблюдался статистически значительно чаще, чем у больных, которым проведен всего один курс РТМ (р=0,02). При многолетнем динамическом наблюдении констатированы снижение индекса SLEDAI2K, нормализация лабораторных показателей и снижение суточной дозы ГКС. Большинство больных хорошо переносили как первый, так и повторные курсы терапии РТМ. Заключение. По результатам многолетнего динамического наблюдения терапия РТМ является высокоэффективным методом лечения больных СКВ рефрактерных к ранее проводимой стандартной терапии ГКС и цитостатиками. В результате наблюдения в течение 3,5 года отмечена хорошая переносимость РТМ, не выявлено повышения риска развития инфекционных осложнений или нежелательных реакций.
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