Атипичный гемолитико-уремический синдром: эволюция лечения и влияние клинико-генетических характеристик на возможность отмены экулизумаба

   Атипичный гемолитико-уремический синдром (аГУС) – это редкий вариант тромботической микроангиопатии (ТМА), ассоциированный с неконтролируемой активацией альтернативного пути комплемента из-за мутаций генов, кодирующих регуляторные белки комплемента, или образования антител к некоторым из этих регуляторов. Триггерами клинической манифестации аГУС могут быть инфекции, сепсис, беременность, аутоиммунные заболевания, трансплантация органов и другие комплемент-активирующие состояния. Ранее единственным вариантом терапии аГУС была плазматерапия – инфузии свежезамороженной плазмы или плазмаобмен, однако эффективность плазматерапии была недостаточной. В настоящее время появилось таргетное лечение – препарат рекомбинантных гуманизированных моноклональных антител против белка комплемента С5 экулизумаб, показавший в ряде исследований высокую эффективность в достижении ремиссии аГУС, восстановлении почечной функции, профилактике ТМА при трансплантации почки. Долгое время оставался нерешенным вопрос об оптимальной продолжительности лечения и возможности отмены экулизумаба у пациентов с ремиссией. Было показано, что после отмены комплемент-блокирующей терапии рецидивы аГУС развивались у 20-35 % пациентов. В статье обсуждаются результаты большого числа публикаций, посвященных лечению экулизумабом и возможности его отмены, в том числе – французского проспективного открытого многоцентрового исследования, выявившего следующие факторы риска рецидива аГУС после отмены экулизумаба: наличие редких вариантов генов комплемента, женский пол, повышенный уровень в плазме растворимого C5b-9 в момент отмены препарата. У пациентов, не имевших редких генетических вариантов, риск рецидива составлял менее 5 %. В целом отмена экулизумаба после достижения полной ремиссии аГУС и восстановления функции почек при низком риске рецидива может обеспечить лучшую переносимость поддерживающего лечения, уменьшение частоты инфекционных осложнений и существенное снижение финансовой нагрузки на систему здравоохранения.

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