safetyriskБезопасность и риск фармакотерапииSafety and Risk of Pharmacotherapy2312-78212619-1164Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)10.30895/2312-7821-2025-13-1-7-19safetyrisk-489Research ArticleГЛАВНАЯ ТЕМА: ИННОВАЦИИ И ВЫЗОВЫ В ФАРМАКОТЕРАПИИ: ОТ РАЗРАБОТКИ НОВЫХ ПРЕПАРАТОВ ДО ОБЕСПЕЧЕНИЯ БЕЗОПАСНОСТИ В КЛИНИЧЕСКОЙ ПРАКТИКЕMAIN TOPIC: INNOVATIONS AND CHALLENGES IN PHARMACOTHERAPY: FROM DEVELOPING NOVEL MEDICINAL PRODUCTS TO ENSURING THEIR CLINICAL SAFETYАнтиамилоидные моноклональные антитела в лечении болезни Альцгеймера — новая надежда? (Обзор)Anti-amyloid Monoclonal Antibodies for Alzheimer’s Disease: A New Hope? (Review)https://orcid.org/0000-0002-3733-6822МазеркинаИ. А.MazerkinaI. A.

Мазеркина Ирина Анатольевна, канд. мед. наук

Петровский б-р, д. 8, стр. 2, Москва, 127051

Irina A. Mazerkina, Cand. Sci. (Med.)

8/2 Petrovsky Blvd, Moscow 127051

mazerkina@expmed.ruФедеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской ФедерацииРоссияScientific Centre for Expert Evaluation of Medicinal ProductsRussian Federation202509042025131719Copyright © Мазеркина И.А., 20252025Мазеркина И.А.Mazerkina I.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.risksafety.ru/jour/article/view/489ВВЕДЕНИЕ

ВВЕДЕНИЕ. Болезнь Альцгеймера, распространение которой коррелирует с увеличением продолжительности жизни населения, является одной из главных причин тяжелых когнитивных расстройств и деменции. В 2021–2024 гг. Управлением по контролю качества пищевых продуктов и лекарственных средств (FDA) были зарегистрированы болезнь-модифицирующие препараты на основе антиамилоидных (анти-Аβ) моноклональных антител (МкАТ): адуканумаб (ускоренная регистрация), леканемаб и донанемаб. Изучение эффективности и безопасности этих препаратов продолжается.

ЦЕЛЬ

ЦЕЛЬ. Оценка перспектив и ограничений антиамилоидной терапии болезни Альцгеймера болезнь-модифицирующими препаратами в контексте современных представлений о патогенетических механизмах этого заболевания.

ОБСУЖДЕНИЕ

ОБСУЖДЕНИЕ. По современным представлениям в патогенезе болезни Альцгеймера основную роль отводят отложению в головном мозге амилоидных бляшек и нейрофибриллярных клубков из патологического гиперфосфорилированного тау-белка, что сопровождается нейродегенеративными изменениями. Патогенез заболевания продолжает изучаться. Механизм действия одобренных FDA для лечения болезни Альцгеймера анти-Аβ МкАТ адуканумаб, леканемаб и донанемаб — активация микроглии с фагоцитозом амилоида и его деградацией; различие между ними заключается в аффинности к разным формам амилоида. Результаты клинических исследований (средняя продолжительность 1,5 года) показали, что все анти-Аβ МкАТ достоверно и значимо уменьшали амилоидную нагрузку в головном мозге (вплоть до полного ее исчезновения при применении донанемаба), а также замедляли когнитивные нарушения у пациентов на ранней стадии болезни Альцгеймера. Замедление когнитивных нарушений было достоверным, но клинически малозначимым. Основные осложнения терапии МкАТ — амилоид-ассоциированные аномалии визуализации (ARIA), определявшиеся у 20–30% пациентов, являются результатом удаления амилоида, чаще возникают в начале лечения и у носителей аллеля APOE ε4. В большинстве случаев ARIA бессимптомны и регрессируют со временем.

ВЫВОДЫ

ВЫВОДЫ. Анти-Аβ МкАТ достоверно показали эффективность в уменьшении амилоидной нагрузки головного мозга и замедлении прогрессирования когнитивных расстройств при болезни Альцгеймера. Однако малая клиническая эффективность, инвазивность диагностики, высокая стоимость диагностики и терапии, дополнительные расходы на мониторинг нежелательных явлений в настоящее время ограничивают широкое применение препаратов этой группы.

INTRODUCTION

INTRODUCTION. Alzheimer’s disease (AD), which becomes more prevalent with increasing life expectancy, is a leading cause of severe cognitive disorders and dementia. In 2021–2024, the Food and Drug Administration (FDA) approved the first disease-modifying therapies (DMTs) based on anti-amyloid monoclonal antibodies (­anti-Aβ mAbs), including aducanumab (accelerated approval), lecanemab, and donanemab. Ongoing studies are evaluating the efficacy and safety of these anti-Aβ mAbs.

AIM

AIM. This review aimed to examine the prospects and limitations of anti-amyloid DMTs for AD in the context of the current understanding of AD pathogenesis mechanisms.

DISCUSSION

DISCUSSION. According to current concepts, the pathogenesis of AD is primarily driven by the aggregation of amyloid plaques and neurofibrillary tangles of hyperphosphorylated tau protein in the brain, which is accompanied by neurodegenerative changes. The pathogenesis of AD is still being studied. The mechanism of action of FDA-approved anti-Aβ mAbs for the treatment of AD (aducanumab, lecanemab, and donanemab) involves microglial activation followed by amyloid phagocytosis and degradation. The mAbs differ in their affinity to different ­amyloid species. Clinical trials (average duration: 1.5 years) have demonstrated that all 3 anti-Aβ mAbs reliably and significantly reduce the brain amyloid burden (up to complete amyloid clearance with donanemab) and slow down cognitive decline in patients with early-stage AD. Although reliable, the reduction in cognitive decline rates is of limited clinical significance. The most common adverse event of mAb therapy is amyloid-associated imaging abnormalities (ARIA) observed in 20–30% of patients. This complication is a result of amyloid clearance and typically occurs early in the course of treatment. APOE ε4 allele carriers have a higher incidence of ARIA than non-carriers. Most reported cases of ARIA were asymptomatic and resolved over time.

CONCLUSIONS

CONCLUSIONS. Anti-Aβ mAbs have shown reliable efficacy in reducing the brain amyloid burden and slowing the progression of cognitive decline in AD. However, the widespread use of anti-Aβ mAbs has been hampered by their limited clinical efficacy, invasiveness of diagnosis, high diagnostic and treatment costs, and additional expenses associated with adverse event monitoring.

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The authors declare that there are no conflicts of interest present.