Фармакотерапия ревматоидного артрита: новая стратегия, новые мишени

Ревматоидный артрит (РА) – хроническое иммуновоспалительное (аутоиммунное) заболевание, проявляющееся прогрессирующей деструкцией суставов, системным воспалением внутренних органов и широким спектром коморбидных заболеваний, связанных с хроническим воспалением, а нередко и с нежелательными лекарственными реакциями (НЛР). Однако, несмотря на большие успехи в ранней диагностике и лечении РА, приведшие к кардинальному улучшению прогноза у многих пациентов, проблема фармакотерапии РА далека от разрешения. Это определяется отсутствием «чувствительных» и «специфичных» «диагностических» и «прогностических» биомаркеров на ранней стадии заболевания и, что самое главное, гетерогенностью механизмов иммунопатогенеза как в дебюте, так и в процессе прогрессирования РА, затрудняющими персонификацию терапии у пациентов. Селективное блокирование медиаторов воспаления с использованием инновационных лекарственных препаратов нередко ассоциируется с «первичной» неэффективностью, «вторичной» резистентностью, развитием генерализованной иммуносупрессии, парадоксальной активацией аутоиммунного процесса и утяжелением течения сопутствующих коморбидных заболеваний. В то же время поиск новых «мишеней» для фармакотерапии РА затруднен, поскольку характер иммунопатологических нарушений у пациентов может существенно отличаться от воспалительного процесса, который имеет место при моделировании артрита у лабораторных животных. В статье обсуждаются новые препараты, применяемые в ревматологии для лечения РА или находящиеся на разных стадиях «преклинических» или клинических исследований: ингибиторы фактора некроза опухоли α, интерлейкина 6 (ИЛ6), ИЛ17, анти-В-клеточная терапия, биспецифические антитела, блокаторы JAK (и других сигнальных молекул), биоэлектронная активация блуждающего нерва, иммунотерапия дендритными клетками и другие виды терапии, а также подходы к вторичной профилактике РА у пациентов с недифференцированным артритом и «клинически подозрительной артралгией», имеющих высокий риск развития РА. Расшифровка механизмов патогенеза РА и хронического воспалительного процесса, в целом, создала предпосылки для разработки новых лекарственных препаратов для профилактики и лечения этого заболевания, внедрение которых в клиническую практику должно привести к кардинальному улучшению прогноза при этом заболевании.

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