Annals of the Russian academy of medical sciencesAnnals of the Russian academy of medical sciencesВестник Российской академии медицинских наук0869-60472414-3545"Paediatrician" Publishers LLC152710.15690/vramn1527DERMATOLOGY and VENEROLOGY: current issuesАКТУАЛЬНЫЕ ВОПРОСЫ ДЕРМАТОВЕНЕРОЛОГИИResearch ArticleMethotrexate Safety in Psoriasis: An OverviewВопросы безопасности применения метотрексата в терапии псориазаhttps://orcid.org/0000-0002-2228-84425530-9490AsoskovaAnastasiia V.АсосковаАнастасия Валерьевна
Russian Federation

PhD student

аспирант кафедры дерматовенерологии и косметологии

stasya.asoskova@mail.ruhttps://orcid.org/0000-0002-4496-36804525-7556SychevDmitry A.СычевДмитрий Алексеевич
Russian Federation

MD, PhD, Professor, Corresponding Member of the RAS

доктор медицинских наук, профессор, член-корреспондент РАН

dmitrysychevrmapo@gmail.comhttps://orcid.org/0000-0002-7625-05038771-4990KubanovAlexey A.КубановАлексей Алексеевич
Russian Federation

MD, PhD, Professor , Corresponding Member of the RAS

доктор медицинских наук, профессор, член-корреспондент РАН

alex@cnikvi.ruRussian Medical Academy of Continuous Professional EducationРоссийская медицинская академия непрерывного профессионального образованияState Scientific Centre of Dermatovenereology and CosmetologyГосударственный научный центр дерматовенерологии и косметологии030920217632542671603202130062021Copyright ©; 2021, "Paediatrician" Publishers LLCCopyright ©; 2021, Издательство "Педиатръ"2021"Paediatrician" Publishers LLCИздательство "Педиатръ"https://vestnikramn.spr-journal.ru/jour/about/submissionshttps://vestnikramn.spr-journal.ru/jour/article/view/1527

Methotrexate is a highly efficacious treatment for psoriasis, but the use of methotrexate may be limited by concerns regarding its adverse reactions. On average, 28.3 % of patients with psoriasis treated by methotrexate develop adverse reactions. The occurrence of adverse drug reactions in some cases leads to the therapy discontinuation, which may be accompanied by psoriasis exacerbation. The purpose of this article is to provide an extensive review of the methotrexate efficacy, safety and tolerability as well as provide a comprehensive understanding of methotrexate pharmacokinetics and pharmacodynamics, methotrexate side effects pathogenesis, approaches to methotrexate safety monitoring, situations in which it is necessary to be vigilant when prescribing methotexate. We also outline current data concerning methotrexate molecular mechanism of action, including new data on its anti-inflammatory activity, that allow us to explain the pathogenesis of a number of adverse drug reactions, as well as discuss possible ways of predicting the methotrexate toxicity, especially focusing on recent advances in the field of pharmacogenetics of methotrexate-induced toxicity and personalized approach to psoriasis treatment.

Метотрексат является высокоэффективным препаратом для системного лечения среднетяжелых и тяжелых форм псориаза, однако токсичность препарата может ограничивать его применение. Токсическое действие метотрексата отмечается в среднем у 28,3٪ пациентов. Возникновение нежелательных лекарственных реакций в некоторых случаях приводит к необходимости отмены препарата, что может сопровождаться обострением заболевания. В обзоре представлены современные данные литературы по вопросам безопасности терапии метотрексатом: описаны молекулярные механизмы действия препарата и новые данные о его противовоспалительной активности, позволяющие объяснить патогенез ряда нежелательных лекарственных реакций, обсуждаются особенности влияния фармакокинетики и фармакодинамики препарата на его токсическое действие, обобщены результаты исследований структуры и механизмов развития нежелательных лекарственных реакций при терапии метотрексатом, описаны ситуации, в которых необходимо проявлять настороженность при назначении метотексата, приведены актуальные подходы к мониторингу его токсического действия, представлены терапевтические подходы к уменьшению риска метотрексат-индуцированной токсичности, а также проанализированы возможные пути прогнозирования риска развития нежелательных лекарственных реакций при терапии метотрексатом с учетом фармакогенетического тестирования, позволяющие подойти к терапии псориаза с позиции персонализированной медицины.

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