cmedasНепрерывное медицинское образование и наукаContinuing Medical Education and Science2949-62923033-585XAGUcmedas-19Research ArticleВНУТРЕННИЕ БОЛЕЗНИINTERNAL DISEASESВЛИЯНИЕ ДОБАВОК ФОЛИЕВОЙ КИСЛОТЫ НА ЭФФЕКТИВНОСТЬ И ПЕРЕНОСИМОСТЬ РАЗНЫХ ФОРМ МЕТОТРЕКСАТА У БОЛЬНЫХ РЕВМАТОИДНЫМ АРТРИТОМEFFECT OF FOLIC ACID SUPPLEMENTATION ON THE EFFICACY AND TOLERABILITY OF DIFFERENT FORMS OF METHOTREXATE IN RHEUMATOID ARTHRITIS PATIENTSДевальдИ. В.DevaldI. V.

Девальд Инесса Валерьевна, кандидат медицинских  наук, доцент кафедры терапии ИДПО

454092, г. Челябинск, ул. Воровского, 64 Тел. +7 (351) 742-82-57

Chelyabinsk

inessa.devald@gmail.comХодусЕ. А.KhodusE. A.

Ходус Елена Андреевна, кандидат медицинских наук,  врач-ревматолог

Челябинск

Chelyabinsk

khoduslena@gmail.comИгнатоваГ. Л.IgnatovaG. L.

Игнатова Галина Львовна, доктор медицинских наук,  профессор, заведующая кафедрой терапии института  дополнительного профессионального  образования ИДПО

Челябинск

Chelyabinsk

iglign@mail.ruБельснерМ. С.BelsnerM. S.

Бельснер Мария Сергеевна, кандидат медицинских  наук, доцент кафедры терапии ИДПО

Челябинск

Chelyabinsk

mariika_04@mail.ruФедеральное государственное бюджетное образовательное учреждение высшего образования «Южно-Уральский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссия«Сlinic of professor Kinsersky»Russian Federation«Клиника профессора Кинзерского»РоссияSouth Ural State Medical UniversityRussian Federation2022270720231743951Copyright © Девальд И.В., Ходус Е.А., Игнатова Г.Л., Бельснер М.С., 20222022Девальд И.В., Ходус Е.А., Игнатова Г.Л., Бельснер М.С.Devald I.V., Khodus E.A., Ignatova G.L., Belsner M.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://cmedas.elpub.ru/jour/article/view/19

Цель работы: оценить влияние добавок фолиевой кислоты (ФК) на эффективность и переносимость таблетированной и инъекционной формы метотрексата (МТ) у больных ревматоидным артритом (РА).Материалы и методы: ретроспективно проанализированы истории болезни 170 пациентов с достоверным диагнозом РА. Возраст пациентов составил 53,7±10,9 лет. Все пациенты получали терапию МТ сроком от 6 до 144 месяцев (87,4±6,9) в дозе от 7,5 до 20 мг/неделю (14±3,8). Больные разделены на две группы: получавших и не получавших стандартные добавки ФК в дозе 5 мг/нед. Оценивалась эффективность и переносимость разных форм МТ в зависимости от назначений с ФК. Эффективность терапии проводили по динамике индекса DAS28. Переносимость определяли по частоте нежелательных явлений (НЯ): стоматит, цитопения, диспепсия, повышение уровня трансаминаз.Результаты: Во-первых, установлено статистически значимое преобладание эффективности МТ без добавок ФК: р=0,02 и OR=0,46; 95%CI 0,23 – 0,91, а именно его инъекционной формы: p< 0,001, OR=16,3; 95%CI 5,08 – 51,3. Во-вторых, синтетическая ФК может увеличивать частоту побочных эффектов: р=0,004, OR=2,52; 95%CI 1,35 – 4,95. Применение подкожной формы МТ без добавок ФК не сопровождается увеличением частоты нежелательных реакций по сравнению с таблетированной формой: p< 0,001, OR=25; 95%CI 7,7 – 80,7 и по сравнению с пациентами, которые получали инъекции МТ с ФК: p=0,002, OR=0,2; 95%CI 0,1 – 0,6. Дополнительный прием ФК не влияет на коррекцию побочных эффектов при применении инъекций МТ и в части случаев способен их нивелировать при использовании таблетированной формы.Заключение: Результаты наблюдения свидетельствуют, что подкожная форма МТ обладает большим терапевтическим эффектом в сравнении с таблетированной. Максимальный лечебный потенциал возможно достичь при инъекционной форме МТ без добавления ФК. Целесообразность рутинного применения ФК при терапии МТ РА вызывает вопросы. Синтетическая ФК может как увеличивать частоту нежелательных явлений перорального МТ, так и нивелировать их. Возможно, разнонаправленность эффектов связана с уровнем фолатов в организме. Развитие побочных эффектов в части случаев корректируется добавками синтетической ФК.

Abstract. Objective: to evaluate the effect of folic acid (FA) supplementation on the efficacy and tolerability of tablet and injectable forms of methotrexate (MT) in patients with rheumatoid arthritis (RA).Materials and methods: the case histories of 170 patients with a reliable diagnosis of RA were retrospectively analyzed. The age of the patients was 53.7±10.9 years.All patients received MT therapy for 6 to 144 months (87.4±6.9) at a dose of 7.5 to 20 mg/week (14±3.8). Patients were divided into two groups: those who received and those who did not receive standard FC supplements at a dose of 5 mg/week. The efficacy and tolerability of different forms of MTs depending on the prescriptions with FC were evaluated. The efficacy of therapy was determined by the dynamics of the DAS28 index. Tolerability was determined by the frequency of adverse events (AEs): stomatitis, cytopenia, dyspepsia, elevated transaminases.Results: First, a statistically significant predominance of the efficacy of MT without FC supplementation was found: p=0.02 and OR=0.46; 95%CI 0.23 to 0.91, and specifically its injectable form: pБ 0.001, OR=16.3; 95%CI 5.08 to 51.3. Second, synthetic FC may increase the frequency of side effects: p=0.004, OR=2.52; 95%CI 1.35 - 4.95. Administration of the subcutaneous form of MT without FC supplementation was not associated with an increased incidence of adverse reactions compared to the tablet form: p< 0.001, OR=25; 95%CI 7.7 - 80.7 and compared to patients who received MT injections with FC: p=0.002, OR=0.2; 95%CI 0.1 - 0.6. Additional intake of FC does not affect the correction of side effects when using MT injections and in some cases is able to level them when using the tablet form. Conclusion: The results of the observation suggest that the subcutaneous form of MT has a greater therapeutic effect compared to the tablet form. The maximum therapeutic potential can be achieved with the injectable form of MTs without the addition of FC. The feasibility of routine use of PC in MT therapy with RA is questionable. Synthetic PC can both increase the frequency of adverse events of oral MTs and neutralize them. It is possible that the multidirectional effects are related to folate levels in the body. The development of side effects in some cases is corrected by supplementation with synthetic FA.

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