rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.47360/1995-4484-2023-188-198rsp-3321Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHЭффективность олокизумаба в отношении коморбидного депрессивного расстройства у больных ревматоидным артритом: предварительные результаты исследованияEfficacy of olokizumab against comorbid depressive disorder in patients with rheumatoid arthritis: Preliminary results of the studyhttps://orcid.org/0000-0001-9437-406XЛисицынаТ. А.LisitsynaT. A.

115522, Москва, Каширское шоссе, 34а

115522, Moscow, Kashirskoye Highway, 34A

talisitsyna@rambler.ruhttps://orcid.org/0000-0002-1504-5645АбрамкинА. А.AbramkinA. A.

115522, Москва, Каширское шоссе, 34а

115522, Moscow, Kashirskoye Highway, 34A

https://orcid.org/0000-0001-5210-2605ВельтищевД. Ю.VeltishchevD. Yu.

107076, Москва, ул. Потешная, 3, корп. 10; 117997, Москва, ул. Островитянова, 1

107076, Moscow, Poteshnaya str., 3, building 10; 117997, Moscow, Ostrovitianova str., 1

https://orcid.org/0000-0001-5839-4637СеравинаО. Ф.SeravinaO. F.

107076, Москва, ул. Потешная, 3, корп. 10

107076, Moscow, Poteshnaya str., 3, building 10

https://orcid.org/0000-0001-6573-4337КовалевскаяО. Б.KovalevskayaO. B.

107076, Москва, ул. Потешная, 3, корп. 10

107076, Moscow, Poteshnaya str., 3, building 10

https://orcid.org/0000-0001-6802-0268БорисоваА. Б.BorisovaA. B.

115522, Москва, Каширское шоссе, 34а; 107076, Москва, ул. Потешная, 3, корп. 10

115522, Moscow, Kashirskoye Highway, 34A; 107076, Moscow, Poteshnaya str., 3, building 10

https://orcid.org/0000-0003-2818-6583ИгнатьевВ. Г.IgnatievV. G.

119421, Москва, Ленинский просп., 111б

119421, Moscow, Leninskiy avenue, 111B

https://orcid.org/0000-0002-1598-8360НасоновЕ. Л.NasonovE. L.

115522, Москва, Каширское шоссе, 34а; 119991, Москва, ул. Трубецкая, 8, стр. 2

115522, Moscow, Kashirskoye Highway, 34A; 119991, Moscow, Trubetskaya str., 8, building 2 

ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»РоссияV.A. Nasonova Research Institute of RheumatologyRussian FederationМосковский научно-исследовательский институт психиатрии – филиал ФГБУ «Национальный медицинский исследовательский центр психиатрии и наркологии им. В.П. Сербского» Минздрава России; ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава РоссииРоссияMoscow Research Institute of Psychiatry – the Branch of the «National Medical Research Center for Psychiatry and Narcology» of the Ministry of Health of the Russian Federation; N.I. Pirogov Russian National Research Medical UniversityRussian FederationМосковский научно-исследовательский институт психиатрии – филиал ФГБУ «Национальный медицинский исследовательский центр психиатрии и наркологии им. В.П. Сербского» Минздрава РоссииРоссияMoscow Research Institute of Psychiatry – the Branch of the «National Medical Research Center for Psychiatry and Narcology» of the Ministry of Health of the Russian FederationRussian FederationФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»; Московский научно-исследовательский институт психиатрии – филиал ФГБУ «Национальный медицинский исследовательский центр психиатрии и наркологии им. В.П. Сербского» Минздрава РоссииРоссияV.A. Nasonova Research Institute of Rheumatology; Moscow Research Institute of Psychiatry – the Branch of the «National Medical Research Center for Psychiatry and Narcology» of the Ministry of Health of the Russian FederationRussian FederationАО «Р-Фарм»РоссияAO «R-Pharm»Russian FederationФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»; ФГАОУ ВО «Первый Московский государственный медицинский университет имени И.М. Сеченова» Минздрава России (Сеченовский Университет)РоссияV.A. Nasonova Research Institute of Rheumatology; I.M. Sechenov First Moscow State Medical University of the Ministry of Health Care of Russian Federation (Sechenov University)Russian Federation202328042023612188198Copyright © Лисицына Т.А., Абрамкин А.А., Вельтищев Д.Ю., Серавина О.Ф., Ковалевская О.Б., Борисова А.Б., Игнатьев В.Г., Насонов Е.Л., 20232023Лисицына Т.А., Абрамкин А.А., Вельтищев Д.Ю., Серавина О.Ф., Ковалевская О.Б., Борисова А.Б., Игнатьев В.Г., Насонов Е.Л.Lisitsyna T.A., Abramkin A.A., Veltishchev D.Y., Seravina O.F., Kovalevskaya O.B., Borisova A.B., Ignatiev V.G., Nasonov E.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/3321Актуальность

Актуальность. Интерлейкин (ИЛ) 6 играет важную роль в патогенезе коморбидной ревматоидному артриту (РА) депрессии, а ингибиторы ИЛ-6, используемые для лечения больных РА, могут обладать антидепрессивным эффектом.

Цель исследования – оценить эффективность российского ингибитора ИЛ-6 олокизумаба (ОКЗ) в отношении симптомов депрессии у больных с умеренной/высокой активностью ревматоидного артрита.

Материал и методы

Материал и методы. К настоящему времени включено 49 больных РА, из них 43 (87,7%) женщины; средний возраст пациентов – 47,8±12,8 года. У большинства пациентов отмечалась высокая активность РА по индексам DAS28-СРБ (Disease Activity Score с определением уровня C-реактивного белка) – 89,8%, SDAI (Simplified Disease Activity Index) – 79,6%, CDAI (Clinical Disease Activity Index) – 75,5%, а также неэффективность стабильной 12-недельной терапии базисными противовоспалительными препаратами (БПВП). У всех пациентов психиатром в соответствии с Международной классификацией болезней 10-го пересмотра в ходе полуструктурированного интервью диагностирована депрессия (хроническая или рекуррентная) различной степени выраженности. На неделе 0 все пациенты рандомизированы методом последовательных номеров в соотношении 1:1:1 в одну из трех групп: в первой проводилось лечение БПВП+ОКЗ 64 мг подкожно 1 раз в 4 недели (n=18); во второй – БПВП+ОКЗ 64 мг подкожно 1 раз в 4 недели + психофармакотерапия (ПФТ; n=26); в третьей – БПВП+ПФТ (n=5). Продолжительность исследования составила 24 недели. Динамика выраженности депрессии оценивалась по шкалам PHQ-9 (Patient Health Questionnaire-9), MADRS (Montgomery – Asberg Depression Rating Scale); тревоги – по HAM-A (Hamilton Anxiety Rating Scale); использовались также экспериментально-психологические проективные методики.

Результаты

Результаты. После 12 и 24 недель терапии отмечено статистически значимое уменьшение выраженности депрессии и тревоги во всех группах пациентов. Однако конечные и исходные значений всех шкал были статистически значимо больше (р<0,05) в группах пациентов, получающих ПФТ: БПВП+ОКЗ+ПФТ (ΔPHQ-9 24–0 =–6,75±3,91; ΔMADRS 24–0 =–22,5±4,83; ΔHAM-A 24-0 =–14,6±5,37) и БПВП+ПФТ (ΔPHQ-9 24–0 =–15,5±3,53; ΔMADRS 24–0 =–25,0±1,41; ΔHAM-A 24-0 =–18,5±3,53), – по сравнению с группой БПВП+ОКЗ (ΔPHQ-9 24-0 =–4,00±3,89; ΔMADRS 24-0 =–5,75±8,29; ΔHAM-A 24–0 =–8,50±8,21). По данным полуструктурированного интервью с психиатром и проективных экспериментально-психологических методик доля больных без депрессии через 24 недели после начала терапии была статистически значимо выше в группах пациентов, получавших ПФТ: 90% в группе БПВП+ОКЗ+ПФТ, 100% в группе БПВП+ПФТ и лишь 25% в группе БПВП+ОКЗ. Терапия ОКЗ способствовала нормализации ночного сна, но не приводила к уменьшению частоты и выраженности когнитивных нарушений.

Выводы

Выводы. ОКЗ обладает антидепрессивным эффектом при применении у пациентов с ревматоидным артритом, приводит к уменьшению частоты нарушений сна, но полный регресс симптомов депрессии при назначении ОКЗ без ПФТ возможен только у 25% больных, преимущественно у пациентов с малой депрессией. Оптимальным для полного регресса депрессии, тревоги и уменьшения частоты и выраженности когнитивных нарушений является сочетание ОКЗ и ПФТ.

Background

Background. Interleukin (IL) 6 plays an important role in the pathogenesis of comorbid rheumatoid arthritis (RA) depression, and IL-6 inhibitors (i) used to treat RA patients may have an antidepressant effect.

Objective – to evaluate the effectiveness of Russian iIL-6 olokizumab (OKZ) in reducing symptoms of depression in patients with moderate/high RA activity.

Material and methods

Material and methods. To date, 49 RA patients have been included, of which 43 (87.7%) are women, with an average age of 47.8±12.8 years; with a predominant high activity of RA according to DAS28 (CRP) indices (89.8%), SDAI (79.6%) and CDAI (75.5%) and inefficacy of stable 12-week therapy of сDMARDs. In all patients, a psychiatrist, in accordance with ICD-10, diagnosed depression (chronic or recurrent) of varying severity during a semi-structured interview. At week 0, all patients were randomized by the method of sequential numbers in a ratio of 1:1:1 to one of the 3 study groups: group 1 – cDMARDs+OKZ 64 mg subcutaneously once every 4 weeks (n=18); group 2 – cDMARDs+OKZ 64 mg subcutaneously once every 4 weeks + psychopharmacotherapy (PPT) (n=26); group 3 – cDMARDs+PPT (n=5). The duration of the study is 24 weeks. The dynamics of depression severity was assessed on the PHQ-9, MADRS scales; anxiety – HAM-A; experimental psychological projective techniques were also used.

Results

Results. After 12 and 24 weeks of therapy, there was a significant decrease in the severity of depression and anxiety in all groups of patients. However, the difference between the final and initial values of all scales was statistically significantly greater (p<0.05) in the groups of patients receiving PPT: cDMARDs+OKZ+PPT (ΔPHQ-9 24–0 =–6.75±3.91; ΔMADRS 24–0 =–22.5±4.83; ΔHAM-A 24-0 =–14.6±5.37) and cDMARDs+PPT (ΔPHQ-9 24–0 =–15.5±3.53; ΔMADRS 24–0 =–25.0±1.41; ΔHAM-A 24-0 =–18.5±3.53), compared with the cDMARDs+OKZ group (ΔPHQ-9 24–0 =–4.00±3.89; ΔMADRS 24-0 =–5.75±8.29; ΔHAM-A 24–0 =–8.50±8.21). According to a semi-structured interview with a psychiatrist and design experimental psychological techniques, the proportion of patients without depression after 24 weeks of therapy was significantly higher in the groups of patients receiving PPT: 90% in the group of cDMARDs+OKZ+PPT and 100% – cDMARDs+PPT, as opposed to 25% in the group of cDMARDs+OKZ. OKZ therapy contributed to the normalization of night sleep but did not lead to a decrease in the frequency and severity of cognitive disorders (CD).

Conclusions

Conclusions. OKZ has an antidepressant effect in RA patients, leads to a decrease in the frequency of sleep disorders, but a com[1]plete regression of depression symptoms is possible because of the appointment of OKZ without PPT only in 25% of RA patients, mainly in patients with mild depression. Optimal for the complete regression of depression, anxiety and a decrease in the frequency and severity of CD is a combination of OKZ and PPT.

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