rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.47360/1995-4484-2023-554-561rsp-3437Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHОпыт применения ингибитора интерлейкина 6 (олокизумаба) у больных ревматоидным артритом в реальной клинической практике: влияние на воспалительную активность и исходы заболеванияExperience with the interleukin 6 inhibitor (Olokizumab) in patients with rheumatoid arthritis in real clinical practice: Influence on inflammatory activity and disease outcomeshttps://orcid.org/0000-0003-2692-399XЛапкинаН. А.LapkinaN. A.

150000, Ярославль, ул. Революционная, 5

150000, Yaroslavl, Revolyutsionnaya str., 5

lanaal@rambler.ruhttps://orcid.org/0000-0001-7847-1679БарановА. А.BaranovA. A.

150000, Ярославль, ул. Революционная, 5

150000, Yaroslavl, Revolyutsionnaya str., 5

https://orcid.org/0000-0002-8846-0401АбайтоваН. Е.AbaytovaN. E.

150000, Ярославль, ул. Революционная, 5

150000, Yaroslavl, Revolyutsionnaya str., 5

https://orcid.org/0000-0002-7979-1313ЛеонтьеваЕ. А.LeontyevaE. A.

150000, Ярославль, ул. Революционная, 5

150000, Yaroslavl, Revolyutsionnaya str., 5

https://orcid.org/0000-0001-7834-0775ЯльцеваН. В.YaltsevaN. V.

150000, Ярославль, ул. Революционная, 5

150000, Yaroslavl, Revolyutsionnaya str., 5

https://orcid.org/0000-0002-9079-5948ШутовА. С.ShutovA. S.

150000, Ярославль, ул. Революционная, 5

150000, Yaroslavl, Revolyutsionnaya str., 5

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

ФГБОУ ВО «Ярославский государственный медицинский университет» Минздрава РоссииРоссияYaroslavl State Medical UniversityRussian 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 Federation202331102023615554561Copyright © Лапкина Н.А., Баранов А.А., Абайтова Н.Е., Леонтьева Е.А., Яльцева Н.В., Шутов А.С., Насонов Е.Л., 20232023Лапкина Н.А., Баранов А.А., Абайтова Н.Е., Леонтьева Е.А., Яльцева Н.В., Шутов А.С., Насонов Е.Л.Lapkina N.A., Baranov A.A., Abaytova N.E., Leontyeva E.A., Yaltseva N.V., Shutov A.S., 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/3437

Цель исследования – оценить в реальной клинической практике эффективность терапии ингибитором интерлейкина 6 (олокизумабом) у больных ревматоидным артритом (РА) в отношении показателей клинико-лабораторной активности заболевания, а также исходов, сообщаемых самим пациентом (PROs, patient reported outcomes). Материал и методы. Обследовано 10 больных с достоверным диагнозом РА: средний возраст больных составил 45,70±17,9 года, длительность заболевания – 9,0 (3,0; 12,0) лет. Пациенты имели умеренную или высокую активность заболевания: оценка по DAS28-СОЭ (Disease Activity Score 28 с определением скорости оседания эритроцитов) – 5,13 (4,34; 5,80) балла; CDAI (Clinical Disease Activity Index) – 30,00 (24,00; 35,00); SDAI (Simplified Disease Activity Index) – 31,86 (24,36; 38,59). Всем пациентам было назначено лечение олокизумабом (ОКЗ) в дозе 64 мг подкожно каждые 4 недели на фоне терапии метотрексатом, лефлуномидом, нестероидными противовоспалительными препаратами и глюкокортикоидами (ГК) (до 10 мг/сут. в пересчете на преднизолон). Трое больных ранее получали тоцилизумаб (внутривенно 1 раз в месяц в дозе 8 мг/кг), введение которого было прекращено по административным причинам за 6–12 месяцев до назначения ОКЗ. Результаты лечения оценивали по динамике клинических, лабораторных показателей (DAS28-СОЭ, SDAI, СDAI, C-реактивный белок (СРБ), СОЭ, IgM ревматоидного фактора (РФ), антитела к циклическому цитруллинсодержащему пептиду (АЦЦП)) и исходов, которые оценивали сами пациенты (PROs): индекс HAQ-DI (Health Assessment Questionnaire – Disability Index); общая оценка состояния здоровья больным (ОСЗБ) по визуальной аналоговой шкале (ВАШ); оценка боли по ВАШ; оценка по шкалам FACIT (Functional Assessment of Chronic Illness Therapy), SF-36 (Short Form 36). В качестве психометрических методик использовались опросник «Тип отношения к болезни (ТОБОЛ)», госпитальная шкала тревоги и депрессии (HADS, Hospital Anxiety and Depression Scale), Торонтская алекситимическая шкала (TAS-26, Toronto Alexithymic Scale 26). Наблюдение проводились до лечения, через 3 и 6 месяцев терапии. Результаты. На фоне терапии ОКЗ через 3 и 6 месяцев по сравнению с исходными уровнями наблюдалось статистически значимое снижение клинических индексов активности РА: DAS28-СОЭ – 5,13 (4,34; 5,80), 3,53 (2,83; 4,26) и 3,48 (2,8; 4,10) балла соответственно; CDAI – 30,00 (24,00; 35,00), 11,00 (6,0; 16,00) и 10,0 (5,0; 15,0) баллов соответственно; SDAI – 31,86 (24,36; 38,59), 11,05 (6,07; 16,07) и 10,17 (7,02; 15,02) балла соответственно; СРБ – 14,30 (7,00; 24,70), 0,70 (0,40; 0,90) и 0,65 (0,20; 3,0) мг/л соответственно. Не отмечено статистически значимой динамики СОЭ, IgM РФ и АЦЦП. Через 3 и 6 месяцев лечения ОКЗ статистически значимо снижались показатели ОСЗБ и выраженности боли по шкале ВАШ, а также наблюдалось улучшение функционального состояния больных по опроснику HAQ-DI показателей усталости (FACIT-F) (p < 0,05). Физический компонент шкалы SF-36 статистически значимо увеличился только к 6-му месяцу терапии (p<0,01), при этом психический компонент не претерпел существенной динамики (p>0,05). В процессе терапии ОКЗ изменялось отношение пациентов к болезни: с эргопатического, неврастенического и сенситивного компонентов в профиле ТОБОЛ до ее начала к гармоничному, эргопатическому и сенситивному профилям к ее окончанию. Кроме того, начиная с 3-го месяца лечения, у больных РА преобладала адаптивная реакция на болезнь. Выявлено снижение уровня тревоги по сравнению с исходным через 3 и 6 месяцев наблюдения; показатели депрессии не претерпели существенных изменений. Заключение. В целом результаты настоящего исследования свидетельствуют об эффективности ОКЗ при РА не только в отношении снижения клинико-лабораторной активности заболевания, но и в отношении исходов, сообщаемых самим пациентом, характеризующих качество жизни и психоэмоциональное состояние больных.

The aim of the study was to evaluate in real clinical practice the effectiveness of therapy with an interleukin-6 inhibitor (olokizumab) in patients with rheumatoid arthritis (RA) in terms of clinical and laboratory activity of the disease, as well as patient-reported outcomes (PROs). Material and methods. 10 patients with a reliable diagnosis of RA were examined: the average age of the patients was 45.70±17.9 years, the duration of the disease was 9.0 (3.0; 12.0) years. Patients were with moderate or high disease activity: DAS28-ESR – 5.13 (4.34; 5.80) points; CDAI – 30.00 (24.00; 35.00); SDAI – 31.86 (24.36; 38,59). All patients were prescribed treatment with olokizumab (OKZ) at a dose of 64 mg subcutaneously every 4 weeks against the background of therapy with methotrexate, leflunomide, non-steroidal anti-inflammatory drugs and glucocorticoids (GC) (up to 10 mg/day in terms of prednisolone). Three patients had previously received tocilizumab (intravenously once a month at a dose of 8 mg/kg), the administration of which was discontinued for administrative reasons 6–12 months before the appointment of OKZ. The results of treatment were assessed by the dynamics of clinical, laboratory parameters (DAS28-ESR, SDAI, СDAI, CRP, ESR, IgM RF, ACCP) and outcomes assessed by the patients themselves (PROs): HAQ-DI index, general assessment of the health status of patients (OSZB) according to VAS, pain according to VAS; scales FACIT, SF-36. As psychometric methods, the questionnaire “Type of attitude towards the disease (TOBOL)”, the Hospital Anxiety and Depression Scale (HADS), and the Toronto Alexithymic Scale (TAS-26) were used. Observation was carried out before treatment, after 3 and 6 months of therapy. Results. Against the background of OKZ therapy, after 3 and 6 months, compared with the baseline, there was a significant decrease in the clinical indices of RA activity: DAS28-ESR – 5.13 (4.34; 5.80), 3.53 (2.83; 4.26) and 3.48 (2.8; 4.10) points respectively; CDAI – 30.00 (24.00; 35.00), 11.00 (6.0; 16.00) and 10.0 (5.0; 15.0) points respectively; SDAI – 31.86 (24.36; 38.59), 11.05 (6.07; 16.07) and 10.17 (7.02; 15.02) points respectively; CRP – 14.30 (7.00; 24.70), 0.70 (0.40; 0.90) and 0.65 (0.20; 3.0) mg/l respectively. No significant dynamics of ESR, RF IgM and ACCP was noted. After 3 and 6 months of treatment with OKZ, there was a significant decrease in OSZB and pain severity according to the VAS scale, and an improvement in the functional state of patients was observed according to the HAQ-DI questionnaire of fatigue indicators (FACIT-F) (p<0.05). The physical component of the SF-36 scale increased significantly only by the 6th month of therapy (p<0.01), while the mental component did not undergo significant changes (p>0.05). In the process of treatment of OKZ, the attitude of patients to the disease changed from the ergopathic, neurasthenic and sensitive components in the TOBOL profile, before it began, then by its end, the dominant ones were harmonious, ergopathic and sensitive profiles. In addition, starting from the 3rd month of treatment in patients with RA, an adaptive response to the disease prevailed. A decrease in the level of anxiety was revealed, compared with the baseline, after 3 and 6 months of observation, depression indicators did not change significantly. Conclusion. In general, the results of this study indicate the effectiveness of ICD in RA, not only in terms of reducing the clinical and laboratory activity of the disease, but also in terms of outcomes reported by the patient himself, characterizing the quality of life and the psycho-emotional state of patients.

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