rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.47360/1995-4484-2023-199-206rsp-3322Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHПереносимость и безопасность ритуксимаба при системной склеродермииSafety and tolerability of rituximab in the treatment of systemic sclerosishttps://orcid.org/0000-0002-5012-0540ГарзановаЛ. А.GarzanovaL. A.

115522, Москва, Каширское шоссе, 34а

115522, Moscow, Kashirskoye Highway, 34A

lyuda-garzanova@yandex.ruhttps://orcid.org/0000-0002-3248-6426АнаньеваЛ. П.AnanyevaL. P.

115522, Москва, Каширское шоссе, 34а

115522, Moscow, Kashirskoye Highway, 34A

https://orcid.org/0000-0003-3650-7658КоневаО. А.KonevaO. A.

115522, Москва, Каширское шоссе, 34а

115522, Moscow, Kashirskoye Highway, 34A

https://orcid.org/0000-0002-0283-9681ДесиноваО. В.DesinovaO. V.

115522, Москва, Каширское шоссе, 34а

115522, Moscow, Kashirskoye Highway, 34A

https://orcid.org/0000-0002-1004-9647СтаровойтоваМ. Н.StarovoytovaM. N.

115522, Москва, Каширское шоссе, 34а

115522, Moscow, Kashirskoye Highway, 34A

https://orcid.org/0000-0003-2667-4284ОвсянниковаО. Б.OvsyannikovaO. B.

115522, Москва, Каширское шоссе, 34а

115522, Moscow, Kashirskoye Highway, 34A

https://orcid.org/0000-0003-4688-9637ШаяхметоваР. У.ShayakhmetovaR. U.

115522, Москва, Каширское шоссе, 34а

115522, Moscow, Kashirskoye Highway, 34A

https://orcid.org/0000-0002-4285-0869ГлуховаС. И.GlukhovaS. I.

115522, Москва, Каширское шоссе, 34а

115522, Moscow, Kashirskoye Highway, 34A

ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»РоссияV.A. Nasonova Research Institute of RheumatologyRussian Federation202328042023612199206Copyright © Гарзанова Л.А., Ананьева Л.П., Конева О.А., Десинова О.В., Старовойтова М.Н., Овсянникова О.Б., Шаяхметова Р.У., Глухова С.И., 20232023Гарзанова Л.А., Ананьева Л.П., Конева О.А., Десинова О.В., Старовойтова М.Н., Овсянникова О.Б., Шаяхметова Р.У., Глухова С.И.Garzanova L.A., Ananyeva L.P., Koneva O.A., Desinova O.V., Starovoytova M.N., Ovsyannikova O.B., Shayakhmetova R.U., Glukhova S.I.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/3322Введение

Введение. Ритуксимаб (РТМ) длительное время используется при системной склеродермии (ССД) и показал хорошую эффективность в лечении кожного фиброза и поражения легких. Однако данных о переносимости и отдаленных нежелательных явлениях (НЯ) на фоне терапии РТМ при ССД недостаточно.

Целью настоящего исследования была оценка переносимости и безопасности ритуксимаба у пациентов с системной склеродермией при длительном наблюдении.

Материал и методы

Материал и методы. В открытое проспективное исследование был включен 151 пациент с ССД, получивший по крайней мере одну инфузию РТМ. В этой группе превалировали женщины (83%). Возраст больных составил в среднем 47,9±13,4 года; продолжительность заболевания – 6,4±5,8 года; период наблюдения после первой инфузии РТМ – 5,6±2,6 года (845,6 пациенто-лет (ПЛ)). Во всех случаях РТМ назначался в дополнение к базисной терапии преднизолоном и/или иммуносупрессантами. НЯ оценивались и регистрировались врачом в стационаре сразу после инфузии РТМ, а затем путем опроса пациентов в течение всего периода наблюдения. Учитывались все причины смерти, независимо от лечения.

Результаты

Результаты. Всего было зарегистрировано 85 (56%) НЯ; общая частота НЯ составила 10/100 ПЛ (95%-й доверительный интервал (95% ДИ): 8–12). Наибольшая частота всех НЯ наблюдалась в первые 6 месяцев после первого курса РТМ, однако по степени тяжести это были в основном легкие и умеренные НЯ (71%). Наиболее частыми НЯ были инфекции – они наблюдались в 40% случаев, при этом серьезных оппортунистических инфекций не было. Общая частота всех инфекций составила 7,1/100 ПЛ (95% ДИ: 5,5–9), серьезных инфекций – 1,5/100 ПЛ (95% ДИ: 0,9–2,6). Инфузионные реакции возникли у 8% больных. Другие НЯ отмечены у 3% (0,6/100 ПЛ; 95% ДИ: 0,3–1,4). Общая частота серьезных НЯ составила 18% (3,2/100 ПЛ; 95% ДИ: 2,2–4,6). При изучении уровня иммуноглобулина G (IgG) в динамике у 78 пациентов было отмечено его статистически значимое снижение на фоне терапии РТМ, однако средние значения оставались в пределах нормы. Зафиксировано 17 летальных исходов (2/100 ПЛ; 95% ДИ: 1,3–3,2). В большинстве случаев больные умерли от прогрессирования недостаточности функций жизненно важных органов, возникшей до начала лечения РТМ.

Заключение

Заключение. В данном исследовании профиль безопасности РТМ при ССД был оценен как благоприятный. Он был сходным с профилем НЯ при использовании РТМ для лечения других аутоиммунных заболеваний. При увеличении кумулятивной дозы РТМ увеличения числа НЯ не наблюдалось. Летальность была сравнима с таковой при других тяжелых аутоиммунных заболеваниях в обсервационных исследованиях. Мониторинг уровня IgG полезен для раннего выявления риска развития инфекционных осложнений у пациентов с ССД, получающих РТМ. РТМ можно рассматривать как относительно безопасный препарат в комплексной терапии ССД, когда стандартная терапия неэффективна или невозможна.

Introduction

Introduction. Rituximab (RTX) has been used for the treatment of systemic sclerosis (SSс) for a long time and has shown good efficacy for skin fibrosis and interstitial lung disease. However, data on tolerability and long-term adverse events (AEs) during RTX therapy in SSc are insufficient.

Objective

Objective. The aim of this study was to assess the tolerability and safety of RTX in patients with SSс in a long-term prospective follow-up.

Materials and methods

Materials and methods. Our open-label prospective study included 151 SSс patients who received at least one RTX infusion. The mean age of the patients was 47.9±13.4 years; the majority of them were women (83%). The mean disease duration was 6.4±5.8 years. The mean follow-up period after the first RTX infusion was 5.6±2.6 years (845.6 patient-years (PY)). All patients received RTX in addition to ongoing therapy with prednisone and/or immunosuppressants. AEs were assessed and recorded by a doctor in the hospital immediately after RTX infusion, then by patient reported outcome during the observation period. All causes of death were considered, regardless of treatment.

Results

Results. A total of 85 (56%) AEs were registered, the overall incidence of AEs was 10/100 PY (95% confidence interval (95% CI): 8–12). The highest frequency of all AEs was observed in the first 2–6 months after the first course of RTX, however, these were mainly mild and moderate AEs (71%). The most frequent AEs were infections, they were observed in 40% of cases, with no serious opportunistic infections reported. The overall incidence of all infections was 7.1/100 PY (95% CI: 5.5–9), serious infections – 1.5/100 PY (95% CI: 0.9–2.6). Infusion reactions occurred in 8% of patients. Other AEs were noted in 3% (0.6/100 PY; 95% CI: 0.3–1.4). The overall incidence of serious AEs was 18% (3.2/100 PY; 95% CI: 2.2–4.6). There was a significant decrease of the immunoglobulin G (IgG) during follow-up, however, its average values remained within normal limits. There were 17 (11%) deaths (2/100 PY; 95% CI: 1.3–3.2). In most cases, patients died from the progression of the major organ failure, which arose before RTX treatment.

Conclusions

Conclusions. In our study, the safety profile of RTX in SSс was assessed as favorable. It was similar to the AE profile in other autoimmune diseases treated with RTX. With an increase in the cumulative dose of RTX, no increase in AEs was observed. The mortality is comparable to the other severe autoimmune diseases in observational studies. Monitoring of Ig G may be useful for patients with SSс on RTX therapy for early detection of the risk of developing infectious complications. RTX could be considered as a relatively safe drug for the complex therapy of SSс when standard therapy is ineffective or impossible.

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