mrjСовременная ревматологияModern Rheumatology Journal1996-70122310-158XIMA-PRESS, LLC10.14412/1996-7012-2024-6-36-45mrj-1664Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL INVESTIGATIONSСравнительное изучение клинической эффективности первого отечественного биоаналога тоцилизумаба по результатам рандомизированного клинического исследования III фазыComparative study of the clinical efficacy of the first domestic bioanalogue of tocilizumab based on the results of a randomized clinical trial of phase IIIhttps://orcid.org/0009-0006-1219-1272АкатоваЕ. В.AkatovaE. V.

127006, Москва, ул. Долгоруковская, 4

4, Dolgorukovskaya Street, Moscow 127006

https://orcid.org/0000-0003-0480-1510БахареваЮ. С.BakharevaYu. S.

630075, Новосибирск, ул. Залесского, 5/1

5/1, Zalesskogo Street, Novosibirsk 630075

https://orcid.org/0000-0002-7134-9598БугроваО. В.BugrovaO. V.

460000, Оренбург, ул. Советская/ул. М. Горького/пер. Дмитриевский, 6/45/7

6/45/7, Sovetskaya Street/M. Gorkiy Street/ Dmitrievskiy Lane, Orenburg 460000

https://orcid.org/0000-0001-5052-912XВиноградоваИ. Б.VinogradovaI. B.

432017, Ульяновск, ул. Третьего Интернационала, 7

7, III Internatzional Street, Ulyanovsk 432017

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115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

https://orcid.org/0009-0003-6919-9775ДревинаЮ. Э.DrevinaYu. E.

420097, Казань, ул. Достоевского, 52

52, Dostoevskogo Street, Kazan 420097

https://orcid.org/0000-0001-7167-2187ЕршоваО. Б.ErshovaO. B.

150003, Ярославль, ул. Советская, 69

69, Sovetskaya Street, Yaroslavl 150003

https://orcid.org/0000-0001-8529-4105ЗоноваЕ. В.ZonovaE. V.

630099, Новосибирск, ул. Коммунистическая, 77

77, Kommunisticheskaya Street, Novosibirsk 630099

https://orcid.org/0000-0001-6349-4587ИвановаЮ. И.IvanovaYu. I.

150000, Ярославль, ул. Революционная, 5

5, Revolutzionnaya Street, Yaroslavl 150000

https://orcid.org/0000-0002-9312-3768ИливановаЕ. П.IlivanovaE. P.

194291, Санкт-Петербург, просп. Луначарского, 45, корп. 1А

45, Lunacharskogo Prospect, Build. 1A, Saint-Petersburg 194291

https://orcid.org/0000-0002-1180-8086КостикМ. М.KostikM. M.

194100, Санкт-Петербург, ул. Литовская, 2

2, Litovskaya Street, Saint-Petersburg 194100

https://orcid.org/0000-0003-1207-6144КречиковаД. Г.KrechikovaD. G.

214025, Смоленск, 1-й Краснофлотский пер., 15

15, 1st Krasnoflotskiy Lane, Smolensk 214025

https://orcid.org/0000-0002-2976-9724КусевичД. А.KusevichD. A.

105554, Москва, ул. 9-я Парковая, 8А

8A, 9th Parkovaya Street, Moscow 105554

https://orcid.org/0000-0003-2427-4148МаслянскийА. Л.MaslyanskyA. L.

197341, Санкт-Петербург, ул. Аккуратова, 2

2, Akkuratova Street, Sain-Petersburg 197341

https://orcid.org/0000-0002-5187-0108МешковА. Д.MeshkovA. D.

129226, Москва, ул. 1-я Леонова, 16

16, 1st Leonova Street, Moscow 129226

МосесоваН. С.MosesovaN. S.

141060, Московская область, Королёв, ул. Станционная, 33

33, Stanzionnya Street, Korolev 141060

https://orcid.org/0000-0002-9224-6643НагорноваК. А.NagornovaK. A.

196158, Санкт-Петербург, просп. Просвещения, 14/4А

14/4A, Prospect Prosvescheniya, Saint-Petersburg 196158

https://orcid.org/0000-0003-2891-4747НосовичД. В.NosovichD. V.

194156, Санкт-Петербург, просп. Энгельса, 27Т

27T, Engels Prospect, Saint-Petersburg 194156

https://orcid.org/0009-0000-7759-1193ПоляковаС. А.PolyakovaS. A.

650070, Кемерово, просп. Молодежный, 6

6, Molodezhny Prospect, Kemerovo 650070

ПоповаТ. А.PopovaT. A.

620043, Екатеринбург, ул. Начдива Васильева, 1/3

1/3, Nachdiva Vasilieva Street, Ekaterinburg 620043

https://orcid.org/0000-0002-2615-7167СмолярчукЕ. А.SmolyarchukE. A.

119991, Москва, Трубецкая ул., 8, стр. 2

8, Trubetskaya Street, Build. 2, Moscow 119991

https://orcid.org/0000-0003-3684-7310СороцкаяВ. Н.SorotskayaV. N.

300053, Тула, 1-й проезд М. Расковой, 1А

1A, 1st M. Raskovoy Proezd, Tula 300053

https://orcid.org/0000-0002-5205-7311ШварцЮ. Г.ShvartsYu. G.

410012, Саратов, ул. Большая Казачья, 112

112, Bolshaya Kazachya Street, Saratov 410012

https://orcid.org/0000-0002-0438-8554ШиловаЛ. Н.ShilovaL. N.

400138, Волгоград, ул. Землячки, 74

41, Kirochnaya Street, St. Petersburg 191015

https://orcid.org/0000-0001-5449-7372ШостакМ. С.ShostakM. S.

191015, Санкт-Петербург, Кирочная ул., 41

41, Kirochnaya Street, St. Petersburg 191015

https://orcid.org/0000-0002-0515-4362ЮнонинИ. Ю.YunoninI. Yu.

50000, Ярославль, ул. Революционная, 5

5, Revolutzionnaya Street, Yaroslavl 150000

https://orcid.org/0000-0002-4548-7532Ахтямова-ГивировскаяН. Е.Akhtyamova-GivirovskayaN. E.

Нина Евгеньевна Ахтямова-Гивировская

123112, Москва, ул. Тестовская, 10

Nina Evgenyevna Akhtyamova-Givirovskaya

10, Testovskaya Street, Moscow 123112

neakhtyamova-givirovskaya@generium.ruhttps://orcid.org/0000-0002-1314-894XХамитовР. А.KhamitovR. A.

123112, Москва, ул. Тестовская, 10

10, Testovskaya Street, Moscow 123112

https://orcid.org/0000-0002-1179-3881МарковаО. А.MarkovaO. A.

123112, Москва, ул. Тестовская, 10

10, Testovskaya Street, Moscow 123112

https://orcid.org/0000-0002-5976-6444ЗагоруйкоЕ. И.ZagoruikoE. I.

123112, Москва, ул. Тестовская, 10

10, Testovskaya Street, Moscow 123112

https://orcid.org/0000-0001-5519-8358ЗуевЕ. В.ZuevE. V.

123112, Москва, ул. Тестовская, 10

10, Testovskaya Street, Moscow 123112

ФГБОУ ВО «Российский университет медицины» Минздрава РоссииРоссияRussian University of Medicine, Ministry of Health of RussiaRussian FederationООО «Эрси Медикал»Россия“RC Medical”Russian FederationФГБОУ ВО «Оренбургский государственный медицинский университет» Минздрава РоссииРоссияOrenburg State Medical University, Ministry of Health of RussiaRussian FederationГУЗ «Ульяновская областная клиническая больница»РоссияUlyanovsk Regional Clinical HospitalRussian FederationФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»РоссияV.A. 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Смоленск»РоссияCentral Clinical Hospital “RZhD-Meditsina”Russian FederationООО «ОЛЛА-МЕД»Россия“OLLA-MED”Russian FederationФГБУ «Национальный медицинский исследовательский центр им. В.А. Алмазова» Минздрава РоссииРоссияAlmazov National Medical Research Center, Ministrry of Health of RussiaRussian FederationФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» – ОСП «Российский геронтологический научно-клинический центр»РоссияPirogov Russian National Research Medical University, Russian Gerontological Scientific and Clinical Center,Russian FederationООО «Семейная поликлиника №4»Россия“Family Policlinics №4”Russian FederationАО «Северо-Западный центр доказательной медицины»РоссияNorth-Western Center for Evidence-Based MedicineRussian FederationООО «Экс Севен Клиникал Ресеч»Россия“X7 Clinical Research”Russian FederationООО «Медицинский центр «Ревма-Мед»РоссияMedical Center “Revma-Med”Russian FederationАО «Центр семейной медицины»Россия“Center for Family Medicine”Russian FederationФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский университет)РоссияI.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)Russian FederationГУЗ «Тульский областной клинический кожно-венерологический диспансер»РоссияTula Regional Clinical Dermato- venerologic DispensaryRussian FederationФГБОУ ВО «Саратовский государственный медицинский университет им. В.И. Разумовского» Минздрава РоссииРоссияSaratov State Medical University named after V.I. Razumovsky, Ministry of Health of RussiaRussian FederationГУЗ «Городская клиническая больница скорой медицинской помощи №25»РоссияCity Clinical Hospital of Emergency Medicine №25Russian FederationФГБОУ ВО «Северо-Западный государственный медицинский университет им И.И. Мечникова» Минздрава РоссииРоссияNorth-Western State Medical University named after I.I. Mechnikov, Ministry of Health of RussiaRussian FederationАО «Генериум»РоссияJSC “Generium”Russian Federation2024131220241863645Copyright © Акатова Е.В., Бахарева Ю.С., Бугрова О.В., Виноградова И.Б., Герасимова Е.В., Древина Ю.Э., Ершова О.Б., Зонова Е.В., Иванова Ю.И., Иливанова Е.П., Костик М.М., Кречикова Д.Г., Кусевич Д.А., Маслянский А.Л., Мешков А.Д., Мосесова Н.С., Нагорнова К.А., Носович Д.В., Полякова С.А., Попова Т.А., Смолярчук Е.А., Сороцкая В.Н., Шварц Ю.Г., Шилова Л.Н., Шостак М.С., Юнонин И.Ю., Ахтямова-Гивировская Н.Е., Хамитов Р.А., Маркова О.А., Загоруйко Е.И., Зуев Е.В., 20242024Акатова Е.В., Бахарева Ю.С., Бугрова О.В., Виноградова И.Б., Герасимова Е.В., Древина Ю.Э., Ершова О.Б., Зонова Е.В., Иванова Ю.И., Иливанова Е.П., Костик М.М., Кречикова Д.Г., Кусевич Д.А., Маслянский А.Л., Мешков А.Д., Мосесова Н.С., Нагорнова К.А., Носович Д.В., Полякова С.А., Попова Т.А., Смолярчук Е.А., Сороцкая В.Н., Шварц Ю.Г., Шилова Л.Н., Шостак М.С., Юнонин И.Ю., Ахтямова-Гивировская Н.Е., Хамитов Р.А., Маркова О.А., Загоруйко Е.И., Зуев Е.В.Akatova E.V., Bakhareva Y.S., Bugrova O.V., Vinogradova I.B., Gerasimova E.V., Drevina Y.E., Ershova O.B., Zonova E.V., Ivanova Y.I., Ilivanova E.P., Kostik M.M., Krechikova D.G., Kusevich D.A., Maslyansky A.L., Meshkov A.D., Mosesova N.S., Nagornova K.A., Nosovich D.V., Polyakova S.A., Popova T.A., Smolyarchuk E.A., Sorotskaya V.N., Shvarts Y.G., Shilova L.N., Shostak M.S., Yunonin I.Y., Akhtyamova-Givirovskaya N.E., Khamitov R.A., Markova O.A., Zagoruiko E.I., Zuev E.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://mrj.ima-press.net/mrj/article/view/1664

В статье рассматриваются результаты сравнительного клинического исследования III фазы по изучению эффективности и безопасности биоаналога (БА) Компларейт (КПР, АО «Генериум», Россия) и референтного препарата Актемра (АТМ, Ф. Хоффманн-Ля Рош Лтд., Швейцария) с целью установления их эквивалентности при лечении пациентов с ревматоидным артритом – РА (NCT06475508 clinicaltrials.gov).

Материал и методы

Материал и методы. В исследование включены пациенты мужского или женского пола в возрасте от 18 до 75 лет с РА со средней или высокой активностью заболевания и недостаточным ответом на монотерапию метотрексатом (МТ), и/или плохой переносимостью МТ, и/или недостаточным ответом либо непереносимостью других стандартных базисных противовоспалительных препаратов в комбинации с МТ или без него. 464 (89,4%) пациента были рандомизированы в соотношении 2:1 в две группы. Исследуемый и референтный препараты вводились внутривенно капельно в дозе 8 мг/кг 1 раз в 4 нед. В качестве первичной конечной точки оценена доля пациентов с ответом по ACR20 после 24 нед терапии.

Результаты и обсуждение

Результаты и обсуждение. Доля ответивших в группе КПР составила 91,2%, а в группе АТМ – 90,7% (р=0,866). Разница между группами – 0,5% (95% доверительный интервал, ДИ от -5,2 до 6,1), что полностью укладывается в заявленные границы признания терапевтической эквивалентности. Сопоставимость БА КПР и референтного препарата АТМ подтверждена также результатами оценки по вторичным конечным точкам: доле пациентов с ответами по ACR50/70, динамике индексов DAS28, SDAI, CDAI, функционального статуса по HAQ, лабораторных показателей воспалительной активности – СОЭ и уровня СРБ. Сопоставимость исследуемого и референтного препаратов продемонстрирована также результатами анализа безопасности.

Заключение

Заключение. Клиническое исследования показало, что препарат КПР является БА препарата АТМ.

The article discusses the results of a comparative phase III clinical trial of the efficacy and safety of the biosimilar Complarate (CPR; JSC Generium, Russia) and the reference drug Actemra (ACT; F. Hoffmann-La Roche Ltd., Switzerland) to assess their equivalence in patients with rheumatoid arthritis, RA (NCT06475508 clinicaltrials.gov).

Materials and methods

Materials and methods. Male and female patients aged 18–75 years with RA with moderate to high disease activity and insufficient response to methotrexate (MTX) monotherapy and/or poor tolerability of MTX and/or insufficient response or intolerance to other standard DMARDs in combination with or without MTX were enrolled in the study. 464 (89.4%) patients were randomized in a 2:1 ratio into two groups. The study and the reference drug were administered as an intravenous infusion at a dose of 8 mg/kg once every 4 weeks. The primary endpoint was the proportion of patients with an ACR20 after 24 weeks of therapy.

Results and discussion

Results and discussion. The proportion of responders in CPR group was 91.2%, and in ACT group – 90.7% (p = 0.866). The difference between the groups was 0.5% (95% CI: -5,2%−6,1%), which is fully within the declared boundaries of recognition of therapeutic equivalence. Comparability of the biosimilar CPR and the reference drug ACT is also confirmed by the results of secondary efficacy endpoints: the proportion of patients with ACR50/70, dynamics of the DAS28, SDAI, CDAI, the functional activity of patients (HAQ), laboratory parameters of inflammatory activity (ESR and CRP). Comparability of the study and the reference drugs is also demonstrated by the results of the safety analysis.

Conclusion

Conclusion. Based on the results of the clinical study, it has been proven that CPR (JSC Generium, Russia) is a biological analogue of ACT (F. Hoffmann-La Roche Ltd., Switzerland).

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