Тоцилизумаб (Tocilizumab)
Международное непатентованное наименование
Тоцилизумаб (Tocilizumab)
Торговое наименование
Актемра®
Производитель, страна
Roche Holding, Switzerland
Лекарственная форма
раствор для подкожного введения, 162 мг/0.9 мл
Механизм действия
Tocilizumab inhibits IL-6-mediated signaling by competitively binding to both soluble and membrane-bound IL-6 receptors. IL-6 is a proinflammatory cytokine that is involved in diverse physiological processes such as T-cell activation, immunoglobulin secretion induction, hepatic acute-phase protein synthesis initiation, and hematopoietic precursor cell proliferation and differentiation stimulation. IL-6 is produced by various cell types, including T- and B-cells, lymphocytes, monocytes, and fibroblasts.
Опыт использования
A retrospective review analyzed 21 patients in which tocilizumab was added to standard COVID-19 therapy.
- Preliminary data suggest tocilizumab may have clinical benefit as adjunctive therapy.
- Clinical symptoms, CT opacity changes, lymphocyte percentage, and Creactive protein levels all improved in these patients; however, no comparators were reported.
Some protocols include recommendations for use.
Additional data regarding clinical efficacy for COVID-19 are being evaluated.
Safety Concerns:
- Risk of GI perforation
- Risk of hepatotoxicity
- Caution in patients with thrombocytopenia and neutropenia
- Infusion-related reactions
Публикации COVID-19
к.м.н. Иващенко Д.В., к.м.н. Отделенов В.А., к.м.н. Мирзаев К.Б., д.м.н., проф. член-корр. РАН Сычев Д.А. Обоснование выбора тоцилизумаба и его режима дозирования при COVID-19. Дозирование форм для подкожного и внутривенно введения. 21 апреля 2020 г. Информационный центр по вопросам фармакотерапии у пациентов с новой коронавирусной инфекцией COVID-19 «ФармаCOVID» на базе ФГБОУ ДПО РМАНПО Минздрава России.
Xu X, Han M, LI T, et al. Effective Treatment of Severe COVID-19 Patients ith Tociliumab. Chinaiv: 202003.00026v1.
Zhang C, Wu Z, Li JW, et al. The cytokine release syndrome (CRS) of severe COVID-19 and Interleukin-6 receptor (IL-6R) antagonist tocilizumab may be the key to reduce the mortality. Int J Antimicrob Agents. 2020. PMID: 32234467.
Zhang W, Zhao Y, Zhang F, et al. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): the perspectives of clinical immunologists from China. Clin Immunol. 2020. PMID: 32222466.
Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020 Mar 11. PMID: 32171076.
Italian Society of Infectious and Tropical Diseases. Handbook for the care of people with disease-COVI 19. Edition 2.0, March 13, 2020.
Клинические исследования
1.
Название протокола
Assessment of Efficacy and Safety of Tocilizumab Compared to DefeROxamine, Associated With Standards Treatments in COVID-19 (+) Patients Hospitalized In Intensive Care in Tunisia. Multicentric, Comparative, Randomized Study
Дата начала и окончания КИ
May 4, 2020 - October 4, 2020
Название организации, проводящей КИ
Abderrahmane Mami Hospital
Страны
Tunisia
Фаза
III
Кол-во пациентов
260
2.
Название протокола
A Phase-II, Open-Label, Randomized, Multicenter Study to Investigate the Pharmacodynamics, Pharmacokinetics, Safety, and Efficacy of 8 mg/kg or 4mg/kg Intravenous Tocilizumab in Patients With Moderate to Severe COVID-19 Pneumonia
Дата начала и окончания КИ
May 4, 2020 - August 3, 2020
Название организации, проводящей КИ
Hoffmann-La Roche
Страны
USA
Фаза
II
Кол-во пациентов
100
3.
Название протокола
Tocilizumab to Prevent the Progression of Hypoxemic Respiratory Failure in Hospitalized Non-Critically Ill Patients With COVID-19
Дата начала и окончания КИ
April 27, 2020 - August 30, 2020
Название организации, проводящей КИ
Massachusetts General Hospital
Страны
USA
Фаза
III
Кол-во пациентов
300
4.
Название протокола
Prognostic Value of Serum Interleukin-6 (IL-6) and Soluble Interleukin-6 Receptor (sIL-6R) in Severe Coronavirus Disease (COVID-19) Pneumonia Treated With Tocilizumab - a Prospective Single Center Study (UHID-COVID19)
Дата начала и окончания КИ
April 16, 2020 - April 15, 2021
Название организации, проводящей КИ
University Hospital for Infectious Diseases
Страны
Croatia
Фаза
-
Кол-во пациентов
30
5.
Название протокола
An Open-label, Randomized, Cross-over Interventional Study to Evaluate the Efficacy and Safety of Tocilizumab Versus Corticosteroids in Hospitalised COVID-19 Patients With High Risk of Progression
Дата начала и окончания КИ
April 15, 2020 - October 31, 2020
Название организации, проводящей КИ
University of Malaya
Страны
Malaysia
Фаза
III
Кол-во пациентов
310
6.
Название протокола
A Prospective, Controlled, Randomized, Multicenter Study to Compare the Efficacy of a Chloroquine Analog (GNS561), an Anti PD-1 (Nivolumab) and an Anti-interleukine-6 Receptor (Tocilizumab) Versus Standard of Care in Patients With Advanced or Metastatic Cancer and SARS-CoV-2 (COVID-19) Infection
Дата начала и окончания КИ
April 15, 2020 - August 2020
Название организации, проводящей КИ
Centre Leon Berard
Страны
France
Фаза
II
Кол-во пациентов
273
7.
Название протокола
Early Institution of Tocilizumab Titration in Non-Critical Hospitalized COVID-19 Pneumonitis
Дата начала и окончания КИ
April 4, 2020 - December 2020
Название организации, проводящей КИ
University of Chicago
Страны
USA
Фаза
II
Кол-во пациентов
50
8.
Название протокола
Efficiency in Management of Organ Dysfunction Associated With Infection by the Novel SARS-CoV-2 Virus (COVID-19) Through a Personalized Immunotherapy Approach: the ESCAPE Clinical Trial
Дата начала и окончания КИ
April 2, 2020 - April 1, 2022
Название организации, проводящей КИ
Hellenic Institute for the Study of Sepsis
Страны
Greece
Фаза
II
Кол-во пациентов
40
9.
Название протокола
Pilot, Randomized, Multicenter, Open-label Clinical Trial of Combined Use of Hydroxychloroquine, Azithromycin, and Tocilizumab for the Treatment of SARS-CoV-2 Infection (COVID-19)
Дата начала и окончания КИ
April 2, 2020 - October 2020
Название организации, проводящей КИ
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Страны
Spain
Фаза
II
Кол-во пациентов
276
10.
Название протокола
Efficacy and Safety of Tocilizumab in the Treatment of Patients With Respiratory Distress Syndrome and Cytokine Release Syndrome Secondary to COVID-19: a Proof of Concept Study
Дата начала и окончания КИ
April 1, 2020 - March 31, 2021
Название организации, проводящей КИ
University of L'Aquila
Страны
Italy
Фаза
-
Кол-во пациентов
30
11.
Название протокола
Treatment of Serious and Critical Patients With COVID-19 With Tocilizumab
Дата начала и окончания КИ
April 1, 2020 - August 1, 2020
Название организации, проводящей КИ
Instituto Nacional de Cancerologia de Mexico
Страны
Mexico
Фаза
II
Кол-во пациентов
200
12.
Название протокола
A Prospective, Randomized, Factorial Design, Interventional Study to Compare the Safety and Efficacy of Combinations of Blockade of Interleukin-6 Pathway and Interleukin-1 Pathway to Best Standard of Care in Improving Oxygenation and Short- and Long-term Outcome of COVID-19 Patients With Acute Hypoxic Respiratory Failure and Systemic Cytokine Release Syndrome
Дата начала и окончания КИ
April 2020 - December 2020
Название организации, проводящей КИ
University Hospital, Ghent
Страны
Belgium
Фаза
III
Кол-во пациентов
342
13.
Название протокола
CORON-ACT - a Multicenter, Double-blind, Randomized Controlled Phase II Trial on the Efficacy and Safety of Tocilizumab in the Treatment of Coronavirus Induced Disease (COVID-19)
Дата начала и окончания КИ
April 2020 - October 2020
Название организации, проводящей КИ
University Hospital Inselspital, Berne
Страны
Switzerland
Фаза
II
Кол-во пациентов
100
14.
Название протокола
Cohort Multiple Randomized Controlled Trials Open-label of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients - Tocilizumab Trial - CORIMUNO-19 - TOCI (CORIMUNO-TOCI)
Дата начала и окончания КИ
March 31, 2020 - December 31, 2021
Название организации, проводящей КИ
Assistance Publique - Hôpitaux de Paris
Страны
France
Фаза
II
Кол-во пациентов
240
15.
Название протокола
An Open-label Randomized Multicenter Study to Evaluate the Efficacy of Early Administration of Tocilizumab (TCZ) in Patients With COVID-19 Pneumonia
Дата начала и окончания КИ
March 31, 2020 - May 30, 2020
Название организации, проводящей КИ
Azienda Unità Sanitaria Locale Reggio Emilia
Страны
Italy
Фаза
II
Кол-во пациентов
398
16.
Название протокола
A Multicenter, Randomized, Open-Label, Phase II Trial to Evaluate the Efficacy and Safety of Checkpoint Blockade in Patients With Coronavirus Disease 2019 (COVID-19)-Related Mild Acute Respiratory Syndrome Nonresponsive to Frontline Therapy
Дата начала и окончания КИ
March 30, 2020 - May 15, 2020
Название организации, проводящей КИ
MedSIR
Страны
Spain
Фаза
II
Кол-во пациентов
24
17.
Название протокола
A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of Tocilizumab in Patients With Severe COVID-19 Pneumonia
Дата начала и окончания КИ
March 25, 2020 - April 8, 2020
Название организации, проводящей КИ
Hoffmann-La Roche
Страны
Canada, Denmark, France, Germany, Italy, Netherlands, Spain, United Kingdom, USA
Фаза
III
Кол-во пациентов
330
18.
Название протокола
Multicenter Study on the Efficacy and Tolerability of Tocilizumab in the Treatment of Patients With COVID-19 Pneumonia
Дата начала и окончания КИ
March 20, 2020 - April 7, 2020
Название организации, проводящей КИ
National Cancer Institute, Naples
Страны
Italy
Фаза
II
Кол-во пациентов
400
19.
Название протокола
Tocilizumab (RoActemra) as Early Treatment of Patients Affected by SARS-CoV2 Infection With Severe Multifocal Interstitial Pneumonia
Дата начала и окончания КИ
March 12, 2020 - May 2020
Название организации, проводящей КИ
Università Politecnica delle Marche
Страны
Italy
Фаза
II
Кол-во пациентов
38
20.
Название протокола
Favipiravir Combined With Tocilizumab in the Treatment of Corona Virus Disease 2019-A Multicenter, Randomized and Controlled Clinical Trial Study
Дата начала и окончания КИ
March 8, 2020 - May 2020
Название организации, проводящей КИ
Peking University First Hospital
Страны
China
Фаза
-
Кол-во пациентов
150
21.
Название протокола
The therapeutic efficacy of combination of Tocilizumab, IVIG and CRRT in sever patients with novel coronavirus pneumonia (COVID-19)
Дата начала и окончания КИ
March 5, 2020 - May 15, 2020
Название организации, проводящей КИ
The Second Affiliated hospital of Xi'an Jiaotong University
Страны
China
Кол-во пациентов
100
22.
Название протокола
Favipiravir Combined With Tocilizumab in the Treatment of novel coronavirus pneumonia (COVID-19) - A Multicenter, Randomized, Controlled Trial
Дата начала и окончания КИ
March 1, 2020 - May 31, 2020
Название организации, проводящей КИ
Peking University First Hospital
Страны
China
Фаза
IV
Кол-во пациентов
150
23.
Название протокола
A Retrospective Study of Evaluating Safety and Efficacy of Tocilizumab Compared to Continuous Renal Replacement Therapy in Controlling CRS Triggered by COVID-19
Дата начала и окончания КИ
February 20, 2020 - June 20, 2020
Название организации, проводящей КИ
Tongji Hospital
Страны
China
Фаза
-
Кол-во пациентов
120
24.
Название протокола
A multicenter, randomized controlled trial for the efficacy and safety of tocilizumab in the treatment of new coronavirus pneumonia (COVID-19)
Дата начала и окончания КИ
February 10, 2020 - May 10, 2020
Название организации, проводящей КИ
The First Affiliated Hospital of University of science and technology of China (Anhui Provincial Hospital)
Страны
China
Фаза
IV
Кол-во пациентов
188