Comparative study of the clinical efficacy of the first domestic bioanalogue of tocilizumab based on the results of a randomized clinical trial of phase III
E. V. Akatova,
Yu. S. Bakhareva,
O. V. Bugrova,
I. B. Vinogradova,
E. V. Gerasimova,
Yu. E. Drevina,
O. B. Ershova,
E. V. Zonova,
Yu. I. Ivanova,
E. P. Ilivanova,
M. M. Kostik,
D. G. Krechikova,
D. A. Kusevich,
A. L. Maslyansky,
A. D. Meshkov,
N. S. Mosesova,
K. A. Nagornova,
D. V. Nosovich,
S. A. Polyakova,
T. A. Popova,
E. A. Smolyarchuk,
V. N. Sorotskaya,
Yu. G. Shvarts,
L. N. Shilova,
M. S. Shostak,
I. Yu. Yunonin,
N. E. Akhtyamova-Givirovskaya,
R. A. Khamitov,
O. A. Markova,
E. I. Zagoruiko,
E. V. Zuev https://doi.org/10.14412/1996-7012-2024-6-36-45
Abstract
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. 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. 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. 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).
Keywords
tocilizumab,
rheumatoid arthritis,
ACR,
DAS28,
clinical disease activity index (CDAI),
simplified disease activity index (SDAI),
monoclonal antibody,
interleukin-6,
randomized trial,
biosimilar
Supporting agencies: Funding for this study was provided by Generium JSC.
About the Authors
E. V. Akatova
Russian University of Medicine, Ministry of Health of Russia
Russian Federation
Russian Federation
4, Dolgorukovskaya Street, Moscow 127006
Yu. S. Bakhareva
“RC Medical”
Russian Federation
Russian Federation
5/1, Zalesskogo Street, Novosibirsk 630075
O. V. Bugrova
Orenburg State Medical University, Ministry of Health of Russia
Russian Federation
Russian Federation
6/45/7, Sovetskaya Street/M. Gorkiy Street/ Dmitrievskiy Lane, Orenburg 460000
I. B. Vinogradova
Ulyanovsk Regional Clinical Hospital
Russian Federation
Russian Federation
7, III Internatzional Street, Ulyanovsk 432017
E. V. Gerasimova
V.A. Nasonova Research Institute of Rheumatology
Russian Federation
Russian Federation
34A, Kashirskoe Shosse, Moscow 115522
Yu. E. Drevina
Research Medical Complex “Vashe Zdorovie”
Russian Federation
Russian Federation
52, Dostoevskogo Street, Kazan 420097
O. B. Ershova
Medical Consultation and Research Center “Praktika”
Russian Federation
Russian Federation
69, Sovetskaya Street, Yaroslavl 150003
E. V. Zonova
Medical Center “Zdorovaya Semya”
Russian Federation
Russian Federation
77, Kommunisticheskaya Street, Novosibirsk 630099
Yu. I. Ivanova
Yaroslavl State Medical University, Ministry of Health of Russia
Russian Federation
Russian Federation
5, Revolutzionnaya Street, Yaroslavl 150000
E. P. Ilivanova
Leningrad Regional Clinical Hospital
Russian Federation
Russian Federation
45, Lunacharskogo Prospect, Build. 1A, Saint-Petersburg 194291
M. M. Kostik
Saint Petersburg State Pediatric Medical University
Russian Federation
Russian Federation
2, Litovskaya Street, Saint-Petersburg 194100
D. G. Krechikova
Central Clinical Hospital “RZhD-Meditsina”
Russian Federation
Russian Federation
15, 1st Krasnoflotskiy Lane, Smolensk 214025
D. A. Kusevich
“OLLA-MED”
Russian Federation
Russian Federation
8A, 9th Parkovaya Street, Moscow 105554
A. L. Maslyansky
Almazov National Medical Research Center, Ministrry of Health of Russia
Russian Federation
Russian Federation
2, Akkuratova Street, Sain-Petersburg 197341
A. D. Meshkov
Pirogov Russian National Research Medical University, Russian Gerontological Scientific and Clinical Center,
Russian Federation
Russian Federation
16, 1st Leonova Street, Moscow 129226
N. S. Mosesova
“Family Policlinics №4”
Russian Federation
Russian Federation
33, Stanzionnya Street, Korolev 141060
K. A. Nagornova
North-Western Center for Evidence-Based Medicine
Russian Federation
Russian Federation
14/4A, Prospect Prosvescheniya, Saint-Petersburg 196158
D. V. Nosovich
“X7 Clinical Research”
Russian Federation
Russian Federation
27T, Engels Prospect, Saint-Petersburg 194156
S. A. Polyakova
Medical Center “Revma-Med”
Russian Federation
Russian Federation
6, Molodezhny Prospect, Kemerovo 650070
T. A. Popova
“Center for Family Medicine”
Russian Federation
Russian Federation
1/3, Nachdiva Vasilieva Street, Ekaterinburg 620043
E. A. Smolyarchuk
I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)
Russian Federation
Russian Federation
8, Trubetskaya Street, Build. 2, Moscow 119991
V. N. Sorotskaya
Tula Regional Clinical Dermato- venerologic Dispensary
Russian Federation
Russian Federation
1A, 1st M. Raskovoy Proezd, Tula 300053
Yu. G. Shvarts
Saratov State Medical University named after V.I. Razumovsky, Ministry of Health of Russia
Russian Federation
Russian Federation
112, Bolshaya Kazachya Street, Saratov 410012
L. N. Shilova
City Clinical Hospital of Emergency Medicine №25
Russian Federation
Russian Federation
41, Kirochnaya Street, St. Petersburg 191015
M. S. Shostak
North-Western State Medical University named after I.I. Mechnikov, Ministry of Health of
Russia
Russian Federation
Russian Federation
41, Kirochnaya Street, St. Petersburg 191015
I. Yu. Yunonin
Yaroslavl State Medical University, Ministry of Health of Russia
Russian Federation
Russian Federation
5, Revolutzionnaya Street, Yaroslavl 150000
N. E. Akhtyamova-Givirovskaya
JSC “Generium”
Russian Federation
Russian Federation
Nina Evgenyevna Akhtyamova-Givirovskaya
10, Testovskaya Street, Moscow 123112
R. A. Khamitov
JSC “Generium”
Russian Federation
Russian Federation
10, Testovskaya Street, Moscow 123112
O. A. Markova
JSC “Generium”
Russian Federation
Russian Federation
10, Testovskaya Street, Moscow 123112
E. I. Zagoruiko
JSC “Generium”
Russian Federation
Russian Federation
10, Testovskaya Street, Moscow 123112
E. V. Zuev
JSC “Generium”
Russian Federation
Russian Federation
10, Testovskaya Street, Moscow 123112
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For citations:
Akatova EV, Bakhareva YS, Bugrova OV, Vinogradova IB, Gerasimova EV, Drevina YE, Ershova OB, Zonova EV, Ivanova YI, Ilivanova EP, Kostik MM, Krechikova DG, Kusevich DA, Maslyansky AL, Meshkov AD, Mosesova NS, Nagornova KA, Nosovich DV, Polyakova SA, Popova TA, Smolyarchuk EA, Sorotskaya VN, Shvarts YG, Shilova LN, Shostak MS, Yunonin IY, Akhtyamova-Givirovskaya NE, Khamitov RA, Markova OA, Zagoruiko EI, Zuev EV. Comparative study of the clinical efficacy of the first domestic bioanalogue of tocilizumab based on the results of a randomized clinical trial of phase III. Sovremennaya Revmatologiya=Modern Rheumatology Journal. 2024;18(6):36-45. (In Russ.) https://doi.org/10.14412/1996-7012-2024-6-36-45
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