Use of olokizumab, a direct interleukin 6 inhibitor, in the treatment of rheumatoid arthritis: real-world evidence
P. A. Shesternya,
A. I. Zagrebneva,
O. V. Antipova,
Yu. V. Arbuzova,
I. G. Bannikova,
L. V. Belozertseva,
E. A. Bogdanova,
S. A. Bykova,
E. A. Vasilenko,
I. B. Vinogradova,
S. Yu. Davidyan,
O. E. Epifanova,
E. V. Zemerova,
M. V. Zlobin,
L. V. Ivanova,
N. A. Ilyina,
L. V. Ilyushina,
E. P. Klyuchnikova,
A. V. Makevnina,
E. R. Myasoutova,
E. E. Nakonechnaya,
A. B. Pavlova,
T. V. Plaksina,
A. V. Rybin,
T. S. Salnikova,
L. V. Solodovnikova,
A. V. Fedorova,
I. A. Cherencova,
E. V. Jakovleva,
S. P. Yakupova,
E. N. Alekseev,
A. M. Lila https://doi.org/10.14412/1996-7012-2025-2-39-49
Abstract
Objective: To study the efficacy and safety of olokizumab (OKZ) in patients with rheumatoid arthritis (RA) in real-life clinical practice.
Material and methods. The observational program was conducted in 73 centers across Russia from Dec 1, 2022 to Jan 31, 2025. It was based on a retrospective analysis of real clinical practice data. Information on patients was collected and analyzed at baseline and after 1, 6, and 12 months of treatment.
Results and discussion. A total of 1,576 patients (81.7% women) with RA, aged 55.0 [44.0; 63.0] years and with RA duration of 100.0 [50.0; 156.0] months, were included in the program. After 6 and 12 months of OKZ therapy, the treatment target (remission/low activity) was achieved in 63.3% and 79.8% of patients by DAS28-CRP, and in 55.4% and 75.5% by CDAI respectively. Gender, age, seropositivity, and use of biologic disease-modifying antirheumatic drugs did not significantly affect the achievement of the treatment goal. During the observation period, a significant proportion of patients were able to discontinue glucocorticoids (GCs): 51.1% of patients received GCs initially, after 6 months, 27.6% of patients still received GCs, and after 12 months, 17.0%. During the observation, OKZ treatment was discontinued in 148 (9.5%) patients: in 50 (3.2%) patients due to insufficient efficacy, in 63 (4.0%) patients due to adverse events, and in 35 (2.2%) patients due to other reasons.
Conclusion. IL-6 inhibition with OKZ is both effective and safe for achieving RA therapy goals in real-world clinical settings.
Supporting agencies: Data collection and statistical processing were carried out with the sponsorship of R-Pharm, JSC
About the Authors
P. A. Shesternya
Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Ministry of Health of Russia
Russian Federation
Russian Federation
Pavel Anatolyevich Shesternya
1, Partizan Zheleznyak Street, Krasnoyarsk 660022
A. I. Zagrebneva
City Clinical Hospital No.52 of Healthcare Department of Moscow
Russian Federation
Russian Federation
3, Pehotnaya Street, Moscow 123182
O. V. Antipova
Irkutsk City Clinical Hospital №1
Russian Federation
Russian Federation
118, Baikalskaya Street, Irkutsk 664046
Yu. V. Arbuzova
Regional Clinical Hospital
Russian Federation
Russian Federation
3, Berezovaya Street, Omsk 644012
I. G. Bannikova
Surgut District Clinical Hospital
Russian Federation
Russian Federation
24, Energetikov Street, Build. 3, Surgut 628408
L. V. Belozertseva
Zabaykalsky Regional Clinical Hospital
Russian Federation
Russian Federation
7, Kokhansky Street, Chita 672038
E. A. Bogdanova
Chelyabinsk Regional Clinical Hospital
Russian Federation
Russian Federation
7, Kokhansky Street, Chita 672038
S. A. Bykova
Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Ministry of Health of Russia; Regional Clinical Hospital
Russian Federation
Russian Federation
1, Partizan Zheleznyak Street, Krasnoyarsk 660022
A, Partizan Zheleznyak Street, Krasnoyarsk 660022
E. A. Vasilenko
Gatchina Interregional Clinical Hospital
Russian Federation
Russian Federation
15A, Roshinskaya Street, Build. 1, Gatchina 188300
I. B. Vinogradova
Ulyanovsk Regional Clinical Hospital
Russian Federation
Russian Federation
7, III Internatzionala Street, Ulyanovsk 432017
S. Yu. Davidyan
National Medical Surgical Center named after N.I. Pirogov, Ministry of Health of Russia
Russian Federation
Russian Federation
70, Nizhnyaya Pervomaiskaya Street, Moscow 105203
O. E. Epifanova
Medical Center “RevmaMed”
Russian Federation
Russian Federation
50, Klary Zetkin Street, Syktyvkar 167031
E. V. Zemerova
Budget institution of the Khanty-Mansiysk Autonomous Okrug Ugra “District Clinical Hospital”
Russian Federation
Russian Federation
40, Kalinin Street, Khanty-Mansiysk 628012
M. V. Zlobin
N.A. Semashko Nizhny Novgorod Regional Clinical Hospital
Russian Federation
Russian Federation
190, Rodionova Street, Nizhniy Novgorod 603093
L. V. Ivanova
Republican Clinical Diagnostic Center of Ministry of Health of the Republic of Udmurtia
Russian Federation
Russian Federation
87Б, Lenina Street, Izhevsk 426009
N. A. Ilyina
Research Institute of Fundamental and Clinical Immunology
Russian Federation
Russian Federation
6, Zalesskogo Street, Build. 9, Novosibirsk 630047
L. V. Ilyushina
Clinical Cardiological Dispensary
Russian Federation
Russian Federation
1, Markova Street, Syktyvkar 167981
E. P. Klyuchnikova
Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Ministry of Health of Russia; Regional Clinical Hospital
Russian Federation
Russian Federation
1, Partizan Zheleznyak Street, Krasnoyarsk 660022
3A, Partizan Zheleznyak Street, Krasnoyarsk 660022
A. V. Makevnina
Moscow Regional Research and Clinical Institute named after M.F. Vladimirsky
Russian Federation
Russian Federation
61/2, Shepkina Street, Moscow 129110
E. R. Myasoutova
Republican Clinical Hospital, Ministry of Health of Republic of Tatarstan
Russian Federation
Russian Federation
138, Orenburgskiy Trakt, Kazan 420064
E. E. Nakonechnaya
Clinical Cardiological Dispensary
Russian Federation
Russian Federation
41, Lermontov Street, Omsk 644044
A. B. Pavlova
”RZhD-Medicine”
Russian Federation
Russian Federation
1Б, Komsomolskaya Street, Ulan-Ude 670002
T. V. Plaksina
N.A. Semashko Nizhny Novgorod Regional Clinical Hospital
Russian Federation
Russian Federation
190, Rodionova Street, Nizhniy Novgorod 603093
A. V. Rybin
Ivanovo Regional Clinical Hospital
Russian Federation
Russian Federation
1, Lyubimova Street, Ivanovo 153000
T. S. Salnikova
Tula Regional Clinical Hospital
Russian Federation
Russian Federation
1A, Yablochkova Street, Tula 300053
L. V. Solodovnikova
Mordovian Republican Central Clinical Hospital
Russian Federation
Russian Federation
14/5, Pobedy Street, Build. 1, Saransk 430013
A. V. Fedorova
Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation
Russian Federation
2, Timakov Street, Novosibirsk 630060
I. A. Cherencova
Regional Clinical Hospital named after S.I. Sergeev
Russian Federation
Russian Federation
9Б, Krasnodarskaya Street, Khabarovsk 680009
E. V. Jakovleva
Research Institute – Regional Clinical Hospital №1 named after Prof. S.V. Ochapovsky, Ministry of Health of Krasnodar Region
Russian Federation
Russian Federation
167, 1st May Street, Krasnodar 350086
S. P. Yakupova
Kazan State Medical University, Ministry of Health of Russia
Russian Federation
Russian Federation
49, Butlerov Street, Kazan 420012
E. N. Alekseev
R-Pharm
Russian Federation
Russian Federation
111, Leninsky Prospect, Build. 2, Moscow 119421
A. M. Lila
V.A. Nasonova Research Institute of Rheumatology; Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia
Russian Federation
Russian Federation
34A, Kashirskoe Shosse, Moscow 115522
2/1, Barrikadnaya Street, Build. 1, Moscow 125993
References
1. Clinical guidelines for Rheumatoid Arthritis. https://www.consultant.ru/document/cons_doc_LAW_495885/8efd5f17af55cb35a770f73937590c642437b7eb/
2. Hunter CA, Jones SA. IL-6 as a keystone cytokine in health and disease. Nat Immunol. 2015 May;16(5):448-57. doi: 10.1038/ni.3153.
3. Aletaha D, Kerschbaumer A, Kastrati K, et al. Consensus statement on blocking interleukin-6 receptor and interleukin-6 in inflammatory conditions: an update. Ann Rheum Dis. 2023 Jun;82(6):773-787. doi: 10.1136/ard-2022-222784. Epub 2022 Aug 11.
4. Avci AB, Feist E, Burmester GR. Targeting IL-6 or IL-6 Receptor in Rheumatoid Arthritis: What Have We Learned? BioDrugs. 2024 Jan;38(1):61-71. doi: 10.1007/s40259-023-00634-1. Epub 2023 Nov 21.
5. Nasonov EL, Feist E. Prospects of interleukin-6 inhibition in rheumatoid arthritis: olokizumab (new monoclonal antibodies to IL-6). Nauchno-prakticheskaya revmatologiya. 2022;60(5):505-518. (In Russ.).
6. https://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=f2bc77b4-6298-4b2e-8f37-18e1baa0b63c
7. http://publication.pravo.gov.ru/document/0001202309010013
8. Nishimoto N, Terao K, Mima T, et al. Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease. Blood. 2008 Nov 15; 112(10):3959-64. doi: 10.1182/blood-2008-05-155846. Epub 2008 Sep 10.
9. Kretsos K, Golor G, Jullion A, et al. Safety and pharmacokinetics of olokizumab, an anti-IL-6 monoclonal antibody, administered to healthy male volunteers: A randomized phase I study. Clin Pharmacol Drug Dev. 2014 Sep;3(5):388-95. doi: 10.1002/cpdd.121. Epub 2014 May 26.
10. Lapkina NA, Baranov AA, Levshin NYu, et al. Dynamics of clinical manifestations and cytokine concentrations in patients with rheumatoid arthritis on the background of olokizumab therapy. Nauchno-prakticheskaya revmatologiya. 2023;61(4):475-484. (In Russ.).
11. Garrison LP Jr, Neumann PJ, Erickson P, et al. Using real-world data for coverage and payment decisions: the ISPOR Real-World Data Task Force report. Value Health. 2007 Sep-Oct;10(5):326-35. doi: 10.1111/j.1524-4733.2007.00186.x.
12. Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices. Guidance for Industry and Food and Drug Administration Staff, issued 31 August 2017. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/usereal-world-evidence-support-regulatory-decision-making-medical-devices
13. Gol'dina TA, Suvorov NI. Routine clinical practice research: from data acquisition to evaluation of medical technologies and decision-making in healthcare. Meditsinskie tekhnologii. Otsenka i vybor. 2018;(1):21-29. (In Russ.).
14. Tony HP, Feist E, Aries PM, et al. Sarilumab reduces disease activity in rheumatoid arthritis patients with inadequate response to janus kinase inhibitors or tocilizumab in regular care in Germany. Rheumatol Adv Pract. 2022 Feb 1;6(1):rkac002. doi: 10.1093/rap/rkac002. eCollection 2022.
15. Emery P, van Hoogstraten H, Thanga velu K, et al. Subcutaneous Sarilumab in Patients With Rheumatoid Arthritis who Previously Received Subcutaneous Sarilumab or Intravenous Tocilizumab: An Open-Label Extension of a Randomized Clinical Trial. ACR Open Rheumatol. 2020 Nov;2(11):672-680. doi: 10.1002/acr2.11188. Epub 2020 Nov 8.
16. Zagrebneva AI, Simonova EN, Mezenova TV, et al. Interleukin 6 receptor inhibitors in the treatment of rheumatoid arthritis during the COVID-19 pandemic, Moscow experience. Sovremennaya revmatologiya = Modern Rheumatology Journal. 2022;16(6):73-79. (In Russ.). doi: 10.14412/1996-7012-2022-6-73-79
17. Baranov AA, Vinogradova IB, Anoshenko va ON, et al. Management of patients with rheumatoid arthritis in real clinical practice: experience of switching from therapy with an interleukin 6 receptor inhibitor to a direct interleukin 6 inhibitor (olokizumab). Nauchnoprakticheskaya revmatologiya. 2023;61(3): 307-319. (In Russ.).
18. Shesternya PA, Baranov AA, Vinogradova IB, et al. Switching from interleukin-6 receptor inhibitors to the direct interleukin-6 inhibitor olokizumab in patients with rheumatoid arth ritis: efficacy and safety during one year of therapy. Sovremennaya revmatologiya = Modern Rheumatology Journal. 2024;18(5): 54-64. (In Russ.). doi: 10.14412/1996-7012-2024-5-54-64
19. England BR, Sayles H, Mikuls TR, et al. Validation of the rheumatic disease comorbi dity index. Arthritis Care Res (Hoboken). 2015 May;67(6):865-72. doi: 10.1002/acr.22456.
20. Nasonov EL, Karateev DE, Satybaldyev AM, et al. Rheumatoid arthritis in the Russian Federation according to the Russian Register of Patients with Arthritis (Message I). Nauchnoprakticheskaya revmatologiya. 2016;54:50-62. (In Russ.).
21. Nasonov E, Fatenejad S, Feist E, et al. Olokizumab, a monoclonal antibody against interleukin 6, in combination with metho trexate in patients with rheumatoid arthritis inadequately controlled by methotrexate: efficacy and safety results of a randomised controlled phase III study. Ann Rheum Dis. 2022 Apr;81(4):469-479. doi: 10.1136/annrheumdis-2021-219876. Epub 2021 Aug 3.
22. Smolen JS, Feist E, Fatenejad S, et al. Olokizumab versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med. 2022 Aug 25;387(8):715-726. doi: 10.1056/NEJMoa2201302.
23. Feist E, Fatenejad S, Grishin S, et al. Olokizumab, a monoclonal antibody against interleukin-6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by tumour necrosis factor inhibitor therapy: efficacy and safety results of a randomised controlled phase III study. Ann Rheum Dis. 2022 Dec;81(12): 1661-1668. doi: 10.1136/ard-2022-222630. Epub 2022 Sep 15.
24. Feist E, Fleischmann RM, Fatenejad S, et al. Olokizumab plus methotrexate: safety and efficacy over 106 weeks of treatment. Ann Rheum Dis. 2024 Oct 21;83(11):1454-1464. doi: 10.1136/ard-2023-225473.
25. Ho Lee Y, Gyu Song G. Comparison of the efficacy and safety of tocilizumab, sari lumab, and olokizumab in patients with active rheumatoid arthritis: a network meta-analysis of randomized controlled trials. Z Rheumatol. 2024 Feb;83(Suppl 1):97-106. doi: 10.1007/s00393-022-01315-0. Epub 2023 Jan 6.
26. https://acrabstracts.org/abstract/the-impact-of-comorbidities-on-the-efficacy-of-il-6-inhibitor-olokizumab-compared-to-adalimumab/
27. Favalli EG. Understanding the Role of Interleukin-6 (IL-6) in the Joint and Beyond: A Comprehensive Review of IL-6 Inhibition for the Management of Rheumatoid Arthritis. Rheumatol Ther. 2020 Sep;7(3):473-516. doi: 10.1007/s40744-020-00219-2. Epub 2020 Jul 30.
28. Zeb S, Khan Z, Ashraf, et al. Relationship Between Serum Interleukin-6 Levels, Systemic Immune-Inflammation Index, and Other Biomarkers Across Different Rheumatoid Arthritis Severity Levels. Cureus. 2024 Oct 24;16(10):e72334. doi: 10.7759/cureus.72334. eCollection 2024 Oct.
29. Berardicurti O, Ruscitti P, Pavlych V, et al. Glucocorticoids in rheumatoid arthritis: the silent companion in the therapeutic strategy. Expert Rev Clin Pharmacol. 2020 Jun;13(6): 593-604. doi: 10.1080/17512433.2020.1772055. Epub 2020 Jun 8.
30. Lauper K, Mongin D, Bergstra SA, et al. Oral glucocorticoid use in patients with rheumatoid arthritis initiating TNF-inhibitors, tocilizumab or abatacept: Results from the international TOCERRA and PANABA observational collaborative studies. Joint Bone Spine. 2024 Mar;91(2):105671. doi: 10.1016/j.jbspin.2023.105671. Epub 2023 Nov 30.
31. Wallace BI, England BR, Baker JF, et al. Lowering Expectations: Glucocorticoid Tapering Among Veterans With Rheumatoid Arthritis Achieving Low Disease Activity on Stable Biologic Therapy. ACR Open Rheumatol. 2023 Sep;5(9):437-442. doi: 10.1002/acr2.11584. Epub 2023 Jul 25.
32. Karateev АЕ, Polishchuk ЕY, Filatova ЕS, et al. Olokizumab effect on chronic pain in rheumatoid arthritis: Results of the PROLOGUE observational study. Int J Rheum Dis. 2024 Oct;27(10):e15320. doi: 10.1111/1756-185X.15320.
33. Potapova AS, Karateev AE, Polishchuk EYu, et al. Reduction of the need for glucocorticoids against the background of therapy with genetically engineered biological drugs and janus kinase inhibitors in rheumatoid arthritis: evidence from real clinical practice. Terapevticheskii arkhiv. 2024;96(5):465-470. (In Russ.).
34. Beuschlein F, Else T, Bancos I, et al. European Society of Endocrinology and Endocrine Society Joint Clinical Guideline: Diagnosis and Therapy of Glucocorticoid-induced Adrenal Insufficiency. J Clin Endocrinol Metab. 2024 Jun 17;109(7):1657-1683. doi: 10.1210/clinem/dgae250.
35.
Review
For citations:
Shesternya PA, Zagrebneva AI, Antipova OV, Arbuzova YV, Bannikova IG, Belozertseva LV, Bogdanova EA, Bykova SA, Vasilenko EA, Vinogradova IB, Davidyan SY, Epifanova OE, Zemerova EV, Zlobin MV, Ivanova LV, Ilyina NA, Ilyushina LV, Klyuchnikova EP, Makevnina AV, Myasoutova ER, Nakonechnaya EE, Pavlova AB, Plaksina TV, Rybin AV, Salnikova TS, Solodovnikova LV, Fedorova AV, Cherencova IA, Jakovleva EV, Yakupova SP, Alekseev EN, Lila AM. Use of olokizumab, a direct interleukin 6 inhibitor, in the treatment of rheumatoid arthritis: real-world evidence. Sovremennaya Revmatologiya=Modern Rheumatology Journal. 2025;19(2):39-49. https://doi.org/10.14412/1996-7012-2025-2-39-49
Views:
736
Email this article 