Practical experience with olokizumab in patients with COVID-19 and high comorbidity

Relevance. Patients with COVID-19 and a high Charlson comorbidity index have an increased risk of severe course and death, however, data on the role of proactive IL-6 blockade in this group remain limited.

Objective. To evaluate the impact of preemptive olokizumab therapy on outcomes in patients with moderate COVID-19 and a Charlson Comorbidity Index (CCI) ≥3.

Materials and methods. A retrospective study in six hospitals in the Russian Federation, which included 213 hospitalized patients with moderate COVID-19 and CCI >3 who met the uniform inclusion and exclusion criteria. The main group (n=134), who received olokizumab in addition to standard therapy, and the control group (n=79), who received only standard therapy, were formed; the use of other biological drugs and JAK inhibitors was excluded. The primary endpoint was hospital mortality, while the secondary endpoint was the frequency and duration of ICU transfer, the need for ventilation, and the duration of ventilation and hospitalization.

Results. The mortality rate was signifi cantly lower in the main group (6.7 % vs 39.2 %; p < 0.001). Olokizumab therapy reduced the need for ICU admission (15.7 % vs 53.2 %; p < 0.001) and shortened mechanical ventilation duration (median duration 8 vs 17 days; p < 0.0001, log-rank test)). Olokizumab emerged as an independent predictor of early mechanical ventilation weaning (HR=2.00; 95 % CI: 1.33–3.01; p < 0.001) and reduced hospital stay (HR=1.61; 95 % CI: 1.11–2.35; p=0.013). The risk of death in the control group was 10.77 times higher (p < 0.001).

Conclusion. In patients with moderate COVID-19 and high comorbidity burden, olokizumab therapy decreases mortality and the need for respiratory support, justifying its use as a preemptive anti-infl ammatory strategy.

1. Sharipova M.M., Ivkina M.V., Arkhangelskaia A.N., et al. Features of the course of COVID-19 in patients with comorbid pathology. Meditsinskiy Sovet. 2022;16(6):44-49. (In Russ.). DOI: 10.21518/2079-701X-2022-16-6-44-49 EDN: RSITDA

2. Drapkina OM, Kontsevaya AV, Kalinina AM, et al. Comorbidity of patients with noncommunicable diseases in general practice. Eurasian guidelines. Cardiovascular Therapy and Prevention. 2024;23(3):3996. (In Russ.). DOI: 10.15829/1728-8800-2024-3996 EDN: AVZLPJ

3. Kabaeva EN, Yakushin MA, Vorobeva AV, et al. Epidemiological Specificity оf COVID-19 Comorbidity. City Healthcare. 2023;4(4):15-22. (In Russ.)/ DOI: 10.47619/2713-2617.zm.2023.v.4i4-15-22 EDN: IFVFNG

4. Kalashnikov E.S., Shapovalova M.A., Polunina E.A. Komorbidnyy fon kak faktor riska neblagopriyatnogo iskhoda pri COVID-19. Journal of New Medical Technologies. 2024;1:33-36 (In Russ.). DOI: 10.24412/1609-2163-2024-1-33-36 EDN: LNVCRG

5. Tuty Kuswardhani RA, Henrina J, Pranata R, et al. Charlson comorbidity index and a composite of poor outcomes in COVID-19 patients: A systematic review and meta-analysis. Diabetes Metab Syndr. 2020;14(6):2103-2109. DOI: 10.1016/j.dsx.2020.10.022

6. Nasonov E, Samsonov M. The role of Interleukin 6 inhibitors in therapy of severe COVID-19. Biomed Pharmacother. 2020;131:110698. DOI: 10.1016/j.biopha.2020.110698

7. Di Salvo E, Di Gioacchino M, Tonacci A, et al. Alarmins, COVID-19 and comorbidities. Ann Med. 2021;53(1):777-785. DOI: 10.1080/07853890.2021.1921252

8. Almada L, Angiolini SC, Dho ND, et al. Different cytokine and chemokine profiles in hospitalized patients with COVID-19 during the first and second outbreaks from Argentina show no association with clinical comorbidities. Front Immunol. 2023;14:1111797. DOI: 10.3389/fimmu.2023.1111797

9. Zyryanov SK, Butranova OI, Abramova AA. Efficacy of interleukin-6 inhibitors as a tool for preventive anti-inflammatory therapy for COVID-19. Kachestvennaya Klinicheskaya Praktika=Good Clinical Practice. 2024;(1):4-16. (In Russ.). DOI: 10.37489/2588-0519-2024-1-4-16 EDN: DSVZBR

10. Lomakin NV, Bakirov BA, Musaev GKh, et al. Clinical efficacy of interleukin-6 receptor inhibition in COVID-19 with levilimab and prospects for its use in cytokine release syndrome of other etiology. BIOpreparaty. Profilaktika, diagnostika, lechenie. 2022;22(4): 446-459. (In Russ.). DOI: 10.30895/2221-996X-2022-22-4-446-459 EDN: AQPNVQ

11. Gupta S, Wang W, Hayek SS, et al. Association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19. JAMA Intern Med. 2021;181(1):41-51. DOI: 10.1001/jamainternmed.2020.6252

12. Demko IV, Gordeeva NV, Kraposhina AYu, et al. Efficacy of interleukin-6 blockers in the treatment of new coronavirus infection. Prakticheskaya pulmonologiya. 2023;(1):44-50. (In Russ.). DOI: 10.24412/2409-6636-2023-12860

13. Fomina DS, Andreev SS, Andrenova GV, et al. Efficacy of olokizumab therapy in patients with mild or moderate COVID-19 with risk factors for progression. Pulmonologiya. 2023;33(5):623-632. (In Russ.). DOI: 10.18093/0869-0189-2023-33-5-623-632 EDN: ADRCLK

14. Goma TV, Kalyagin AN, Ryzhkova OV, at al. Efficacy of olocizumab in treatment of COVID-19 patients. Acta Biomedica Scientifica. 2022;7(5-2):86-95. (In Russ.). DOI: 10.29413/ABS.2022-7.5-2.9 EDN: OTXFRD

15. Antonov VN, Ignatova GL, Pribytkova OV, et al. Experience of olokizumab use in COVID-19 patients. Terapevticheskii Arkhiv. 2020;92(12):148-154. (In Russ.). DOI: 10.26442/00403660.2020.12.200522 EDN: DVKXDJ

16. Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373-383. DOI: 10.1016/0021-9681(87)90171-8

17. Sarhan RM, Madney YM, Abou Warda AE, et al. Therapeutic efficacy, mechanical ventilation, length of hospital stay, and mortality rate in severe COVID-19 patients treated with tocilizumab. Int J Clin Pract. 2021;75(6):e14079. DOI: 10.1111/ijcp.14079

18. REMAP-CAP Investigators, Gordon AC, Mouncey PR, et al. Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19. N Engl J Med. 2021;384(16):1491-1502. DOI: 10.1056/NEJMoa2100433

19. WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, Shankar-Hari M, Vale CL, et al. Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19: A Meta-analysis. JAMA. 2021;326(6):499-518. DOI: 10.1001/jama.2021.11330

20. Novikov P, Brovko M, Akulkina L, et al. Efficacy and safety of olokizumab, interleukin-6 inhibitor, in hospitalized patients with COVID-19. Klinicheskaya farmakologiya i terapiya. 2022;32(2):51-56. (In Russ.). DOI: 10.32756/0869-5490-2022-2-51-56 EDN: UCHWCU

21. Shesternya PA, Zagrebneva AI, Antipova OV, et al. Use of the direct interleukin 6 inhibitor olokizumab in the treatment of rheumatoid arthritis: real-world clinical practice data. Sovremennaya Revmatologiya. 2025;19(2):39-49. (In Russ.). DOI: 10.14412/1996-7012-2025-2-39-49 EDN: LDOYGO

22. Liang P, Li Y, Meng L, et al. Prognostic significance of serum interleukin-6 in severe/critical COVID-19 patients treated with tocilizumab: a detailed observational study analysis. Sci Rep. 2024;14(1):29634. DOI: 10.1038/s41598-024-81028-3

23. Yang L, Xie X, Tu Z, et al. The signal pathways and treatment of cytokine storm in COVID-19. Signal Transduct Target Ther. 2021;6(1):255. DOI: 10.1038/s41392-021-00679-0

24. Speake C, Habib T, Lambert K, et al. IL-6-targeted therapies to block the cytokine or its receptor drive distinct alterations in T cell function. JCI Insight. 2022;7(22):e159436. DOI: 10.1172/jci.insight.159436

25. Salama C, Han J, Yau L, et al. Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia. N Engl J Med. 2021;384(16):1503-1516. DOI: 10.1056/NEJMoa2030340

26. Topolyanskaya SV, Rachina SA, Lytkina KA, et al. Interleukin-6 inhibitor olokizumab in hospitalized adults with moderate COVID-19: results of a single-center observational study. West Kazakhstan Medical Journal. 2024;66(4):453-459. DOI: 10.18502/wkmj.v66i4.17780