Efficiency of Levilimab in patients with moderate and severe COVID-19

Objective: evaluation of the clinical and economic efficiency of using Levilimab in the treatment of moderate and severe COVID-19 based on real world data (RWD).
Material and methods. A single-center observational retrospective case-control study was performed. According to the matching algorithm, 834 pairs of patients with moderate and 347 pairs with severe infection were selected, similar in gender, age, vaccination status, severity of the disease and the level of C-reactive protein.
Results. The clinical efficiency of Levilimab with respect to in-hospital mortality was demonstrated both for the moderate course (6% in the Levilimab group and 10% in the standard therapy group; odds ratio (OR) 1.71; 95% confidence interval (CI) 1.19–2.47; p<0.01) and for the severe course of COVID-19 (63% and 82%, respectively; OR 2.70; 95% CI 1.90–3.82; p<0.01). The costs per 1 treated patient were also higher in the Levilimab therapy groups: the difference in costs compared to the standard therapy group for patients with moderate disease was 54 665.30 rubles, with severe disease – 91 285.85 rubles. The estimated cost of the additional effectiveness of Levilimab for the moderate course of the disease was 13,666.32 rubles, for the severe course – 4,804.51 rubles.
Conclusion. The use of Levilimab for the treatment of moderate and severe COVID-19 is feasible both from a clinical and economic points of view. Conducting RWD trials is an important tool to understand the effectiveness of medical technologies in real clinical practice.

1. Temporary methodological recommendations. Prevention, diagnosis and treatment of new coronavirus infection COVID-19. Version 15 (22.02.2022). Available at: https://static-0.minzdrav.gov.ru/system/attachments/attaches/000/059/392/original/%D0%92%D0%9C%D0%A0_COVID-19_V15.pdf (in Russ.) (accessed 25.01.2023).

2. Gomon Yu.M., Kolbin A.S., Kalyapin A.A., et al. The use of janus kinase and anti-IL inhibitors in the Russian Federation in COVID-19: pharmacoepidemiological study. HIV and Immunosuppression. [In print] (in Russ.).

3. Lomakin N.V., Bakirov B.A., Protsenko D.N., et al. The efficacy and safety of levilimab in severely ill COVID-19 patients not requiring mechanical ventilation: results of a multicenter randomized double-blind placebo-controlled phase III CORONA clinical study. Inflamm Res. 2021; 70 (10–12): 1233–46. https://doi.org/10.1007/s00011-021-01507-5.

4. Tavlueva E.V., Ivanov I.G., Lytkina K.A., et al. The use of levilimab in patients with a new coronavirus infection (COVID-19) in real clinical practice. Clinical Pharmacology and Therapy. 2021; 30 (3): 31–7 (in Russ.). https://doi.org/10.32756/0869-5490-2021-3-31-37.

5. Khripun A.I., Starshinin A.V., Antipova Yu.O., et al. Levilimab and baricitinib prescribing experience in outpatient COVID-19 patients’ treatment. Therapeutic Archive. 2022; 94 (5): 668–74 (in Russ.). https://doi.org/10.26442/00403660.2022.05.2016.

6. A living WHO guideline on drugs for COVID-19. BMJ. 2020; 370: m3379. https://doi.org/https://doi.org/10.1136/bmj.m3379.

7. Zhukova O.V., Khokhlov A.L. Clinical and economic constituents of the application of dexamethasone and tocilizumab in the therapy for severe conditions in patients with COVID-19. FARMAKOEKONOMIKA. Sovremennaya farmakoekonomika i farmakoepidemiologiya / FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2021; 14 (1): 16–27 (in Russ.). https://doi.org/10.17749/2070-4909/farmakoekonomika.2021.060.

8. Frolov M.Yu., Salasyuk A.S., Rogov V.A. Evaluation of the economic effect of biological therapy in patients with severe COVID-19 and cytokine storm. FARMAKOEKONOMIKA. Sovremennaya farmakoekonomika i farmakoepidemiologiya / FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2020; 13 (4): 377–87 (in Russ.). https://doi.org/10.17749/2070-4909/farmakoekonomika.2020.076.

9. Territorial CHI Fund of Saint Petersburg. General Tariff Agreement. Available at: https://spboms.ru/page/mo#Генеральное-тарифноесоглашение (in Russ.) (accessed 25.01.2023).

10. Instructions for Ilsira® medical use. Available at: https://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=21cb-c69d-0615-4a1b-81fe-6cfcce747840 (in Russ.) (accessed 25.01.2023).

11. Singer M., Deutschman C.S., Seymour C.W., et al. The Third International Consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016; 315 (8): 801–10. https://doi.org/10.1001/jama.2016.0287.

12. Cowman K., Rossi J., Gendlina I., et al. Elucidating the role of procalcitonin as a biomarker in hospitalized COVID-19 patients. Diagn Microbiol Infect Dis. 2022; 103 (4): 115721. https://doi.org/10.1016/j.diagmicrobio.2022.115721.

13. Vazzana N., Dipaola F., Ognibene S. Procalcitonin and secondary bacterial infections in COVID-19: association with disease severity and outcomes. Acta Clin Belg. 2022; 77 (2): 268–72. https://doi.org/10.1080/17843286.2020.1824749.

14. Tikhova G.P. Data missing: how to solve and how to escape the problem. Regional Anesthesia and Acute Pain Management. 2016; 10 (3): 205–9 (in Russ.). https://doi.org/10.18821/1993-6508-2016-10-3-205-209.

15. Solodovnikov A.G., Sorokina E.Yu., Goldina T.A. Real-world data: from planning to analysis. Medical Technologies. Assessment and Choice. 2020; 41 (3): 9–16 (in Russ.). https://doi.org/10.17116/medtech2020410319.

16. Methodological recommendations for conducting a comparative clinical and economic evaluation of a medicinal product (new edition). Approved by the Order of FSBI "Center for Healthcare Quality Assessment and Control" of the Ministry of Health of the RF of 29.12.2018 No. 242-od. Available at: https://rosmedex.ru/complex (in Russ.) (accessed 25.01.2023).

17. Decision of the EEC Council of 17.03.2022 No. 36 "On amendments to the rules for registration and examination of drugs for medical use". Available at: https://www.alta.ru/tamdoc/22sr0036/ (in Russ.) (accessed 25.01.2023).

18. Kolbin A.S. (Ed.) Studies of real clinical practice. Мoscow: OKI Publ.: Buki Vedi; 2020: 208 pp. (in Russ.).

19. Kolbin A.S. Resolution based on the results of the conference: "RWD/ RWE – Research Tools of Real-World Clinical Practice Today and Tomorrow". Real-World Data & Evidence. 2021; 1 (1): 21–4 (in Russ.). https://doi.org/10.37489/2782-3784-myrwd-5.

20. Collins R., Bowman L., Landray M., Peto R. The magic of randomization versus the myth of real-world evidence. N Engl J Med. 2020; 382 (7): 674–8. https://doi.org/10.1056/NEJMsb1901642.

21. Miksad R.A., Abernethy A.P. Harnessing the power of real-world evidence (RWE): a checklist to ensure regulatory-grade data quality. Clin Pharmacol Ther. 2018; 103 (2): 202–5. https://doi.org/10.1002/cpt.946.

22. Cocoros N.M., Arlett P., Dreyer N.A., et al. The certainty framework for assessing real-world data in studies of medical product safety and effectiveness. Clin Pharmacol Ther. 2021; 109 (5); 1189–96. https://doi.org/10.1002/cpt.2045.

23. Decree of the Government of the RF of 28.08.2014 No. 871 (ed. of 03.12.2020) “On approval of the rules for the formation of lists of medicines for medical use and the minimum range of medicines necessary for the provision of medical care”. Available at: http://www.consultant.ru/document/cons_doc_LAW_167999/ (in Russ.) (accessed 25.01.2023).