Preview

Neurology, Neuropsychiatry, Psychosomatics

Advanced search

Experience with anti-B-cell therapy in the pathogenetic treatment of multiple sclerosis

https://doi.org/10.14412/2074-2711-2019-1-59-65

Full Text:

Abstract

One of the promising areas in the pathogenetic treatment of multiple sclerosis (MS) is anti-B-cell therapy using ocrelizumab, an anti-CD20 monoclonal antibody. The drug is indicated for primary progressive MS (PPMS), secondary progressive MS (SPMS) and exacerbations, and highly active MS.

Objective: to analyze the use of the drug in 32 patients with different types of MS in everyday neurological practice.

Patients and methods. The investigation included 32 patients diagnosed with MS using the 2017 McDonald criteria: 12 patients with PPMS, 12 with highly active MS and 8 with SPMS and exacerbations. The median Expanded Disability Status Scale (EDSS) score was 4.0; the most severe course of the disease was observed in patients with SPMS. All the patients received a treatment cycle of 600-mg intravenous ocrelizumab injections (with an infusion pump) every 6 months; the initial dose was by 300 mg every 2 weeks. The follow-up period was 6 to 18 months.

Results and discussion. During ocrelizumab therapy, the patients with PPMS showed stabilization of EDSS score; and 6 (50%) had even its slight decrease by 0.5–1.0 scores, which may be caused by compensation for the existing symptoms due to pathogenetic treatment. In highly active MS, only 1 of the 12 ocrelizumab-treated patients had an ongoing exacerbation of the disease. During a subsequent 6–18-month follow-up, magnetic resonance imaging revealed that none of the patients had manifestations of MS activity; the EDSS score decreased in all the patients, indicating their achievement of stable remission. Six (75%) of the 8 patients with SPMS and exacerbations also displayed a decrease in EDSS score in the absence of exacerbations. No adverse events, including infusion reactions, were recorded during drug administration. The drug has a good tolerance and safety profile and ease-to-use.

Conclusion. Ocrelizumab therapy with will be able to improve the quality of treatment in patients with different types of MS, which is of great medical and social importance

About the Authors

O. V. Boyko
N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia; Yusupov Hospital, OOO «Neuro-Clinic»
Russian Federation
1, Ostrovityanov St., Moscow 117997, 17, Nagornaya St., Build. 6, Moscow 117186


S. V. Petrov
Yusupov Hospital, OOO «Neuro-Clinic»
Russian Federation
17, Nagornaya St., Build. 6, Moscow 117186


N. Yu. Lashch
N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia
Russian Federation
1, Ostrovityanov St., Moscow 117997


M. R. Guseva
N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia
Russian Federation
1, Ostrovityanov St., Moscow 117997


A. N. Boyko
N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia; Yusupov Hospital, OOO «Neuro-Clinic»
Russian Federation

Aleksey Nikolaevich Boyko

1, Ostrovityanov St., Moscow 117997, 17, Nagornaya St., Build. 6, Moscow 117186



References

1. Cragg MS, Walshe CA, Ivanov AO, Glennie MJ. The biology of CD20 and its potential as a target for mAb therapy. Curr Dir Autoimmun. 2005;8:140-74. doi: 10.1159/000082102

2. Klein C, Lammens A, Schafer W, et al. Epitope interactions of monoclonal antibodies targeting CD20 and their relationship to functional properties. MAbs. 2013 Jan-Feb;5(1):22- 33. doi: 10.4161/mabs.22771. Epub 2012 Dec 4.

3. Milo R. Therapeutic strategies targeting B-cells in multiple sclerosis. Autoimmun Rev. 2016 Jul;15(7):714-8. doi: 10.1016/j.autrev.2016.03.006. Epub 2016 Mar 9.

4. Bittner S, Ruck T, Wiendl H, et al. Targeting B cells in relapsing-remitting multiple sclerosis: from pathophysiology to optimal clinical management. Ther Adv Neurol Disord. 2017 Jan;10(1):51-66. doi: 10.1177/1756285616666741. Epub 2016 Sep 2.

5. Absinta M, Vuolo L, Rao A, et al. Gadolinium-based MRI characterization of leptomeningeal inflammation in multiple sclerosis. Neurology. 2015 Jul 7;85(1):18-28. doi: 10.1212/WNL.0000000000001587. Epub 2015 Apr 17.

6. Magliozzi R, Howell O, Vora A, et al. Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology. Brain. 2007 Apr;130(Pt 4):1089-104.

7. Boiko OV, Khoroshilova II, Petrov SV, et al. Possible additional mechanisms of action of ocrelizumab in multiple sclerosis (on the example of a clinical case). Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2018;(2):116-20. (In Russ.).

8. Gingele S, Jacobus TL, Konen FF, et al. Ocrelizumab depletes CD20? T cells in multiple sclerosis patients. Cells. 2018 Dec 28;8(1). pii: E12. doi: 10.3390/cells8010012.

9. Lublin FD. New multiple sclerosis phenotypic classification. Eur Neurol. 2014;72 Suppl 1: 1-5. doi: 10.1159/000367614. Epub 2014 Sep 26.

10. Hauser SL, Bar-Or A, Comi G, et al; OPERA I and OPERA II Clinical Investigators. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2017 Jan 19; 376(3):221-234. doi: 10.1056/NEJMoa1601277. Epub 2016 Dec 21.

11. Montalban X, Hauser SL, Kappos L, et al; ORATORIO Clinical Investigators. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2017 Jan 19;376(3): 209-220. doi: 10.1056/NEJMoa1606468. Epub 2016 Dec 21.

12. Montalban X, Gold R, Thompson AJ, et al. ECTRIMS/EAN guideline on the pharmacological treatment of people with multiple sclerosis. Mult Scler. 2018 Feb;24(2):96-120. doi: 10.1177/1352458517751049. Epub 2018 Jan 20.

13. Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018 Feb; 17(2):162-173. doi: 10.1016/S1474-4422(17)30470-2. Epub 2017 Dec 21.

14. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983 Nov;33(11): 1444-52.

15. Kremenchutzky M, Rice GP, Baskerville J, et al.The natural history of multiple sclerosis: a geographically based study 9: observations on the progressive phase of the disease. Brain. 2006 Mar;129(Pt 3):584-94. Epub 2006 Jan 9.

16. Popova EV, Bryukhov VV, Boiko AN, Krotenkova MV. Primary-progressive multiple sclerosis as atypical demyelinating process. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2016;(2):42-6. (In Russ.).

17. Vlasov YaV, Churakov MV, Kurapov MA, et al. Primary-progressive multiple sclerosis in Russia: medical and sociological research involving patients and neurologists. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2018; (2):40-6. (In Russ.)

18. Soerensen PS. New management algorithms in multiple sclerosis. Curr Opin Neurol. 2014 Jun;27(3):246-59. doi: 10.1097/WCO.0000000000000096.

19. Boiko AN, Gusev EI. Modern algorithms of diagnosis and treatment of multiple sclerosis based on individual assessment of the patient's condition. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2017; (2):92-106. (In Russ.).

20. Criteria of treatment failure and the cancellation of PITRS of the first line and replace to second-line drugs. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2015;(8-2):44. (In Russ.).

21. Instruction for medical use of ocrelizumab (OCREVUS®). Ministry of health of the Russian Federation. http://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=1e285065-d8dd-4438-b4f8-6358eced347c&t=c1311926-a0fe-4493-ba2b-e2874b4190f7.

22. Fox EJ, Markowitz C, Applebee A, et al. Ocrelizumab reduces progression of upper extremity impairment in patients with primary progressive multiple sclerosis: Findings from the phase III randomized ORATORIO trial. Mult Scler. 2018 Dec;24(14):1862-1870. doi: 10.1177/1352458518808189. Epub 2018 Nov 12.

23. Wolinsky J, Montalban X, Arnold DL, et al. Evaluation of No Evidence of Progression (NEP) in Patients With Primary Progressive Multiple Sclerosis in the ORATORIO Trial. Presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2017; February 23-25; Orlando, FL, USA. Poster P015.

24. Hauser SL, Belachew S, Kappos L. Ocrelizumab in primary progressive and relapsing multiple sclerosis. N Engl J Med. 2017 Apr 27;376(17):1694. doi: 10.1056/NEJMc1702076.


For citation:


Boyko O.V., Petrov S.V., Lashch N.Y., Guseva M.R., Boyko A.N. Experience with anti-B-cell therapy in the pathogenetic treatment of multiple sclerosis. Neurology, Neuropsychiatry, Psychosomatics. 2019;11(1):59-65. (In Russ.) https://doi.org/10.14412/2074-2711-2019-1-59-65

Views: 145


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2074-2711 (Print)
ISSN 2310-1342 (Online)