Treatment targeted for B lymphocytes – significant progress in the treatment of multiple sclerosis


Authors: J. Piťha
Authors‘ workplace: Neurologická klinika 1. LF UK a VFN Praha ;  Neurologické oddělení, Krajská zdravotní, a. s. – Nemocnice Teplice o. z., Teplice
Published in: Cesk Slov Neurol N 2018; 81(4): 395-402
Category: Review Article
doi: https://doi.org/10.14735/amcsnn2018395

Overview

The article summarizes the findings regarding the complex involvement of B lymphocytes in the development and maintenance of autoimmune inflammation in MS. Substances that cause B cell depletion are mentioned. The greatest attention is paid to ocrelizumab, its mechanism of action, the results of clinical trials and adverse effects. Ocrelizumab is the first monoclonal antibody that targets B cells that are significantly involved in the immunopathogenesis of MS. It is approved for the treatment of patients with relapsing remitting, but also primary, progressive MS. Ocrelizumab is a drug with excellent adherence and a very good benefit/risk ratio.

Key words:
multiple sclerosis – ocrelizumab – B cells – biological treatment – NEDA

The author declare he has no potential con­flicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manu­script met the ICMJE “uniform requirements” for biomedical papers.


Sources

1. Hafler DA, Slavik JM, Anderson DE et al. Multiple sclerosis. Immunol Rev 2005; 204: 208–231.

2. O‘Brien K, Gran B, Rostami A. T-cell based immunotherapy in experimental autoimmune encephalomyelitis and multiple sclerosis. Immunotherapy 2010; 2(1): 99–115.

3. Monson NL, Cravens PD, Frohman EM et al. Effect of rituximab on the peripheral blood and cerebrospinal fluid B cells in patients with primary progressive multiple sclerosis. Arch Neurol 2005; 62(2): 258–264.

4. Stüve O, Cepok S, Elias B et al. Clinical stabilization and effective B-lymphocyte depletion in the cerebrospinal fluid and peripheral blood of a patient with fulminant relapsing-remitting multiple sclerosis. Arch Neurol 2005; 62(10): 1620–1623.

5. Tedder TF, Engel P. CD20: a regulator of cell-cycle progression of B lymphocytes. Immunol Today 1994; 15(9): 450–454.

6. Kinzel S, Weber MS. B cell-directed therapeutics in multiple sclerosis: rationale and clinical evidence. CNS Drugs 2016; 30(12): 1137–1148.

7. Kabat EA, Freesman DA et al. A study of the crystal­line albumin, gamma globulin and total protein in the cerebrospinal fluid of 100 cases of multiple sclerosis and in other diseases. Am J Med Sci 1950; 219(1): 55–64.

8. Boster A, Ankeny DP, Racke MK. The potential role of B cell-targeted therapies in multiple sclerosis. Drugs 2010; 70(18): 2343–2356. doi: 10.2165/ 11585230-000000000-00000.

9. Dobson R, Ramagopalan S, Davis A et al. Cerebrospinal fluid oligoclonal bands in multiple sclerosis and clinically isolated syndromes: a meta-analysis of prevalence, prognosis and effect of latitude. J Neurol Neurosurg Psychiatry 2013; 84(8): 909–914. doi: 10.1136/ jnnp-2012-304695.

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

11. Zeman AZ, Kidd D, McLean BN et al. A study of oligoclonal band negative multiple sclerosis. J Neurol Neurosurg Psychiatry 1996; 60(1): 27–30.

12. Villar LM, Masjuan J, González-Porqué P et al. Intrathecal IgM synthesis in neurologic diseases: relationship with disability in MS. Neurology 2002; 58(5): 824–826.

13. Lock C, Hermans G, Pedotti R et al. Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat Med 2002; 8(5): 500–508.

14. Lucchinetti C, Brück W, Parisi J et al. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 2000; 47(6): 707–717.

15. Epstein LG, Prineas JW, Raine CS. Attachment of myelin to coated pits on macrophages in experimental allergic encephalomyelitis. J Neurol Sci 1983; 61(3): 341–348.

16. Owens GP, Bennett JL, Lassmann H et al. Antibodies produced by clonally expanded plasma cells in multiple sclerosis cerebrospinal fluid. Ann Neurol 2009; 65(6): 639–649. doi: 10.1002/ ana.21641.

17. Flach AC, Litke T, Strauss J et al. Autoantibody-boosted T-cell reactivation in the target organ trig­gers manifestation of autoimmune CNS disease. Proc Natl Acad Sci U S A 2016; 113(12): 3323–3328. doi: 10.1073/ pnas.1519608113.

18. Serafini B, Rosicarelli B, Magliozzi R et al. Detection of ectopic B-cell follicles with germinal centers in the meninges of patients with secondary progressive multiple sclerosis. Brain Pathol 2004; 14(2): 164–174.

19. Magliozzi R, Howell OW, Reeves C et al. A gradient of neuronal loss and meningeal inflammation in multiple sclerosis. Ann Neurol 2010; 68(4): 477–493. doi: 10.1002/ ana.22230.

20. Michel L, Touil H, Pikor NB. B cells in the multiple sclerosis central nervous system: trafficking and contribution to CNS-compartmentalized inflammation. Front Immunol 2015; 6: 636. doi: 10.3389/ fimmu.2015.00636.

21. Blauth K, Owens GP, Bennett J. The ins and outs of B cells in multiple sclerosis. Front Immunol 2015; 6: 565. doi: 10.3389/ fimmu.2015.00565.

22. von Büdingen HC, Kuo TC, Sirota M et al. B cell exchange across the blood-brain barrier in multiple sclerosis. J Clin Invest 2012; 122(12): 4533–4543. doi: 10.1172/ JCI63842.

23. Bittner S, Ruck T, Wiendl H et al. Targeting B cellsin relapsing-remitting multiple sclerosis: from patho­-physiology to optimal clinical management. TherAdv Neurol Disord 2017; 10(1): 51–66. doi: 10.1177/ 1756285616666741.

24. Bossen C, Schneider P. BAFF, APRIL and their receptors: structure, function and signaling. Semin Immunol 2006; 18: 263–275.

25. Nakayamada S, Tanaka Y. BAFF- and APRIL-target­­ed therapy in systemic autoimmune diseases. Inflamm Regen 2016; 36: 6. doi: 10.1186/ s41232-016-0015-4.

26. Serafini B, Rosicarelli B, Magliozzi R et al. Detection of ectopic B-cell follicles with germinal centers in the meninges of patients with secondary progressive multiple sclerosis. Brain Pathol 2004; 14(2): 164–174.

27. Howell OW, Reeves CA, Nicholas R et al. Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis. Brain 2011; 134(9): 2755–2771. doi: 10.1093/ brain/ awr182.

28. Kinzel S, Lehmann-Horn K, Torke S et al. Myelin-reactive antibodies initiate T cell-mediated CNS autoimmune disease by opsonization of endogenous antigen. Acta Neuropathol 2016; 132(1): 43–58. doi: 10.1007/ s00401-016-1559-8.

29. Li R, Rezk A, Miyazaki Y et al. Proinflammatory GM-CSF-producing B cells in multiple sclerosis and B cell depletion therapy. Sci Transl Med 2015; 7(310): 310ra166. doi: 10.1126/ scitranslmed.aab4176.

30. Shen P, Fillatreau S. Antibody-independent functions of B cells: a focus on cytokines. Nat Rev Immunol 2015; 15(7): 441–451. doi: 10.1038/ nri3857.

31. Fillatreau S, Sweenie CH, Mcgeachy MJ et al. B cells regulate autoimmunity by provision of IL-10. Nat Rev Immunol 2002; 3(10): 944–950. doi: 10.1038/ ni833.

32. Shen P, Roch T, Lampropoulou V et al. IL-35-producing B cells are critical regulators of immunity dur­ing autoimmune and infectious diseases. Nature 2014; 507(7492): 366–370. doi: 10.1038/ nature12979.

33. Weber MS, Prod’homme T, Patarroyo JC et al. B-cell activation influences T-cell polarization and outcome of anti-CD20 B-cell depletion in central nervous system autoimmunity. Ann Neurol 2010; 68(3): 369–383. doi: 10.1002/ ana.22081.

34. Brimnes MK, Hansen BE, Nielsen LK et al. Uptake and presentation of myelin basic protein by normal human B cells. PLoS One 2014; 9(11): e113388. doi: 10.1371/ journal.pone.0113388.

35. Abulayha A, Bredan A, El Enshasy H et al. Rituximab: modes of action, remaining dispute and future perspective. Future Oncol 2014; 10(15): 2481–2492. doi: 10.2217/ fon.14.146.

36. Roche s. r. o, Evropská agentura pro léčivé přípravky. MabThera: souhrn údajů o přípravku. [online]. Dostupné z URL: http:/ / www.ema.europa.eu/ docs/ cs_CZ/ document_library/ EPAR_-_Product_Information/ human/ 000165/ WC500025821.pdf.

37. Gasperi C, Stuve O, Hemmer B. B cell-directed therapies in multiple sclerosis. Neurodegener Dis Manag 2016; 6(1): 37–47. doi: 10.2217/ nmt.15.67.

38. Milo R. Therapeutic strategies targeting B-cells in multiple sclerosis. Autoimmun Rev 2016; 15: 714–718.

39. Cree BA, Lamb S, Morgan K et al. An open label study of the effects of rituximab in neuromyelitis optica. Neurology 2005; 64(7): 1270–1272. doi: 10.1212/ 01.WNL.0000159399.81861.D5.

40. Lebrun C, Bourg V, Tieulie N et al. Successful treatment of refractory generalized myasthenia gravis with rituximab. Eur J Neurol 2009; 16(2): 246–250. doi: 10.1111/ j.1468-1331.2008.02399.x.

41. Benedetti L, Briani C, Franciotta D et al. Rituximab in patients with chronic inflammatory demyelinating polyradiculoneuropathy: a report of 13 cases and review of the literature. J Neurol Neurosurg Psychiatry 2011; 82(3): 306–308. doi: 10.1136/ jnnp.2009.188912.

42. Fasano S, Gordon P, Hajji R et al. Rituximab in the treatment of inflammatory myopathies: a review. Rheumatology (Oxford) 2017; 56(1): 26–36. doi: 10.1093/ rheumatology/ kew146.

43. Kuye IO, Smith GP. the use of rituximab in the management of refractory dermatomyositis. J Drugs Dermatol 2017; 16(2): 162–166.

44. Kappos L, Li D, Calabresi P et al. Ocrelizumab in relapsing-remitting multiple sclerosis: a phase II, randomised, placebo-controlled, multicentre trial. Lancet 2011; 378(9805): 1779–1787. doi: 10.1016/ S0140-6736(11)61649-8.

45. Klotz L, Wiendl H. Monoclonal antibodies in neuroinflammatory diseases. Expert Opin Biol Ther 2013; 13(6): 831–846. doi: 10.1517/ 14712598.2013.767329.

46. Sorensen PS, Lisby S, Grove R et al. Safety and efficacy of ofatumumab in relapsing-remitting multiple sclerosis: a phase II study. Neurology 2014; 82(7): 573–581. doi: 10.1212/ WNL.0000000000000125.

47. Bar-Or A, Grove R, Austin A et al.  The MIRROR study: a randomized, double-blind, placebo-controlled, paral­lel-group, dose-ranging study to investigate the safety and MRI efficacfy of subcutaneous ofatumumab in subjects with relapsing-remitting multiple sclerosis (RRMS) (I7-1.007). Neurology 2014; 82 (10 Suppl).

48. Halliley J, Tipton C, Liesveld J et al. Long-lived plasma cells are contained within the CD19(-)Cd38(hi)Cd138(+) subset in human bone marrow. Immunity 2015; 43(1): 132–145. doi: 10.1016/ j.immuni.2015.06.016.

49. Edwards JC, Cambridge G. B-cell targeting in rheu-matoid arthritis and other autoimmune dis­eases. Nat Rev Immunol 2006; 6(5): 394–403. doi: 10.1038/ nri1838.

50. Boster A, Ankeny D, Racke M. The potential role of B cell-targeted therapies in multiple sclerosis. Drugs 2010; 70(18): 2343–2356. doi: 10.2165/ 11585230-000000000-00000.

51. Kappos L, Hartung HP, Freedman MS et al. Atacicept in multiple sclerosis (ATAMS): a randomised, placebo-controlled, double-blind, phase II trial. Lancet Neurol 2014; 13(4): 353–363. doi: 10.1016/ S1474-4422(14)70028-6.

52. Sergott RC, Bennett JL, Rieckmann P et al. ATON: results from a Phase II randomized trial of the B-cell-targeting agent atacicept in patients with optic neuritis. J Neurol Sci 2015; 351(1–2): 174–178. doi: 10.1016/ j.jns.2015.02.019.

53. Hauser SL, Bar-Or A, Comi G et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med 2017; 376(3): 221–234. doi: 10.1056/ NEJMoa1601277.

54. Montalban X, Hauser SL, Kappos L et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med 2017; 376(3): 209–220. doi: 10.1056/ NEJMoa1606468.

55. Polman CH, Reingold SC, Banwell B et al. Dia­gnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011; 69(2): 292–302. doi: 10.1002/ ana.22366.

56. Polman CH, Reingold SC, Edan G et al. Dia­gnostic criteria for multiple sclerosis: 2005 revisions to the „McDonald Criteria“. Ann Neurol 2005; 58(6): 840–846. doi: 10.1002/ ana.20703.

57. Havrdová E, Arnold DL, Bar-Or A et al. No evidence of disease activity (NEDA) analysis by epochs in patients with relapsing multiple sclerosis treated with ocrelizumab vs interferon beta-1a. Mult Scler J Exp Transl Clin 2018; 4(1): 205521731870642. doi: 10.1177/ 2055217318760642.

58. Stahnke AM, Holt KM. Ocrelizumab: a new B-cell therapy for relapsing remitting and primary progressive multiple sclerosis. Ann Pharmacother 2018; 52(5): 473–483. doi: 10.1177/ 1060028017747635.

59. Frasco MA, Shih T, Incerti D et al. Incremental net monetary benefit of ocrelizumab relative to subcutaneous interferon β-1a. J Med Econ 2017; 20(10): 1074–1082. doi: 10.1080/ 13696998.2017.1357564.

60. Lehmann-Horn K, Kinzel S, Werber MS. Deciphering the role od B cells in multiple sclerosis – towards specific targeting of pathogenic function Int J Mol Sci 2017; 18(10): 144–162.

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Paediatric neurology Neurosurgery Neurology

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