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2015 | 15 | 3 | 150–154
Article title

Przeciwciało monoklonalne przeciw CD20 w terapii postaci rzutowej i pierwotnie postępującej stwardnienia rozsianego – wyniki badań klinicznych III fazy

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Title variants
EN
Anti-CD20 monoclonal antibody in multiple sclerosis therapy: the results of phase 3 clinical studies on relapsing and primary progressive multiple sclerosis
Languages of publication
EN PL
Abstracts
EN
Multiple sclerosis is an inflammatory and demyelinating disease of the central nervous system. Impaired cell-mediated and humoral immunity play an important role in the pathogenesis of the disease. B lymphocytes play an important role in the presentation of own antigens to T lymphocytes and in the production of pro-inflammatory cytokines and autoantibodies. In primary progressive multiple sclerosis a degenerative reaction with axonopathy and neuronal damage are predominant features. A monoclonal antibody against CD20 B lymphocytes was used in clinical studies on relapsing multiple sclerosis (OPERA I and II studies) and on primary progressive MS (ORATORIO study). A statistically significant reduction of the annualised relapse rate, clinically defined progression and contrast-enhanced T2-weighted magnetic resonance imaging lesions was demonstrated for relapsing multiple sclerosis in the group of patients treated with ocrelizumab compared to patients receiving interferon beta-1a. A statistically significant reduction of clinically defined progression, T2-weighted lesions and changes in brain volume in magnetic resonance imaging was found for primary progressive multiple sclerosis in the group of patients treated with ocrelizumab compared to placebo. The safety profile of ocrelizumab was satisfactory and was not significantly different from the profile in the control groups. It seems that ocrelizumab affects CD20 B lymphocytes in a clinically beneficial way and that phase 3 clinical study results may be the basis for its registration and common use in clinical practice.
PL
Stwardnienie rozsiane to zapalno-demielinizacyjna choroba ośrodkowego układu nerwowego, w której patogenezie istotną rolę odgrywają zaburzenia odpowiedzi immunologicznej komórkowej i humoralnej. Rola limfocytów B jest istotna w prezentacji własnych antygenów komórkom T, produkcji prozapalnych cytokin i autoprzeciwciał. W postaci pierwotnie postępującej stwardnienia rozsianego dominuje odczyn zwyrodnieniowy z aksonopatią i uszkodzeniem neuronalnym. Przeciwciało monoklonalne przeciw limfocytom B CD20 zostało zastosowane w badaniach klinicznych dotyczących postaci rzutowej (OPERA I, II) i pierwotnie postępującej (ORATORIO). W postaci rzutowej wykazano istotną statystycznie redukcję rocznego wskaźnika rzutów, klinicznie potwierdzonej progresji, zmian wzmacniających się po podaniu kontrastu i zmian w sekwencji T2 w obrazowaniu metodą rezonansu magnetycznego w grupie chorych leczonych okrelizumabem w porównaniu z grupą pacjentów otrzymujących interferon beta-1a. W postaci pierwotnie postępującej stwierdzono istotną statystycznie redukcję klinicznie potwierdzonej progresji, zmian w sekwencji T2 i objętości mózgu w badaniu rezonansu magnetycznego w grupie leczonych okrelizumabem w stosunku do placebo. Profil bezpieczeństwa okrelizumabu był zadowalający i nie różnił się znacząco od profilu w grupach kontrolnych. Wydaje się, że wpływ leku na limfocyty B CD20 przynosi korzyść kliniczną oraz że wyniki badań III fazy mogą być podstawą do rejestracji i szerokiego stosowania okrelizumabu w praktyce klinicznej.
Discipline
Publisher

Year
Volume
15
Issue
3
Pages
150–154
Physical description
Contributors
  • Centrum Terapii SM, Katowice, Polska
References
  • Bar-Or A, Fawaz L, Fan B et al.: Abnormal B-cell cytokine responses a trigger of T-cell-mediated disease in MS? Ann Neurol 2010; 67: 452–461.
  • Crawford A, MacLeod M, Schumacher T et al.: Primary T cel expansion and differentiation in vivo requires antigen presentation by B cells. J Immunol 2006; 176: 3498–3506.
  • Criste G, Trapp B, Dutta R: Axonal loss in multiple sclerosis: causes and mechanisms. Handb Clin Neurol 2014: 122: 101–113.
  • Filippi M, Charil A, Rovaris M et al.: Insights from magnetic resonance imaging. Handb Clin Neurol 2014: 122: 115–149.
  • Hartung H, Aktas O, Menge T et al.: Immune regulation of multple sclerosis. Handb Clin Neurol 2014: 122: 3–14.
  • Hauser SL, Comi GC, Hartung HP et al.; on behalf of the OPERA I and II clinical investigators: Efficacy and safety of ocrelizumab in relapsing multiple sclerosis – results of the phase III double-blind, interferon beta-1a-controlled OPERA I and II studies. Presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis, October 7–10, 2015a, Barcelona, Spain. Platform presentation number 190.
  • Hauser S, Comi G, Hartung HP et al.: Baseline demographics anddisease characteristics from OPERA I and II, two phase III trials evaluating ocrelizumab in patients with relapsing multiple sclerosis. Presented at the American Academy of Neurology’s 67th Annual Meeting; April 18–25, 2015b; Washington, DC. P7.201.
  • Lisak RP, Benjamins JA, Nedelkoska L et al.: Secretory products of multiple sclerosis B cells are cytotoxic to oligodendroglia in vitro. J Neuroimmunol 2012; 246: 85–95.
  • Magliozzi R, Howell OW, Reeves C et al.: A gradient of neuronal loss and meningeal inflammation in multiple sclerosis. Ann Neurol 2010; 68: 477–493.
  • Montalban X, Hemmer B, Rammohan K et al.: Baseline demographics and disease characteristics from ORATORIO, a phase III trial evaluating ocrelizumab in patients with primary progressive multiple sclerosis. Presented at the American Academy of Neurology’s 67th Annual Meeting; April 18–25, 2015a; Washington, DC. P7.017.
  • Montalban X, Hemmer B, Rammohan K et al.; on behalf of the ORATORIO Clinical Investigators: Efficacy and safety of ocrelizumab in primary progressive multiple sclerosis – results of the placebo-controlled, double-blind, Phase III ORATORIO study. Presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis, October 7–10, 2015b, Barcelona, Spain. Platform presentation number 228.
  • Polman CH, Reingold SC, Edan G et al.: Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria.” Ann Neurol 2005; 58: 840–846.
  • 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: 164–174.
  • Simon JH: MRI outcomes in the diagnosis and disease course of multiple sclerosis. Handb Clin Neurol 2014; 122: 405–425.
  • Bar-Or A, Fawaz L, Fan B et al.: Abnormal B-cell cytokine responses a trigger of T-cell-mediated disease in MS? Ann Neurol 2010; 67: 452–461.
  • Crawford A, MacLeod M, Schumacher T et al.: Primary T cel expansion and differentiation in vivo requires antigen presentation by B cells. J Immunol 2006; 176: 3498–3506.
  • Criste G, Trapp B, Dutta R: Axonal loss in multiple sclerosis: causes and mechanisms. Handb Clin Neurol 2014: 122: 101–113.
  • Filippi M, Charil A, Rovaris M et al.: Insights from magnetic resonance imaging. Handb Clin Neurol 2014: 122: 115–149.
  • Hartung H, Aktas O, Menge T et al.: Immune regulation of multple sclerosis. Handb Clin Neurol 2014: 122: 3–14.
  • Hauser SL, Comi GC, Hartung HP et al.; on behalf of the OPERA I and II clinical investigators: Efficacy and safety of ocrelizumab in relapsing multiple sclerosis – results of the phase III double-blind, interferon beta-1a-controlled OPERA I and II studies. Presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis, October 7–10, 2015a, Barcelona, Spain. Platform presentation number 190.
  • Hauser S, Comi G, Hartung HP et al.: Baseline demographics anddisease characteristics from OPERA I and II, two phase III trials evaluating ocrelizumab in patients with relapsing multiple sclerosis. Presented at the American Academy of Neurology’s 67th Annual Meeting; April 18–25, 2015b; Washington, DC. P7.201.
  • Lisak RP, Benjamins JA, Nedelkoska L et al.: Secretory products of multiple sclerosis B cells are cytotoxic to oligodendroglia in vitro. J Neuroimmunol 2012; 246: 85–95.
  • Magliozzi R, Howell OW, Reeves C et al.: A gradient of neuronal loss and meningeal inflammation in multiple sclerosis. Ann Neurol 2010; 68: 477–493.
  • Montalban X, Hemmer B, Rammohan K et al.: Baseline demographics and disease characteristics from ORATORIO, a phase III trial evaluating ocrelizumab in patients with primary progressive multiple sclerosis. Presented at the American Academy of Neurology’s 67th Annual Meeting; April 18–25, 2015a; Washington, DC. P7.017.
  • Montalban X, Hemmer B, Rammohan K et al.; on behalf of the ORATORIO Clinical Investigators: Efficacy and safety of ocrelizumab in primary progressive multiple sclerosis – results of the placebo-controlled, double-blind, Phase III ORATORIO study. Presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis, October 7–10, 2015b, Barcelona, Spain. Platform presentation number 228.
  • Polman CH, Reingold SC, Edan G et al.: Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria.” Ann Neurol 2005; 58: 840–846.
  • 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: 164–174.
  • Simon JH: MRI outcomes in the diagnosis and disease course of multiple sclerosis. Handb Clin Neurol 2014; 122: 405–425.
Document Type
review
Publication order reference
Identifiers
YADDA identifier
bwmeta1.element.psjd-e99bb167-9acf-402b-b805-2c98ee5feb6f
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