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Review

Anti-CD20 monoclonal antibodies in multiple sclerosis

&
Pages 359-371 | Received 03 May 2016, Accepted 04 Oct 2016, Published online: 21 Oct 2016

References

  • Leray E, Moreau T, Fromont A, et al. Epidemiology of multiple sclerosis. Rev Neurol (Paris). 2016;172(1):3–13.
  • Krumbholz M, Meinl E. B cells in MS and NMO: pathogenesis and therapy. Semin Immunopathol. 2014;36(3):339–350.
  • Faissner S, Nikolayczik J, Chan A, et al. Plasmapheresis and immunoadsorption in patients with steroid refractory multiple sclerosis relapses. J Neurol. 2016;263(6):1092–1098.
  • Cortese I, Chaudhry V, So YT, et al. Evidence-based guideline update: plasmapheresis in neurologic disorders: report of the therapeutics and technology assessment subcommittee of the American Academy of Neurology. Neurology. 2011 Jan 18;76(3):294–300.
  • Kappos L, Hartung HP, Freedman MS, et al. Atacicept in multiple sclerosis (ATAMS): a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Neurol. 2014;13(4):353–363.
  • Beauchemin P, Carruthers R. MS arising during Tocilizumab therapy for rheumatoid arthritis. Mult Scler. 2016;22(2):254–256.
  • Sato H, Kabayashi D, Abe A, et al. Tocilizumab treatment safety in rheumatoid arthritis in a patient with multiple sclerosis: a case report. BMC Res Notes. 2014;7:641.
  • Hauser S, Waubant E, Arnold DL, et al. B-cell depletion with rituximab in relapsing remitting multiple sclerosis. N Engl J Med. 2008;358(7):676–688.
  • Kappos L, Li D, Calabresi PA, et al. Ocrelizumab in relapsing-remitting multiple sclerosis: a phase II, randomised, placebo-controlled, multicentre trial. Lancet. 2011;378(9805):1779–1787.
  • 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.
  • Piątosa B, Wolska-Kuśnierz B, Pac M, et al. B cell subsets in healthy children: reference values for evaluation of B cell maturation process in peripheral blood. Cytometry. 2010;78B:372–381.
  • Harwood NE, Batista FD. Early events in B cell activation. Annu Rev Immunol. 2010;28:185–210.
  • Yuseff MI, Pierobon P, Reversat A, et al. How B cells capture, process and present antigens: a crucial role for cell polarity. Nat Rev Immunol. 2013;13(7):475–486.
  • Seifert M, Küppers R. Human memory B cells. Leukemia. 2016 Aug 26. doi:10.1038/leu.2016.226. [ Epub ahead of print].
  • Leandro MJ. B-cell subpopulations in humans and their differential susceptibility to depletion with anti-CD20 monoclonal antibodies. Arthritis Res Ther. 2013;15(Suppl 1):S3.
  • Stolp J, Turka LA, Wood KJ. B cells with immune-regulating function in transplantation. Nat Rev Nephrol. 2014;10(7):389–397.
  • Fillatreau S, Sweenie CH, McGeachy MJ, et al. B cells regulate autoimmunity by provision of IL-10. Nat Immunol. 2002;3(10):944–950.
  • 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.
  • Kessel A, Haj T, Peri R, et al. Human CD19+CD25high B regulatory cells suppress proliferation of CD4+ T cells and enhance Foxp3 and CTLA-4 expression in T-regulatory cells. Autoimmun Rev. 2012;11(9):670–677.
  • Kabat EA, Moore DH, Landow H. An electrophoretic study of the protein components in cerebrospinal fluid and their relationship to the serum proteins. J Clin Invest. 1942;21(5):571–577.
  • Villar LM, Masjuan J, González-Porqué P, et al. Intrathecal IgM synthesis predicts the onset of new relapses and a worse disease course in MS. Neurology. 2002;59(4):555–559.
  • Willis SN, Stathopoulos P, Chastre A, et al. Investigating the antigen specificity of multiple sclerosis central nervous system-derived immunoglobulins. Front Immunol. 2015;6:600.
  • Disanto G, Morahan JM, Barnett MH, et al. The evidence for a role of B cells in multiple sclerosis. Neurology. 2012;78(11):823–832.
  • Von Büdingen HC, Tanuma N, Villoslada P, et al. Immune responses against the myelin oligodendrocyte glycoprotein in experimentalautoimmune demyelination. J Clin Immunol. 2001;21(3):155–170.
  • Zhou D, Srivastava R, Nessler S, et al. Identification of a pathogenic antibody response to native myelin oligodendrocyte glycoprotein. PNAS. 2006;103(50):19057–19062.
  • Meinl E, Krumbholz M, Hohlfeld R. B lineage cells in the inflammatory central nervous system environment: migration, maintenance, local antibody production, and therapeutic modulation. Ann Neurol. 2006;59:880–892.
  • Hottenrott T, Dersch R, Berger B, et al. The intrathecal, polyspecific antiviral immune response in neurosarcoidosis, acute disseminated encephalomyelitis and autoimmune encephalitis compared to multiple sclerosis in a tertiary hospital cohort. Fluids Barriers CNS. 2015;12:27.
  • Jarius S, Eichhorn P, Jacobi C, et al. The intrathecal, polyspecific antiviral immune response: specific for MS or a general marker of CNS autoimmunity? J Neurol Sci. 2009;280(1–2):98–100.
  • Cepok S, Rosche B, Grummel V, et al. Short-lived plasma blasts are the main B cell effector subset during the course of multiple sclerosis. Brain. 2005;128:1667–1676.
  • Cepok S, Jacobsen M, Schock S, et al. Patterns of cerebrospinal fluid pathology correlate with disease progression in multiple sclerosis. Brain. 2001;124:2169–2176.
  • Elliott C, Lindner M, Arthur A, et al. Functional identification of pathogenic autoantibody responses in patients with multiple sclerosis. Brain. 2012;135(6):1819–1833.
  • Lucchinetti CF, Bruck W, Parisi JE, et al. Heterogenity of multiple sclerosis lesions: implication for the pathogenesis of demyelination. Ann Neurol. 2001;47:707–717.
  • Barnett MH, Parratt JD, Cho ES, et al. Immunoglobulins and complement in postmortem multiple sclerosis tissue. Ann Neurol. 2009;65:32–46.
  • Molnarfi N, Schulze-Topphoff U, Weber MS, et al. MHC class II-dependent B cell APC function is required for induction of CNS autoimmunity independent of myelin-specific antibodies. J Exp Med. 2013;210(13):2921–2937.
  • 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 CNS autoimmunity. Ann Neurol. 2010;68(3):369–383.
  • Rodriguez-Pinto D. B cells as antigen presenting cells. Cell Immunol. 2005;238(2):67–75.
  • Harp CT, Ireland S, Davis LS, et al. Memory B cells from a subset of treatment-naïve relapsing-remitting multiple sclerosis patients elicit CD4(+) T-cell proliferation and IFN-γ production in response to myelin basic protein and myelin oligodendrocyte glycoprotein. Eur J Immunol. 2010;40:2942–2956.
  • Sellebjerg F, Jensen J, Ryder LP, et al. Costimulatory CD80 (B7-1) and CD86 (B7-2) on cerebrospinal fluid cells in multiple sclerosis. J Neuroimmunol. 1998;84:179–187.
  • Bao Y, Cao X. The immune potential and immunopathology of cytokine-producing Bcell subsets: a comprehensive review. J Autoimmun. 2014;55:10e23.
  • Ma N, Xing C, Xiao H. BAFF suppresses IL-15 expresion in B cells. J Immunol. 2014;192(9):4192–4201.
  • Serada S, Fujimoto M, Mihara M, et al. IL-6 blockade inhibits the induction of myelin antigen-specific Th17 cells and Th1 cells in experimental autoimmune encephalomyelitis. Proc Natl Acad Sci USA. 2008;105(26):9041–9046.
  • Barr TA, Shen P, Brown S, et al. B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6-producing B cells. J Exp Med. 2012;209(5):1001–1010.
  • 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.
  • Kinnunen T, Chamberlain N, Morbach H, et al. Specific peripheral B cell tolerance defects in patients with multiple sclerosis. J Clin Invest. 2013;123:2737–2741.
  • Duddy M, Niino M, Adatia F, et al. Distinct effector cytokine profiles of memory and naïve human B cell subsets and implication in multiple sclerosis. J Immunol. 2007;178(10):6092–6099.
  • Gomez-Nicola D, Spagnolo A, Guaza C, et al. Aggravated experimental autoimmune encephalomyelitis in IL-15 knockout mice. Exp Neurol. 2010;222(2):235–242.
  • Rentzos M, Cambouri C, Rombos A, et al. IL-15 is elevated in serum and cerebrospinal fluid of patients with multiple sclerosis. J Neurol Sci. 2006;241(1–2):25–29.
  • 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.
  • Lucchinetti CF, Popescu BFG, Bunyan RF, et al. Inflammatory cortical demyelination in early multiple sclerosis. N Engl J Med. 2011;365(23):2188–2197.
  • 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;130(4):1089–1104.
  • Choi SR, Howell OW, Carassiti D, et al. Meningeal inflammation plays a role in the pathology of primary progressive multiple sclerosis. Brain. 2012;135(10):2925–2937.
  • 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.
  • Haider L, Zrzavy T, Hametner S, et al. The topograpy of demyelination and neurodegeneration in the multiple sclerosis brain. Brain. 2016;136:807–815.
  • Blauth K, Owens GP, Bennett JL. The ins and outs of B cells in multiple sclerosis. Front Immunol. 2015;6:1–7.
  • Fomby P, Cherlin AJ. Inflammatory cell trafficking across the blood-brain barrier (BBB): chemokine regulation and in vitro models. Immunol Rev. 2012;248(1):228–239.
  • Krumbholz M, Theil D, Derfuss T, et al. BAFF is produced by astrocytes and up-regulated in multiple sclerosis lesions and primary central nervous system lymphoma. J Exp Med. 2005;201(2):195–200.
  • Haugen M, Frederiksen JL, Degn M. B cell follicle-like structures in multiple sclerosis—with focus on the role of B cell activating factor. J Neuroimmunol. 2014;273:1–7.
  • Kowarik MC, Cepok S, Sellner J, et al. CXCL13 is the major determinant for B cell recruitment to the CSF during neuroinflammation. J Neuroinflammation. 2012;9(1):93.
  • Magliozzi R, Columba-Cabezas S, Serafini B. Intracerebral expression of CXCL13 and BAFF is accompanied by formation of lymphoid follicle-like structures in the meninges of mice with relapsing experimental autoimmune encephalomyelitis. J Neuroimmunol. 2004;148:11–23.
  • Sellebjerg F, Bornsen L, Khademi M, et al. Increased cerebrospinal fluid concentrations of the chemokine CXCL13 in active MS. Neurology. 2009;73(23):2003–2010.
  • Ragheb S, Li Y, Simon K, et al. Multiple sclerosis: BAFF and CXCL13 in cerebrospinal fluid. Mult Scler. 2011;17(7):819–829.
  • Brettschneider J, Czerwoniak A, Senel M, et al. The chemokine CXCL13 is a prognostic marker in clinically isolated syndrome (CIS). PLoS One. 2010;5(8):8–13.
  • Khademiv M, Kockum I, Andersson ML. Cerebrospinal fluid CXCL13 in multiple sclerosis: a suggestive prognostic marker for the disease course. Mult Scler. 2010;17(3):335–343.
  • Ferraro D, Galli V, Vitetta F, et al. Cerebrospinal fluid CXCL13 in clinically isolated syndrome patients: association with oligoclonal IgM bands and prediction of multiple sclerosis diagnosis. J Neuroimmunol. 2015;283(2015):64–69.
  • Serafini B, Severa M, Columba-Cabezas S. Epstein-Barr virus latent infection and BAFF expression in B cells in the multiple sclerosis brain: implications for viral persistence and intrathecal B-cell activation. J Neuropathol Exp Neurol. 2010;69(7):677–693.
  • Sargsyan SA, Shearer AJ, Ritchie AM, et al. Absence of Epstein-Barr virus in the brain and CSF of patients with multiple sclerosis. Neurology. 2010;74(14):1127–1135.
  • Peferoen LAN, Lamers F, Lodder LNR, et al. Epstein Barr virus is not a characteristic feature in the central nervous system in established multiple sclerosis. Brain. 2010;133(5):e137.
  • Lovato L, Willis SN, Rodig SJ, et al. Related B cell clones populate the meninges and parenchyma of patients with multiple sclerosis. Brain. 2011;134(2):534–541.
  • Von Büdingen H-C, Tc K, Sirota M, et al. B cell exchange across the blood-brain barrier in multiple sclerosis. J Clin Invest. 2012;122(12):24–28.
  • Beers SA, Chan CHT, French RR, et al. CD20 as a target for therapeutic type I and II monoclonal antibodies. Semin Hematol. 2010;47:107–114.
  • Tipton TR, Roghanian A, Oldham RJ, et al. Antigenic modulation limits the effector cell mechanisms employed by type I anti-CD20 monoclonal antibodies. Blood. 2015;125(12):1901–1909.
  • Boross P, Leusen JH. Mechanisms of action of CD20 antibodies. Am J Cancer Res. 2012;2(6):676–690.
  • Weiskopf K, Weissman IL. Macrophages are critical effectors of antibody therapies for cancer. mABs. 2015;7(2):303–310.
  • Beum PV, Lindorfer M, Beurskens F, et al. Complement activation on B lymphocytes opsonized with rituximab or ofatumumab produces substantial changes in membrane structure preceding cell lysis. J Immunol. 2008;181(1):822–832.
  • Renaudineau Y, Devauchelle-Pensec V, Hanrotel C, et al. Monoclonal anti-CD20 antibodies: mechanisms of action and monitoring of biological effects. Jt Bone Spine. 2009;76(5):458–463.
  • vanMeerten T, Hagenbeek A. CD20-Targeted therapy: the next generation of antibodies. Semin Hematol. 2010;47(2):199–210.
  • Cragg MS, Morgan SM, Chan HTC, et al. Complement-mediated lysis by anti-CD20 mAb correlates with segregation into lipid rafts. Blood. 2003;101(3):1045–1052.
  • Ghesquières H, Larrabee BR, Haioun C, et al. FCGR3A/2A polymorphisms and diffuse large B-cell lymphoma outcome treated with immunochemo therapy: a meta-analysis on 1134 patients from two prospective cohorts. Hematol oncol 2010. doi:10.1002/hon.2305. [Epub ahead of print].
  • Reff ME, Carner K, Chambers KS, et al. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood. 1994;83:435–445.
  • Official information about of indications and usage of rituximab by FDA. Label approved on dec 2014. Retrieved oct 2016 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/103705s5432lbl.pdf
  • Artron G, Dacheux L, Salles G, et al. Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor Fc gamma RIII a gene. Blood. 2002;99(3):754–758.
  • Kim SH, Jeong IH, Hyun JW, et al. Treatment outcomes with rituximab in 100 patients with neuromyelitis optica: influence of FCGR3A polymorphisms on the therapeutic response to rituximab. JAMA Neurol. 2015;72(9):989–995.
  • Lee YH, Bae SC, Song GG. Functional FCGR3A 158 V/F and IL-6-174 C/G polymorphisms predict response to biologic therapy in patients with rheumatoid arthritis: a meta-analysis. Rheumatol Int. 2014;34(10):1409–1415.
  • Kobayashi H, Matsunaga Y, Uchiyama Y, et al. Novel humanized anti-CD20 antibody BM-ca binds to a unique epitope and exerts stronger cellular activity than others. Cancer Med. 2013;2(2):130–143.
  • Mössner E, Brünker P, Moser S. Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell–mediated B-cell cytotoxicity. Blood. 2010;22:4393–4402.
  • De Jong RN, Beurskens FJ, Verploegen S, et al. A novel platform for the potentiation of therapeutic antibodies based on antigen-dependent formation of IgG hexamers at the cell surface. PLoS Biol. 2016;14(1):e1002344.
  • Klein C, Lammens A, Schifer W, et al. Epitope interactions of monoclonal antibodies targeting CD20 and their relationship to functional properties. MAbs. 2013;5(1):22–33.
  • Zhang B. Ofatumumab. mAbs. 2009;1(4):326–331.
  • Kalaycio ME, George Negrea O, Allen SL, et al. Subcutaneous injections of low doses of humanized anti-CD20 veltuzumab: a phase I study in chronic lymphocytic leukemia. Leuk Lymphoma. 2016;57(4):803–811.
  • Awasthi A, Ayello J, Van de Ven C, et al. Obinutuzumab (GA101) compared to rituximab significantly enhances cell death and antibody-dependent cytotoxicity and improves overall survival against CD20(+) rituximab-sensitive/-resistant Burkitt lymphoma (BL) and precursor B-acute lymphoblastic leukaemia (pre-B-ALL): potential targeted therapy in patients with poor risk CD20(+) BL and pre-B-ALL. Br J Haematol. 2015;171(5):763–775.
  • Gabellier L, Cartron G. Obinutuzumab for relapsed or refractory indolent non-Hodgkin’s lymphomas. TherAdvHematol. 2016 Apr;7(2):85–93.
  • Leonard JP, Gregory SA, Smith H, et al. CHOP chemotherapy followed by tositumomab and iodine-131 tositumomab for previously untreated diffuse large B-cell lymphoma. Clin Lymphoma Myeloma Leuk. 2016;16(4):191–196.
  • Bar-Or A, Calabresi PAJ, Arnold D, et al. Rituximab in relapsing- remitting multiple sclerosis: a 72-week, open-label, phase i trial. Ann Neurol. 2008;63:395–400.
  • 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.
  • Hawker K, O’Connor P, Freedman MS, et al. Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebo-controlled multicentre trial. Ann Neurol. 2009;66(4):460–471.
  • Quan C, ZhangBao J, Lu J, et al. The immune balance between memory and regulatory B cells in NMO and the changes of the balance after methylprednisolone or rituximab therapy. J Neuroimmunol. 2015;282:45–53.
  • Maurer MA, Rakocevic G, Leung CS, et al. Rituximab induces sustained reduction of pathogenic B cells in patients with peripheral nervous system autoimmunity. J Clin Invest. 2012;122:1393–1402.
  • Pers JO, Daridon C, Bendaoud B, et al. B-cell depletion and repopulation in autoimmune diseases. Clinic Rev Allerg Immunol. 2008;34:50–55.
  • Anolik JH, Barnard J, Owen T, et al. Delayed memory B cell recovery in peripheral blood and lymphoid tissue in systemic lupus erythematosus after B cell depletion therapy. Arthritis Rheum. 2007;56:3044–3056.
  • Palanichamy A, Jahn S, Nickles D, et al. Rituximab efficiently depletes increased CD20-expressing T cells in multiple sclerosis patients. J Immunol. 2014;193:580–586.
  • Tokunaga M, Saito K, Kawabata D, et al. Efficacy of rituximab (anti-CD20) for refractory systemic lupus erythematosus involving the central nervous system. Ann Rheum Dis. 2007;66:470–477.
  • Vallerskog T, Gunnarsson I, Widhe M, et al. Treatment with rituximab affects both the cellular and the humoral arm of the immune system in patients with SLE. Clin Immunol. 2007;122:62–74.
  • Cross AH, Stark JL, Lauber J, et al. Rituximab reduces B cells and T cells in cerebrospinal fluid of multiple sclerosis patients. J Neuroimmunol. 2006;180:63–70.
  • Martin MP, Cravens PD, Winger R, et al. Depletion of B lymphocytes from cerebral perivascular spaces by rituximab. Arch Neurol. 2009;66(8):1016–1020.
  • Naismith RT, Piccio L, Lyons J, et al. Rituximab add-on therapy for breakthrough relapsing multiple sclerosis. Neurology. 2010;74(23):1860–1867.
  • Petereit HF, Rubbert-Roth A. Rituximab levels in cerebrospinal fluid of patients with neurological autoimmune disorders. Mult Scler. 2009;15:189–192.
  • Rubenstein JL, Combs D, Rosenberg J, et al. Rituximab therapy for CNS lymphomas: targeting the leptomeningeal compartment. Blood. 2003;101(2):466–468.
  • Lehmann-Horn K, Kinzel S, Feldmann L, et al. Intrathecal anti-CD20 efficiently depletes meningeal B cells in CNS autoimmunity. Ann ClinTransl Neurol. 2014;1(7):490–496.
  • Svenningsson A, Bergman J, Dring A, et al. Rapid depletion of B lymphocytes by ultra-low-dose rituximab delivered intrathecally. Neurol Neuroimmunol Neuroinflamm. 2015;2;e79.
  • Gredler V, Mader S, Schanda K, et al. Clinical and immunological follow-up of B-cell depleting therapy in CNS demyelinating diseases. J Neurol Sci. 2013;328:77–82.
  • Lavie F, Micelli-Richard C, Ittah M, et al. Increase of B cell-activating factor of the TNF family (BAFF) after rituximab treatment: insights into a new regulating system of BAFF production. Ann Rheum Dis. 2007;66:700–702.
  • Topping J, Dobson R, Lapin S, et al. The effects of intrathecal rituximab on biomarkers in multiple sclerosis. Mult Scler Relat Disord. 2016;6:49–53.
  • De Flon P, Gunnarsson M, Laurell K, et al. Reduced inflammation in relapsing-remitting multiple sclerosis after therapy switch to rituximab. Neurology. 2016;87:141–147.
  • Tony H-P, Burmester G, Schulze-Koops H, et al. Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID). Arthritis Res Ther. 2011;13(3):R75.
  • Clifford DB, Ances B, Costello C, et al. Rituximab-associated progressive multifocal leukoencephalopathy in rheumatoid arthritis. Arch Neurol. 2011;68(9):1156–1164.
  • Mozessohn L, Chan KK, Feld JJ, et al. Hepatitis B reactivation in HBsAg-negative/HBcAb-positive patients receiving rituximab for lymphoma: a meta-analysis. J Viral Hepat. 2015;22(10):842–849.
  • Lutt JR, Pisculli ML, Weinblatt ME, et al. Severe non tuberculous mycobacterial infection in 2 patients receiving rituximab for refractory myositis. J Rheumatol. 2008;35(8):1683–1685.
  • Komori M, Lin YC, Cortese I, et al. Insufficient disease inhibition by intrathecal rituximab in progressive multiple sclerosis. Ann ClinTransl Neurol. 2016;3(3):166–179.
  • Kappos L, Li D, Calabresi PA, et al. Long-term safety and efficacy of ocrelizumab in patients with relapsing-remitting multiple sclerosis:Week 144 results of a Phase II, randomised, multicentre trial. Poster 362 presented at the American Academy of Neurology (AAN) 65th Annual Meeting 2013. Retrieved from http://www.medscape.com/viewarticle/781671 and http://www.adelphigroup.com/acl/11-10-12/poster1.pdf
  • Fyfe I. Ocrelizumab excites ECTRIMS. Nat Rev Neurol. Advance online publication 3 Nov 2015. doi:10.1038/nrneurol.2015.210
  • Hauser SL, Comi GC, Hartung H-P, et al. 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. 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis 2015. Platform presentation number 190. Retrieved from http://www.roche.com/dam/jcr:819946d8-6c14-45e1-81f4-bfd438816321/en/irp151012.pdf
  • Montalban X, Hemmer B, Rammohan K et al. A randomized, double-blind, parallel-group, placebo-controlled phase iii trial to evaluate efficacy and safety of ocrelizumab in primary progressive multiple sclerosis. Poster P.023. Presented at the American Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2016; 2016 Feb 18–20; New Orleans, LA.
  • Sorensen PS, Kavanagh ST, Austin DJ et al. Follow-up data from the mirror study: a dose-ranging study of subcutaneous ofatumumab in subjects with relapsing-remitting multiple sclerosis. Poster 048 Presented at the 2014 Joint ACTRIMS-ECTRIMS Meeting (MS Boston 2014); 2014 Sep 10–13;

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