Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
CNS Drugs
Published in: CNS Drugs 1/2012

01-01-2012 | Review Article

Monoclonal Antibodies and Recombinant Immunoglobulins for the Treatment of Multiple Sclerosis

Authors: Henrik Gensicke, David Leppert, Özgür Yaldizli, Raija L. P. Lindberg, Matthias Mehling, Prof. Ludwig Kappos, Jens Kuhle

Published in: CNS Drugs | Issue 1/2012

Login to get access

Abstract

Multiple sclerosis (MS) is an inflammatory and degenerative disease leading to demyelination and axonal damage in the CNS. Autoimmunity plays a central role in MS pathogenesis. Per definition, monoclonal antibodies are recombinant biological compounds with a well defined target, thus carrying the promise of targeting pathogenic cells or molecules with high specificity, avoiding undesired off-target effects. Natalizumab was the first monoclonal antibody to be approved for the treatment of MS. Several other monoclonal antibodies are in development and have demonstrated promising efficacy in phase II studies. They can be categorized according to their mode of action into compounds targeting (i) leukocyte migration into the CNS (natalizumab); (ii) cytolytic antibodies (rituximab, ocrelizumab, ofatumumab, alemtuzumab); or (iii) antibodies and recombinant proteins targeting cytokines and chemokines and their receptors (daclizumab, ustekinumab, atacicept, tabalumab [Ly-2127399], secukinumab [AIN457]). In this review, we discuss the specific molecular targets, clinical efficacy and safety of these compounds and discuss criteria to anticipate the position of monoclonal antibodies in the diversifying armamentarium of MS therapy in the coming years.
Literature
1.
2.
Pugliatti M, Rosati G, Carton H, et al. The epidemiology of multiple sclerosis in Europe. Eur J Neurol 2006; 13(7): 700–22PubMedCrossRef
3.
Rovaris M, Confavreux C, Furlan R, et al. Secondary progressive multiple sclerosis: current knowledge and future challenges. Lancet Neurol 2006; 5(4): 343–54PubMedCrossRef
4.
5.
Girouard N, Theoret G. Management strategies for improving the tolerability of interferons in the treatment of multiple sclerosis. Can J Neurosci Nurs 2008; 30(4): 18–25PubMed
6.
Leary SM, Miller DH, Stevenson VL, et al. Interferon beta-1a in primary progressive MS: an exploratory, randomized, controlled trial. Neurology 2003; 60(1): 44–51PubMedCrossRef
7.
Montalban X. Overview of European pilot study of interferon beta-1b in primary progressive multiple sclerosis. Mult Scler 2004; 10 Suppl. 1: S62; discussion 62-4PubMedCrossRef
8.
Wolinsky JS, Shochat T, Weiss S, et al. Glatiramer acetate treatment in PPMS: why males appear to respond favorably. J Neurol Sci 2009; 286(1-2): 92–8PubMedCrossRef
9.
Wolinsky JS. The PROMiSe trial: baseline data review and progress report. Mult Scler 2004; 10 Suppl. 1: S65–71; discussion S71-2PubMedCrossRef
10.
Cohen JA, Cutter GR, Fischer JS, et al. Benefit of interferon beta-1a on MSFC progression in secondary progressive MS. Neurology 2002; 59(5): 679–87PubMedCrossRef
11.
Randomized controlled trial of interferon-beta-1a in secondary progressive MS: clinical results. Neurology 2001; 56 (11): 1496-504
12.
Panitch H, Miller A, Paty D, et al. Interferon beta-1b in secondary progressive MS: results from a 3-year controlled study. Neurology 2004; 63(10): 1788–95PubMedCrossRef
13.
European Study Group on interferon beta-1b in secondary progressive MS: placebo-controlled multicentre randomised trial of interferon beta-1b in treatment of secondary progressive multiple sclerosis. Lancet 1998; 352 (9139): 1491-7
14.
Loo L, Robinson MK, Adams GP. Antibody engineering principles and applications. Cancer J 2008; 14(3): 149–53PubMedCrossRef
15.
Calogiuri G, Ventura MT, Mason L, et al. Hypersensitivity reactions to last generation chimeric, humanized [correction of umanized] and human recombinant monoclonal antibodies for therapeutic use. Curr Pharm Des 2008; 14(27): 2883–91PubMedCrossRef
16.
Mechetner E. Development and characterization of mouse hybridomas. Methods Mol Biol 2007; 378: 1–13PubMedCrossRef
17.
Hohlfeld R, Wekerle H. Drug insight: using monoclonal antibodies to treat multiple sclerosis. Nat Clin Pract Neurol 2005; 1(1): 34–44PubMedCrossRef
18.
Monaco S, Turri E, Zanusso G, et al. Treatment of inflammatory and paraproteinemic neuropathies. Curr Drug Targets Immune Endocr Metabol Disord 2004; 4(2): 141–8PubMedCrossRef
19.
Briani C, Zara G, Zambello R, et al. Rituximab-responsive CIDP [letter]. Eur J Neurol 2004; 11(11): 788PubMedCrossRef
20.
Finsterer J. Treatment of immune-mediated, dysimmune neuropathies. Acta Neurol Scand 2005; 112(2): 115–25PubMedCrossRef
21.
Kilidireas C, Anagnostopoulos A, Karandreas N, et al. Rituximab therapy in monoclonal IgM-related neuropathies. Leuk Lymphoma 2006; 47(5): 859–64PubMedCrossRef
22.
Gorson KC, Natarajan N, Ropper AH, et al. Rituximab treatment in patients with IVIg-dependent immune poly-neuropathy: a prospective pilot trial. Muscle Nerve 2007; 35(1): 66–9PubMedCrossRef
23.
Pranzatelli MR, Tate ED, Travelstead AL, et al. Immunologic and clinical responses to rituximab in a child with opsoclonus-myoclonus syndrome. Pediatrics 2005; 115(1): e115–9PubMed
24.
Burke MJ, Cohn SL. Rituximab for treatment of opsoclonus-myoclonus syndrome in neuroblastoma. Pediatr Blood Cancer 2008; 50(3): 679–80PubMedCrossRef
25.
Pranzatelli MR, Tate ED, Travelstead AL, et al. Rituximab (anti-CD20) adjunctive therapy for opsoclonusmyoclonus syndrome. J Pediatr Hematol Oncol 2006; 28(9): 585–93PubMedCrossRef
26.
Ertle F, Behnisch W, Al Mulla NA, et al. Treatment of neuroblastoma-related opsoclonus-myoclonus-ataxia syndrome with high-dose dexamethasone pulses. Pediatr Blood Cancer 2008; 50(3): 683–7PubMedCrossRef
27.
Leen WG, Weemaes CM, Verbeek MM, et al. Rituximab and intravenous immunoglobulins for relapsing post-infectious opsoclonus-myoclonus syndrome. Pediatr Neurol 2008; 39(3): 213–7PubMedCrossRef
28.
Corapcioglu F, Mutlu H, Kara B, et al. Response to rituximab and prednisolone for opsoclonus-myoclonusataxia syndrome in a child with ganglioneuroblastoma. Pediatr Hematol Oncol 2008; 25(8): 756–61PubMedCrossRef
29.
Pranzatelli MR, Tate ED, Travelstead AL, et al. Long-term cerebrospinal fluid and blood lymphocyte dynamics after rituximab for pediatric opsoclonus-myoclonus. J Clin Immunol 2010; 30(1): 106–13PubMedCrossRef
30.
Pranzatelli MR, Tate ED, Swan JA, et al. B cell depletion therapy for new-onset opsoclonus-myoclonus. Mov Disord 2010; 25(2): 238–42PubMedCrossRef
31.
Pranzatelli MR, Tate ED, Verhulst SJ, et al. Pediatric dosing of rituximab revisited: serum concentrations in opsoclonus-myoclonus syndrome. J Pediatr Hematol Oncol 2010; 32(5): e167–72PubMedCrossRef
32.
Bell J, Moran C, Blatt J. Response to rituximab in a child with neuroblastoma and opsoclonus-myoclonus. Pediatr Blood Cancer 2008; 50(2): 370–1PubMedCrossRef
33.
Baek WS, Bashey A, Sheean GL. Complete remission induced by rituximab in refractory, seronegative, muscle-specific, kinase-positive myasthenia gravis [letter]. J Neurol Neurosurg Psychiatry 2007; 78(7): 771PubMedCrossRef
34.
Zebardast N, Patwa HS, Novella SP, et al. Rituximab in the management of refractory myasthenia gravis. Muscle Nerve 2010; 41(3): 375–8PubMedCrossRef
35.
Lindberg C, Bokarewa M. Rituximab for severe myasthenia gravis: experience from five patients. Acta Neurol Scand 2010; 122(4): 225–8PubMedCrossRef
36.
Maddison P, McConville J, Farrugia ME, et al. The use of rituximab in myasthenia gravis and Lambert-Eaton myasthenic syndrome. J Neurol Neurosurg Psychiatry 2010; 82(6): 671–3PubMedCrossRef
37.
Hain B, Jordan K, Deschauer M, et al. Successful treatment of MuSK antibody-positive myasthenia gravis with rituximab. Muscle Nerve 2006; 33(4): 575–80PubMedCrossRef
38.
Cree BA, Lamb S, Morgan K, et al. An open label study of the effects of rituximab in neuromyelitis optica. Neurology 2005; 64(7): 1270–2PubMedCrossRef
39.
Capobianco M, Malucchi S, di Sapio A, et al. Variable responses to rituximab treatment in neuromyelitis optica (Devic’s disease). Neurol Sci 2007; 28(4): 209–11PubMedCrossRef
40.
Jacob A, Weinshenker BG, Violich I, et al. Treatment of neuromyelitis optica with rituximab: retrospective analysis of 25 patients. Arch Neurol 2008; 65(11): 1443–8PubMedCrossRef
41.
Baker MR, Das M, Isaacs J, et al. Treatment of stiff person syndrome with rituximab. J Neurol Neurosurg Psychiatry 2005; 76(7): 999–1001PubMedCrossRef
42.
Venhoff N, Rizzi M, Salzer U, et al. Monozygotic twins with stiff person syndrome and autoimmune thyroiditis: rituximab inefficacy in a double-blind, randomised, placebo controlled crossover study. Ann Rheum Dis 2009; 68(9): 1506–8PubMedCrossRef
43.
Dupond JL, Essalmi L, Gil H, et al. Rituximab treatment of stiff-person syndrome in a patient with thymoma, diabetes mellitus and autoimmune thyroiditis. J Clin Neurosci 2010; 17(3): 389–91PubMedCrossRef
44.
Katoh N, Matsuda M, Ishii W, et al. Successful treatment with rituximab in a patient with stiff-person syndrome complicated by dysthyroid ophthalmopathy. Intern Med 2010; 49(3): 237–41PubMedCrossRef
45.
Bacorro EA, Tehrani R. Stiff-person syndrome: persistent elevation of glutamic acid decarboxylase antibodies despite successful treatment with rituximab. J Clin Rheumatol 2010; 16(5): 237–9PubMedCrossRef
46.
Dalakas MC, Rakocevic G, Schmidt J, et al. Effect of alemtuzumab (CAMPATH 1-H) in patients with inclusion-body myositis. Brain 2009; 132 (Pt 6): 1536–44PubMedCrossRef
47.
48.
Berlin C, Berg EL, Briskin MJ, et al. Alpha 4 beta 7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1. Cell 1993; 74(1): 185–95PubMedCrossRef
49.
Rudick RA, Sandrock A. Natalizumab: alpha 4-integrin antagonist selective adhesion molecule inhibitors for MS. Expert Rev Neurother 2004; 4(4): 571–80PubMedCrossRef
50.
del Pilar MM, Cravens PD, Winger R, et al. Decrease in the numbers of dendritic cells and CD4+ T cells in cerebral perivascular spaces due to natalizumab. Arch Neurol 2008; 65(12): 1596–603CrossRef
51.
Steinman L. Blocking adhesion molecules as therapy for multiple sclerosis: natalizumab. Nat Rev Drug Discov 2005; 4(6): 510–8PubMedCrossRef
52.
Niino M, Bodner C, Simard ML, et al. Natalizumab effects on immune cell responses in multiple sclerosis. Ann Neurol 2006; 59(5): 748–54PubMedCrossRef
53.
Tchilian EZ, Owen JJ, Jenkinson EJ. Anti-alpha 4 integrin antibody induces apoptosis in murine thymocytes and staphylococcal enterotoxin B-activated lymph node T cells. Immunology 1997; 92(3): 321–7PubMedCrossRef
54.
Lindberg RL, Achtnichts L, Hoffmann F, et al. Natalizumab alters transcriptional expression profiles of blood cell subpopulations of multiple sclerosis patients. J Neuroimmunol 2008; 194(1-2): 153–64PubMedCrossRef
55.
Stuve O, Gold R, Chan A, et al. alpha4-Integrin antagonism with natalizumab: effects and adverse effects. J Neurol 2008; 255 Suppl. 6: 58–65PubMedCrossRef
56.
Yednock TA, Cannon C, Fritz LC, et al. Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin. Nature 1992; 356(6364): 63–6PubMedCrossRef
57.
Tubridy N, Behan PO, Capildeo R, et al. The effect of anti-alpha4 integrin antibody on brain lesion activity in MS: the UK Antegren Study Group. Neurology 1999; 53(3): 466–72PubMedCrossRef
58.
Miller DH, Khan OA, Sheremata WA, et al. A controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2003; 348(1): 15–23PubMedCrossRef
59.
Goodman AD, Rossman H, Bar-Or A, et al. GLANCE: results of a phase 2, randomized, double-blind, placebo-controlled study. Neurology 2009; 72(9): 806–12PubMedCrossRef
60.
Rudick RA, Stuart WH, Calabresi PA, et al. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med 2006; 354(9): 911–23PubMedCrossRef
61.
Polman CH, O’Connor PW, Havrdova E, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006; 354(9): 899–910PubMedCrossRef
62.
Bar-Or A, Calabresi PA, Arnold D, et al. Rituximab in relapsing-remitting multiple sclerosis: a 72-week, open-label, phase I trial. Ann Neurol 2008; 63(3): 395–400PubMedCrossRef
63.
Hauser SL, Waubant E, Arnold DL, et al. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med 2008; 358(7): 676–88PubMedCrossRef
64.
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 multicenter trial. Ann Neurol 2009; 66(4): 460–71PubMedCrossRef
65.
Naismith RT, Piccio L, Lyons JA, et al. Rituximab add-on therapy for breakthrough relapsing multiple sclerosis: a 52-week phase II trial. Neurology 2010; 74(23): 1860–7PubMedCrossRef
66.
Kappos L, Li D, Calabresi PA, et al. Ocrelizumab in relapsing-remitting multiple sclerosis: results of a phase II randomized placebo-controlled multicenter trial. Lancet. Epub 2011 Oct 31
67.
Soelberg Sorensen P, Drulovic J, Havrdova E, et al. Magnetic resonance imaging (MRI) efficacy of ofatumumab in relapsing-remitting multiple sclerosis (RRMS): 24-week results of a phase II study [abstract no. 136 plus oral presentation]. Presented at the 26th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS); 2010 Oct 13-16; Gothenburg
68.
Coles AJ, Compston DA, Selmaj KW, et al. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med 2008; 359(17): 1786–801PubMedCrossRef
69.
Wynn D, Kaufman M, Montalban X, et al. Daclizumab in active relapsing multiple sclerosis (CHOICE study): a phase 2, randomised, double-blind, placebo-controlled, add-on trial with interferon beta. Lancet Neurol 2010; 9(4): 381–90PubMedCrossRef
70.
Segal BM, Constantinescu CS, Raychaudhuri A, et al. Repeated subcutaneous injections of IL12/23 p40 neutralising antibody, ustekinumab, in patients with relapsing-remitting multiple sclerosis: a phase II, double-blind, placebo-controlled, randomised, dose-ranging study. Lancet Neurol 2008; 7(9): 796–804PubMedCrossRef
71.
Plitz T. Design of a four-arm, randomized, placebo-controlled phase II study of 36 weeks of atacicept mono-therapy in relapsing multiple sclerosis [abstract]. Mult Scler 2008; 14 Suppl. 1: 173
72.
Hartung HP. Atacicept: a new B lymphocyte-targeted therapy for multiple sclerosis. Nervenarzt 2009; 80(12): 1462–72PubMedCrossRef
73.
Sergott R. Design of an exploratory two-arm, randomized, placebo controlled phase II study of 36 weeks of atacicept treatment in patients with optic neuritis as clinically isolated syndrome [abstract]. Mult Scler 2008; 14 Suppl. 1: 177
74.
Miller DH, Soon D, Fernando KT, et al. MRI outcomes in a placebo-controlled trial of natalizumab in relapsing MS. Neurology 2007; 68(17): 1390–401PubMedCrossRef
75.
Havrdova E, Galetta S, Hutchinson M, et al. Effect of natalizumab on clinical and radiological disease activity in multiple sclerosis: a retrospective analysis of the Natalizumab Safety and Efficacy in Relapsing-Remitting Multiple Sclerosis (AFFIRM) study. Lancet Neurol 2009; 8(3): 254–60PubMedCrossRef
76.
O’Connor P, Goodman A, Kappos L, et al. The efficacy of natalizumab monotherapy over 3 years of treatment in patients with relapsing multiple sclerosis [abstract no. P06.082]. Presented at the 59th Annual Meeting of the American Academy of Neurology; 2007 Apr 28-May 5; Boston (MA)
77.
O’Connor P, Polman C, Goodman A, et al. Efficacy and safety of natalizumab in the STRATA study [abstract no. P06.127]. Presented at the 61st Annual Meeting of the American Academy of Neurology; 2009 Apr 25-May 2; Seattle (WA)
78.
O’Connor PW, Goodman A, Kappos L, et al. Disease activity return during natalizumab treatment interruption in patients with multiple sclerosis. Neurology 2011; 76(22): 1858–65PubMedCrossRef
79.
Calabresi PA, Giovannoni G, Confavreux C, et al. The incidence and significance of anti-natalizumab antibodies: results from AFFIRM and SENTINEL. Neurology 2007; 69(14): 1391–403PubMedCrossRef
80.
Kleinschmidt-DeMasters BK, Tyler KL. Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis. N Engl J Med 2005; 353(4): 369–74PubMedCrossRef
81.
Langer-Gould A, Atlas SW, Green AJ, et al. Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. N Engl J Med 2005; 353(4): 375–81PubMedCrossRef
82.
Van Assche G, Van Ranst M, Sciot R, et al. Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn’s disease. N Engl J Med 2005; 353(4): 362–8PubMedCrossRef
83.
Yousry TA, Major EO, Ryschkewitsch C, et al. Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy. N Engl J Med 2006; 354(9): 924–33PubMedCrossRef
84.
Panzara M, Belcher G, Kooijmans M, et al. Use of natalizumab in patients with relapsing multiple sclerosis: update safety results from TOUCH™ and TYGRIS. Presented at the 23rd Congress of the European Commitee for the Treatment and Research in Multiple Sclerosis; 2007 Oct 11-14; Prague, 565
85.
Bozic C, Belcher G, Kroojimans M, et al. The safety of natalizumab in patients with relapsing multiple sclerosis: an update from TOUCH™ and TYGRIS [abstract no. P06.082]. Presented at the 59th Annual Meeting of the American Academy of Neurology; 2007 April 28-May 5; Boston (MA)
86.
87.
Kappos L, Bates D, Edan G, et al. Natalizumab treatment for multiple sclerosis: updated recommendations for patient selection and monitoring. Lancet Neurol 2011; 10(8): 745–58PubMedCrossRef
88.
Rudick RA, O’Connor PW, Polman CH, et al. Assessment of JC virus DNA in blood and urine from natalizumab-treated patients. Ann Neurol 2010; 68(3): 304–10PubMedCrossRef
89.
Chen Y, Bord E, Tompkins T, et al. Asymptomatic reactivation of JC virus in patients treated with natalizumab. N Engl J Med 2009; 361(11): 1067–74PubMedCrossRef
90.
Sadiq SA, Puccio LM, Brydon EW. JCV detection in multiple sclerosis patients treated with natalizumab. J Neurol 2010; 257(6): 954–8PubMedCrossRef
91.
Gorelik L, Goelz S, Sandrock AW. Asymptomatic reactivation of JC virus in patients treated with natalizumab. N Engl J Med 2009; 361(25): 2487–8PubMedCrossRef
92.
Jilek S, Jaquiery E, Hirsch HH, et al. Immune responses to JC virus in patients with multiple sclerosis treated with natalizumab: a cross-sectional and longitudinal study. Lancet Neurol 2010; 9(3): 264–72PubMedCrossRef
93.
Antonsson A, Green AC, Mallitt KA, et al. Prevalence and stability of antibodies to the BK and JC polyomaviruses: a long-term longitudinal study of Australians. J Gen Virol 2010; 91 (Pt 7): 1849–53PubMedCrossRef
94.
Egli A, Infanti L, Dumoulin A, et al. Prevalence of polyomavirus BK and JC infection and replication in 400 healthy blood donors. J Infect Dis 2009; 199(6): 837–46PubMedCrossRef
95.
Kean JM, Rao S, Wang M, et al. Seroepidemiology of human polyomaviruses. PLoS Pathog 2009; 5(3): e1000363PubMedCrossRef
96.
Knowles WA, Pipkin P, Andrews W, et al. Population-based study of antibody to the human polyomaviruses BKV and JCV and the simian polyomavirus SV 40. J Med Virol 2003; 71(1): 115–23PubMedCrossRef
97.
Padgett BL, Walker DL. Prevalence of antibodies in human sera against JC virus, an isolate from a case of progressive multifocal leukoencephalopathy. J Infect Dis 1973; 127(4): 467–70PubMedCrossRef
98.
Stolt A, Sasnauskas K, Koskela P, et al. Seroepidemiology of the human polyomaviruses. J Gen Virol 2003; 84 (Pt 6): 1499–504PubMedCrossRef
99.
Gorelik L, Lerner M, Bixler S, et al. Anti-JC virus antibodies: implications for PML risk stratification. Ann Neurol 2010; 68(3): 295–303PubMedCrossRef
100.
Goelz SE, Gorelik L, Subramanyam M. Assay design and sample collection can affect anti-John Cunningham virus antibody detection. Ann Neurol 2011; 69(2): 429–30PubMedCrossRef
101.
Schweikert A, Kremer M, Ringel F, et al. Primary central nervous system lymphoma in a patient treated with natalizumab. Ann Neurol 2009; 66(3): 403–6PubMedCrossRef
102.
Bozic C, LaGuette J, Panzara MA, et al. Natalizumab and central nervous system lymphoma: no clear association. Ann Neurol 2009; 66(3): 261–2PubMedCrossRef
103.
Zecca C, Nessi F, Bernasconi E, et al. Ocular toxoplasmosis during natalizumab treatment. Neurology 2009; 73(17): 1418–9PubMedCrossRef
104.
Algazi AP, Kadoch C, Rubenstein JL. Biology and treatment of primary central nervous system lymphoma. Neurotherapeutics 2009; 6(3): 587–97PubMedCrossRef
105.
De AB, Dotti G, Quintarelli C, et al. Generation of Epstein-Barr virus-specific cytotoxic T lymphocytes resistant to the immunosuppressive drug tacrolimus (FK506). Blood 2009; 114(23): 4784–91CrossRef
106.
Finelli PF, Naik K, DiGiuseppe JA, et al. Primary lymphoma of CNS, mycophenolate mofetil and lupus. Lupus 2006; 15(12): 886–8PubMedCrossRef
107.
Mullen JT, Vartanian TK, Atkins MB. Melanoma complicating treatment with natalizumab for multiple sclerosis. N Engl J Med 2008; 358(6): 647–8PubMedCrossRef
108.
Panzara MA, Bozic C, Sandrock AW. More on melanoma with transdifferentiation. N Engl J Med 2008; 359(1): 99–100PubMedCrossRef
109.
Bozic C, Christiano LM, Hyde R, et al. Utilisation and safety of natalizumab in patients with relapsing multiple sclerosis [abstract no. P893]. Mult Scler 2010; 16 Suppl. 10: S315
110.
Edwards JC, Cambridge G. B-cell targeting in rheumatoid arthritis and other autoimmune diseases. Nat Rev Immunol 2006; 6(5): 394–403PubMedCrossRef
111.
Cardarelli PM, Quinn M, Buckman D, et al. Binding to CD20 by anti-B1 antibody or F(ab′)(2) is sufficient for induction of apoptosis in B-cell lines. Cancer Immunol Immunother 2002; 51(1): 15–24PubMedCrossRef
112.
Clynes RA, Towers TL, Presta LG, et al. Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets. Nat Med 2000; 6(4): 443–6PubMedCrossRef
113.
Pedersen IM, Buhl AM, Klausen P, et al. The chimeric anti-CD20 antibody rituximab induces apoptosis in B-cell chronic lymphocytic leukemia cells through a p38 mitogen activated protein-kinase-dependent mechanism. Blood 2002; 99(4): 1314–9PubMedCrossRef
114.
Reff ME, Carner K, Chambers KS, et al. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD 20. Blood 1994; 83(2): 435–45PubMed
115.
Nadler LM, Stashenko P, Hardy R, et al. Characterization of a human B cell-specific antigen (B2) distinct from B 1. J Immunol 1981; 126(5): 1941–7PubMed
116.
Rieckmann P, Wilson GL, Thevenin C, et al. Analysis of cis-acting elements present in the CD20/B1 antigen promoter. J Immunol 1991; 147(11): 3994–9PubMed
117.
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(1-2): 63–70PubMedCrossRef
118.
Stuve 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): 1620–3PubMedCrossRef
119.
Piccio L, Naismith RT, Trinkaus K, et al. Changes in B- and T-lymphocyte and chemokine levels with rituximab treatment in multiple sclerosis. Arch Neurol 2010; 67(6): 707–14PubMedCrossRef
120.
Ruhstaller TW, Amsler U, Cerny T. Rituximab: active treatment of central nervous system involvement by non-Hodgkin’s lymphoma? Ann Oncol 2000; 11(3): 374–5PubMedCrossRef
121.
Rubenstein JL, Combs D, Rosenberg J, et al. Rituximab therapy for CNS lymphomas: targeting the leptomeningeal compartment. Blood 2003; 101(2): 466–8PubMedCrossRef
122.
Cohen SB, Emery P, Greenwald MW, et al. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum 2006; 54(9): 2793–806PubMedCrossRef
123.
Cvetkovic RS, Perry CM. Rituximab: a review of its use in non-Hodgkin’s lymphoma and chronic lymphocytic leukaemia. Drugs 2006; 66(6): 791–820PubMedCrossRef
124.
Edwards JC, Szczepanski L, Szechinski J, et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med 2004; 350(25): 2572–81PubMedCrossRef
125.
Berentsen S, Ulvestad E, Langholm B, et al. Primary chronic cold agglutinin disease: a population based clinical study of 86 patients. Haematologica 2006; 91(4): 460–6PubMed
126.
Gurcan HM, Keskin DB, Stern JN, et al. A review of the current use of rituximab in autoimmune diseases. Int Immunopharmacol 2009; 9(1): 10–25PubMedCrossRef
127.
Kotani T, Takeuchi T, Kawasaki Y, et al. Successful treatment of cold agglutinin disease with anti-CD20 antibody (rituximab) in a patient with systemic lupus erythematosus. Lupus 2006; 15(10): 683–5PubMedCrossRef
128.
Pijpe J, van Imhoff GW, Spijkervet FK, et al. Rituximab treatment in patients with primary Sjogren’s syndrome: an open-label phase II study. Arthritis Rheum 2005; 52(9): 2740–50PubMedCrossRef
129.
Sansonno D, De Re V, Lauletta G, et al. Monoclonal antibody treatment of mixed cryoglobulinemia resistant to interferon alpha with an anti-CD 20. Blood 2003; 101(10): 3818–26PubMedCrossRef
130.
Shanafelt TD, Madueme HL, Wolf RC, et al. Rituximab for immune cytopenia in adults: idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, and Evans syndrome. Mayo Clin Proc 2003; 78(11): 1340–6PubMedCrossRef
131.
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(4): 470–5PubMedCrossRef
132.
Zaja F, Bacigalupo A, Patriarca F, et al. Treatment of refractory chronic GVHD with rituximab: a GITMO study. Bone Marrow Transplant 2007; 40(3): 273–7PubMedCrossRef
133.
Collins-Burow B, Santos ES. Rituximab and its role as maintenance therapy in non-Hodgkin lymphoma. Expert Rev Anticancer Ther 2007; 7(3): 257–73PubMedCrossRef
134.
Eisenberg R, Looney RJ. The therapeutic potential of anti-CD20 ‘what do B-cells do?’. Clin Immunol 2005; 117(3): 207–13PubMedCrossRef
135.
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): 258–64PubMedCrossRef
136.
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(4): 452–61PubMedCrossRef
137.
Carson KR, Bennett CL. Rituximab and progressive multi-focal leukoencephalopathy: the jury is deliberating. Leuk Lymphoma 2009; 50(3): 323–4PubMedCrossRef
138.
Carson KR, Focosi D, Major EO, et al. Monoclonal antibody-associated progressive multifocal leucoencephalopathy in patients treated with rituximab, natalizumab, and efalizumab: a Review from the Research on Adverse Drug Events and Reports (RADAR) Project. Lancet Oncol 2009; 10(8): 816–24PubMedCrossRef
139.
140.
Genovese MC, Kaine JL, Lowenstein MB, et al. Ocrelizumab, a humanized anti-CD20 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: a phase I/II randomized, blinded, placebo-controlled, dose-ranging study. Arthritis Rheum 2008; 58(9): 2652–61PubMedCrossRef
141.
Robak T, Robak E. New anti-CD20 monoclonal antibodies for the treatment of B-cell lymphoid malignancies. Biodrugs 2011; 25(1): 13–25PubMedCrossRef
142.
Shields RL, Namenuk AK, Hong K, et al. High resolution mapping of the binding site on human IgG1 for Fc gamma RI, Fc gamma RII, Fc gamma RIII, and FcRn and design of IgG1 variants with improved binding to the Fc gamma R. J Biol Chem 2001; 276(9): 6591–604PubMedCrossRef
143.
144.
Emery P, Rigby W, Tak PP, et al. Serious infections with ocrelizumab in rheumatoid arthritis: pooled results from double-blind periods of the ocrelizumab phase III RA program [abstract]. Arthritis Rheum 2010; 62 Suppl. 10: 414
145.
van Meerten T, Rozemuller H, Hol S, et al. HuMab-7D8, a monoclonal antibody directed against the membrane-proximal small loop epitope of CD20 can effectively eliminate CD20low expressing tumor cells that resist rituximab mediated lysis. Haematologica 2010; 95(12): 2063–71PubMedCrossRef
146.
Natsume A, Niwa R, Satoh M. Improving effector functions of antibodies for cancer treatment: enhancing ADCC and CDC. Drug Des Devel Ther 2009; 3: 7–16PubMed
147.
Cheson BD. Ofatumumab, a novel anti-CD20 monoclonal antibody for the treatment of B-cell malignancies. J Clin Oncol 2010; 28(21): 3525–30PubMedCrossRef
148.
Ostergaard M, Baslund B, Rigby W, et al. Ofatumumab, a human anti-CD20 monoclonal antibody, for treatment of rheumatoid arthritis with an inadequate response to one or more disease-modifying antirheumatic drugs: results of a randomized, double-blind, placebo-controlled, phase I/II study. Arthritis Rheum 2010; 62(8): 2227–38PubMedCrossRef
149.
Ostergaard M, Wiell C, Dawes P, et al. First clinical results of HuMAx-CD20 fully human monoclonal IGG1 antibody treatment in rheumatoid arthritis [abstract no. P0018]. Ann Rheum Dis 2006; 65 Suppl. 2: 58
150.
Coiffier B, Lepretre S, Pedersen LM, et al. Safety and efficacy of ofatumumab, a fully human monoclonal anti-CD20 antibody, in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: a phase 1-2 study. Blood 2008; 111(3): 1094–100PubMedCrossRef
151.
Hagenbeek A, Gadeberg O, Johnson P, et al. First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase 1/2 trial. Blood 2008; 111(12): 5486–95PubMedCrossRef
152.
Genmab. A double-blind, randomized, placebo-controlled, multicenter, dose-finding trial of ofatumumab in RRMS patients [ClinicalTrials.gov identifier NCT00640328]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​www.​clinicaltrials.​gov [Accessed 2008 Mar 18]
153.
154.
Gilleece MH, Dexter TM. Effect of Campath-1H antibody on human hematopoietic progenitors in vitro. Blood 1993; 82(3): 807–12PubMed
155.
Riechmann L, Clark M, Waldmann H, et al. Reshaping human antibodies for therapy. Nature 1988; 332(6162): 323–7PubMedCrossRef
156.
Cox AL, Thompson SA, Jones JL, et al. Lymphocyte homeostasis following therapeutic lymphocyte depletion in multiple sclerosis. Eur J Immunol 2005; 35(11): 3332–42PubMedCrossRef
157.
Coles AJ, Wing M, Smith S, et al. Pulsed monoclonal antibody treatment and autoimmune thyroid disease in multiple sclerosis. Lancet 1999; 354(9191): 1691–5PubMedCrossRef
158.
Coles AJ, Cox A, Le PE, et al. The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy. J Neurol 2006; 253(1): 98–108PubMedCrossRef
159.
Thompson SA, Jones JL, Cox AL, et al. B-cell reconstitution and BAFF after alemtuzumab (Campath-1H) treatment of multiple sclerosis. J Clin Immunol 2010; 30(1): 99–105PubMedCrossRef
160.
Coles AJ, Wing MG, Molyneux P, et al. Monoclonal antibody treatment exposes three mechanisms underlying the clinical course of multiple sclerosis. Ann Neurol 1999; 46(3): 296–304PubMedCrossRef
161.
Moreau T, Thorpe J, Miller D, et al. Preliminary evidence from magnetic resonance imaging for reduction in disease activity after lymphocyte depletion in multiple sclerosis. Lancet 1994; 344(8918): 298–301PubMedCrossRef
162.
Cossburn M, Pace AA, Jones J, et al. Autoimmune disease after alemtuzumab treatment for multiple sclerosis in a multicenter cohort. Neurology 2011; 77(6): 573–9PubMedCrossRef
163.
Jones JL, Phuah CL, Cox AL, et al. IL-21 drives secondary autoimmunity in patients with multiple sclerosis, following therapeutic lymphocyte depletion with alemtuzumab (Campath-1H). J Clin Invest 2009; 119(7): 2052–61PubMed
164.
Genzyme. Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis, Study One (CARE-MS I). [Clinical Trials.gov identifier NCT00530348] US National Institutes of Health, Clinical Trials.gov [online]. Available from URL: http://​www.​clinicaltrials.​gov [Accessed 2011 Jun 30]
165.
Genzyme. Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis, Study Two (CARE-MS II). [Clinical Trials.gov identifier NCT00548405] US National Institutes of Health, Clinical Trials.gov [online]. Available from URL: http://​www.​clinicaltrials.​gov [Accessed 2011 Jun 30]
166.
Kirkman RL, Shapiro ME, Carpenter CB, et al. A randomized prospective trial of anti-Tac monoclonal anti-body in human renal transplantation. Transplant Proc 1991; 23 (1 Pt 2): 1066–7PubMed
167.
Martin R. Humanized anti-CD25 antibody treatment with daclizumab in multiple sclerosis. Neurodegener Dis 2008; 5(1): 23–6PubMedCrossRef
168.
Waldmann TA, Longo DL, Leonard WJ, et al. Interleukin 2 receptor (Tac antigen) expression in HTLV-I-associated adult T-cell leukemia. Cancer Res 1985; 45(9 Suppl. ): 4559s–62sPubMed
169.
Uchiyama T, Broder S, Waldmann TA. A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells: I. Production of anti-Tac monoclonal antibody and distribution of Tac (+) cells. J Immunol 1981; 126(4): 1393–7PubMed
170.
Bielekova B, Catalfamo M, Reichert-Scrivner S, et al. Regulatory CD56(bright) natural killer cells mediate immunomodulatory effects of IL-2Ralpha-targeted therapy (daclizumab) in multiple sclerosis. Proc Natl Acad Sci U S A 2006; 103(15): 5941–6PubMedCrossRef
171.
Waldmann TA, O’Shea J. The use of antibodies against the IL-2 receptor in transplantation. Curr Opin Immunol 1998; 10(5): 507–12PubMedCrossRef
172.
173.
Bielekova B, Howard T, Packer AN, et al. Effect of anti-CD25 antibody daclizumab in the inhibition of inflammation and stabilization of disease progression in multiple sclerosis. Arch Neurol 2009; 66(4): 483–9PubMedCrossRef
174.
Sandrini S. Use of IL-2 receptor antagonists to reduce delayed graft function following renal transplantation: a review. Clin Transplant 2005; 19(5): 705–10PubMedCrossRef
175.
Lehky TJ, Levin MC, Kubota R, et al. Reduction in HTLV-I proviral load and spontaneous lymphoproliferation in HTLV-I-associated myelopathy/tropical spastic paraparesis patients treated with humanized anti-Tac. Ann Neurol 1998; 44(6): 942–7PubMedCrossRef
176.
Nussenblatt RB, Fortin E, Schiffman R, et al. Treatment of noninfectious intermediate and posterior uveitis with the humanized anti-Tac mAb: a phase I/II clinical trial. Proc Natl Acad Sci U S A 1999; 96(13): 7462–6PubMedCrossRef
177.
Waldmann TA. Anti-Tac (daclizumab, Zenapax) in the treatment of leukemia, autoimmune diseases, and in the prevention of allograft rejection: a 25-year personal odyssey. J Clin Immunol 2007; 27(1): 1–18PubMedCrossRef
178.
Bielekova B, Richert N, Howard T, et al. Humanized anti-CD25 (daclizumab) inhibits disease activity in multiple sclerosis patients failing to respond to interferon beta. Proc Natl Acad Sci U S A 2004; 101(23): 8705–8PubMedCrossRef
179.
Rose JW, Watt HE, White AT, et al. Treatment of multiple sclerosis with an anti-interleukin-2 receptor monoclonal antibody. Ann Neurol 2004; 56(6): 864–7PubMedCrossRef
180.
Rose JW, Burns JB, Bjorklund J, et al. Daclizumab phase II trial in relapsing and remitting multiple sclerosis: MRI and clinical results. Neurology 2007; 69(8): 785–9PubMedCrossRef
181.
Biogen Idec. Efficacy and safety of daclizumab high yield process versus interferon β 1a in patients with relapsing-remitting multiple sclerosis. [Clinical Trials.gov identifier NCT01064401] US National Institutes of Health, Clinical Trials.gov [online]. Available from URL: http://​www.​clinicaltrials.​gov [Accessed 2011 Jun 30]
182.
Ali EN, Healy BC, Stazzone LA, et al. Daclizumab in treatment of multiple sclerosis patients. Mult Scler 2009; 15(2): 272–4PubMedCrossRef
183.
Sabatine MS, Poh KK, Mega JL, et al. Case records of the Massachusetts General Hospital. Case 36-2007: a 31-year-old woman with rash, fever, and hypotension. N Engl J Med 2007; 357(21): 2167–78PubMedCrossRef
184.
Brok HP, van Meurs M, Blezer E, et al. Prevention of experimental autoimmune encephalomyelitis in common marmosets using an anti-IL-12p40 monoclonal antibody. J Immunol 2002; 169(11): 6554–63PubMed
185.
Cua DJ, Sherlock J, Chen Y, et al. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 2003; 421(6924): 744–8PubMedCrossRef
186.
Langrish CL, Chen Y, Blumenschein WM, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 2005; 201(2): 233–40PubMedCrossRef
187.
Li Y, Chu N, Hu A, et al. Increased IL-23p19 expression in multiple sclerosis lesions and its induction in microglia. Brain 2007; 130 (Pt 2): 490–501PubMedCrossRef
188.
Vaknin-Dembinsky A, Balashov K, Weiner HL. IL-23 is increased in dendritic cells in multiple sclerosis and down-regulation of IL-23 by antisense oligos increases dendritic cell IL-10 production. J Immunol 2006; 176(12): 7768–74PubMed
189.
Windhagen A, Newcombe J, Dangond F, et al. Expression of costimulatory molecules B7-1 (CD80), B7-2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions. J Exp Med 1995; 182(6): 1985–96PubMedCrossRef
190.
Oppmann B, Lesley R, Blom B, et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 2000; 13(5): 715–25PubMedCrossRef
191.
Trinchieri G, Scott P. Interleukin-12: a proinflammatory cytokine with immunoregulatory functions. Res Immunol 1995; 146(7-8): 423–31PubMedCrossRef
192.
Kikly K, Liu L, Na S, et al. The IL-23/Th(17) axis: therapeutic targets for autoimmune inflammation. Curr Opin Immunol 2006; 18(6): 670–5PubMedCrossRef
193.
’t Hart BA, Brok HP, Remarque E, et al. Suppression of ongoing disease in a nonhuman primate model of multiple sclerosis by a human-anti-human IL-12p40 antibody. J Immunol 2005; 175(7): 4761–8PubMed
194.
Constantinescu CS, Wysocka M, Hilliard B, et al. Antibodies against IL-12 prevent superantigen-induced and spontaneous relapses of experimental autoimmune encephalomyelitis. J Immunol 1998; 161(9): 5097–104PubMed
195.
Kasper LH, Everitt D, Leist TP, et al. A phase I trial of an interleukin-12/23 monoclonal antibody in relapsing multiple sclerosis. Curr Med Res Opin 2006; 22(9): 1671–8PubMedCrossRef
196.
Longbrake EE, Racke MK. Why did IL-12/IL-23 antibody therapy fail in multiple sclerosis? Expert Rev Neurother 2009; 9(3): 319–21PubMedCrossRef
197.
Segal BM, Shevach EM. IL-12 unmasks latent autoimmune disease in resistant mice. J Exp Med 1996; 184(2): 771–5PubMedCrossRef
198.
Gross JA, Johnston J, Mudri S, et al. TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease. Nature 2000; 404(6781): 995–9PubMedCrossRef
199.
Gross JA, Dillon SR, Mudri S, et al. TACI-Ig neutralizes molecules critical for B cell development and autoimmune disease: impaired B cell maturation in mice lacking BLyS. Immunity 2001; 15(2): 289–302PubMedCrossRef
200.
Schneider P, Mackay F, Steiner V, et al. BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth. J Exp Med 1999; 189(11): 1747–56PubMedCrossRef
201.
Schneider P. The role of APRIL and BAFF in lymphocyte activation. Curr Opin Immunol 2005; 17(3): 282–9PubMedCrossRef
202.
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): 195–200PubMedCrossRef
203.
Thangarajh M, Masterman T, Rot U, et al. Increased levels of APRIL (a proliferation-inducing ligand) mRNA in multiple sclerosis. J Neuroimmunol 2005; 167(1-2): 210–4PubMedCrossRef
204.
Marsters SA, Yan M, Pitti RM, et al. Interaction of the TNF homologues BLyS and APRIL with the TNF receptor homologues BCMA and TACI. Curr Biol 2000; 10(13): 785–8PubMedCrossRef
205.
Dall’Era M, Chakravarty E, Wallace D, et al. Reduced B lymphocyte and immunoglobulin levels after atacicept treatment in patients with systemic lupus erythematosus: results of a multicenter, phase Ib, double-blind, placebo-controlled, dose-escalating trial. Arthritis Rheum 2007; 56(12): 4142–50PubMedCrossRef
206.
Kalled SL. The role of BAFF in immune function and implications for autoimmunity. Immunol Rev 2005; 204: 43–54PubMedCrossRef
207.
Munafo A, Priestley A, Nestorov I, et al. Safety, pharmaco-kinetics and pharmacodynamics of atacicept in healthy volunteers. Eur J Clin Pharmacol 2007; 63(7): 647–56PubMedCrossRef
208.
Nestorov I, Munafo A, Papasouliotis O, et al. Pharmaco-kinetics and biological activity of atacicept in patients with rheumatoid arthritis. J Clin Pharmacol 2008; 48(4): 406–17PubMedCrossRef
209.
Tak PP, Thurlings RM, Rossier C, et al. Atacicept in patients with rheumatoid arthritis: results of a multicenter, phase Ib, double-blind, placebo-controlled, dose-escalating, single- and repeated-dose study. Arthritis Rheum 2008; 58(1): 61–72PubMedCrossRef
210.
Pena-Rossi C, Nasonov E, Stanislav M, et al. An exploratory dose-escalating study investigating the safety, tolerability, pharmacokinetics and pharmacodynamics of intravenous atacicept in patients with systemic lupus erythematosus. Lupus 2009; 18(6): 547–55PubMedCrossRef
211.
EMD Serono. Atacicept in combination with rituximab in subjects with rheumatoid arthritis (August III). [Clinical Trials.gov identifier NCT00664521] US National Institutes of Health, Clinical Trials.gov [online]. Available from URL: http://​www.​clinicaltrials.​gov [Accessed 2011 Jun 30]
212.
Genovese MC. Phase 2 study of safety and efficacy of a novel anti-BAFF monoclonal antibody, in patients with RA treated with methotrexate (MTX). ACR/ARHP 2009 Annual Scientific Meeting; 2009 Oct 17-21; Philadelphia (PA)
213.
Eli Lilly and Company. A study of patients with relapsing remitting multiple sclerosis. [Clinical Trials.gov identifier NCT00882999] US National Institutes of Health, Clinical Trials.gov [online]. Available from URL: http://​www.​clinicaltrials.​gov [Accessed 2011 Jun 30]
214.
Hueber W, Patel DD, Dryja T, et al. Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis. Sci Transl Med 2010; 2(52): 52ra72CrossRef
215.
Novartis Pharmaceuticals. A randomized, multi-center, double-blind, proof-of-concept study to assess the effect of multiple infusions of AIN457 (10mg/kg) versus placebo on disease activity (MRI scans) in patients with relapsing-remitting multiple sclerosis [ClinicalTrials.gov identifier NCT01051817]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​clinicaltrials.​gov [Accessed 2010 Jan 19]
216.
Hausmann OV, Seitz M, Villiger PM, et al. The complex clinical picture of side effects to biologicals. Med Clin North Am 2010; 94(4): 791–804, xi-iiPubMedCrossRef
217.
Wiendl H, Neuhaus O, Kappos L, et al. Multiple sclerosis: current review of failed and discontinued clinical trials of drug treatment. Nervenarzt 2000; 71(8): 597–610PubMedCrossRef
218.
Hohlfeld R, Wiendl H. The ups and downs of multiple sclerosis therapeutics. Ann Neurol 2001; 49(3): 281–4PubMedCrossRef
219.
Wiendl H, Hohlfeld R. Therapeutic approaches in multiple sclerosis: lessons from failed and interrupted treatment trials. Biodrugs 2002; 16(3): 183–200PubMedCrossRef
220.
Kappos L, Radue EW, O’Connor P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med 2010; 362(5): 387–401PubMedCrossRef
221.
Cohen JA, Barkhof F, Comi G, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 2010; 362(5): 402–15PubMedCrossRef
222.
Comi G, Pulizzi A, Rovaris M, et al. Effect of laquinimod on MRI-monitored disease activity in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study. Lancet 2008; 371(9630): 2085–92PubMedCrossRef
223.
Kappos L, Gold R, Miller DH, et al. Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study. Lancet 2008; 372(9648): 1463–72PubMedCrossRef
224.
Miller D, Weber T, Montalban X, et al. Phase II trial of firategrast shows that oral anti-alpha4 therapy can suppress new MRI lesions in relapsing-remitting multiple sclerosis [abstract no. 113 plus oral presentation]. Presented at the 26th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS); 2010 Oct 13–16; Gothenburg
225.
O’Connor PW, Li D, Freedman MS, et al. A phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapses. Neurology 2006; 66(6): 894–900PubMedCrossRef
226.
Miller A, O’Connor P, Wolinsky JS, et al. Clinical and MRI outcomes from a phase III trial (TEMSO) of oral teriflunomide in multiple sclerosis with relapses [abstract no. S41.002]. Program and abstracts of the American Academy of Neurology (AAN) 63rd Annual Meeting; 2011 Apr 9-16; Honolulu (HI)
Metadata
Title
Monoclonal Antibodies and Recombinant Immunoglobulins for the Treatment of Multiple Sclerosis
Authors
Henrik Gensicke
David Leppert
Özgür Yaldizli
Raija L. P. Lindberg
Matthias Mehling
Prof. Ludwig Kappos
Jens Kuhle
Publication date
01-01-2012
Publisher
Springer International Publishing
Published in
CNS Drugs / Issue 1/2012
Print ISSN: 1172-7047
Electronic ISSN: 1179-1934
DOI
https://doi.org/10.2165/11596920-000000000-00000

Other articles of this Issue 1/2012

CNS Drugs 1/2012 Go to the issue

Original Research Article

Pharmacokinetics, Drug Interactions and Exposure-Response Relationship of Eslicarbazepine Acetate in Adult Patients with Partial-Onset Seizures

Leading Article

Pharmacological Interventions for the Treatment of Smokeless Tobacco Use

Review Article

Defining the Role of Baclofen for the Treatment of Alcohol Dependence

Review Article

Clinically Significant Drug Interactions with Newer Antidepressants