Disease modifying drugs in multiple sclerosis: Mechanisms of action and new drugs in the Horizon

CNS and Neurological Disorders - Drug Targets

Volumn 11, Issue 5, 2012, Pages 610-623

  Marta, Monica ^a   Giovannoni, Gavin ^a  

^a QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

Mechanisms of action; Multiple sclerosis; Treatments

Indexed keywords

ALEMTUZUMAB; AUBAGIO; BETA INTERFERON; BETA1A INTERFERON; CLADRIBINE; DACLIZUMAB; FINGOLIMOD; FUMARIC ACID DIMETHYL ESTER; GELATINASE B; GLATIRAMER; INTERFERON BETA SERINE; INTERLEUKIN 12P40; INTERLEUKIN 23; LAQUINIMOD; LEMTRADA; NATALIZUMAB; NEUTROPHIL COLLAGENASE; OCRELIZUMAB; RITUXIMAB; TERIFLUNOMIDE; UNCLASSIFIED DRUG;

ABDOMINAL PAIN; APOPTOSIS; ARTICLE; BLOOD BRAIN BARRIER; DEMYELINATING DISEASE; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG MECHANISM; FATIGUE; FEVER; FLU LIKE SYNDROME; FLUSHING; HEADACHE; HUMAN; INFUSION RELATED REACTION; INSOMNIA; MULTIPLE SCLEROSIS; NAUSEA; NEUROIMAGING; NUCLEAR MAGNETIC RESONANCE IMAGING; PRURITUS; RASH; RELAPSE; RESPIRATORY TRACT INFECTION; SCORING SYSTEM; SIDE EFFECT; URINARY TRACT INFECTION; URTICARIA;

EID: 84863979575     PISSN: 18715273     EISSN: 19963181     Source Type: Journal    
DOI: 10.2174/187152712801661301     Document Type: Article

References (116)

1. de Weerd, N.A.; Samarajiwa, S.A.; Hertzog, P.J. Type I interferon receptors: biochemistry and biological functions. J. Biol. Chem., 2007, 282(28), 20053-20057.
2. Yong, V.W.; Chabot, S.; Stuve, O.; Williams, G. Interferon beta in the treatment of multiple sclerosis: mechanisms of action. Neurology, 1998, 51(3), 682-689.
3. Noronha, A.; Toscas, A.; Jensen, M.A. Interferon beta decreases T cell activation and interferon gamma production in multiple sclerosis. J. Neuroimmunol., 1993, 46(1-2), 145-153.
4. Brod, S.A.; Marshall, G.D.; Henninger, E.M.; Sriram, S.; Khan, M.; Wolinsky, J.S. Interferon-beta 1b treatment decreases tumor necrosis factor-alpha and increases interleukin-6 production in multiple sclerosis. Neurology, 1996, 46(6), 1633-1638.
5. Chen, M.; Chen, G.; Nie, H.; Zhang, X.; Niu, X.; Zang, Y.C.Q.; Skinner, S.M.; Zhang, J.Z.; Killian, J.M.; Hong, J. Regulatory effects of IFN-beta on production of osteopontin and IL-17 by CD4+ T Cells in MS. Eur. J. Immunol., 2009, 39(9), 2525-2536.
6. Durelli, L.; Conti, L.; Clerico, M.; Boselli, D.; Contessa, G.; Ripellino, P.; Ferrero, B.; Eid, P.; Novelli, F. T-helper 17 cells expand in multiple sclerosis and are inhibited by interferon-beta. Ann. Neurol., 2009, 65(5), 499-509.
7. Zula, J.A.; Green, H.C.; Ransohoff, R.M.; Rudick, R.A.; Stark, G.R.; van Boxel-Dezaire, A.H.H. The role of cell type-specific responses in IFN therapy of multiple sclerosis. Proc. Natl. Acad. Sci. USA, 2011, 108(49), 19689-19694.
8. Alexander, J.S.; Harris, M.K.; Wells, S.R.; Mills, G.; Chalamidas, K.; Ganta, V.C.; McGee, J.; Jennings, M.H.; Gonzalez-Toledo, E.; Minagar, A. Alterations in serum MMP-8, MMP-9, IL-12p40 and IL-23 in multiple sclerosis patients treated with interferon-beta1b. Mult. Scler., 2010, 16(7), 801-809.
9. Müller, M.; Frese, A.; Nassenstein, I.; Hoppen, M.; Marziniak, M.; Ringelstein, E.B.; Kim, K.S.; Schäbitz, W-R.; Kraus, J. Serum from interferon-{beta}-1b-treated patients with early multiple sclerosis stabilizes the blood-brain barrier in vitro. Mult. Scler., 2011, 18(2), 236-239.
10. Niemelä, J.; Ifergan, I.; Yegutkin, G.G.; Jalkanen, S.; Prat, A.; Airas, L. IFN-beta regulates CD73 and adenosine expression at the blood-brain barrier. Eur. J. Immunol., 2008, 38(10), 2718-2726.
11. Mills, J.H.; Thompson, L.F.; Mueller, C.; Waickman, A.T.; Jalkanen, S.; Niemela, J.; Airas, L.; Bynoe, M.S. CD73 is required for efficient entry of lymphocytes into the central nervous system during experimental autoimmune encephalomyelitis. Proc. Natl. Acad. Sci. USA, 2008, 105(27), 9325-9330.
12. Comabella, M.; Lünemann, J.D.; Río, J.; Sánchez, A.; López, C.; Julià, E.; Fernández, M.; Nonell, L.; Camiña-Tato, M.; Deisenhammer, F.; Caballero, E.; Tortola, M.T.; Prinz, M.; Montalban, X.; Martin, R. A type I interferon signature in monocytes is associated with poor response to interferon-beta in multiple sclerosis. Brain, 2009, 132(Pt 12), 3353-3365.
13. Bustamante, M.F.; Fissolo, N.; Río, J.; Espejo, C.; Costa, C.; Mansilla, M.J.; Lizasoain, I.; Angeles Moro, M.; Carmen Edo, M.; Montalban, X.; Comabella, M. Implication of the Toll-like receptor 4 pathway in the response to interferon in multiple sclerosis. Ann. Neurol., 2011, 70(4), 634-645.
14. van Baarsen, L.G.M.; Vosslamber, S.; Tijssen, M.; Baggen, J.M.C.; van der Voort, L.F.; Killestein, J.; van der Pouw Kraan, T.T.M.; Polman, C.H.; Verweij, C.L. Pharmacogenomics of interferon-beta therapy in multiple sclerosis: baseline IFN signature determines pharmacological differences between patients. PloS One, 2008, 3(4), e1927.
15. The IFNB Multiple Sclerosis Study Group. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. The IFNB Multiple Sclerosis Study Group. Neurology, 1993, 43(4), 655-661.
16. Paty, D.W.; Li, D.K. Interferon beta-1b is effective in relapsingremitting multiple sclerosis. II. MRI analysis results of a multicenter, randomized, double-blind, placebo-controlled trial. UBC MS/MRI Study Group and the IFNB Multiple Sclerosis Study Group. Neurology, 1993, 43(4), 662-667.
17. Rudick, R.A.; Goodkin, D.E.; Jacobs, L.D.; Cookfair, D.L.; Herndon, R.M.; Richert, J.R.; Salazar, A.M.; Fischer, J.S.; Granger, C.V.; Simon, J.H.; Alam, J.J.; Simonian, N.A.; Campion, M.K.; Bartoszak, D.M.; Bourdette, D.N.; Braiman, J.; Brownscheidle, C.M.; Coats, M.E.; Cohan, S.L.; Dougherty, D.S.; Kinkel, R.P.; Mass, M.K.; Munschauer, F.E.; Priore, R.L.; Whitham, R.H. Impact of interferon beta-1a on neurologic disability in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Neurology, 1997, 49(2), 358-363.
18. Simon, J.H.; Jacobs, L.D.; Campion, M.; Wende,; K. Simonian, N.; Cookfair, D.L.; Rudick, R.A.; Herndon, R.M.; Richert, J.R.; Salazar, A.M.; Alam, J.J.; Fischer, J.S.; Goodkin, D.E.; Granger, C.V.; Lajaunie, M.; Martens-Davidson, A.L.; Meyer, M.; Sheeder, J.; Choi, K.; Scherzinger, A.L.; Bartoszak, D.M.; Bourdette, D.N.; Braiman, J.; Brownscheidle, C.M.; Whitham, R.H. Magnetic resonance studies of intramuscular interferon beta-1a for relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group. Ann. Neurol., 1998, 43(1), 79-87.
19. Jacobs, L.D.; Cookfair, D.L.; Rudick, R.A.; Herndon, R.M.; Richert, J.R.; Salazar, A.M.; Fischer, J.S.; Goodkin, D.E.; Granger, C.V.; Simon, J.H.; Alam, J.J.; Bartoszak, D.M.; Bourdette, D.N.; Braiman, J.; Brownscheidle, C.M.; Coats, M.E.; Cohan, S.L.; Dougherty, D.S.; Kinkel, R.P.; Mass, M.K.; Munschauer, F.E.; Priore, R.L.; Pullicino, P.M.; Scherokman, B.J.; Whitham, R.H. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Ann. Neurol., 1996, 39(3), 285-294.
20. PRISMS-Study-Group. Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group. Lancet, 1998, 352(9139), 1498-1504.
21. Li, D.K.; Paty, D.W. Magnetic resonance imaging results of the PRISMS trial: a randomized, double-blind, placebo-controlled study of interferon-beta1a in relapsing-remitting multiple sclerosis. Prevention of Relapses and Disability by Interferon-beta1a Subcutaneously in Multi. Ann. Neurol., 1999, 46(2), 197-206.
22. Panitch, H.; Goodin, D.S.; Francis, G.; Chang, P.; Coyle, P.K.; O'Connor, P.; Monaghan, E.; Li, D.; Weinshenker, B. Randomized, comparative study of interferon beta-1a treatment regimens in MS: The EVIDENCE Trial. Neurology, 2002, 59(10), 1496-1506.
23. PRISMS Study Group. PRISMS-4: Long-term efficacy of interferonbeta-1a in relapsing MS. Neurology, 2001, 56(12), 1628-1636.
24. Polman, C.; Kappos, L.; Freedman, M.S.; Edan, G.; Hartung, H-P.; Miller, D.H.; Montalbán, X.; Barkhof, F.; Selmaj, K.; Uitdehaag, B.M.J.; Dahms, S.; Bauer, L.; Pohl, C.; Sandbrink, R. Subgroups of the BENEFIT study: risk of developing MS and treatment effect of interferon beta-1b. J. Neurol., 2008, 255(4), 480-487.
25. Kappos, L.; Freedman, M.S.; Polman, C.H.; Edan, G.; Hartung, H-P.; Miller, D.H.; Montalbán, X.; Barkhof, F.; Radü, E-W.; Bauer, L.; Dahms, S.; Lanius, V.; Pohl, C.; Sandbrink, R. Effect of early versus delayed interferon beta-1b treatment on disability after a first clinical event suggestive of multiple sclerosis: a 3-year follow-up analysis of the BENEFIT study. Lancet, 2007, 370(9585), 389-397.
26. Kappos, L.; Freedman, M.S.; Polman, C.H.; Edan, G.; Hartung, H-P.; Miller, D.H.; Montalbán, X.; Barkhof, F.; Radü, E-W.; Metzig, C.; Bauer, L.; Lanius, V.; Sandbrink, R.; Pohl, C. Long-term effect of early treatment with interferon beta-1b after a first clinical event suggestive of multiple sclerosis: 5-year active treatment extension of the phase 3 BENEFIT trial. Lancet Neurol., 2009, 8(11), 987-997.
27. Jacobs, L.D.; Beck, R.W.; Simon, J.H.; Kinkel, R.P.; Brownscheidle, C.M.; Murray, T.J.; Simonian, N.A.; Slasor, P.J.; Sandrock, A.W. Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group. N. Engl. J. Med., 2000, 343(13), 898-904.
28. Beck, R.W.; Chandler, D.L.; Cole, S.R.; Simon, J.H.; Jacobs, L.D.; Kinkel, R.P.; Selhorst, J.B.; Rose, J.W.; Cooper, J.A.; Rice, G.; Murray, T.J.; Sandrock, A.W. Interferon beta-1a for early multiple sclerosis: CHAMPS trial subgroup analyses. Ann. Neurol., 2002, 51(4), 481-490.
29. Kinkel, R.P.; Kollman, C.; O'Connor, P.; Murray, T.J.; Simon, J.; Arnold, D.; Bakshi, R.; Weinstock-Gutman, B.; Brod, S.; Cooper, J.; Duquette, P.; Eggenberger, E.; Felton, W.; Fox, R.; Freedman, M.; Galetta, S.; Goodman, A.; Guarnaccia, J.; Hashimoto, S.; Horowitz, S.; Javerbaum, J.; Kasper, L.; Kaufman, M.; Kerson, L.; Mass, M.; Rammohan, K.; Reiss, M.; Rolak, L.; Rose, J.; Scott, T.; Selhorst, J.; Shin, R.; Smith, C.; Stuart, W.; Thurston, S.; Wall, M. IM interferon beta-1a delays definite multiple sclerosis 5 years after a first demyelinating event. Neurology, 2006, 66(5), 678-684.
30. O'Connor, P.; Kinkel, R.P.; Kremenchutzky, M. Efficacy of intramuscular interferon beta-1a in patients with clinically isolated syndrome: analysis of subgroups based on new risk criteria. Mult. Scler., 2009, 15(6), 728-734.
31. Comi, G.; Filippi, M.; Barkhof, F.; Durelli, L.; Edan, G.; Fernández, O.; Hartung, H.; Seeldrayers, P.; Sørensen, P.S.; Rovaris, M.; Martinelli, V.; Hommes, O.R. Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet, 2001, 357(9268), 1576-1582.
32. Filippi, M.; Rovaris, M.; Inglese, M.; Barkhof, F.; De Stefano, N.; Smith, S.; Comi, G. Interferon beta-1a for brain tissue loss in patients at presentation with syndromes suggestive of multiple sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet, 2004, 364(9444), 1489-1496.
33. Comi, G.; De Stefano, N.; Freedman, M.S.; Barkhof, F.; Polman, C.H.; Uitdehaag, B.M.; Casset-Semanaz, F.; Hennessy, B.; Moraga, M.S.; Rocak, S.; Stubinski, B.; Kappos, L. Comparison of two dosing frequencies of subcutaneous interferon beta-1a in patients with a first clinical demyelinating event suggestive of multiple sclerosis (REFLEX), a phase 3 randomised controlled trial. Lancet Neurol., 2011, 11(1), 33-41.
34. Durelli, L.; Verdun, E.; Barbero, P.; Bergui, M.; Versino, E.; Ghezzi, A.; Montanari, E.; Zaffaroni, M. Every-other-day interferon beta-1b versus once-weekly interferon beta-1a for multiple sclerosis: results of a 2-year prospective randomised multicentre study (INCOMIN). Lancet, 2002, 359(9316), 1453-1460.
35. Johnson, K.P.; Brooks, B.R.; Cohen, J.A.; Ford, C.C.; Goldstein, J.; Lisak, R.P.; Myers, L.W.; Panitch, H.S.; Rose, J.W.; Schiffer, R.B. Copolymer 1 reduces relapse rate and improves disability in relapsingremitting multiple sclerosis: results of a phase III multicenter, doubleblind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group. Neurology, 1995, 45(7), 1268-1276.
36. Johnson, K.P.; Brooks, B.R.; Cohen, J.A.; Ford, C.C.; Goldstein, J.; Lisak, R.P.; Myers, L.W.; Panitch, H.S.; Rose, J.W.; Schiffer, R.B.; Vollmer, T.; Weiner, L.P.; Wolinsky, J.S. Extended use of glatiramer acetate (Copaxone) is well tolerated and maintains its clinical effect on multiple sclerosis relapse rate and degree of disability. Copolymer 1 Multiple Sclerosis Study Group. Neurology, 1998, 50(3), 701-708.
37. Wolinsky, J.S.; Narayana, P.A.; Johnson, K.P. United States open-label glatiramer acetate extension trial for relapsing multiple sclerosis: MRI and clinical correlates. Multiple Sclerosis Study Group and the MRI Analysis Center. Mult. Scler., 2001, 7(1), 33-41.
38. Johnson, K.P.; Brooks, B.R.; Ford, C.C.; Goodman, A.; Guarnaccia, J.; Lisak, R.P.; Myers, L.W.; Panitch, H.S.; Pruitt, A.; Rose, J.W.; Kachuck, N.; Wolinsky, J.S. Sustained clinical benefits of glatiramer acetate in relapsing multiple sclerosis patients observed for 6 years. Copolymer 1 Multiple Sclerosis Study Group. Mult. Scler., 2000, 6(4), 255-266.
39. Comi, G.; Filippi, M.; Wolinsky, J.S. European/Canadian multicenter, double-blind, randomized, placebo-controlled study of the effects of glatiramer acetate on magnetic resonance imaging-measured disease activity and burden in patients with relapsing multiple sclerosis. European/Canadian Gla. Ann. Neurol., 2001, 49(3), 290-297.
40. Rovaris, M.; Comi, G.; Rocca, M.A.; Valsasina, P.; Ladkani, D.; Pieri, E.; Weiss, S.; Shifroni, G.; Wolinsky, J.S.; Filippi, M. Long-term follow-up of patients treated with glatiramer acetate: a multicentre, multinational extension of the European/Canadian double-blind, placebo-controlled, MRI-monitored trial. Mult. Scler., 2007, 13(4), 502-508.
41. Comi, G.; Martinelli, V.; Rodegher, M.; Moiola, L.; Bajenaru, O.; Carra, A.; Elovaara, I.; Fazekas, F.; Hartung, H.P.; Hillert, J.; King, J.; Komoly, S.; Lubetzki, C.; Montalban, X.; Myhr, K.M.; Ravnborg, M.; Rieckmann, P.; Wynn, D.; Young, C.; Filippi, M. Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study), a randomised, double-blind, placebo-controlled trial. Lancet, 2009, 374(9700), 1503-1511.
42. Sørensen, P.S. REGARD: what can we learn from randomised, openlabel, head-to-head studies? Lancet Neurol., 2008, 7(10), 864-866.
43. Coles, A. Trials of diminishing relapses for diminishing returns. Lancet Neurol., 2009, 8(10), 870-871.
44. Barbero, P.; Bergui, M.; Versino, E.; Ricci, A.; Zhong, J.J.; Ferrero, B.; Clerico, M.; Pipieri, A.; Verdun, E.; Giordano, L.; Durelli, L. Everyother-day interferon beta-1b versus once-weekly interferon beta-1a for multiple sclerosis (INCOMIN Trial) II: analysis of MRI responses to treatment and correlation with Nab. Mult. Scler., 2006, 12(1), 72-76.
45. Koch-Henriksen, N.; Sørensen, P.S.; Christensen, T.; Frederiksen, J.; Ravnborg, M.; Jensen, K.; Heltberg, A.; Kristensen, O.; Stenager, E.; Petersen, T.; Hansen, T. A randomized study of two interferon-beta treatments in relapsing-remitting multiple sclerosis. Neurology, 2006, 66(7), 1056-1060.
46. Mikol, D.D.; Barkhof, F.; Chang, P.; Coyle, P.K.; Jeffery, D.R.; Schwid, S.R.; Stubinski, B.; Uitdehaag, B.M.J. Comparison of subcutaneous interferon beta-1a with glatiramer acetate in patients with relapsing multiple sclerosis (the REbif vs Glatiramer Acetate in Relapsing MS Disease [REGARD] study), a multicentre, randomised, parallel, open-label trial. Lancet Neurol., 2008, 7(10), 903-914.
47. O'Connor, P.; Filippi, M.; Arnason, B.; Comi, G.; Cook, S.; Goodin, D.; Hartung, H-P.; Jeffery, D.; Kappos, L.; Boateng, F.; Filippov, V.; Groth, M.; Knappertz, V.; Kraus, C.; Sandbrink, R.; Pohl, C.; Bogumil, T. 250 microg or 500 microg interferon beta-1b versus 20 mg glatiramer acetate in relapsing-remitting multiple sclerosis: a prospective, randomised, multicentre study. Lancet Neurol., 2009, 8(10), 889-897.
48. Cadavid, D.; Wolansky, L.J.; Skurnick, J.; Lincoln, J.; Cheriyan, J.; Szczepanowski, K.; Kamin, S.S.; Pachner, A.R.; Halper, J.; Cook, S.D. Efficacy of treatment of MS with IFNbeta-1b or glatiramer acetate by monthly brain MRI in the BECOME study. Neurology, 2009, 72(23), 1976-1983.
49. DeLuca, G.C.; Williams, K.; Evangelou, N.; Ebers, G.C.; Esiri, M.M. The contribution of demyelination to axonal loss in multiple sclerosis. Brain, 2006, 129(Pt 6), 1507-1516.
50. Kutzelnigg, A.; Lucchinetti, C.F.; Stadelmann, C.; Brück, W.; Rauschka, H.; Bergmann, M.; Schmidbauer, M.; Parisi, J.E.; Lassmann, H. Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain, 2005, 128(Pt 11), 2705-2712.
51. Andersen, O. Predicting a window of therapeutic opportunity in multiple sclerosis. Brain, 2010, 133(7), 1863-1865.
52. Vartanian, T. An examination of the results of the EVIDENCE, INCOMIN, and phase III studies of interferon beta products in the treatment of multiple sclerosis. Clin. Ther., 2003, 25(1), 105-118.
53. Miller, D.H.; Leary, S.M. Treatment of clinically isolated syndrome: to be PreCISe. Lancet, 2009, 374(9700), 1475-1476.
54. Río, J.; Castilló, J.; Rovira, A.; Tintoré, M.; Sastre-Garriga, J.; Horga, A.; Nos, C.; Comabella, M.; Aymerich, X.; Montalbán, X. Measures in the first year of therapy predict the response to interferon beta in MS. Mult. Scler., 2009, 15(7), 848-853.
55. Prosperini, L.; Gallo, V.; Petsas, N.; Borriello, G.; Pozzilli, C. One-year MRI scan predicts clinical response to interferon beta in multiple sclerosis. Eur. J. Neurol., 2009, 16(11), 1202-1209.
56. Stüve, O. The effects of natalizumab on the innate and adaptive immune system in the central nervous system. J. Neurol. Sci., 2008, 274(1-2), 39-41.
57. Stüve, O.; Marra, C.M.; Jerome, K.R.; Cook, L.; Cravens, P.D.; Cepok, S.; Frohman, E.M.; Phillips, J.T.; Arendt, G.; Hemmer, B.; Monson, N.L.; Racke, M.K. Immune surveillance in multiple sclerosis patients treated with natalizumab. Ann. Neurol., 2006, 59(5), 743-747.
58. Stüve, O.; Gold, R.; Chan, A.; Mix, E.; Zettl, U.; Kieseier, B.C. alpha4-Integrin antagonism with natalizumab: effects and adverse effects. J. Neurol., 2008, 255(Suppl), 58-65.
59. Stüve, O.; Marra, C.M.; Bar-Or, A.; Niino, M.; Cravens, P.D.; Cepok, S.; Frohman, E.M.; Phillips, J.T.; Arendt, G.; Jerome, K.R.; Cook, L.; Grand'Maison, F.; Hemmer, B.; Monson, N.L.; Racke, M.K. Altered CD4+/CD8+ T-cell ratios in cerebrospinal fluid of natalizumab-treated patients with multiple sclerosis. Arch. Neurol., 2006, 63(10), 1383-1387.
60. Planas, R.; Jelci, I.; Schippling, S.; Martin, R.; Sospedra, M. Natalizumab treatment perturbs memory-and marginal zone-like b-cell homing in secondary lymphoid organs in multiple sclerosis. Eur. J. Immunol., 2011, 42(3), 790-798.
61. Saure, C.; Warnke, C.; Zohren, F.; Schroeder, T.; Bruns, I.; Cadeddu, R.P.; Weigelt, C.; Fischer, U.; Kobbe, G.; Hartung, H-P.; Adams, O.; Kieseier, B.C.; Haas, R. Natalizumab and Impedance of the Homing of CD34+ Hematopoietic Progenitors. Arch. Neurol., 2011, 68(11), 1428-1431.
62. Miller, D.H.; Khan, O.A.; Sheremata, W.A.; Blumhardt, L.D.; Rice, G.P.A.; Libonati, M.A.; Willmer-Hulme, A.J.; Dalton, C.M.; Miszkiel, K.A.; O'Connor, P.W. A controlled trial of natalizumab for relapsing multiple sclerosis. N. Engl. J. Med., 2003, 348(1), 15-23.
63. Polman, C.H.; O'Connor, P.W.; Havrdova, E.; Hutchinson, M.; Kappos, L.; Miller, D.H.; Phillips, J.T.; Lublin, F.D.; Giovannoni, G.; Wajgt, A.; Toal, M.; Lynn, F.; Panzara, M.A.; Sandrock, A.W. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N. Engl. J. Med., 2006, 354(9), 899-910.
64. Hutchinson, M.; Kappos, L.; Calabresi, P.A.; Confavreux, C.; Giovannoni, G.; Galetta, S.L.; Havrdova, E.; Lublin, F.D.; Miller, D.H.; O'Connor, P.W.; Phillips, J.T.; Polman, C.H.; Radue, E-W.; Rudick, R.A.; Stuart, W.H.; Wajgt, A.; Weinstock-Guttman, B.; Wynn, D.R.; Lynn, F.; Panzara, M.A. The efficacy of natalizumab in patients with relapsing multiple sclerosis: subgroup analyses of AFFIRM and SENTINEL. J. Neurol., 2009, 256(3), 405-415.
65. Miller, D.H.; Soon, D.; Fernando, K.T.; MacManus, D.G.; Barker, G.J.; Yousry, T.A.; Fisher, E.; O'Connor, P.W.; Phillips, J.T.; Polman, C.H.; Kappos, L.; Hutchinson, M.; Havrdova, E.; Lublin, F.D.; Giovannoni, G.; Wajgt, A.; Rudick, R.; Lynn, F.; Panzara, M.A.; Sandrock, A.W. MRI outcomes in a placebo-controlled trial of natalizumab in relapsing MS. Neurology, 2007, 68(17), 1390-1401.
66. Rudick, R.A.; Miller, D.; Hass, S.; Hutchinson, M.; Calabresi, P.A.; Confavreux, C.; Galetta, S.L.; Giovannoni, G.; Havrdova, E.; Kappos, L.; Lublin, F.D.; Miller, D.H.; O'Connor, P.W.; Phillips, J.T.; Polman, C.H.; Radue, E-W.; Stuart, W.H.; Wajgt, A.; Weinstock-Guttman, B.; Wynn, D.R.; Lynn, F.; Panzara, M.A. Health-related quality of life in multiple sclerosis: effects of natalizumab. Ann. Neurol., 2007, 62(4), 335-346.
67. Phillips, J.T.; Giovannoni, G.; Lublin, F.D.; O'Connor, P.W.; Polman, C.H.; Willoughby, E.; Aschenbach, W.; Pace, A.; Hyde, R.; Munschauer, F.E. Sustained improvement in Expanded Disability Status Scale as a new efficacy measure of neurological change in multiple sclerosis: treatment effects with natalizumab in patients with relapsing multiple sclerosis. Mult. Scler., 2011, 17(8), 970-979.
68. Havrdova, E.; Galetta, S.; Hutchinson, M.; Stefoski, D.; Bates, D.; Polman, C.H.; Connor, P.W.; Giovannoni, G.; Phillips, J.T.; Lublin, F.D.; Pace, A.; Kim, R.; Hyde, R. 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), 254-260.
69. Dalton, C.M.; Miszkiel, K.A.; Barker, G.J.; MacManus, D.G.; Pepple, T.I.; Panzara, M.; Yang, M.; Hulme, A.; O'Connor, P.; Miller, D.H. Effect of natalizumab on conversion of gadolinium enhancing lesions to T1 hypointense lesions in relapsing multiple sclerosis. J. Neurol., 2004, 251(4), 407-413.
70. Oturai, A.B.; Koch-Henriksen, N.; Petersen, T.; Jensen, P.E.H.; Sellebjerg, F.; Sorensen, P.S. Efficacy of natalizumab in multiple sclerosis patients with high disease activity: a Danish nationwide study. Eur. J. Neurol., 2009, 16(3), 420-423.
71. Putzki, N.; Kollia, K.; Woods, S.; Igwe, E.; Diener, H.C.; Limmroth, V. Natalizumab is effective as second line therapy in the treatment of relapsing remitting multiple sclerosis. Eur. J. Neurol., 2009, 16(3), 424-426.
72. Putzki, N.; Yaldizli, O.; Mäurer, M.; Cursiefen, S.; Kuckert, S.; Klawe, C.; Maschke, M.; Tettenborn, B.; Limmroth, V. Efficacy of natalizumab in second line therapy of relapsing-remitting multiple sclerosis: results from a multi-center study in German speaking countries. Eur. J. Neurol., 2010, 17(1), 31-37.
73. Calabresi, P.A.; Giovannoni, G.; Confavreux, C.; Galetta, S.L.; Havrdova, E.; Hutchinson, M.; Kappos, L.; Miller, D.H.; O'Connor, P.W.; Phillips, J.T.; Polman, C.H.; Radue, E-W.; Rudick, R.A.; Stuart, W.H.; Lublin, F.D.; Wajgt, A.; Weinstock-Guttman, B.; Wynn, D.R.; Lynn, F.; Panzara, M.A. The incidence and significance of antinatalizumab antibodies: results from AFFIRM and SENTINEL. Neurology, 2007, 69(14), 1391-1403.
74. O'Connor, P.W.; Goodman, A.; Kappos, L.; Lublin, F.D.; Miller, D.H.; Polman, C.; Rudick, R.A.; Aschenbach, W.; Lucas, N. Disease activity return during natalizumab treatment interruption in patients with multiple sclerosis. Neurology, 2011, 76(22), 1858-1865.
75. Kappos, L.; Bates, D.; Edan, G.; Eraksoy, M.; Garcia-Merino, A.; Grigoriadis, N.; Hartung, H-P.; Havrdová, E.; Hillert, J.; Hohlfeld, R.; Kremenchutzky, M.; Lyon-Caen, O.; Miller, A.; Pozzilli, C.; Ravnborg, M.; Saida, T.; Sindic, C.; Vass, K.; Clifford, D.B.; Hauser, S.; Major, E.O.; O'Connor, P.W.; Weiner, H.L.; Clanet, M.; Gold, R.; Hirsch, H.H.; Radü, E-W.; Sørensen, P.S.; King, J. Natalizumab treatment for multiple sclerosis: updated recommendations for patient selection and monitoring. Lancet Neurol., 2011, 10(8), 745-758.
76. Bozic, C.; Richman, S.; Plavina, T.; Natarajan, A.; Scanlon, J.V.; Subramanyam, M.; Sandrock, A.; Bloomgren, G. Anti-John Cunnigham virus antibody prevalence in multiple sclerosis patients: Baseline results of STRATIFY-1. Ann. Neurol., 2011, 70(5), 713-721.
77. Melin, A.; Outteryck, O.; Collongues, N.; Zéphir, H.; Fleury, M.C.; Blanc, F.; Lacour, A.; Ongagna, J.C.; Berteloot, A.S.; Vermersch, P.; de Sèze, J. Effect of natalizumab on clinical and radiological disease activity in a French cohort of patients with relapsing-remitting multiple sclerosis. J. Neurol., 2011, Epub ahead of print.
78. Sorensen, P.S. How effective is natalizumab as second-line treatment for multiple sclerosis in daily clinical praxis? Eur. J. Neurol., 2009, 16(3), 287-288.
79. Zemann, B.; Kinzel, B.; Müller, M.; Reuschel, R.; Mechtcheriakova, D.; Urtz, N.; Bornancin, F.; Baumruker, T.; Billich, A. Sphingosine kinase type 2 is essential for lymphopenia induced by the immunomodulatory drug FTY720. Blood, 2006, 107(4), 1454-1458.
80. Cohen, J.A.; Chun, J. Mechanisms of fingolimod's efficacy and adverse effects in multiple sclerosis. Ann. Neurol., 2011, 69(5), 759-777.
81. Sanchez, T.; Estrada-Hernandez, T.; Paik, J-H.; Wu, M-T.; Venkataraman, K.; Brinkmann, V.; Claffey, K.; Hla, T. Phosphorylation and action of the immunomodulator FTY720 inhibits vascular endothelial cell growth factor-induced vascular permeability. J. Biol. Chem., 2003, 278(47), 47281-47290.
82. Paugh, S.W.; Payne, S.G.; Barbour, S.E.; Milstien, S.; Spiegel, S. The immunosuppressant FTY720 is phosphorylated by sphingosine kinase type 2. FEBS Lett., 2003, 554(1-2), 189-193.
83. Ontaneda, D.; Cohen, J.A. Potential mechanisms of efficacy and adverse effects in the use of fingolimod (FTY720). Expert Rev. Clin. Pharmacol., 2011, 4(5), 567-570.
84. Kappos, L.; Radue, E-W.; O'Connor, P.; Polman, C.; Hohlfeld, R.; Calabresi, P.; Selmaj, K.; Agoropoulou, C.; Leyk, M.; Zhang-Auberson, L.; Burtin, P. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N. Engl. J. Med., 2010, 362(5), 387-401.
85. Cohen, J.A.; Barkhof, F.; Comi, G.; Hartung, H-P.; Khatri, B.O.; Montalban, X.; Pelletier, J.; Capra, R.; Gallo, P.; Izquierdo, G.; Tiel-Wilck, K.; de Vera, A.; Jin, J.; Stites, T.; Wu, S.; Aradhye, S.; Kappos, L. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N. Engl. J. Med., 2010, 362(5), 402-415.
86. Khatri, B.; Barkhof, F.; Comi, G.; Hartung, H-P.; Kappos, L.; Montalban, X.; Pelletier, J.; Stites, T.; Wu, S.; Holdbrook, F.; Zhang-Auberson, L.; Francis, G.; Cohen, J.A. Comparison of fingolimod with interferon beta-1a in relapsing-remitting multiple sclerosis: a randomised extension of the TRANSFORMS study. Lancet Neurol., 2011, 10(6), 520-529.
87. Mehling, M.; Brinkmann, V.; Antel, J.; Bar-Or, A.; Goebels, N.; Vedrine, C.; Kristofic, C.; Kuhle, J.; Lindberg, R.L.P.; Kappos, L. FTY720 therapy exerts differential effects on T cell subsets in multiple sclerosis. Neurology, 2008, 71(16), 1261-1267.
88. Johnson, T.A.; Lapierre, Y.; Bar-Or, A.; Antel, J.P. Distinct properties of circulating CD8+ T cells in FTY720-treated patients with multiple sclerosis. Arch. Neurol., 2010, 67(12), 1449-1455.
89. Mehling, M.; Lindberg, R.; Raulf, F.; Kuhle, J.; Hess, C.; Kappos, L.; Brinkmann, V. Th17 central memory T cells are reduced by FTY720 in patients with multiple sclerosis. Neurology, 2010, 75(5), 403-410.
90. Johnson, T.A.; Evans, B.L.; Durafourt, B.A.; Blain, M.; Lapierre, Y.; Bar-Or, A.; Antel, J.P. Reduction of the peripheral blood CD56(bright) NK lymphocyte subset in FTY720-treated multiple sclerosis patients. J. Immunol., 2011, 187(1), 570-579.
91. Kowarik, M.C.; Pellkofer, H.L.; Cepok, S.; Korn, T.; Kümpfel, T.; Buck, D.; Hohlfeld, R.; Berthele, A.; Hemmer, B. Differential effects of fingolimod (FTY720) on immune cells in the CSF and blood of patients with MS. Neurology, 2011, 76(14), 1214-1221.
92. Johnson, T.A.; Shames, I.; Keezer, M.; Lapierre, Y.; Haegert, D.G.; Bar-Or, A.; Antel, J. Reconstitution of circulating lymphocyte counts in FTY720-treated MS patients. Clin. Immunol., 2010, 137(1), 15-20.
93. Killestein, J.; Rudick, R.A.; Polman, C.H. Oral treatment for multiple sclerosis. Lancet Neurol., 2011, 10(11), 1026-1034.
94. Cook, S.; Vermersch, P.; Comi, G.; Giovannoni, G.; Rammohan, K.; Rieckmann, P.; Sørensen, P.S.; Hamlett, A.; Miret, M.; Weiner, J.; Viglietta, V.; Musch, B.; Greenberg, S.J. Safety and tolerability of cladribine tablets in multiple sclerosis: the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study. Mult. Scler., 2011, 17(5), 578-593.
95. Giovannoni, G.; Comi, G.; Cook, S.; Rammohan, K.; Rieckmann, P.; Soelberg S.P.; Vermersch, P.; Chang, P.; Hamlett, A.; Musch, B.; Greenberg, S.J. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis. N. Engl. J. Med., 2010, 362(5), 416-426.
96. Giovannoni, G.; Cook, S.; Rammohan, K.; Rieckmann, P.; Sørensen, P.S.; Vermersch, P.; Hamlett, A.; Viglietta, V.; Greenberg, S. Sustained disease-activity-free status in patients with relapsing-remitting multiple sclerosis treated with cladribine tablets in the CLARITY study: a posthoc and subgroup analysis. Lancet Neurol., 2011, 10(4), 329-337.
97. Polman, C.; Barkhof, F.; Sandberg-Wollheim, M.; Linde, A.; Nordle, O.; Nederman, T. Treatment with laquinimod reduces development of active MRI lesions in relapsing MS. Neurology, 2005, 64(6), 987-991.
98. Comi, G.; Pulizzi, A.; Rovaris, M.; Abramsky, O.; Arbizu, T.; Boiko, A.; Gold, R.; Havrdova, E.; Komoly, S.; Selmaj, K.W.; Sharrack, B.; Filippi, M. 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), 2085-2092.
99. Kappos, L.; Gold, R.; Miller, D.H.; Macmanus, D.G.; Havrdova, E.; Limmroth, V.; Polman, C.H.; Schmierer, K.; Yousry, T.A.; Yang, M.; Eraksoy, M.; Meluzinova, E.; Rektor, I.; Dawson, K.T.; Sandrock, A.W.; O'Neill, G.N. 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), 1463-1472.
100. MacManus, D.G.; Miller, D.H.; Kappos, L.; Gold, R.; Havrdova, E.; Limmroth, V.; Polman, C.H.; Schmierer, K.; Yousry, T.A.; Eraksoy, M.; Meluzinova, E.; Dufek, M.; Yang, M.; O'Neill, G.N.; Dawson, K. BG-12 reduces evolution of new enhancing lesions to T1-hypointense lesions in patients with multiple sclerosis. J. Neurol., 2011, 258(3), 449-456.
101. Kappos, L.; Gold, R.; Miller, D.H.; Macmanus, D.G.; Havrdova, E.; Limmroth, V.; Polman, C.H.; Schmierer, K.; Yousry, T.A.; Eraksoy, M.; Meluzinova, E.; Dufek, M.; Yang, M.; Dawson, K.; O'Neill, G.N. Effect of BG-12 on contrast-enhancing lesions in patients with relapsing-remitting multiple sclerosis: subgroup analyses from the phase 2b study. Mult. Scler., 2011, 18(3), 314-321.
102. Gold, R.; Wolinsky, J.S. Pathophysiology of multiple sclerosis and the place of teriflunomide. Acta Neurol. Scand., 2011, 124(2), 75-84.
103. Claussen, M.C.; Korn, T.;Immune mechanisms of new therapeutic strategies in MS-Teriflunomide. Clin. Immunol., 2011, 142(1), 49-56.
104. O'Connor, P.; Wolinsky, J.S.; Confavreux, C.; Comi, G.; Kappos, L.; Olsson, T.; Benzerdjeb, H.; Truffinet, P.; Wang, L.; Miller, A.; Freedman, M.S. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N. Engl. J. Med., 2011, 365(14), 1293-1303.
105. Hill-Cawthorne, G.A.; Button, T.; Tuohy, O.; Jones, J.L.; May, K.; Somerfield, J.; Green, A.; Giovannoni, G.; Compston, D.A.S.; Fahey, M.T.; Coles, A.J. Long term lymphocyte reconstitution after alemtuzumab treatment of multiple sclerosis. J. Neurol. Neurosurg. Psychiatry, 2011, 83(3), 298-304.
106. Coles, A.J.; Compston, D.A.S.; Selmaj, K.W.; Lake, S.L.; Moran, S.; Margolin, D.H.; Norris, K.; Tandon, P.K. Alemtuzumab vs interferon beta-1a in early multiple sclerosis. N. Engl. J. Med., 2008, 359(17), 1786-1801.
107. Jones, J.L.; Anderson, J.M.; Phuah, C-L.; Fox, E.J.; Selmaj, K.; Margolin, D.; Lake, S.L.; Palmer, J.; Thompson, S.J.; Wilkins, A.; Webber, D.J.; Compston, D.A.S.; Coles, A.J. Improvement in disability after alemtuzumab treatment of multiple sclerosis is associated with neuroprotective autoimmunity. Brain, 2010, 133(Pt 8), 2232-2247.
108. Coles, A.J.; Fox, E.; Vladic, A.; Gazda, S.K.; Brinar, V.; Selmaj, K.W.; Bass, A. D-D.; Wynn, D.R.; Margolin, D.H.; Lake, S.L.; Moran, S.; Palmer, J.; Smith, M.S.; Compston, D.A.S. Alemtuzumab versus interferon beta-1a in early relapsing-remitting multiple sclerosis: posthoc and subset analyses of clinical efficacy outcomes. Lancet Neurol., 2011, 10(4), 338-348.
109. Cossburn, M.; Pace, A.A.; Jones, J.; Ali, R.; Ingram, G.; Baker, K.; Hirst, C.; Zajicek, J.; Scolding, N.; Boggild, M.; Pickersgill, T.; Ben-Shlomo, Y.; Coles, A.; Robertson, N.P. Autoimmune disease after alemtuzumab treatment for multiple sclerosis in a multicenter cohort. Neurology, 2011, 77(6), 573-579.
110. Jones, J.L.; Phuah, C-L.; Cox, A.L.; Thompson, S.A.; Ban, M.; Shawcross, J.; Walton, A.; Sawcer, S.J.; Compston, A.; Coles, A.J. IL-21 drives secondary autoimmunity in patients with multiple sclerosis, following therapeutic lymphocyte depletion with alemtuzumab (Campath-1H). J. Clin. Invest., 2009, 119(7), 2052-2061.
111. Wynn, D.; Kaufman, M.; Montalban, X.; Vollmer, T.; Simon, J.; Elkins, J.; O'Neill, G.; Neyer, L.; Sheridan, J.; Wang, C.; Fong, A.; Rose, J.W. 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), 381-390.
112. Hauser, S.L.; Waubant, E.; Arnold, D.L.; Vollmer, T.; Antel, J.; Fox, R.J.; Bar-Or, A.; Panzara, M.; Sarkar, N.; Agarwal, S.; Langer-Gould, A.; Smith, C.H. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N. Engl. J. Med., 2008, 358(7), 676-688.
113. Bar-Or, A.; Calabresi, P.A.J.; Arnold, D.; Markowitz, C.; Shafer, S.; Kasper, L.H.; Waubant, E.; Gazda, S.; Fox, R.J.; Panzara, M.; Sarkar, N.; Agarwal, S.; Smith, C.H. Rituximab in relapsing-remitting multiple sclerosis: a 72-week, open-label, phase I trial. Ann. Neurol., 2008, 63(3), 395-400.
114. He, D.; Zhou, H.; Han, W.; Zhang, S. Rituximab for relapsing-remitting multiple sclerosis. Cochrane Database Syst. Rev., 2011, 12:CD009130.
115. Naismith, R.T.; Piccio, L.; Lyons, J.A.; Lauber, J.; Tutlam, N.T.; Parks, B.J.; Trinkaus, K.; Song, S.K.; Cross, A.H. Rituximab add-on therapy for breakthrough relapsing multiple sclerosis: a 52-week phase II trial. Neurology, 2010, 74(23), 1860-1867.
116. Kappos, L.; Li, D.; Calabresi, P.A.; O'Connor, P.; Bar-Or, A.; Barkhof, F.; Yin, M.; Leppert, D.; Glanzman, R.; Tinbergen, J.; Hauser, S.L. Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial. Lancet, 2011, 378(9805), 1779-1787.