Emerging multiple sclerosis oral therapies

Neurology

Volumn 74, Issue 1 SUPPL., 2010, Pages

  Rammohan, Kottil W ^a,b   Shoemaker, Jennifer ^a,c  

^a MS Center   (United States)

^b THE OHIO STATE UNIVERSITY COLLEGE OF MEDICINE   (United States)

^c Expert Medical Education   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BETA1A INTERFERON; BG 00012; CLADRIBINE; FINGOLIMOD; FUMARIC ACID; GLATIRAMER; LAQUINIMOD; TERIFLUNOMIDE; UNCLASSIFIED DRUG;

ALANINE AMINOTRANSFERASE BLOOD LEVEL; CLINICAL TRIAL; DRUG DOSE COMPARISON; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; DRUG MEGADOSE; HUMAN; LOW DRUG DOSE; MULTIPLE SCLEROSIS; NONHUMAN; PRIORITY JOURNAL; RECURRENCE RISK; RELAPSE; REVIEW; RISK BENEFIT ANALYSIS; SIDE EFFECT; SYMPTOM;

EID: 74249102004     PISSN: 00283878     EISSN: 1526632X     Source Type: Journal    
DOI: 10.1212/WNL.0b013e3181c97f89     Document Type: Article

References (50)

1. Copaxone [package insert]. Kansas City, MO: Teva Neuroscience Inc; 2009.
2. Betaseron [package insert]. Montville, NJ: Bayer Health-Care Pharmaceuticals, Inc; 2008.
3. Rebif [package insert]. Rockland, MA: EMD Serono, Inc; 2009.
4. Avonex [package insert]. Cambridge, MA: Biogen Idec, Inc; 2008.
5. 5. 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;354:899-910. (Pubitemid 43313657)
6. Hawker K. B-cell-targeted treatment for multiple sclerosis: mechanism of action and clinical data. Curr Opin Neurol 2008;21(suppl 1):S19-S25.
7. 7. Fox EJ. Management of worsening multiple sclerosis with mitoxantrone: a review. Clin Ther 2006;28:461-474. (Pubitemid 44208782)
8. 8. Czeloth N, Bernhardt G, Hofmann F, Genth H, Forster R. Sphingosine-1-phosphate mediates migration of mature dendritic cells. J Immunol 2005;175:2960-2967. (Pubitemid 41170513)
9. Osinde M, Dev K, Novartis. The sphingosine-1-phosphate receptor subtype-1 stimulates ERK phosphorylation in astrocytes. Presented at the 22nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis. 2006;12(suppl 2):P792. Abstract.
10. 10. Kimura A, Ohmori T, Ohkawa R, et al. Essential roles of sphingosine 1-phosphate/Sl.Pl receptor axis in the migration of neural stem cells toward a site of spinal cord injury. Stem Cells 2007;25:115-124. (Pubitemid 46052981)
11. 11. Sanna MG, Liao J, Jo E, et al. Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and. S1P3, respectively, regulate lymphocyte recirculation and heart rate. J Biol Chem 2004;279:13839-13848. (Pubitemid 38468916)
12. 12. Brinkmann V, Davis MD, Heise CE, et al. The immune modulator FTY720 targets sphingosine 1-phosphate receptors. J Biol Chem 2002;277:21453-21457. (Pubitemid 34952287)
13. 13. Rausch M, Hiestand P, Foster CA, Baumann DR, Cannet C, Rudin M. Predictability of FTY720 efficacy in experimental autoimmune encephalomyelitis by in vivo macrophage tracking: clinical implications for ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging. J Magn Reson Imaging 2004;20:16-24. (Pubitemid 38857512)
14. 14. Fujino M, Funeshima N, Kitazawa Y, et al. Amelioration of experimental autoimmune encephalomyelitis in Lewis rats by FTY720 treatment. J Pharmacol Exp Ther 2003; 305:70-77. (Pubitemid 36378136)
15. Storch M, Rausch M, Hiestand. P, Balatoni B, Foster C. FTY720 not only prevents EAE onset, as assessed by MRI, but also reverses established neurological deficits and extensive demyelination. Presented at the 22nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis; 2006:12(suppl 2):P188. Abstract.
16. Schwab SR, Cyster JG. Finding a way out: lymphocyte egress from lymphoid organs. Nat Immunol 2007;8: 1295-1301.
17. Mehling M, Brinkmann V, Antel J, et al. FTY720 therapy exerts differential effects on T cell subsets in multiple sclerosis. Neurology 2008;71:1261-1267.
18. Schmouder R, Aradhye S, O'Connor P, Kappos L, Pharmaceuticals N, St. Michael's Hospital (Toronto, CA). Pharmacodynamic effects of oral fmgolimod (FTY720). Presented at the 22nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis; 2006:12(suppl 2):P378. Abstract.
19. Brinkmann V, Cyster JG, Hla T. FTY720: sphingosine 1-phosphate receptor-1. in the control of lymphocyte egress and endothelial barrier function. Am J Transplant 2004;4: 1019-1.025.
20. Horga A, Montalban X. FTY720 (fmgolimod) for relapsing multiple sclerosis. Expert RevNeurother 2008;8:699-714. (Pubitemid 351656821)
21. O'Connor P, Comi G, Montalban X, et al. Oral, fmgolimod (FTY720) in multiple sclerosis: two-year results of a phase II extension study. Neurology 2009;72:73-79.
22. Trial watch: phase III promise for oral multiple sclerosis therapy. Nat Rev Drug Discov 2009;8:98.
23. Cohen J, Pelletier J, Kappos L, et al. Oral fingolimod (FTY720) significantly reduced relapse rate compared with intramuscular interferon beta-1a in relapsing-remitting multiple sclerosis: clinical results from a 12-month phase III study (TRANSFORMS). Presented at European Committee for Treatment and Research in Multiple Sclerosis Annual Meeting; September 9-12, 2009; Düsseldorf) Germany.
24. National Multiple Sclerosis Society's Advisory Committee on Trials of New Drugs in MS. In: Clinical Trials in Multiple Sclerosis 2009: Planned, In Progress, Recently Completed. Available at: http://www.nationalmssociety.org/ clinicaltrials. Accessed June 1, 2009.
25. Yang JS, Xu LY, Xiao BG, Hedlund G, Link H. Laquinimod (ABR-215062) suppresses the development of experimental autoimmune encephalomyelitis, modulates the Th1/Th2 balance and induces the Th3 cytokine TGF-beta in Lewis rats. J Neuroimmunol 2004;156:3-9. (Pubitemid 39310510)
26. Brunmark C, Runstrom A, Ohlsson L, et al. The new orally active immunoregulator laquinimod (ABR-215062) effectively inhibits development and relapses of experimental autoimmune encephalomyelitis. J Neuroimmunol 2002;130:163-172. (Pubitemid 35240003)
27. 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;371:2085-2092. (Pubitemid 351842581)
28. Comi G, Abramsky O, Arbizu T, et al. Oral laquinimod in patients with relapsing-remitting multiple sclerosis: 9-month double-blind active extension of the multicenter, randomized, double-blind, parallel-group placebocontrolled study. Mult Scler 2008;14:S37.
29. Comi G, Abramsky O, Arbizu T, et al. Long-term open extension of oral laquinimod in patients with relapsing multiple sclerosis shows favourable safety and sustained low relapse rate and MRI activity. Presented at European Committee for Treatment and Research in Multiple Sclerosis Annual Meeting; September 9-12, 2009; Dusseldorf, Germany.
30. Sørensen PS, Vollmer T, Arnold DL, et al. Benefit-to-risk ratio comparison of oral laquinimod and interferon beta-1a IM in relapsing-remitting multiple sclerosis: study design of the 2-year phase III BRAVO trial. Presented at European Committee for Treatment and Research in Multiple Sclerosis Annual Meeting; September 9-12, 2009; Düsseldorf, Germany.
31. Comi G, Jeffery D, Kappos L, et al. Baseline demographics of a placebo-controlled, double-blind, randomised study of oral laquinimod 0.6 mg in treating relapsing-remitting multiple sclerosis: the ALLEGRO study. Presented at European Committee for Treatment and Research in Multiple Sclerosis Annual Meeting; September 9-12, 2009; Düsseldorf, Germany.
32. Carson DA, Wasson DB, Tactic R, Yu A. Specific toxicity of 2-clilorodeoxyadenosine toward resting and proliferating human lymphocytes. Blood 1983;62:737-743.
33. Kawasaki H, Carrera CJ, Piro LD, Saven A, Kipps TJ, Carson DA. Relationship of deoxycytidine kinase and cytoplasmic 5′-nucleotidase to the chemotherapeutic efficacy of 2-chlorodeoxyadenosine. Blood 1993;81:597-601. (Pubitemid 23040848)
34. Beutler E, Sipe JC, Romine JS, Koziol JA, McMillan R, Zyroff J. The treatment of chronic progressive multiple sclerosis with cladribine. Proc Natl Acad Sci USA 1996;93: 1716-1720. (Pubitemid 26075191)
35. Rice GP, Filippi M, Comi G. Cladribine and progressive MS: clinical and MRI outcomes of a multicenter controlled trial. Cladribine MRI Study Group. Neurology 2000;54:1145-1155. (Pubitemid 30151860)
36. Bartosik-Psujek H, Belniak E, Mitosek-Szcwczyk K, Dobosz B, Stelmasiak Z. Interleukin-8 and. RANTES levels in patients with relapsing-remitting multiple sclerosis (RR-MS) treated with cladribine. Acta Neurol Scand 2004;109: 390-392.
37. Giovannoni G, Comi G, Cook S, et al. Clinical outcomes with cladribine tablets in the 96-week, phase III, double-blind, placebo-controlled CLARITY study in patients with relapsing-remitting multiple sclerosis. Presented at European Committee for Treatment and Research in Multiple Sclerosis Annual Meeting; September 9-12, 2009; Düsseldorf, Germany.
38. Lukashcv M, Zeng W, Ryan S, et al. Activation of Nrf2 and modulation of disease progression in EAE models by BG00012 (dimethyl fumaratc) suggests a novel mechanism of action combining anti-inflammatory and neuroprotective modalities. Presented at the 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis. Mult Scler 2007;13(suppl 2):P503. Abstract.
39. Itoh K, Chiba T, Takahashi S, et al. An Nrf2/smali Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun 1997;236:313-322.
40. 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; 372:1463-1.472.
41. Linker RA, Lee DH, Stangel M, Gold R. Fumarates for the treatment of multiple sclerosis: potential mechanisms of action and clinical, studies. Expert Rev Neurother 2008;8: 1683-1690.
42. Xu X, Williams JW, Gong H, Finnegan A, Chong AS. Two activities of the immunosuppressive metabolite of leflunomide, A77 1726 Inhibition of pyrimidine nucleotide synthesis and protein tyrosine phosphorylation. Biochem Pharmacol 1996;52:527-534.
43. Zeyda M, Poglitsch M, Geyeregger R, et al. Disruption of the interaction of T cells with antigen-presenting cells by the active leflunomide metabolite teriflunomide: involvement of impaired integrin activation and immunologic synapse formation. Arthritis Rheum 2005;52:2730-2739. (Pubitemid 41369101)
44. Manna SK, Aggarwal BB. Immunosuppressive leflunomide metabolite (A77 1726) blocks TNF-dependent nuclear factor-kappa B activation and gene expression. J Immunol 1999;162:2095-2102.
45. Mattar T, Kochhar K, Bartlett R, Bremer EG, Finnegan A. Inhibition of the epidermal growth factor receptor tyrosine kinase activity by leflunomide. FEBS Lett 1993;334:161-164.
46. Deage V, Burger D, Dayer JM. Exposure of T lymphocytes to leflunomide but not to dexamethasone favors the production by monocytic cells of interleukin-1 receptor antagonist and the tissue-inhibitor of metalloproteinases-1 over that of interleukin-1 beta and metalloproteinases. Eur Cytokine Netw 1998;9:663-668. (Pubitemid 29033934)
47. Tallantyre E, Evangelou N, Constantinescu CS. Spotlight on teriflunomide. Int MS J 2008;15:62-68.
48. O'Connor PW, Li D, Frcedman MS, et al. A Phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapses. Neurology 2006;66:894-900. (Pubitemid 43739766)
49. Freedman M, Wolinsky JS, Byrnes WJ. Oral teriflunomide or placebo added to interferon beta, for 6 months in patients with relapsing multiple sclerosis: safety and efficacy results. Presented at European Committee for Treatment and Research in Multiple Sclerosis Annual Meeting; September 9-12, 2009; Düsseldorf, Germany.
50. Goodman AD, Brown TR, Krupp LB, et al. Sustained-release oral fam pridine in multiple sclerosis: a randomised, double-blind, controlled trial. Lancet 2009;373: 732-738.