본문 바로가기
KERD
논문KCI 등재

Oral Disease-Modifying Therapies for Multiple Sclerosis

2

조회

0

다운로드

2

인용

0

참고문헌

키워드

초록

Classical multiple sclerosis (MS) treatments using first-line injectable drugs, although widelyapplied, remain a major concern in terms of therapeutic adherence and efficacy. New oral drugsrecently approved for MS treatment represent significant advances in therapy. The oral route ofadministration clearly promotes patient satisfaction and increases therapeutic compliance. However, these drugs may also have safety and tolerability issues, and a thorough analysis ofthe risks and benefits is required. Three oral drugs have been approved by regulatory agenciesfor MS treatment: fingolimod, teriflunomide, and dimethyl fumarate. This article reviews themechanisms of action, safety, and efficacy of these drugs and two other drugs that have yieldedpositive results in phase III trials: cladribine and laquinimod.

Abstract

Classical multiple sclerosis (MS) treatments using first-line injectable drugs, although widelyapplied, remain a major concern in terms of therapeutic adherence and efficacy. New oral drugsrecently approved for MS treatment represent significant advances in therapy. The oral route ofadministration clearly promotes patient satisfaction and increases therapeutic compliance. However, these drugs may also have safety and tolerability issues, and a thorough analysis ofthe risks and benefits is required. Three oral drugs have been approved by regulatory agenciesfor MS treatment: fingolimod, teriflunomide, and dimethyl fumarate. This article reviews themechanisms of action, safety, and efficacy of these drugs and two other drugs that have yieldedpositive results in phase III trials: cladribine and laquinimod.

참고문헌 (82)

  1. Fujita T, "Fungal metabolites. Part 11. A potent immunosuppressive activity found in Isaria sinclairii metabolite", J Antibiot, 47, pp.208~215 (1994)
  2. Massberg S, "Fingolimod and sphingosine-1-phosphate--modifiers of lymphocyte migration", N Engl J Med, 355, pp.1088~1091 (2006)
  3. Schwab SR, "Finding a way out: lymphocyte egress from lymphoid organs", Nat Immunol, 8, pp.1295~1301 (2007)
  4. Dev KK, "Brain sphingosine-1-phosphate receptors: implication for FTY720 in the treatment of multiple sclerosis", Pharmacol Ther, 117, pp.77~93 (2008)
  5. Mehling M, "FTY720 therapy exerts differential effects on T cell subsets in multiple sclerosis", Neurology, 71, pp.1261~1267 (2008)
  6. Brinkmann V, "The immune modulator FTY720 targets sphingosine 1-phosphate receptors", J Biol Chem, 277, pp.21453~21457 (2002)
  7. Mandala S, "Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists", Science, 296, pp.346~349 (2002)
  8. Brinkmann V, "FTY720: sphingosine 1-phosphate receptor-1 in the control of lymphocyte egress and endothelial barrier function", Am J Transplant, 4, pp.1019~1025 (2004)
  9. Matloubian M, "Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1", Nature, 427, pp.355~360 (2004)
  10. Killestein J, "Oral treatment for multiple sclerosis", Lancet Neurol, 10, pp.1026~1034 (2011)
  11. Cohen JA, "Mechanisms of fingolimod’s efficacy and adverse effects in multiple sclerosis", Ann Neurol, 69, pp.759~777 (2011)
  12. Conway D, "Emerging oral therapies in multiple sclerosis", Curr Neurol Neurosci Rep, 10, pp.381~388 (2010)
  13. Kappos L, "Oral fingolimod (FTY720) for relapsing multiple sclerosis", N Engl J Med, 355, pp.1124~1140 (2006)
  14. O’Connor P, "Oral fingolimod (FTY720) in multiple sclerosis: two-year results of a phase II extension study", Neurology, 72, pp.73~79 (2009)
  15. Comi G, "Phase II study of oral fingolimod (FTY720) in multiple sclerosis: 3-year results", Mult Scler, 16, pp.197~207 (2010)
  16. Kira J, "Fingolimod (FTY720) therapy in Japanese patients with relapsing multiple sclerosis over 12 months: results of a phase 2 observational extension", BMC Neurol, 14, pp.21~ (2014)
  17. Izquierdo G, "Five-year results from a phase 2 study of oral fingolimod in relapsing multiple sclerosis", Mult Scler, 20, pp.877~881 (2014)
  18. Kappos L, "A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis", N Engl J Med, 362, pp.387~401 (2010)
  19. Cohen JA, "Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis", N Engl J Med, 362, pp.402~415 (2010)
  20. Calabresi PA, "Safety and efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (FREEDOMS II): a double-blind, randomised, placebo-controlled, phase 3 trial", Lancet Neurol, 13, pp.545~556 (2014)
  21. Miller D, "Study design and baseline characteristics of the INFORMS study: fingolimod in patients with primary progressive multiple sclerosis (P07. 116)", Neurology, 80, pp.P07~116 (2013)
  22. Gold R, "Assessment of cardiac safety during fingolimod treatment initiation in a real-world relapsing multiple sclerosis population: a phase 3b, open-label study", J Neurol, 261, pp.267~276 (2014)
  23. Koyrakh L, "The heart rate decrease caused by acute FTY720 administration is mediated by the G protein-gated potassium channel I", Am J Transplant, 5, pp.529~536 (2005)
  24. "Summary of product characteristics" (2011)[URL]
  25. "Summary of product characteristics" (2012)[URL]
  26. "Highlights of prescribing information: these highlights do not include all the information needed to use GILENYA (TM) safely and effectively" (2012)[URL]
  27. Bruneau JM, "Purification of human dihydro-orotate dehydrogenase and its inhibition by A77 1726, the active metabolite of leflunomide", Biochem J, 336(2), pp.299~303 (1998)
  28. Herrmann ML, "Leflunomide: an immunomodulatory drug for the treatment of rheumatoid arthritis and other autoimmune diseases", Immunopharmacology, 47, pp.273~289 (2000)
  29. Merrill JE, "Teriflunomide reduces behavioral, electrophysiological, and histopathological deficits in the Dark Agouti rat model of experimental autoimmune encephalomyelitis", J Neurol, 256, pp.89~103 (2009)
  30. Greene S, "Inhibition of dihydroorotate dehydrogenase by the immunosuppressive agent leflunomide", Biochem Pharmacol, 50, pp.861~867 (1995)
  31. Davis JP, "The immunosuppressive metabolite of leflunomide is a potent inhibitor of human dihydroorotate dehydrogenase", Biochemistry, 35, pp.1270~1273 (1996)
  32. Cherwinski HM, "The immunosuppressant leflunomide inhibits lymphocyte proliferation by inhibiting pyrimidine biosynthesis", J Pharmacol Exp Ther, 275, pp.1043~1049 (1995)
  33. Rückemann K, "Leflunomide inhibits pyrimidine de novo synthesis in mitogen-stimulated T-lymphocytes from healthy humans", J Biol Chem, 273, pp.21682~21691 (1998)
  34. Siemasko KF, "Regulation of B cell function by the immunosuppressive agent leflunomide", Transplantation, 61, pp.635~642 (1996)
  35. Sartori A, "Teriflunomide: a novel oral treatment for relapsing multiple sclerosis", Expert Opin Pharmacother, 15, pp.1019~1027 (2014)
  36. Bar-Or A, "Teriflunomide effect on immune response to influenza vaccine in patients with multiple sclerosis", Neurology, 81, pp.552~558 (2013)
  37. O’Connor PW, "A Phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapses", Neurology, 66, pp.894~900 (2006)
  38. O’Connor P, "Randomized trial of oral teriflunomide for relapsing multiple sclerosis", N Engl J Med, 365, pp.1293~1303 (2011)
  39. Miller A, "TOPIC main outcomes: efficacy and safety of once-daily oral teriflunomide in patients with clinically isolated syndrome", 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis, pp.2~5 (2013)
  40. Vermersch P, "Teriflunomide versus subcutaneous interferon beta-1a in patients with relapsing multiple sclerosis: a randomised, controlled phase 3 trial", Mult Scler, 20, pp.705~716 (2014)
  41. Confavreux C, "Oral teriflunomide for patients with relapsing multiple sclerosis (TOWER): a randomised, double-blind, placebo-controlled, phase 3 trial", Lancet Neurol, 13, pp.247~256 (2014)
  42. "Highlights of prescribing information: these highlights do not include all the infromation needed to use AUBAGIO (R) safely and effectively" (2012)[URL]
  43. "BG 12: BG 00012, BG 12", Oral Fumarate, FAG-201, second-generation fumarate derivative--Fumapharm, Drugs R D, pp.2005, 6[DOI]
  44. de Jong R, "Selective stimulation of T helper 2 cytokine responses by the anti-psoriasis agent monomethylfumarate", Eur J Immunol, 26, pp.2067~2074 (1996)
  45. Schilling S, "Fumaric acid esters are effective in chronic experimental autoimmune encephalomyelitis and suppress macrophage infiltration", Clin Exp Immunol, 145, pp.101~107 (2006)
  46. Treumer F, "Dimethylfumarate is a potent inducer of apoptosis in human T cells", J Invest Dermatol, 121, pp.1383~1388 (2003)
  47. Cannella B, "Adhesion-related molecules in the central nervous system. Upregulation correlates with inflammatory cell influx during relapsing experimental autoimmune encephalomyelitis", Lab Invest, 65, pp.23~31 (1991)
  48. Lossinsky AS, "Wisniewski HM. Sites of egress of inflammatory cells and horseradish peroxidase transport across the blood-brain barrier in a murine model of chronic relapsing experimental allergic encephalomyelitis", Acta Neuropathol, 78, pp.359~371 (1989)
  49. Vandermeeren M, "Dimethylfumarate is an inhibitor of cytokine-induced E-selectin, VCAM-1, and ICAM-1 expression in human endothelial cells", Biochem Biophys Res Commun, 234, pp.19~23 (1997)
  50. Loewe R, "Dimethylfumarate inhibits tumor-necrosis-factor-induced CD62E expression in an NF-kappa B-dependent manner", J Invest Dermatol, 117, pp.1363~1368 (2001)
  51. Kappos L, "Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study", Lancet, 372, pp.1463~1472 (2008)
  52. Itoh K, "An Nrf2", small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements, 1997, pp.236, 313~322
  53. Venugopal R, "Nrf2 and Nrf1 in association with Jun proteins regulate antioxidant response element-mediated expression and coordinated induction of genes encoding detoxifying enzymes", Oncogene, 17, pp.3145~3156 (1998)
  54. Chen XL, "Activation of Nrf2", ARE pathway protects endothelial cells from oxidant injury and inhibits inflammatory gene expression, 2006, pp.290, H1862~H1870
  55. Scannevin RH, "Fumarates promote cytoprotection of central nervous system cells against oxidative stress via the nuclear factor (erythroid-derived 2)-like 2 pathway", J Pharmacol Exp Ther, 341, pp.274~284 (2012)
  56. Schimrigk S, "Oral fumaric acid esters for the treatment of active multiple sclerosis: an open-label, baseline-controlled pilot study", Eur J Neurol, 13, pp.604~610 (2006)
  57. Gold R, "Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis", N Engl J Med, 367, pp.1098~1107 (2012)
  58. Fox RJ, "Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis", N Engl J Med, 367, pp.1087~1097 (2012)
  59. Huynh E, "Cladribine in the treatment of hairy cell leukemia: initial and subsequent results", Leuk Lymphoma, 50(1), pp.12~17 (2009)
  60. Hartung HP, "Development of oral cladribine for the treatment of multiple sclerosis", J Neurol, 257, pp.163~170 (2010)
  61. Liliemark J, "The clinical pharmacokinetics of cladribine", Clin Pharmacokinet, 32, pp.120~131 (1997)
  62. Beutler E, "Cladribine (2-chlorodeoxyadenosine)", Lancet, 340, pp.952~956 (1992)
  63. Sipe JC, "Cladribine in treatment of chronic progressive multiple sclerosis", Lancet, 344, pp.9~13 (1994)
  64. Beutler E, "The treatment of chronic progressive multiple sclerosis with cladribine", Proc Natl Acad Sci U S A, 93, pp.1716~1720 (1996)
  65. Rice GP, "Cladribine and progressive MS: clinical and MRI outcomes of a multicenter controlled trial", Neurology, 54, pp.1145~1155 (2000), Cladribine MRI Study Group
  66. Romine JS, "A double-blind, placebo-controlled, randomized trial of cladribine in relapsing-remitting multiple sclerosis", Proc Assoc Am Physicians, 111, pp.35~44 (1999)
  67. Giovannoni G, "A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis", N Engl J Med, 362, pp.416~426 (2010)
  68. Leist TP, "Effect of oral cladribine on time to conversion to clinically definite multiple sclerosis in patients with a first demyelinating event (ORACLE MS): a phase 3 randomised trial", Lancet Neurol, 13, pp.257~267 (2014)
  69. Cook S, "Safety and tolerability of cladribine tablets in multiple sclerosis: the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study", Mult Scler, 17, pp.578~593 (2011)
  70. Andersen O, "Svenningsson A, Runmarker B, Linde AS, et al. Linomide reduces the rate of active lesions in relapsing-remitting multiple sclerosis", Neurology, 47, pp.895~900 (1996)
  71. Noseworthy JH, "Linomide in relapsing and secondary progressive MS: part I: trial design and clinical results. North American Linomide Investigators", Neurology, 54, pp.1726~1733 (2000)
  72. Wolinsky JS, "Linomide in relapsing and secondary progressive MS: part II: MRI results. MRI Analysis Center of the University of Texas-Houston, Health Science Center, and the North American Linomide Investigators", Neurology, 54, pp.1734~1741 (2000)
  73. Yang JS, "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, 2004, pp.156, 3~9
  74. Linker R, "Laquinimod induces up-regulation of neurotrophins in serum of patients with relapsing-remitting multiple sclerosis", 25th Congress of the European Committee for the Treatment and Research in Multiple Sclerosis, pp.9~12 (2009)
  75. Polman C, "Treatment with laquinimod reduces development of active MRI lesions in relapsing MS", Neurology, 64, pp.987~991 (2005)
  76. Comi G, "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, 371, pp.2085~2092 (2008)
  77. Comi G, "Oral laquinimod in patients with relapsing-remitting multiple sclerosis: 36-week double-blind active extension of the multi-centre, randomized, double-blind, parallel-group placebo-controlled study", Mult Scler, 16, pp.1360~1366 (2010)
  78. Comi G, "Placebo-controlled trial of oral laquinimod for multiple sclerosis", N Engl J Med, 366, pp.1000~1009 (2012)
  79. Filippi M, "Placebo-controlled trial of oral laquinimod in multiple sclerosis: MRI evidence of an effect on brain tissue damage", J Neurol Neurosurg Psychiatry, 85, pp.851~858 (2014)
  80. Vollmer TL, "A randomized placebo-controlled phase III trial of oral laquinimod for multiple sclerosis", J Neurol, 261, pp.773~783 (2014)
  81. Vollmer T, "Multicentre, randomized, placebo controlled study to evaluate the efficacy, safety and tolerability of two doses of oral laquinimod (0.6mg", day and 1.2mg, 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis, pp.2013[DOI]
  82. Varrin-Doyer M, "Laquinimod, an up-and-coming immunomodulatory agent for treatment of multiple sclerosis", Exp Neurol, 262, pp.66~71 (2014)

관련 논문AI추천

Changes in the Multiple Sclerosis Treatment Paradigm. What Do We Do Now and What Were We Doing Before?Berenice Silva, Cecilia Pita, Lucía Zavala, María Bárbara Eizaguirre, Orlando Garcea, Ricardo Alonso대한신경과학회 · Journal of Clinical Neurology2018 · 제14권 제4호Current Updates on the Diagnosis and Management of Multiple Sclerosis for the General NeurologistArchit B Baskaran, Edith L Graham, Elena Grebenciucova, Thomas Shoemaker대한신경과학회 · Journal of Clinical Neurology2023 · 제19권 제3호Monoclonal Antibody Therapies for Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder김우준, 김호진대한신경과학회 · Journal of Clinical Neurology2020 · 제16권 제3호Safety and Temporal Pattern of the Lymphocyte Count During Fingolimod Therapy in Patients With Multiple Sclerosis: Real-World Korean Experience김승우, 김호진, 신하영, Eunhee Sohn, Jeeyoung Oh, Ju-Hong Min, Jungmin So, Ki Hoon Kim, Kwang-Kuk Kim, Nam-Hee Kim, Sa-Yoon Kang, Seong-il Oh, So-Young Huh, Su-Hyun Kim, Sung-Min Kim, Tai-Seung Nam, Yeon Hak Chung, Young-Min Lim, Young Nam Kwon대한신경과학회 · Journal of Clinical Neurology2022 · 제18권 제6호Outcome of COVID-19 Infection in Patients With Multiple Sclerosis Who Received Disease-Modifying Therapies: A Systematic Review and Meta-AnalysisDan Zhou, Jing Sun, ManXia Wang, Mengjiao Sun, Ning Liu, Wenjing Zhang, WuHan Yu대한신경과학회 · Journal of Clinical Neurology2023 · 제19권 제4호Impact of Siponimod on Clinical and Radiological Parameters of Secondary Progressive Multiple Sclerosis: A Real-World Prospective StudyAlexandra Akrivaki, Athanasios K. Chasiotis, Dimitrios K. Kitsos, Evangelia Dimitriadou, Georgios Tsivgoulis, Konstantina Stavrogianni, Maria Chondrogianni, Maria-Ioanna Stefanou, Niki Christouli, Sotirios Giannopoulos, Vasileios Giannopapas, Vassiliki Smyrni대한신경과학회 · Journal of Clinical Neurology2024 · 제20권 제6호

이 간행물의 다른 논문 (14건)