Teriflunomide (Aubagio®) for the treatment of multiple sclerosis

Experimental Neurology

Volumn 262, Issue Part A, 2014, Pages 57-65

  Bar Or, Amit ^a  

^a MCGILL UNIVERSITY   (Canada)

Author keywords

Aubagio; Immune modulation; Leflunomide; Multiple sclerosis; Teriflunomide; Treatment

Indexed keywords

BETA INTERFERON; BETA1A INTERFERON; GLATIRAMER; PLACEBO; TERIFLUNOMIDE; CROTONIC ACID DERIVATIVE; TOLUIDINE DERIVATIVE;

ADVERSE OUTCOME; ANTIINFLAMMATORY ACTIVITY; BODY GROWTH; DIARRHEA; DISEASE MODEL; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CONTRAINDICATION; DRUG EFFICACY; DRUG MECHANISM; DRUG METABOLISM; DRUG RESPONSE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; EXPERIMENTAL ANIMAL; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; HAIR LOSS; HUMAN; HYPERBILIRUBINEMIA; HYPERTENSION; HYPERTRANSAMINASEMIA; IMMUNE RESPONSE; IN VITRO STUDY; IN VIVO STUDY; INFECTION; MULTIPLE SCLEROSIS; NAUSEA; NONHUMAN; PHARMACODYNAMICS; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PREGNANCY; RANDOMIZED CONTROLLED TRIAL (TOPIC); RELAPSE; REVIEW; TREATMENT DURATION; TREATMENT PLANNING; ANIMAL; CLINICAL TRIAL (TOPIC); DRUG SCREENING; IMMUNOLOGY; IMMUNOMODULATION;

ANIMALS; CLINICAL TRIALS AS TOPIC; CROTONATES; DRUG EVALUATION, PRECLINICAL; HUMANS; IMMUNOMODULATION; MULTIPLE SCLEROSIS; TOLUIDINES;

EID: 84908657665     PISSN: 00144886     EISSN: 10902430     Source Type: Journal    
DOI: 10.1016/j.expneurol.2014.06.005     Document Type: Review

References (52)

1. Bar-Or A., Freedman M.S., Kremenchutzky M., Menguy-Vacheron F., Bauer D., Jodl S., et al. Teriflunomide effect on immune response to influenza vaccine in patients with multiple sclerosis. Neurology 2013, 81(6):552-558. (Aug 6).
2. Bar-Or A., Larouche R., Legrand B., Miller B., Benamor M., Truffinet P., et al. Immune response to neoantigen and recall antigens in healthy subjects receiving teriflunomide. ECTRIMS Poster 622. Mult. Scler. J. 2013, 19(S1):74-558.
3. Bar-Or A., Pachner A., Menguy-Vacheron F., Kaplan J., Wiendl H. Teriflunomide and its mechanism of action in multiple sclerosis. Drugs 2014, 74(6):659-674. (Apr).
4. Bielekova B., Sung M.H., Kadom N., Simon R., McFarland H., Martin R. Expansion and functional relevance of high-avidity myelin-specific CD4+ T cells in multiple sclerosis. J. Immunol. 2004, 172(6):3893-3904. (Mar 15).
5. Bruneau J.M., Yea C.M., Spinella-Jaegle S., Fudali C., Woodward K., Robson P.A., et al. Purification of human dihydro-orotate dehydrogenase and its inhibition by A77 1726, the active metabolite of leflunomide. Biochem. J. 1998, 336(Pt 2):299-303. (Dec 1).
6. Brunetti L., Wagner M.L., Maroney M., Ryan M. Teriflunomide for the treatment of relapsing multiple sclerosis: a review of clinical data. Ann. Pharmacother. 2013, 47(9):1153-1160. (Sep).
7. Cherwinski H.M., Cohn R.G., Cheung P., Webster D.J., Xu Y.Z., Caulfield J.P., et al. The immunosuppressant leflunomide inhibits lymphocyte proliferation by inhibiting pyrimidine biosynthesis. J. Pharmacol. Exp. Ther. 1995, 275(2):1043-1049. (Nov).
8. Confavreux C., Li D.K., Freedman M.S., Truffinet P., Benzerdjeb H., Wang D., Bar-Or A., Traboulsee A.L., Reiman L.E., O'Connor P.W., Teriflunomide Multiple Sclerosis Trial Group Long-term follow-up of a phase 2 study of oral teriflunomide in relapsing multiple sclerosis: safety and efficacy results up to 8.5years. Mult. Scler. 2012, 18(9):1278-1289. (Sep).
9. Confavreux C., O'Connor P., Comi G., Freedman M.S., Miller A.E., Olsson T.P., Wolinsky J.S., Bagulho T., Delhay J.L., Dukovic D., Truffinet P., Kappos L., TOWER Trial Group Oral teriflunomide for patients with relapsing multiple sclerosis (TOWER): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol. 2014, 13(3):247-256. (Mar).
10. Dimitrova P., Skapenko A., Herrmann M.L., Schleyerbach R., Kalden J.R., Schulze-Koops H. Restriction of de novo pyrimidine biosynthesis inhibits Th1 cell activation and promotes Th2 cell differentiation. J. Immunol. 2002, 169(6):3392-3399. (Sep 15).
11. European Agency for the Evaluation of Medicinal Products Committee for Proprietary Medicinal Products: Note for Guidance on Harmonization of Requirements for Influenza Vaccines 1997, European Agency for the Evaluation of Medicinal Products, London.
12. Fairbanks L.D., Bofill M., Ruckemann K., Simmonds H.A. Importance of ribonucleotide availability to proliferating T-lymphocytes from healthy humans. Disproportionate expansion of pyrimidine pools and contrasting effects of de novo synthesis inhibitors. J. Biol. Chem. 1995, 270(50):29682-29689. (Dec 15).
13. Freedman M.S. Teriflunomide in relapsing multiple sclerosis: therapeutic utility. Ther. Adv. Chronic Dis. 2013, 4(5):192-205. (Sep).
14. Freedman M.S., Wolinsky J.S., Wamil B., et al. Oral teriflunomide plus glatiramer acetate in relapsing multiple sclerosis. Int. J. MS Care 2011, 13(Suppl. 3):17.
15. Freedman M.S., Wolinsky J.S., Wamil B., Confavreux C., Comi G., Kappos L., Olsson T.P., Miller A., Benzerdjeb H., Li H., Simonson C., O'Connor P.W. Teriflunomide Multiple Sclerosis Trial Group and the MRI Analysis Center. Teriflunomide added to interferon-β in relapsing multiple sclerosis: a randomized phase II trial. Neurology 2012, 78(23):1877-1885. (Jun 5, Epub 2012 May 23).
16. Freedman M., Wolinsky J., Comi G., et al. Safety and efficacy of teriflunomide in patients with relapsing multiple sclerosis treated with interferon beta. Paper presented at: 8th World Congress on Controversies in Neurology 2014, (Berlin, Germany).
17. Fuentealba R.A., Marasa J., Diamond M.I., Piwnica-Worms D., Weihl C.C. An aggregation sensing reporter identifies leflunomide and teriflunomide as polyglutamine aggregate inhibitors. Hum. Mol. Genet. 2012, 21(3):664-680. (Feb 1).
18. Garnock-Jones K.P. Teriflunomide: a review of its use in relapsing multiple sclerosis. CNS Drugs 2013, 27(12):1103-1123. (Dec).
19. Gold R., Wolinsky J.S. Pathophysiology of multiple sclerosis and the place of teriflunomide. Acta Neurol. Scand. 2011, 124(2):75-84. (Aug).
20. Herrmann M.L., Schleyerbach R., Kirschbaum B.J. Leflunomide: an immunomodulatory drug for the treatment of rheumatoid arthritis and other autoimmune diseases. Immunopharmacology 2000, 47:273-289.
21. Iglesias-Bregna D., Hanak S., Ji Z., Petty M., Liu L., Zhang D., et al. Effects of prophylactic and therapeutic teriflunomide in transcranial magnetic stimulation-induced motor-evoked potentials in the Dark Agouti rat model of experimental autoimmune encephalomyelitis. J. Pharmacol. Exp. Ther. 2013, 347(1):203-211. (Jul 26).
22. Jameson S.C. Maintaining the norm: T-cell homeostasis. Nat. Rev. Immunol. 2002, 2(8):547-556. (Aug).
23. Keen H.I., Conaghan P.G., Tett S.E. Safety evaluation of leflunomide in rheumatoid arthritis. Expert Opin. Drug Saf. 2013, 12(4):581-588. (Jul).
24. Kieseier B.C., Wiendl H. New evidence for teriflunomide in multiple sclerosis. Lancet Neurol. 2014, 13(3):234-235. (Mar).
25. Kieseier B., Stüve O., Benamor M., et al. Updated pregnancy outcomes from the teriflunomide clinical development programme: retrospective analysis of the teriflunomide clinical trial database. Mult. Scler. 2013, 19:74 P541.
26. Korn T., Magnus T., Toyka K., Jung S. Modulation of effector cell functions in experimental autoimmune encephalomyelitis by leflunomide-mechanisms independent of pyrimidine depletion. J. Leukoc. Biol. 2004, 76(5):950-960. (Nov).
27. Leist T., Freedman M.S., Kappos L., et al. Pooled safety data from three placebo-controlled teriflunomide studies. Mult. Scler. 2013, 19:74. (P633).
28. Li L., Liu J., Delohery T., Zhang D., Arendt C., Jones C. The effects of teriflunomide on lymphocyte subpopulations in human peripheral blood mononuclear cells. J. Neuroimmunol. 2013, 265(1-2):82-90. (Oct).
29. Lu E., Wang B.W., Alwan S., Synnes A., Dahlgren L., Sadovnick A.D., Tremlett H. A review of safety-related pregnancy data surrounding the oral disease-modifying drugs for multiple sclerosis. CNS Drugs 2014, 28(2):89-94. (Feb).
30. Merrill J.E., Hanak S., Pu S.F., Liang J., Dang C., Iglesias-Bregna D., et al. Teriflunomide reduces behavioral, electrophysiological, and histopathological deficits in the Dark Agouti rat model of experimental autoimmune encephalomyelitis. J. Neurol. 2009, 256(1):89-103. (Jan).
31. Miller A.E., O'Connor P., Wolinsky J.S., Confavreux C., Kappos L., Olsson T.P., Truffinet P., Wang L., D'Castro L., Comi G., Freedman M.S., Teriflunomide Multiple Sclerosis Trial Group Pre-specified subgroup analyses of a placebo-controlled phase III trial (TEMSO) of oral teriflunomide in relapsing multiple sclerosis. Mult. Scler. 2012, 18(11):1625-1632. (Nov).
32. Miller A., Wolinsky J., Kappos L., et al. TOPIC: efficacy and safety of once-daily oral teriflunomide in patients with first clinical episode consistent with multiple sclerosis. Neurology 2014, 82(Suppl. 10):PL2.002.
33. O'Connor P.W., Li D., Freedman M.S., Bar-Or A., Rice G.P., Confavreux C., Paty D.W., Stewart J.A., Scheyer R., Teriflunomide Multiple Sclerosis Trial Group, University of British Columbia MS/MRI Research Group A Phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapses. Neurology 2006, 66(6):894-900. (Mar 28).
34. O'Connor P., Wolinsky J.S., Confavreux C., Comi G., Kappos L., Olsson T.P., Benzerdjeb H., Truffinet P., Wang L., Miller A., Freedman M.S., TEMSO Trial Group Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N. Engl. J. Med. 2011, 365(14):1293-1303. (Oct 6).
35. O'Connor P.W., Lublin F.D., Wolinsky J.S., Confavreux C., Comi G., Freedman M.S., Olsson T.P., Miller A.E., Dive-Pouletty C., Bégo-Le-Bagousse G., Kappos L. Teriflunomide reduces relapse-related neurological sequelae, hospitalizations and steroid use. J. Neurol. 2013, 260(10):2472-2480. (Oct).
36. Oh J., O'Connor P.W. Teriflunomide for the treatment of multiple sclerosis. Semin. Neurol. 2013, 33(1):45-55. (Feb).
37. Osiri M., Shea B., Robinson V., Suarez-Almazor M., Strand V., Tugwell P., Wells G. Leflunomide for the treatment of rheumatoid arthritis: a systematic review and metaanalysis. J. Rheumatol. 2003, 30(6):1182-1190. (Jun).
38. Pachner A., Li L. Teriflunomide ameliorates disability progression in the Theiler's virus-induced demyelinating disease model of MS [P05.196] | AAN 2013. Neurology 2013, 78:P05.196.
39. Pearce E.L. Metabolism in T cell activation and differentiation. Curr. Opin. Immunol. 2010, 22(3):314-320. (Jun).
40. Posevitz V., Chudyka D., Kurth F., Wiendl H. Teriflunomide suppresses antigen induced T-cell expansion in a TCR avidity dependent fashion (P1107). Mult. Scler. J. 2012, 18(S4):509-520.
41. Ringheim G.E., Lee L., Laws-Ricker L., Delohery T., Liu L., Zhang D., Colletti N., Soos T.J., Schroeder K., Fanelli B., Tian N., Arendt C.W., Iglesias-Bregna D., Petty M., Ji Z., Qian G., Gaur R., Weinstock D., Cavallo J., Telsinskas J., McMonagle-Strucko K. Teriflunomide attenuates immunopathological changes in the dark agouti rat model of experimental autoimmune encephalomyelitis. Front. Neurol. 2013, 4:169.
42. Ringshausen I., Oelsner M., Bogner C., Peschel C., Decker T. The immunomodulatory drug Leflunomide inhibits cell cycle progression of B-CLL cells. Leukemia 2008, 22(3):635-638. (Mar).
43. Ruckemann K., Fairbanks L.D., Carrey E.A., Hawrylowicz C.M., Richards D.F., Kirschbaum B., et al. Leflunomide inhibits pyrimidine de novo synthesis in mitogen-stimulated T-lymphocytes from healthy humans. J. Biol. Chem. 1998, 273(34):21682-21691. (Aug 21).
44. Sartori A., Carle D., Freedman M.S. Teriflunomide : a novel oral treatment for relapsing multiple sclerosis. Expert Opin. Pharmacother. 2014, 15(7):1019-1027. (May).
45. Singer B., Comi G., Miller A., Olsson T., Wolinsky J.S., Kappos L., et al. Frequency of infections during treatment with teriflunomide: pooled data from three placebo-controlled teriflunomide studies | AAN 2013. Neurology 2013, 80(1):1001-112005. P01.171.
46. Tsunoda I., Fujinami R.S. Neuropathogenesis of Theiler's murine encephalomyelitis virus infection, an animal model for multiple sclerosis. J. Neuroimmune Pharmacol. 2010, 5(3):355-369. (Sep).
47. Vermersch P., Czlonkowska A., Grimaldi L.M., et al. Teriflunomide versus subcutaneous interferon beta-1a in patients with relapsing multiple sclerosis: a randomised, controlled phase 3 trial. Mult. Scler. 2014, 20(6):705-716.
48. Warnke C., Stüve O., Kieseier B.C. Teriflunomide for the treatment of multiple sclerosis. Clin. Neurol. Neurosurg. 2013, 115(Suppl. 1):S90-S94. (Dec).
49. Wiese M.D., Rowland A., Polasek T.M., Sorich M.J., O'Doherty C. Pharmacokinetic evaluation of teriflunomide for the treatment of multiple sclerosis. Expert Opin. Drug Metab. Toxicol. 2013, 9(8):1025-1035. (Aug).
50. Wingerchuk D.M., Carter J.L. Multiple sclerosis: current and emerging disease-modifying therapies and treatment strategies. Mayo Clin. Proc. 2014, 89(2):225-240. (Feb).
51. Wolinsky J.S., Narayana P.A., Nelson F., Datta S., O'Connor P., Confavreux C., Comi G., Kappos L., Olsson T.P., Truffinet P., Wang L., Miller A., Freedman M.S., Teriflunomide Multiple Sclerosis Oral (TEMSO) Trial Group Magnetic resonance imaging outcomes from a phase III trial of teriflunomide. Mult. Scler. 2013, 19(10):1310-1319. (Sep).
52. Zeyda M., Poglitsch M., Geyeregger R., Smolen J.S., Zlabinger G.J., Horl W.H., 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(9):2730-2739. (Sep).