97
Views
2
CrossRef citations to date
0
Altmetric
Review

Emerging oral immunomodulating agents – focus on teriflunomide for the treatment of multiple sclerosis

, &
Pages 15-28 | Published online: 13 Mar 2012

References

  • NoseworthyJLucchinettiCRodriguezMWeinshenkerBGMultiple SclerosisN Engl J Med200034393895211006371
  • PugliattiMSotgiuSRosatiGThe worldwide prevalence of multiple sclerosisClin Neurol Neurosurg200210418219112127652
  • RosatiGThe prevalence of multiple sclerosis in the world: an updateNeurol Sci20012211713911603614
  • DuquettePMurrayTJPleinesJMultiple sclerosis in childhood: clinical profile in 125 patientsJ Ped19871113359363
  • RuetADeloireMOualletJCMolinierSBrochetBPredictive factors for multiple sclerosis in patients with clinically isolated spinal cord syndromeMult Scler201117331231821071465
  • MillerDBarkhofFMontalbanXThompsonAFilippiMClinically isolated syndromes suggestive of multiple slcerosis, part 1: natural history, pathogenesis, diagnosis, and prognosisLancet Neurol2005428128815847841
  • MowryEMPesicMGrimesBDeenSRBacchettiPWaubantEClinical predictors of early second event in patients with clinically isolated syndromeJ Neurol20092561061106619252775
  • LebrunCBensaCDeboverieMClub Francophone de la Sclérose en PlaquesAssociation between clinical conversion to multiple sclerosis in radiologically isolated syndrome and magnetic resonance imaging, cerebrospinal fluid, and visual evoked potential: follow-up of 70 patientsArch Neurol200966784184619597085
  • PolmanCReingoldSBanwellBDiagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteriaAnn Neurol20116929230221387374
  • ScalfariANeuhausADegenhardtAThe natural history of multiple sclerosis, a geographically based study 10: relapses and long-term disabilityBrain20101331914192920534650
  • DisantoGBerlangaAJHandelAEHeterogeneity in multiple sclerosis: scratching the surface of a complex diseaseAutoimmune Dis. 2011 Article ID 93235112201110.4061/2011/932351 Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005811/?tool=pubmedAccessed February 3, 2012
  • ConfavreuxCVukusicSNatural history of multiple sclerosis: a unifying conceptBrain200612960661616415308
  • LibbeyJEMcCoyLLFujinamiRSMolecular mimicry in multiple sclerosisInt Rev Neurobiol200779127147 Available from: http://www.sciencedirect.com/science/article/pii/S0074774207790062Accessed February 3, 201217531840
  • NguyenMDJulienJPRivestSInnate immunity: the missing link in neuroprotection and neurodegenerationNat Rev Neurosci2002321622711994753
  • ChandranSHuntDJoannidesAZhaoCCompstonAFranklinRJMMyelin repair: the role of stem and precursor cells in multiple sclerosisPhil Trans R Soc B Biol Sci2008363171183
  • FisnikuLKBrexPAAltmannDRDisability and T2 MRI lesions: a 20-year follow-up of patients with relapse onset of multiple sclerosisBrain200813180881718234696
  • BermelRABakshiRThe measurement and clinical relevance of brain atrophy in multiple sclerosisLancet Neurol2006515817016426992
  • TrappBDPetersonJRansohoffMRudickRMorkSBoLAxonal transection in the lesions of multiple sclerosisN Engl J Med19983382782859445407
  • BrexPACiccarelliOO’RiordanJISailerMThompsonAJMillerDHA longitudinal study of abnormalities on MRI and disability from multiple sclerosisN Engl J Med2002246158164
  • TrappBDNaveKAMultiple sclerosis: An immune or n eurodegenerative disorder?Annu Rev Neurosci20083124726918558855
  • StüveOKnowns and unknowns in the future of multiple sclerosis treatmentJ Neurol Sci2009287Suppl 1S30S3620106346
  • LucchinettiCBrückWParisiJScheithauerBRodriguezMLassmanHHeterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelinationAnn Neurol20004770771710852536
  • KasperLHShoemakerJMultiple sclerosis immunology: the healthy immune system vs the MS immune systemNeurology201074Suppl 1S2S820038759
  • DalakasMCB cells as therapeutic targets in autoimmune neurological disordersNat Clin Pract Neurol200841055756718813230
  • BruneauJMYeaCMSpinella-JaegleSPurification of human dihydro-orotate dehydrogenase and its inhibition by A77 1726, the active metabolite of leflunomideBiochem J1998336Pt 22993039820804
  • ChenJJJonesMEThe cellular location of dihydroorotate dehydrogenase: relation to de novo biosynthesis of pyrimidinesArch Biochem Biophys197617618290184741
  • CherwinskiHMCohnRGCheungPThe immunosuppres-sant leflunomide inhibits lymphocyte proliferation by inhibiting pyrimidine biosynthesisJ Pharmacol Exp Ther19952752104310497473131
  • RuckemannKFairbanksLDCarreyEALeflunomide inhibits pyrimidine de novo synthesis in mitogen-stimulated T-lymphocytes from healthy humansJ Biol Chem19982733421682216919705303
  • SiemaskoKFChongASWilliamsJWBrennerEGFinneganARegulation of B cell function by the immunosuppressive agent leflunomideTransplantation19966146356428610393
  • ClaussenMCKornTImmune mechanisms of new therapeutic strategies in MS – teriflunomideClin Immunol20121421495621367665
  • FoxRIHermanMLFrangouCGMechanism of action for leflunomide in rheumatoid arthritisClin Immunol199993319820810600330
  • FairbanksLDBofillMRuckemannKSimmondsHAImportance of ribonucleotide availability to proliferating T-lymphocytes from healthy humans. Disproportionate expansion of pyrimidine pools and contrasting effects of de novo synthesis inhibitorsJ Biol Chem19952705029682296898530356
  • KornTMagnusTToykaKJungSModulation of effector cell functions in experimental autoimmune encephalomyelitis by leflunomide – mechanisms independent of pyrimidine depletionJ Leukoc Biol200476595096015328336
  • GoldRWolinskyJSPathophysiology of multiple sclerosis and the place of teriflunomideActa Neurol Scand20111242758420880295
  • KornTToykaKHartungHPJungSSuppression of experimental autoimmune neuritis by leflunomideBrain200112491791180211522581
  • ElderRTXuXWilliamsJWGongHFinneganAChongASThe immunosuppressive metabolite of leflunomide, A77 1726, affects murine T cells through two biochemical mechanismsJ Immunol1997159122279200434
  • SiemaskoKChongASJackHMGongHWilliamsJWFinneganAInhibition of JAK3 and STAT6 tyrosine phosphorylation by the immu-nosuppressive drug leflunomide leads to a block in IG1 productionJ Immunol19981604158115889469413
  • Gonzalez-AlvaroIOrtizAMDominguez-JimenezCAragon-BodiADiaz SanchezBSanchez-MadridFInhibition of tumor necrosis factor and IL-17 production by leflunomide involves the JAK/STAT pathwayAnn Rheum Dis200968101644165018957484
  • XuXWilliamsJWGongHFinneganAChongASTwo activities of the immunosuppressive metabolite of leflunomide, A77 1726. Inhibition of pyrimidine nucleotide synthesis and protein tyrosine phosphorylationBiochem Pharmacol19965245275348759024
  • HermannMLSchleyerbachRKirschbaumBJLeflunomide: an immunomodulatory drug for the treatment of rheumatoid arthritis and other autoimmune diseasesImmunopharmacology2000472–327328910878294
  • TallantyreEEvangelouNConstantinescuCSSpotlight on t eriflunomideInt MS J2008152626818782502
  • BartlettRRDimitrijevicMMattarTLeflunomide (HWA 486), a novel immunomodulating compound for the treatment of autoimmune disorders and reactions leading to transplantation rejectionAgents Actions1991321–210212058454
  • ZeydaMPoglitschMGeyereggerRDisruption of the interaction of T cells with antigen-presenting cells by the active leflunomide metabolite teriflunomide: involvement of impaired integrin activation and immunologic synapse formationArthritis Rheum20055292730273916142756
  • DéageVBurgerDDayerJMExposure 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 metalloproteinasesEur Cytokine Netw1998946636689889411
  • DimitrovaPSkopenkoAHermannMLRestriction of de novo pyrimidine biosynthesis inhibits Th1 cell activation and promotes Th2 cell differentiationJ Immunol200216963392339912218161
  • HamiltonLCVojnovicIWarnerTDA771726, the active metabolite of leflunomide, directly inhibits the activity of cyclo-oxygenase-2 in vitro and in vivo in a substrate-sensitive mannerBr J Pharmacol199912771589159610455314
  • MiljkovicDSamardzicTMostarica StojkovicMStosic-GrujicicSPopadicDTrajkovicVLeflunomide inhibits activation of inducible nitric oxide synthase in rat astrocytesBrain Res20018891–233133811166726
  • JankovicVSamardzicTStosic-GrujicicSPopadicDTrajkovicVCell-specific inhibition of inducible nitric oxide synthase activation by leflunomideCell Immunol20001992738010698616
  • CutoloMSulliAGhiorzoPPizzorniCCraviottoCVillaggioBAnti-inflammatory effects of leflunomide on cultured synovial macrophages from patients with rheumatoid arthritisAnn Rheum Dis200362429730212634225
  • KraanMCde KosterBMElferinkJGPostWJBreedveldFCTakPPInhibition of neutrophil migration soon after initiation of treatment with leflunomide or methotrexate in patients with rheumatoid arthritis: findings in a prospective, randomized, double-blind clinical trial in fifteen patientsArthritis Rheum20004371488149510902750
  • LimsakunTMenguy-VacheronFPharmacokinetics of oral teriflunomide, a novel oral disease-modifying agent under investigation for the treatment of multiple sclerosisNeurology201074A415
  • RozmanBClinical pharmacokinetics of leflunomideClin P harmacokinet2002416421430
  • O’ConnorPWLiDFreedmanMSTeriflunomide Multiple Sclerosis Trial GroupBritish Columbia MS/MRI Research GroupA phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapsesNeurology200666689490016567708
  • O’ConnorPWFreedmanMSBar-OrARiceGPConfavreuxCTraboulseeAOral teriflunomide is effective and well tolerated in multiple sclerosis with relapses: results of an open-label 144-week extension study22nd Congress of the European Committee for the Treatment and Research in Multiple SclerosisSeptember 27–30, 2006Madrid, Spain Abstract9 28, 2006
  • O’ConnorPWolinskyJConfavreuxCA placebo-controlled phase III trial (TEMSO) of oral teriflunomide in relapsing multiple sclerosis: clinical efficacy and safety outcomesMultiple Sclerosis201016Suppl 10S7S39
  • O’ConnorPWolinskyJSConfavreuxCTEMSO Trial GroupRandomized trial of oral teriflunomide for relapsing multiple sclerosisN Engl J Med2011365141293130321991951
  • FreedmanMWolinskyJSFranginGAOral teriflunomide or placebo added to glatiramer acetate for 6 months in patients with relapsing multiple sclerosis: safety and efficacy resultsNeurology2010749A293
  • FreedmanMSWolinskyJSByrnesWJOral teriflunomide or placebo added to interferon beta for months in patients with relapsing multiple sclerosis: safety and efficacy resultsMult Scler2009159S273 Poster 878
  • GenzymeGenzyme reports top-line results for TENERE study of oral Teriflunomide in relapsing multiple sclerosis [press release]Cambridge, MAGenzyme20111220 Available from: http://www.businesswire.com/news/genzyme/20111219006550/enAccessed February 24, 2012
  • Leflunomide [package insert]Bridgewater, NJSanofi-Aventis U.S. LLC2010
  • WarnatzKPeterHHSchumacherMInfectious CNS disease as a differential diagnosis in systemic rheumatic disease: three case reports and a review of the literatureAnn Rheum Dis2003215057
  • BrentRLTeratogen update: reproductive risks of leflunomide (Arava); a pyrimidine synthesis inhibitor: counseling women taking lefunomide before or during pregnancy and men taking leflunomide who are contemplating fathering a childTeratology200163210611211241434
  • ChamberCDJohnsonDLRobinsonLKOrganization of Teratology Information Specialists Collaborative Research GroupBirth outcomes in women who have taken leflunomide during pregnancyArthritis Rheum20106251494150320131283
  • PattiFOptimizing the benefit of multiple sclerosis therapy: the importance of treatment adherencePatient Prefer Adherence2010419 Published online February 4, 2010. PMCID: PMC281989820165593
  • PortaccioEZipoliVSiracusaGSorbiSAmatoMPLong-term a dherence to interferon B therapy in relapsing-remitting multiple sclerosisEur Neurol20085913113510.1159/00011187518057899
  • O’RourkeKETHutchinsonMStopping beta-interferon therapy in multiple sclerosis: an analysis of stopping patternsMult Scler200511465015732266
  • TremlettHLOgelJInterrupted therapy: stopping and switching of the β-interferons prescribed for MSNeurology200361455155412939437
  • BruceJMHancockLMArnettPLynchSTreatment adherence in multiple sclerosis: association with emotional status, personality, and cognitionJ Behav Med20103321922720127401
  • CarrollWMOral Therapy for multiple sclerosis – sea change or incremental step?N Engl J Med2010326456458
  • PalmerAMTeriflunomide, an inhibitor of dihydroorotate d ehydrogenase for the potential oral treatment of multiple sclerosisCurr Opin Investig Drugs2010111113131323
  • Merck SeronoMerck Serono: regulatory update on Cladribine tablets [press release]GenevaMerck;2011622 Available from: http://www.merckserono.com/corp.merckserono_2011/en/images/20110622_en_tcm1494_76074.pdfAccessed February 24, 2012
  • PortaccioEEvidence-based assessment of potential use of fingolimod in treatment of relapsing multiple sclerosisCore Evid20116132121468239
  • CohenJABarkhofFComiGTRANSORMS Study GroupOral fingolimod or intramuscular interferon for relapsing multiple sclerosisN Engl J Med2010362540241520089954
  • KapposLRadueEWO’ConnorPFREEDOMS Study GroupA placebo-controlled trial of oral fingolimod in relapsing multiple sclerosisN Engl J Med2010362538740120089952
  • PolmanCBarkhofFSandberg-WollheimMLindeANordleONedermanTTreatment with laquinimod reduces development of active MRI lesions in relapsing MSNeurology200564698799115781813
  • ComiGPulizziARovarisMLAQ/506 Study GroupEffect of laquinimod on MRI-monitored disease activity in patients with relapsing–remitting multiple sclerosis: a multicentre, r andomised, double-blind, placebo-controlled phase IIb studyLancet200837196302085209218572078
  • American Academy of Neurology(AAN) 63rd Annual Meeting: Abstract P05.288Presented April 12, 2011
  • Teva Pharmaceuticals IncInvestigational laquinimod demonstrates its potential as a new oral treatment for RRMS [press release]Jerusalem and Lund, SwedenTeva20111019 Available from: http://www.tevapharm.com/en-US/Media/News/Pages/2011/1618694.aspxAccessed February 24, 2012
  • KapposLGoldRMillerDHBG-12 Phase IIb Study InvestigatorsEfficacy and safety of oral fumarate in patients with relapsing–remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb studyLancet200837296481463147218970976
  • Biogen IdecBiogen Idec announces positive top-line results from the first Phase 3 trial investigating oral BG-12 (DIMETHYL FUMARATE) in multiple sclerosis [press release]Weston, MABiogen Idec2011 [April 11]. Available from: http://www.biogenidec.com/press_release_details.aspx?ID=5981&ReqId=1548648Accessed February 24, 2012