Teriflunomide for the treatment of relapsing multiple sclerosis: A review of clinical data

Annals of Pharmacotherapy

Volumn 47, Issue 9, 2013, Pages 1153-1160

  Brunetti, Luigi ^a   Wagner, Mary L ^a   Maroney, Megan ^a   Ryan, Melody ^b  

^a RUTGERS UNIVERSITY   (United States)

^b UNIVERSITY OF KENTUCKY   (United States)

Author keywords

Oral therapy; Relapsing multiple sclerosis; Teriflunomide

Indexed keywords

ALANINE AMINOTRANSFERASE; BETA1A INTERFERON; CYCLOSPORIN; ELTROMBOPAG; FINGOLIMOD; FUMARIC ACID DIMETHYL ESTER; GAMMA GLUTAMYLTRANSFERASE; GEFITINIB; GLATIRAMER; INTERFERON BETA SERINE; MITOXANTRONE; NATALIZUMAB; ORAL CONTRACEPTIVE AGENT; TERIFLUNOMIDE; WARFARIN;

ACUTE KIDNEY FAILURE; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALOPECIA; AREA UNDER THE CURVE; ARTICLE; BONE MARROW SUPPRESSION; BREAST MILK; BRONCHITIS; CONSTIPATION; DIARRHEA; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG ELIMINATION; DRUG HALF LIFE; DRUG METABOLISM; DRUG RESPONSE; DRUG WITHDRAWAL; ELEVATED BLOOD PRESSURE; EXPANDED DISABILITY STATUS SCALE; GAMMA GLUTAMYL TRANSFERASE BLOOD LEVEL; HEADACHE; HUMAN; HYPERKALEMIA; INTERSTITIAL LUNG DISEASE; LEUKOCYTE COUNT; LIVER FUNCTION; LIVER TOXICITY; MAXIMUM PLASMA CONCENTRATION; MONOTHERAPY; MULTIPLE SCLEROSIS; NAUSEA; NUCLEAR MAGNETIC RESONANCE IMAGING; OPEN STUDY; OUTCOME ASSESSMENT; PARESTHESIA; PEER REVIEW; PERIPHERAL NEUROPATHY; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN BINDING; RANDOMIZED CONTROLLED TRIAL (TOPIC); RECURRENCE RISK; RELAPSE; RHINOPHARYNGITIS; SIDE EFFECT; SINUSITIS; SKIN MANIFESTATION; STEADY STATE; THROMBOCYTE COUNT; UPPER ABDOMINAL PAIN; URINARY TRACT INFECTION;

ORAL THERAPY; RELAPSING MULTIPLE SCLEROSIS; TERIFLUNOMIDE;

ANIMALS; CROTONATES; DRUG INTERACTIONS; HUMANS; IMMUNOSUPPRESSIVE AGENTS; MULTIPLE SCLEROSIS, RELAPSING-REMITTING; TOLUIDINES;

EID: 84884496743     PISSN: 10600280     EISSN: 15426270     Source Type: Journal    
DOI: 10.1177/1060028013500647     Document Type: Article

References (29)

1. Ryan M. Multiple sclerosis. In: Chisholm-Burns MA, Wells BG, Schwinghammer TL, Malone PM, Kolesar JM, DiPiro JT, eds. Pharmacotherapy: Principles and Practice. 3rd ed. New York, NY: McGraw-Hill Medical; 2013:443-456.
2. Weinshenker BG, Bass B, Rice GP, et al. The natural history of multiple sclerosis: a geographically based study: I: clinical course and disability. Brain. 1989;112:133-146.
3. Aubagio (teriflunomide) [product information]. Cambridge, MA: Genzyme Corp; September 2012.
4. Red Book Online System. Greenwood Village, CO: Thomson Reuters (Healthcare), Inc.
5. Nwankwo E, Allington DR, Rivey MP. Emerging oral immunodulating agents-focus on teriflunomide for treatment of multiple sclerosis. Degener Neurol Neuromuscul Dis. 2012;2:15-28.
6. He D, Xu Z, Dong S, et al. Teriflunomide for multiple sclerosis. Cochrane Database Syst Rev. 2012;(12):CD009882.
7. Davis JP, Cain GA, Pitts WJ, Magolda RL, Copeland RA. The immunosuppressive metabolite of leflunomide is a potent inhibitor of human dihydroorotate dehydrogenase. Biochemistry. 1996;35:1270-1273.
8. Fox RI, Herrmann ML, Frangou CG, et al. Mechanism of action for leflunomide in rheumatoid arthritis. Clin Immunol. 1999;93:198-208.
9. Gold R, Wolinsky JS. Pathophysiology of multiple sclerosis and the place of teriflunomide. Acta Neurol Scand. 2011;124:75-84.
10. 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.
11. Limsakun T, Menguy-Vacheron F. Pharmacokinetics of oral teriflunomide, a novel oral disease-modifying agent under investigation for the treatment of multiple sclerosis. Neurology. 2010;74(suppl 2):A415.
12. Rozman B. Clinical pharmacokinetics of leflunomide. Clin Pharmacokinet. 2002;41:421-430.
13. O'Connor PW, Li D, Freedman MS, et al. A phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapses. Neurology. 2006;66:894-900.
14. National Institutes of Health. Oral teriflunomide or placebo added to glatiramer acetate for 6 months in patients with relapsing multiple sclerosis: safety and efficacy results. http://clinicaltrials.gov/ct2/show/NCT00475865?term=teriflunomi de+glatiramer&rank=1. Accessed April 10, 2013.
15. Freedman MS, Wolinsky JS, Wamil B, et al. Teriflunomide added to interferon-β in relapsing multiple sclerosis. Neurology. 2012;78:1877-1885.
16. O'Connor P, Wolinsky JS, Confavreux C, et al. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med. 2011;365:1293-1303.
17. O'Connor PW, Wolinsky JS, Confavreux C, et al. Extension of a phase III trial (TEMSO) of oral teriflunomide in multiple sclerosis with relapses: clinical and MRI data 5 years after initial randomisation. ECTRIMS/ACTRIMS. Amsterdam, The Netherlands. P9242011
18. National Institutes of Health. A study comparing the effectiveness and safety of teriflunomide and interferon β-1a in patients with relapsing multiple sclerosis (TENERE). http://www.clinicaltrials.gov/ct2/show/results/NCT00883337?term =tenere&rank=1. Accessed February 28, 2013.
19. Kappos L, Comi G, Confavreux C, et al. The efficacy and safety of teriflunomide in patients with relapsing MS: results from TOWER, a phase III placebo controlled study. Presented at: 28th Congress of the European Committee for the Treatment and Research in Multiple Sclerosis (ECTRIMS); October 12, 2012; Lyon, France. http://www.posters2view. com/ectrims2012/view.php?nu=88. Accessed February 29, 2013.
20. Goldman MD, Motl RW, Rudick RA. Possible outcome measures for clinical trials in patients with multiple sclerosis. Ther Adv Neurol Disord. 2010;3:229-239.
21. Rudick R, Lee J, Cutter G, et al. Significance of disability progression in a clinical trial in relapse-remitting multiple sclerosis: eight year follow-up. Arch Neurol 2010;67:1329-35.
22. National Institutes of Health. Phase III study with teriflunomide versus placebo in patients with first clinical symptom of multiple sclerosis (TOPIC). http://clinicaltrials.gov/ct2/show/NCT00622700. Accessed July 31, 2013.
23. National Institutes of Health. Efficacy and safety of teriflunomide in patients with relapsing multiple sclerosis and treated with interferon-β. http://www.clinicaltrials.gov/ct2/results?ter m=TERACLES&view=results. Accessed February 28, 2013.
24. Confavreux C, Li DK, Freedman MS, et al; 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 8.5 years. Mult Scler. 2012;18:1278-1289.
25. Bergner R, Peters L, Schmitt V, Loffler C. Leflunomide in dialysis patients with rheumatoid arthritis-a pharmacokinetic study. Clin Rheumatol. 2013;32:267-270.
26. Steinberg S, Faris RJ, Chang CF, Chan A, Tankersley MA. Impact of adherence to interferons in the treatment of multiple sclerosis. Clin Drug Investig. 2010;30:89-100.
27. Cohen JA, Barkhof F, Comi G, et al. TRANSFORMS Study Group. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med. 2010;362:402-415.
28. Kappos L, Radue EW, O'Connor P, et al; FREEDOMS Study Group. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med. 2010;362:387-401.
29. Chamber CD, Johnson DL, Robinson LK, et al. Birth outcomes in women who have taken leflunomide during pregnancy. Arthritis Rheum. 2010;62:1494-1503.