Clinical efficacy of BG-12 (dimethyl fumarate) in patients with relapsing-remitting multiple sclerosis: Subgroup analyses of the CONFIRM study

Journal of Neurology

Volumn 260, Issue 9, 2013, Pages 2286-2296

  Hutchinson, Michael ^a   Fox, Robert J ^b   Miller, David H ^c   Phillips, J Theodore ^d   Kita, Mariko ^e   Havrdova, Eva ^f   O'Gorman, John ^g   Zhang, Ray ^g   Novas, Mark ^g   Viglietta, Vissia ^g   Dawson, Katherine T ^g  

^a ST VINCENT S UNIVERSITY HOSPITAL   (Ireland)

^b LERNER RESEARCH INSTITUTE   (United States)

^c UNIVERSITY COLLEGE LONDON   (United Kingdom)

^d BAYLOR INSTITUTE FOR IMMUNOLOGY RESEARCH   (United States)

^e VIRGINIA MASON MEDICAL CENTER   (United States)

^f CHARLES UNIVERSITY   (Czech Republic)

^g BIOGEN   (United States)

Author keywords

BG 12; Dimethyl fumarate; Glatiramer acetate; Multiple sclerosis; Randomized controlled trial; Subgroup analysis

Indexed keywords

FUMARIC ACID DIMETHYL ESTER; GLATIRAMER; PLACEBO;

ADULT; ARTICLE; CONTROLLED STUDY; DRUG EFFICACY; EXPANDED DISABILITY STATUS SCALE; FEMALE; HUMAN; MAJOR CLINICAL STUDY; MALE; MEDICAL HISTORY; MULTIPLE SCLEROSIS; NEUROIMAGING; NUCLEAR MAGNETIC RESONANCE IMAGING; PHASE 3 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RECURRENCE RISK; TREATMENT OUTCOME;

ADULT; DISEASE PROGRESSION; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; FUMARATES; HUMANS; IMMUNOSUPPRESSIVE AGENTS; MAGNETIC RESONANCE IMAGING; MALE; MULTIPLE SCLEROSIS, RELAPSING-REMITTING; PEPTIDES; RECURRENCE;

EID: 84884337463     PISSN: 03405354     EISSN: 14321459     Source Type: Journal    
DOI: 10.1007/s00415-013-6968-1     Document Type: Article

References (28)

1. US Food and Drug Administration (2013) TECFIDERA™ prescribing information. http://www.accessdata.fda.gov/drugsatfda-docs/label/2013/204063lbl. pdf. Accessed 2 April 2013
2. Kappos L, Gold R, Miller DH, Macmanus DG, Havrdova E, Limmroth V, Polman CH, Schmierer K, Yousry TA, Yang M, Eraksoy M, Meluzinova E, Rektor I, Dawson KT, Sandrock AW, O'Neill GN (2008) Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study. Lancet 372:1463-1472
3. Gold R, Kappos L, Arnold DL, Bar-Or A, Giavannoni G, Selmaj K, Tornatore C, Sweetser MT, Yang M, Sheikh SI, Dawson KT, On behalf of the DEFINE Study Investigators (2012) Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med 367:1098-1107
4. Fox RJ, Miller DH, Phillips JT, Hutchinson M, Havrdova E, Kita M, Yang M, Raghupathi K, Novas M, Sweetser MT, Viglietta V, Dawson KT, On behalf of the CONFIRM Study Investigators (2012) Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med 367:1087-1097
5. Lucchinetti C, Bruck W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H (2000) Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 47:707-717
6. Tremlett H, Zhao Y, Rieckmann P, Hutchinson M (2010) New perspectives in the natural history of multiple sclerosis. Neurology 74:2004-2015
7. Chofflon M (2005) Mechanisms of action for treatments in multiple sclerosis: does a heterogeneous disease demand a multi-targeted therapeutic approach? BioDrugs 19:299-308
8. Degenhardt A, Ramagopalan SV, Scalfari A, Ebers GC (2009) Clinical prognostic factors in multiple sclerosis: a natural history review. Nat Rev Neurol 5:672-682
9. Disanto G, Berlanga AJ, Handel AE, Para AE, Burrell AM, Fries A, Handunnetthi L, De Luca GC, Morahan JM (2010) Heterogeneity in multiple sclerosis: scratching the surface of a complex disease. Autoimmune Dis 2011:932351
10. Mowry EM (2011) Natural history of multiple sclerosis: early prognostic factors. Neurol Clin 29:279-292
11. Renoux C (2011) Natural history of multiple sclerosis: long-term prognostic factors. Neurol Clin 29:293-308
12. Brex PA, Ciccarelli O, O'Riordan JI, Sailer M, Thompson AJ, Miller DH (2002) A longitudinal study of abnormalities on MRI and disability from multiple sclerosis. N Engl J Med 346:158-164
13. Confavreux C, Vukusic S, Adeleine P (2003) Early clinical predictors and progression of irreversible disability in multiple sclerosis: an amnesic process. Brain 126:770-782
14. Losseff NA, Miller DH, Kidd D, Thompson AJ (2001) The predictive value of gadolinium enhancement for long-term disability in relapsing-remitting multiple sclerosis-preliminary results. Mult Scler 7:23-25
15. Scott TF, Schramke CJ, Novero J, Chieffe C (2000) Short-term prognosis in early relapsing-remitting multiple sclerosis. Neurology 55:689-693
16. Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O'Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69:292-302
17. Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an Expanded Disability Status Scale (EDSS). Neurology 33:1444-1452
18. ICH harmonised tripartite guideline-guideline for good clinical practice: E6 (R1) (1996) International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use, June 10, 1996. http://www.ich.org/fileadmin/Public-Web-Site/ICH-Products/Guidelines/Efficacy/ E6-R1/Step4/E6-R1-Guideline.pdf. Accessed 30 March 2011
19. World Medical Association (2010) Declaration of Helsinki: ethical principles for medical research involving human subjects. http://www.wma.net/en/ 30publications/10policies/b3/. Accessed 22 Nov 2010
20. European Medicines Agency (EMA) (2006) Committee for medicinal products for human use (CHMP). Guideline on clinical investigation of medicinal products for the treatment of multiple sclerosis. http://www.ema.europa.eu/docs/en-GB/ document-library/Scientific-guideline/2009/09/WC500003485.pdf. Accessed 11 Feb 2011
21. Bar-Or A, Gold R, Kappos L, Arnold DL, Giovannoni G, Selmaj K, O'Gorman J, Stephan M, Dawson KT (2012) Clinical efficacy of BG-12 (dimethyl fumarate) in patients with relapsing-remitting multiple sclerosis: subgroup analyses of the DEFINE study. Submitted to J Neurol
22. Kappos L, Gold R, Miller DH, Macmanus DG, Havrdova E, Limmroth V, Polman CH, Schmierer K, Yousry TA, Eraksoy M, Meluzinova E, Dufek M, Yang M, Dawson K, O'Neill GN (2011) Effect of BG-12 on contrast-enhancing lesions in patients with relapsing-remitting multiple sclerosis: subgroup analyses from the phase 2b study. Mult Scler 18:314-321
23. Coles AJ, Fox E, Vladic A, Gazda SK, Brinar V, Selmaj KW, Bass AD, Wynn DR, Margolin DH, Lake SL, Moran S, Palmer J, Smith MS, Compston DA (2011) Alemtuzumab versus interferon beta-1a in early relapsing-remitting multiple sclerosis: post hoc and subset analyses of clinical efficacy outcomes. Lancet Neurol 10:338-348
24. Devonshire V, Havrdova E, Radue EW, O'Connor P, Zhang-Auberson L, Agoropoulou C, Haring DA, Francis G, Kappos L (2012) Relapse and disability outcomes in patients with multiple sclerosis treated with fingolimod: subgroup analyses of the double-blind, randomised, placebo-controlled FREEDOMS study. Lancet Neurol 11:420-428
25. Giovannoni G, Cook S, Rammohan K, Rieckmann P, Soelberg Sørensen P, Vermersch P, Hamlett A, Viglietta V, Greenberg S (2011) Sustained disease-activity-free status in patients with relapsing-remitting multiple sclerosis treated with cladribine tablets in the CLARITY study: a post hoc and subgroup analysis. Lancet Neurol 10:329-337
26. Hutchinson M, Kappos L, Calabresi PA, Confavreux C, Giovannoni G, Galetta SL, Havrdova E, Lublin FD, Miller DH, O'Connor PW, Phillips JT, Polman CH, Radue EW, Rudick RA, Stuart WH, Wajgt A, Weinstock-Guttman B, Wynn DR, Lynn F, Panzara MA (2009) The efficacy of natalizumab in patients with relapsing multiple sclerosis: subgroup analyses of AFFIRM and SENTINEL. J Neurol 256:405-415
27. Miller AE, O'Connor P, Wolinsky JS, Confavreux C, Kappos L, Olsson TP, Truffinet P, Wang L, D'Castro L, Comi G, Freedman MS (2012) Pre-specified subgroup analyses of a placebo-controlled phase III trial (TEMSO) of oral teriflunomide in relapsing multiple sclerosis. Mult Scler 18:1625-1632
28. Tremlett H, Zhao Y, Joseph J, Devonshire V (2008) Relapses in multiple sclerosis are age- and time-dependent. J Neurol Neurosurg Psychiatry 79:1368-1374