Fingolimod Versus Dimethyl-fumarate in Multiple Sclerosis

Summary

This will be a 1:1 randomized open label trial. European and outside Europe centres will be involved. Aim of the project is to conduct a head-to-head comparison of effectiveness of two approved disease modifying treatments (DMTs) in patients with relapsing remitting multiple sclerosis (RRMS). The term effectiveness refers to efficacy in a real life setting: this is intended to be in fact the first pragmatic multi-centre randomised controlled trial to directly assess the effectiveness of the new oral agents approved for MS (fingolimod/FTY versus dimethyl-fumarate/DMF) on disease activity, disability progression, quality of life, functioning and symptoms. It will be a randomized trial taking place in clinical care setting and comparing existing therapies, any of which may constitute standard care for naive patients or sub optimal responders to first-line drugs. Post hoc analysis will also identify the better treatment strategy on the different patient subgroups. Patient overall disease experience will be considered for the first time as the most important outcome. In fact, in addition to classical "no evidence of disease activity" (NEDA), a new composite NEDA taking account also of patient point of view and quality of life, will be proposed. Finally,the specific effectiveness profile of the two DMTs will be addressed, by exploring comparative benefits on different outcomes (disease activity, disability progression, brain atrophy, quality of life, fatigue, psychiatric and cognitive symptoms, medication satisfaction).

Timeline

Start

2017-04-30

Primary completion

2019-10-30

Completion

2019-10-30

Publications

• Background Patsopoulos NA. A pragmatic view on pragmatic trials. Dialogues Clin Neurosci. 2011;13(2):217-24. doi: 10.31887/DCNS.2011.13.2/npatsopoulos.
• Background Calabresi PA, Radue EW, Goodin D, Jeffery D, Rammohan KW, Reder AT, Vollmer T, Agius MA, Kappos L, Stites T, Li B, Cappiello L, von Rosenstiel P, Lublin FD. 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. 2014 Jun;13(6):545-56. doi: 10.1016/S1474-4422(14)70049-3. Epub 2014 Mar 28.
• Background Kappos L, Radue EW, O'Connor P, Polman C, Hohlfeld R, Calabresi P, Selmaj K, Agoropoulou C, Leyk M, Zhang-Auberson L, Burtin P; FREEDOMS Study Group. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med. 2010 Feb 4;362(5):387-401. doi: 10.1056/NEJMoa0909494. Epub 2010 Jan 20.
• Background Fox RJ, Miller DH, Phillips JT, Hutchinson M, Havrdova E, Kita M, Yang M, Raghupathi K, Novas M, Sweetser MT, Viglietta V, Dawson KT; CONFIRM Study Investigators. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med. 2012 Sep 20;367(12):1087-97. doi: 10.1056/NEJMoa1206328.
• Background Gold R, Kappos L, Arnold DL, Bar-Or A, Giovannoni G, Selmaj K, Tornatore C, Sweetser MT, Yang M, Sheikh SI, Dawson KT; DEFINE Study Investigators. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med. 2012 Sep 20;367(12):1098-107. doi: 10.1056/NEJMoa1114287.
• Background Cohen JA, Barkhof F, Comi G, Hartung HP, Khatri BO, Montalban X, Pelletier J, Capra R, Gallo P, Izquierdo G, Tiel-Wilck K, de Vera A, Jin J, Stites T, Wu S, Aradhye S, Kappos L; TRANSFORMS Study Group. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med. 2010 Feb 4;362(5):402-15. doi: 10.1056/NEJMoa0907839. Epub 2010 Jan 20.
• Background Hutchinson M, Fox RJ, Havrdova E, Kurukulasuriya NC, Sarda SP, Agarwal S, Siddiqui MK, Taneja A, Deniz B. Efficacy and safety of BG-12 (dimethyl fumarate) and other disease-modifying therapies for the treatment of relapsing-remitting multiple sclerosis: a systematic review and mixed treatment comparison. Curr Med Res Opin. 2014 Apr;30(4):613-27. doi: 10.1185/03007995.2013.863755. Epub 2013 Nov 26.
• Background Giovannoni G, Cook S, Rammohan K, Rieckmann P, Sorensen PS, Vermersch P, Hamlett A, Viglietta V, Greenberg S; CLARITY study group. 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. 2011 Apr;10(4):329-37. doi: 10.1016/S1474-4422(11)70023-0.
• Background Nixon R, Bergvall N, Tomic D, Sfikas N, Cutter G, Giovannoni G. No evidence of disease activity: indirect comparisons of oral therapies for the treatment of relapsing-remitting multiple sclerosis. Adv Ther. 2014 Nov;31(11):1134-54. doi: 10.1007/s12325-014-0167-z. Epub 2014 Nov 21.

Drugs

Indications