Fingolimod versus intramuscular interferon in patient subgroups from TRANSFORMS

被引:68
作者
Cohen, Jeffrey A. [1 ]
Barkhof, Frederik [2 ]
Comi, Giancarlo [3 ]
Izquierdo, Guillermo [4 ]
Khatri, Bhupendra [5 ]
Montalban, Xavier [6 ,7 ]
Pelletier, Jean [8 ,9 ]
Eckert, Benjamin [10 ]
Haering, Dieter A. [11 ]
Francis, Gordon [10 ]
机构
[1] Cleveland Clin, Neurol Inst, Mellen Ctr U10, Cleveland, OH 44195 USA
[2] Vrije Univ Amsterdam Med Ctr, Image Anal Ctr, Amsterdam, Netherlands
[3] Univ Vita Salute San Raffaele, Dept Neurol, Milan, Italy
[4] Virgen Macarena Univ Hosp, Dept Neurol, Seville, Spain
[5] St Lukes Med Ctr, Milwaukee, WI USA
[6] Vall dHebron Univ Hosp, Dept Neurol Neuroimmunol, Barcelona, Spain
[7] Vall dHebron Univ Hosp, Cemcat, Barcelona, Spain
[8] CHU La Timone, Dept Neurol, Marseille, France
[9] CHU La Timone, CRMBM CNRS7339, Marseille, France
[10] Novartis Pharmaceut, E Hanover, NJ USA
[11] Novartis Pharma AG, Basel, Switzerland
关键词
Multiple sclerosis; Randomized clinical trial; Fingolimod; Interferon-beta; MRI; Subgroup analysis; REMITTING MULTIPLE-SCLEROSIS; DOUBLE-BLIND; ORAL FINGOLIMOD; DISABILITY; BETA-1A; PROGRESSION; THERAPY; TRIAL; AGE;
D O I
10.1007/s00415-013-6932-0
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
In the 12-month phase 3 TRANSFORMS study, fingolimod showed greater efficacy than intramuscular interferon beta (IFN beta)-1a in patients with relapsing-remitting multiple sclerosis (RRMS). This study analyzed fingolimod efficacy compared with IFN beta-1a in patient subgroups from TRANSFORMS. Patients were randomized to receive fingolimod or weekly IM IFN beta-1a for 12 months. Analyses of efficacy included annualized relapse rate (ARR), and magnetic resonance imaging (MRI) measures [gadolinium (Gd)-enhancing T1 lesions, new/newly enlarged (active) T2 lesions, brain volume change]. Subgroups were defined based on demographics, disease characteristics (baseline EDSS score, relapse rate, and MRI parameters), and response to previous therapy. Fingolimod 0.5 mg reduced ARR over 12 months by 32-59 % relative to IFN beta-1a in all subgroups defined by demographic factors or baseline disease characteristics. Fingolimod also reduced the number of new Gd-enhancing lesions, active T2 lesions, and the rate of brain volume loss, versus IFN beta-1a in most (95 %) subgroups. In patients with high disease activity despite IFN beta treatment in the year before study, fingolimod 0.5 mg reduced ARR by 61 % relative to IFN beta-1a. Reductions in lesion counts and brain volume loss also favored fingolimod in these patients. In conclusion, consistently better efficacy was observed for fingolimod compared with IFN beta-1a across different subgroups of patients with RRMS.
引用
收藏
页码:2023 / 2032
页数:10
相关论文
共 18 条
[1]   A longitudinal study of abnormalities on MRI and disability from multiple sclerosis [J].
Brex, PA ;
Ciccarelli, O ;
O'Riordan, JI ;
Sailer, M ;
Thompson, AJ ;
Miller, DH .
NEW ENGLAND JOURNAL OF MEDICINE, 2002, 346 (03) :158-164
[2]   Oral Fingolimod or Intramuscular Interferon for Relapsing Multiple Sclerosis [J].
Cohen, Jeffrey A. ;
Barkhof, Frederik ;
Comi, Giancarlo ;
Hartung, Hans-Peter ;
Khatri, Bhupendra O. ;
Montalban, Xavier ;
Pelletier, Jean ;
Capra, Ruggero ;
Gallo, Paolo ;
Izquierdo, Guillermo ;
Tiel-Wilck, Klaus ;
de Vera, Ana ;
Jin, James ;
Stites, Tracy ;
Wu, Stacy ;
Aradhye, Shreeram ;
Kappos, Ludwig .
NEW ENGLAND JOURNAL OF MEDICINE, 2010, 362 (05) :402-415
[3]   Age at disability milestones in multiple sclerosis [J].
Confavreux, C ;
Vukusic, S .
BRAIN, 2006, 129 :595-605
[4]   Early clinical predictors and progression of irreversible disability in multiple sclerosis: an amnesic process [J].
Confavreux, C ;
Vukusic, S ;
Adeleine, P .
BRAIN, 2003, 126 :770-782
[5]   Relapse and disability outcomes in patients with multiple sclerosis treated with fingolimod: subgroup analyses of the double-blind, randomised, placebo-controlled FREEDOMS study [J].
Devonshire, Virginia ;
Havrdova, Eva ;
Radue, Ernst Wilhelm ;
O'Connor, Paul ;
Zhang-Auberson, Lixin ;
Agoropoulou, Catherine ;
Haering, Dieter Adrian ;
Francis, Gordon ;
Kappos, Ludwig .
LANCET NEUROLOGY, 2012, 11 (05) :420-428
[6]   Randomised double-blind placebo-controlled study of interferon β-1a in relapsing/remitting multiple sclerosis [J].
Ebers, GC ;
Rice, G ;
Lesaux, J ;
Paty, D ;
Oger, J ;
Li, DKB ;
Beall, S ;
Devonshire, V ;
Hashimoto, S ;
Hooge, J ;
Kastrukoff, L ;
Krieger, C ;
Mezei, M ;
Seland, P ;
Vorobeychi, G ;
Morrison, W ;
Nelson, J ;
Freedman, MS ;
Chrisie, S ;
Nelson, R ;
Rabinovitch, H ;
Freedman, C ;
Hartung, HP ;
Rieckmann, P ;
Archelos, J ;
Jung, S ;
Weilbach, F ;
Flachenecke, P ;
Sauer, J ;
Hommes, O ;
Jongen, P ;
Brouwer, S ;
McLeod, J ;
Pollard, J ;
Ng, R ;
Sandberg-Wollheim, M ;
Källén, K ;
Nilsson, P ;
Ekberg, R ;
Lundgren, A ;
Jadbäck, G ;
Wikström, J ;
Multanen, J ;
Valjakka, M ;
Carton, H ;
Lissoir, F ;
Declerq, I ;
Vieren, M ;
Peeters, E ;
Dubois, B .
LANCET, 1998, 352 (9139) :1498-1504
[7]   Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. [J].
Jacobs, LD ;
Beck, RW ;
Simon, JH ;
Kinkel, RP ;
Brownscheidle, CM ;
Murray, TJ ;
Simonian, NA ;
Slasor, PJ ;
Sandrock, AW .
NEW ENGLAND JOURNAL OF MEDICINE, 2000, 343 (13) :898-904
[8]   Intramuscular interferon beta-1 alpha for disease progression in relapsing multiple sclerosis [J].
Jacobs, LD ;
Cookfair, DL ;
Rudick, RA ;
Herndon, RM ;
Richert, JR ;
Salazar, AM ;
Fischer, JS ;
Goodkin, DE ;
Granger, CV ;
Simon, JH ;
Alam, JJ ;
Bartoszak, DM ;
Bourdette, DN ;
Braiman, J ;
Brownscheidle, CM ;
Coats, ME ;
Cohan, SL ;
Dougherty, DS ;
Kinkel, RP ;
Mass, MK ;
Munschauer, FE ;
Priore, RL ;
Pullicino, PM ;
Scherokman, BJ ;
WeinstockGuttman, B ;
Whitman, RH ;
Baird, WC ;
Fillmore, M ;
Bona, LM ;
ColonRuiz, ME ;
Nadine, BS ;
Donovan, A ;
Bennett, S ;
Kieffer, YM ;
Umhauer, MA ;
Miller, CE ;
Kilic, AK ;
Sargent, EL ;
Schachter, M ;
Shucard, DW ;
Weider, V ;
Catalano, BA ;
Cervi, JM ;
Czekay, C ;
Farrell, JL ;
Filippini, JS ;
Matyas, RC ;
Michienzi, KE ;
Ito, M ;
OMalley, JA .
ANNALS OF NEUROLOGY, 1996, 39 (03) :285-294
[9]   A Placebo-Controlled Trial of Oral Fingolimod in Relapsing Multiple Sclerosis [J].
Kappos, Ludwig ;
Radue, Ernst-Wilhelm ;
O'Connor, Paul ;
Polman, Chris ;
Hohlfeld, Reinhard ;
Calabresi, Peter ;
Selmaj, Krzysztof ;
Agoropoulou, Catherine ;
Leyk, Malgorzata ;
Zhang-Auberson, Lixin ;
Burtin, Pascale .
NEW ENGLAND JOURNAL OF MEDICINE, 2010, 362 (05) :387-401
[10]   Comparison of fingolimod with interferon beta-1a in relapsing-remitting multiple sclerosis: a randomised extension of the TRANSFORMS study [J].
Khatri, Bhupendra ;
Barkhof, Frederik ;
Comi, Giancarlo ;
Hartung, Hans-Peter ;
Kappos, Ludwig ;
Montalban, Xavier ;
Pelletier, Jean ;
Stites, Tracy ;
Wu, Stacy ;
Holdbrook, Fred ;
Zhang-Auberson, Lixin ;
Francis, Gordon ;
Cohen, Jeffrey A. ;
Cohen, J. ;
Barkhof, F. ;
Comi, G. ;
Hartung, H.P. ;
Khatri, B. ;
Montalban, X. ;
Pelletier, J. ;
Easton, D. ;
Calandra, T. ;
DiMarco, J. ;
Hudson, L. ;
Kesselring, J. ;
Laupacis, A. ;
Temkin, N. ;
Weinshenker, B. ;
Zarbin, M. ;
Barkhof, F. ;
Poppe, P. ;
Luetic, G. ;
Cristiano, E. ;
Caceres, F. ;
Garcea, O. ;
Correale, J. ;
Ballario, C. ;
Piedrabuena, R. ;
Pollard, J. ;
Beran, R. ;
Hodgkinson, S. ;
Schwartz, R. ;
Heard, R. ;
King, J. ;
Butzkueven, H. ;
Maida, E.M. ;
Vass, K. ;
Franta-Elmer, C. ;
Berger, T. ;
Aichner, F. .
LANCET NEUROLOGY, 2011, 10 (06) :520-529