Subgroup and sensitivity analyses of annualized relapse rate over 2 years in the ADVANCE trial of peginterferon beta-1a in patients with relapsing-remitting multiple sclerosis

被引:12
作者
Newsome, Scott D. [1 ,6 ]
Kieseier, Bernd C. [2 ,3 ]
Arnold, Douglas L. [4 ,5 ]
Shang, Shulian [3 ]
Liu, Shifang [3 ]
Hung, Serena [3 ]
Sabatella, Guido [3 ]
机构
[1] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA
[2] Univ Dusseldorf, Fac Med, Dept Neurol, Dusseldorf, Germany
[3] Biogen, Cambridge, MA USA
[4] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada
[5] NeuroRx Res, Montreal, PQ, Canada
[6] Johns Hopkins Univ Hosp, Pathol 627, Johns Hopkins Neuroimmunol & Neuroinfect Dis, 600 N Wolfe St, Baltimore, MD 21287 USA
关键词
Interferon; Pegylated; Peginterferon beta-1a; Multiple sclerosis; Relapsing-remitting; Clinical trial; Phase; 3; PEGYLATED INTERFERON BETA-1A; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; MULTICENTER;
D O I
10.1007/s00415-016-8182-4
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
ADVANCE was a 2-year, double-blind, placebo-controlled, Phase 3 study in 1512 patients aged 18-65 years with relapsing-remitting multiple sclerosis, which demonstrated that peginterferon beta-1a 125 mcg administered subcutaneously every 2 or 4 weeks led to significant reductions in annualized relapse rate (ARR) compared with placebo. This analysis examined ARR over 2 years in ADVANCE across subgroups. Patients were treated with peginterferon beta-1a every 2 weeks or every 4 weeks, or placebo during Year 1. Thereafter, patients on placebo were re-randomized to peginterferon beta-1a every 2 weeks or every 4 weeks (delayed treatment). Subgroup analyses were conducted by demographics and baseline disease characteristics. The following results compared ARR in these subgroups for patients in continuous 2-week treatment versus continuous 4-week treatment. ARR was similar in most demographic and baseline disease characteristic subgroups evaluated within the peginterferon beta-1a every-2-week arm or every-4-week arm over 2 years. Although for both doses some differences in the point estimates for ARR were noted among the subgroups, considerable overlap in the confidence intervals suggested that the efficacy of peginterferon beta-1a is similar in all patients irrespective of gender, age, body weight, geographical region, and disease activity at initiation of treatment. Within each peginterferon beta-1a dosing group, ARR was generally similar across most subgroups.
引用
收藏
页码:1778 / 1787
页数:10
相关论文
共 8 条
[1]   PEGylated Interferon Beta-1a: Meeting an Unmet Medical Need in the Treatment of Relapsing Multiple Sclerosis [J].
Baker, Darren P. ;
Pepinsky, Robert Blake ;
Brickelmaier, Margot ;
Gronke, Robert S. ;
Hu, Xiao ;
Olivier, Kenneth ;
Lerner, Michaela ;
Miller, Larisa ;
Crossman, Mary ;
Nestorov, Ivan ;
Subramanyam, Meena ;
Hitchman, Stacy ;
Glick, Gabrielle ;
Richman, Sandra ;
Liu, Shifang ;
Zhu, Ying ;
Panzara, Michael A. ;
Davar, Gudarz .
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 2010, 30 (10) :777-785
[2]   Pegylated interferon beta-1a for relapsing-remitting multiple sclerosis (ADVANCE): a randomised, phase 3, double-blind study [J].
Calabresi, Peter A. ;
Kieseier, Bernd C. ;
Arnold, Douglas L. ;
Balcer, Laura J. ;
Boyko, Alexey ;
Pelletier, Jean ;
Liu, Shifang ;
Zhu, Ying ;
Seddighzadeh, All ;
Hung, Serena ;
Deykin, Aaron .
LANCET NEUROLOGY, 2014, 13 (07) :657-665
[3]   INTERFERON BETA-1B IS EFFECTIVE IN RELAPSING-REMITTING MULTIPLE-SCLEROSIS - CLINICAL-RESULTS OF A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL [J].
DUQUETTE, P ;
GIRARD, M ;
DESPAULT, L ;
DUBOIS, R ;
KNOBLER, RL ;
LUBLIN, FD ;
KELLEY, L ;
FRANCIS, GS ;
LAPIERRE, Y ;
ANTEL, J ;
FREEDMAN, M ;
HUM, S ;
GREENSTEIN, JI ;
MISHRA, B ;
MULDOON, J ;
WHITAKER, JN ;
EVANS, BK ;
LAYTON, B ;
SIBLEY, WA ;
LAGUNA, J ;
KRIKAWA, J ;
PATY, DW ;
OGER, JJ ;
KASTRUKOFF, LF ;
MOORE, GRW ;
HASHIMOTO, SA ;
MORRISON, W ;
NELSON, J ;
GOODIN, DS ;
MASSA, SM ;
GUTTERIDGE, E ;
ARNASON, BGW ;
NORONHA, A ;
REDER, AT ;
MARTIA, R ;
EBERS, GC ;
RICE, GPA ;
LESAUX, J ;
JOHNSON, KP ;
PANITCH, HS ;
BEVER, CT ;
CONWAY, K ;
WALLENBERG, JC ;
BEDELL, L ;
VANDENNOORT, S ;
WEINSHENKER, B ;
WEISS, W ;
REINGOLD, S ;
PACHNER, A ;
TAYLOR, W .
NEUROLOGY, 1993, 43 (04) :655-661
[4]   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
[5]   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
[6]   COPOLYMER-1 REDUCES RELAPSE RATE AND IMPROVES DISABILITY IN RELAPSING-REMITTING MULTIPLE-SCLEROSIS - RESULTS OF A PHASE-III MULTICENTER, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL [J].
JOHNSON, KP ;
BROOKS, BR ;
COHEN, JA ;
FORD, CC ;
GOLDSTEIN, J ;
LISAK, RP ;
MYERS, LW ;
PANITCH, HS ;
ROSE, JW ;
SCHIFFER, RB ;
VOLLMER, T ;
WEINER, LP ;
WOLINSKY, JS ;
BIRD, SJ ;
CONSTANTINESCU, C ;
KOLSON, DL ;
GONZALEZSCARANO, F ;
BRENNAN, D ;
PFOHL, D ;
MANDLER, RN ;
ROSENBERG, GA ;
JEFFREY, C ;
BARGER, GR ;
GANDHI, B ;
MOORE, PM ;
ROGERS, LR ;
LISAK, D ;
SMITH, L ;
ELLISON, GW ;
BAUMHEFNER, RW ;
CRAIG, SL ;
JALBUT, SS ;
KATZ, E ;
CONWAY, KL ;
BURNS, JB ;
SHIBA, C ;
GIANG, DW ;
PETRIE, MD ;
GUARNACCIA, JB ;
ANDERSON, S ;
MCKEON, A ;
MCCARTHY, M ;
THOMAS, AB ;
VRIESENDORP, FJ ;
AUSTIN, SG ;
LINDSEY, JW ;
DIMACHKIE, M ;
CERRETA, E ;
KACHUCK, N ;
MCCARTHY, KA .
NEUROLOGY, 1995, 45 (07) :1268-1276
[7]   Peginterferon beta-1a in multiple sclerosis: 2-year results from ADVANCE [J].
Kieseier, Bernd C. ;
Arnold, Douglas L. ;
Balcer, Laura J. ;
Boyko, Alexey A. ;
Pelletier, Jean ;
Liu, Shifang ;
Zhu, Ying ;
Seddighzadeh, Ali ;
Hung, Serena ;
Deykin, Aaron ;
Sheikh, Sarah I. ;
Calabresi, Peter A. .
MULTIPLE SCLEROSIS JOURNAL, 2015, 21 (08) :1025-1035
[8]   PEGylation of Interferon-β-1a A Promising Strategy in Multiple Sclerosis [J].
Kieseier, Bernd C. ;
Calabresi, Peter A. .
CNS DRUGS, 2012, 26 (03) :205-214