Contributions
Abstract: P791
Type: Poster
Abstract Category: Therapy - disease modifying - 32 Others
Background: REVEAL was designed as a 1-year, multicentre, randomized, rater-blinded, prospective phase 4 study comparing natalizumab and fingolimod in patients with active relapsing-remitting multiple sclerosis (RRMS). Although the study closed early (for non-safety/ non-efficacy reasons), data permitted comparison of effects occurring shortly after treatment initiation.
Objective: To compare onset of efficacy with natalizumab and fingolimod in REVEAL.
Methods: Patients were assigned to open-label intravenous natalizumab 300 mg every 4 weeks (n=54) or oral fingolimod 0.5 mg once daily (n=54). Magnetic resonance imaging was scheduled every 4 weeks for the first 24 weeks and then at weeks 36 and 52; relapses and adverse events (AEs) were assessed at scheduled visits. Analyses included Kaplan-Meier and Cox regression for time to event; negative binomial regression for annualized relapse rate (ARR) and number of T1 gadolinium-enhancing (Gd+) lesions; and a negative binomial generalized estimating equation for cumulative Gd+ lesions over time.
Results: As expected for a randomized study, demographics, disease characteristics and follow-up time (median 39 weeks) were generally similar between groups. Natalizumab patients were less likely than fingolimod patients to develop new Gd+ lesions, with a cumulative probability of 40.68% vs 57.99% (hazard ratio [HR]=1.678 [95% confidence interval [CI]: 0.865-3.255]; P=0.1258) of developing ≥1 lesion and 11.54% vs 48.48% (HR=4.053 [95% CI: 1.474-11.144]; P=0.0067) of developing ≥2 lesions. The natalizumab group consistently had 63%-72% fewer Gd+ lesions, with between-group differences apparent within 4 weeks and reaching significance by week 16 (P=0.0251). ARR was 83% lower with natalizumab than with fingolimod (0.05 vs 0.29; P=0.0236), and cumulative probability of relapse was 1.85% with natalizumab vs 22.28% with fingolimod (HR=12.184 [95% CI: 1.552-95.634]; P=0.0174). AEs were consistent with known safety profiles.
Conclusions: These results extend previous work showing that natalizumab has benefits soon after initiation, demonstrating that onset of reduced disease activity occurred more rapidly, and to a greater extent, with natalizumab than with fingolimod in patients with active RRMS. However, given early study closure, available data did not permit primary endpoint evaluation, so these results should be interpreted with caution.
Acknowledgement: Dr. Diogo Amarante (Biogen, Cambridge, MA), who contributed substantially to the data acquisition and execution of the REVEAL trial, passed away prior to development of this abstract and therefore cannot qualify for authorship per ICMJE criteria. The authors gratefully acknowledge his contributions to this study.
Disclosure: Supported by Biogen.
SL, QD, NC, P-RH: employees of and may hold stock and/or stock options in Biogen.
HB: compensation for consulting from Biogen, Merck Serono, Novartis; research support from Biogen, Merck Serono.
DJ: research funding from Biogen, Genentech; personal compensation for speaking or consulting services from Acorda, Bayer, Biogen, Genentech, GlaxoSmithKline, Novartis, Questcor, Serono, Teva.
DLA: has served on advisory boards for, received speaker honoraria from, served as a consultant for, or received research support from Bayer, Biogen, Coronado Biosciences, the Consortium of Multiple Sclerosis Centers, Eli Lilly, EMD Serono, Genentech, Genzyme, GlaxoSmithKline, Merck Serono, MS Forum, NeuroRx Research, Novartis, Opexa Therapeutics, Roche, Teva, the Canadian Institutes of Health Research, the Multiple Sclerosis Society of Canada, the S.A. Serono Symposia International Foundation; holds stock in NeuroRx Research.
MF: serves as editor-in-chief of the Journal of Neurology and on the scientific advisory board for Teva; has received compensation for consulting services and/or speaking activities from Biogen, Excemed, Novartis, Teva Pharmaceutical Industries; has received research support from Biogen, Novartis, Teva Pharmaceutical Industries, the Alzheimer's Drug Discovery Foundation (ADDF), ARiSLA (Fondazione Italiana di Ricerca per la SLA), Cure PSP, the Italian Ministry of Health, the Jacques and Gloria Gossweiler Foundation (Switzerland), La Fondazione Italiana Sclerosi Multipla.
JJGG: serves on the editorial boards of Multiple Sclerosis Journal and Neurology; has received speaker honoraria from Biogen, Genzyme, Merck Serono, Novartis, Teva; has received research support from Biogen; has served on the boards of the Dutch MS Research Foundation and the Progressive MS Alliance.
Abstract: P791
Type: Poster
Abstract Category: Therapy - disease modifying - 32 Others
Background: REVEAL was designed as a 1-year, multicentre, randomized, rater-blinded, prospective phase 4 study comparing natalizumab and fingolimod in patients with active relapsing-remitting multiple sclerosis (RRMS). Although the study closed early (for non-safety/ non-efficacy reasons), data permitted comparison of effects occurring shortly after treatment initiation.
Objective: To compare onset of efficacy with natalizumab and fingolimod in REVEAL.
Methods: Patients were assigned to open-label intravenous natalizumab 300 mg every 4 weeks (n=54) or oral fingolimod 0.5 mg once daily (n=54). Magnetic resonance imaging was scheduled every 4 weeks for the first 24 weeks and then at weeks 36 and 52; relapses and adverse events (AEs) were assessed at scheduled visits. Analyses included Kaplan-Meier and Cox regression for time to event; negative binomial regression for annualized relapse rate (ARR) and number of T1 gadolinium-enhancing (Gd+) lesions; and a negative binomial generalized estimating equation for cumulative Gd+ lesions over time.
Results: As expected for a randomized study, demographics, disease characteristics and follow-up time (median 39 weeks) were generally similar between groups. Natalizumab patients were less likely than fingolimod patients to develop new Gd+ lesions, with a cumulative probability of 40.68% vs 57.99% (hazard ratio [HR]=1.678 [95% confidence interval [CI]: 0.865-3.255]; P=0.1258) of developing ≥1 lesion and 11.54% vs 48.48% (HR=4.053 [95% CI: 1.474-11.144]; P=0.0067) of developing ≥2 lesions. The natalizumab group consistently had 63%-72% fewer Gd+ lesions, with between-group differences apparent within 4 weeks and reaching significance by week 16 (P=0.0251). ARR was 83% lower with natalizumab than with fingolimod (0.05 vs 0.29; P=0.0236), and cumulative probability of relapse was 1.85% with natalizumab vs 22.28% with fingolimod (HR=12.184 [95% CI: 1.552-95.634]; P=0.0174). AEs were consistent with known safety profiles.
Conclusions: These results extend previous work showing that natalizumab has benefits soon after initiation, demonstrating that onset of reduced disease activity occurred more rapidly, and to a greater extent, with natalizumab than with fingolimod in patients with active RRMS. However, given early study closure, available data did not permit primary endpoint evaluation, so these results should be interpreted with caution.
Acknowledgement: Dr. Diogo Amarante (Biogen, Cambridge, MA), who contributed substantially to the data acquisition and execution of the REVEAL trial, passed away prior to development of this abstract and therefore cannot qualify for authorship per ICMJE criteria. The authors gratefully acknowledge his contributions to this study.
Disclosure: Supported by Biogen.
SL, QD, NC, P-RH: employees of and may hold stock and/or stock options in Biogen.
HB: compensation for consulting from Biogen, Merck Serono, Novartis; research support from Biogen, Merck Serono.
DJ: research funding from Biogen, Genentech; personal compensation for speaking or consulting services from Acorda, Bayer, Biogen, Genentech, GlaxoSmithKline, Novartis, Questcor, Serono, Teva.
DLA: has served on advisory boards for, received speaker honoraria from, served as a consultant for, or received research support from Bayer, Biogen, Coronado Biosciences, the Consortium of Multiple Sclerosis Centers, Eli Lilly, EMD Serono, Genentech, Genzyme, GlaxoSmithKline, Merck Serono, MS Forum, NeuroRx Research, Novartis, Opexa Therapeutics, Roche, Teva, the Canadian Institutes of Health Research, the Multiple Sclerosis Society of Canada, the S.A. Serono Symposia International Foundation; holds stock in NeuroRx Research.
MF: serves as editor-in-chief of the Journal of Neurology and on the scientific advisory board for Teva; has received compensation for consulting services and/or speaking activities from Biogen, Excemed, Novartis, Teva Pharmaceutical Industries; has received research support from Biogen, Novartis, Teva Pharmaceutical Industries, the Alzheimer's Drug Discovery Foundation (ADDF), ARiSLA (Fondazione Italiana di Ricerca per la SLA), Cure PSP, the Italian Ministry of Health, the Jacques and Gloria Gossweiler Foundation (Switzerland), La Fondazione Italiana Sclerosi Multipla.
JJGG: serves on the editorial boards of Multiple Sclerosis Journal and Neurology; has received speaker honoraria from Biogen, Genzyme, Merck Serono, Novartis, Teva; has received research support from Biogen; has served on the boards of the Dutch MS Research Foundation and the Progressive MS Alliance.