Contributions
Abstract: 251
Type: LB Oral
Abstract Category: Late Breaking News
Background: The efficacy of alemtuzumab, a highly effective anti-CD52 agent, was shown to be superior compared with interferon β in relapsing-remitting multiple sclerosis (MS). However, its efficacy relative to other potent therapies is unknown.
Objective: To compare treatment effectiveness of alemtuzumab vs natalizumab, fingolimod and interferon β.
Methods: 3936 patients (72% female, median follow-up 2.9 years, age 35, Expanded Disability Status Scale [EDSS] 2.5) from MSBase and MS centres in Cambridge, Cardiff, Bristol, Swansea, Dublin and Dresden were included. The inclusion criteria consisted of relapsing-remitting MS, on-treatment follow-up ≥6 months, 1 baseline and 2 follow-up EDSS scores and availability of the minimum dataset. Three pairwise comparisons of alemtuzumab vs natalizumab, fingolimod or interferon were carried out. Propensity score was used to match on demographic and clinical characteristics, using 1:2 variable matching and 0.1 caliper. Multivariable clustered weighted models were used to compare annualised relapse rates (ARR; negative binomial model) or cumulative hazard of relapses, and 6-month confirmed EDSS progression or regression events (Andersen-Gill survival models). Six sensitivity analyses for matching strategy, inclusion of secondary progressive MS, or high pre-treatment ARR or prior on-treatment relapses were carried out.
Results: The included cohort consisted of 189, 2155, 828 and 1160 patients treated with alemtuzumab, interferon, fingolimod or natalizumab, respectively. Compared to interferon, alemtuzumab was associated with lower ARR (0.5 vs 0.2, p=10-16) and lower risk of EDSS progression and more likely EDSS reduction in patients with previously highly active MS (hazard ratio(HR)=4, p=0.02). Compared to fingolimod, ARR was lower on alemtuzumab (0.3 vs 0.15, p=10-11). Importantly, no differences in ARR (0.2 both groups, p=0.8) and EDSS progression were found between alemtuzumab and natalizumab. The likelihood of EDSS reduction was higher on natalizumab (HR=2.9, p=10-4). Sensitivity analyses largely confirmed the above results. Statistical power was sufficient to demonstrate clinically meaningful effects.
Conclusion: We have replicated the outcomes of the pivotal trials, showing a superior efficacy of alemtuzumab vs interferon β. Alemtuzumab is superior to fingolimod in reducing ARR. Alemtuzumab and natalizumab show similar effects on relapse activity but natalizumab is associated with greater reduction in disability.
Disclosure: TK served on scientific advisory boards for Roche, Genzyme, Novartis, Merck and Biogen, has received conference travel support and/or speaker honoraria from WebMD Global, Novartis, Biogen, Sanofi, Genzyme, Teva, BioCSL and Merck and has received research support from Biogen.
JWLB has received travel expenses from Novartis and Sanofi-Genzyme.
NRn has received lecture honoraria and consultancy fees from Biogen, Genzyme, and Novartis and has received research funding from Novartis and Genzyme.
MW did not disclose any conflict of interests.
NS has received research support from Biogen, Sanofi-Genzyme, Merck-Serono and Teva.
OP received honoraria and support to attend scientific meetings, speakers" fees, and advisory boards from Biogen, Genzyme, Novartis, Teva, Merck Serono and Roche.
TZ has received compensation for consulting services from Almirall, Biogen Idec, Bayer, Genzyme, GlaxoSmithKline, MSD, Merck Serono, Novartis, Sanofi, Teva, and Synthon, and has received research support from Bayer, Biogen Idec, the Hertie Foundation, the Roland Ernst Foundation, the German Diabetes Foundation, Merck Serono, Novartis, Teva, and Sanofi Aventis. Further, he is a lead investigator in the PANGAEA and PEARL study.
MH served on a medical advisory board for the CONFIRM study [BG00012] for Biogen-Idec, serves on the editorial board of the Multiple Sclerosis journal, has received speaker"s honoraria from Novartis, Biogen Idec and Bayer-Schering and receives research support from Dystonia Ireland, the Health Research Board of Ireland and the European Dystonia Foundation.
CM has received research grants from Biogen, Genzyme, Novartis, Teva, Bayer and honoraria as a consultant from Biogen, Genzyme, Novartis and Roche.
VJ received conference travel support from Novartis and Merck Serono.
TS received honoraria for consultancy, funding for travel and compensation for serving on scientific advisory boards from Biogen and speaker honoraria from Novartis.
DHa received speaker honoraria and consulting fees from Biogen, Merck Serono, Teva and Novartis, as well as support for research activities from Biogen and research grants from Charles University in Prague (PRVOUK-P26/LF1/4 and Czech Ministry of Health (NT13237-4/2012).
EH received speaker honoraria and consultant fees from Biogen, Merck Serono, Novartis, Genzyme and Teva, as well as support for research activities from Biogen, Merck Serono and research grants from Charles University in Prague (PRVOUK-P26/LF1/4 and Czech Ministry of Health (NT13237-4/2012).
MT received speaker honoraria from Biogen-Idec, Bayer-Schering, Sanofi Aventis, Merck-Serono, Teva , Novartis and Almirall; has received research grants for her Institution from Biogen-Idec, Merck-Serono, and Novartis.
GI received speaking honoraria from Biogen, Novartis, Sanofi, Merck Serono and Teva.
AL is a Bayer, Biogen, Genzyme, Merck Advisory Board Member. She received travel grants and honoraria from Bayer, Biogen, Merck, Novartis, Sanofi, Teva and Fondazione Italiana Sclerosi Multipla (FISM). Her institution received research grants from Bayer, Biogen, Merck, Novartis, Sanofi , Teva and Fondazione Italiana Sclerosi Multipla (FISM).
AP did not declare any competing interests.
MG received consulting fees from Teva Canada Innovation, Biogen, Novartis and Genzyme Sanofi; lecture payments from Teva Canada Innovation, Novartis and EMD Serono. He has also received a research grant from Canadian Institutes of Health Research.
PD served on editorial boards and has been supported to attend meetings by EMDSerono, Biogen, Novartis, Genzyme, and TEVA Neuroscience. He holds grants from the CIHR and the MS Society of Canada and has received funding for investigator-initiated trials from Biogen, Novartis, and Genzyme.
PG is a Novartis, Teva-neuroscience, Biogen and Genzyme advisory board member, consultant for Merck Serono, received payments for lectures by Merck Serono, Teva-Neuroscience and Canadian Multiple sclerosis society, and received grants for travel from Teva-Neuroscience and Novartis.
RA received honororia from Biologix, Biogen, Bayer, Genpharm, Genzyme, Merck-Serono, GSK and Novartis, and served on advisory board for Biologix, Biogen, Bayer, Genpharm, Genzyme, Novartis, Genzyme, Merck-Serono and Novartis.
EP served on scientific advisory boards for Merck Serono, Genzyme and Biogen; he has received honoraria and travel grants from Sanofi Aventis, UCB, Lundbeck, Novartis, Bayer Schering, Biogen, Merck Serono, Genzyme and Teva; he has received travel grants and equipment from "Associazione Marchigiana Sclerosi Multipla e altre malattie neurologiche".
PS received travel grants and speaking honoraria from Bayer Schering, Biogen, Merck Serono, Novartis, Sanofi/Genzyme and Teva.
RH received honoraria as consultant on scientific advisory boards from Merck-Serono, Biogen, Genzyme-Sanofi and Teva, research funding from Merck-Serono and Biogen, and speaker honoraria from Sanofi-Genzyme and Novartis.
JLS accepted travel compensation from Novartis, Biogen and Merck Serono. Her institution receives the honoraria for talks and advisory board commitment and also clinic support from Bayer Health Care, Biogen, CSL, Genzyme Sanofi, Merck Serono, Novartis and Teva.
RFB received speaking honoraria from Biogen, Novartis, Merck Serono and Teva.
MT received travel grants from Merck Serono, Novartis, Bayer-Schering, Merck-Serono and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis.
VVP received travel grants and honoraria for consultancy and lectures from Biogen, Bayer Schering, Genzyme, Merck, Roche, Teva and Novartis Pharma.
Csilla Rozsa received speaker honoraria from Bayer Schering, Novartis and Biogen, congress and travel expense compensations from Biogen, Teva, Merck Serono and Bayer Schering.
FG received honoraria or research funding from Biogen, Genzyme, Novartis, Teva Neurosciences, Mitsubishi and ONO Pharmaceuticals.
CB received conference travel support from Biogen, Novartis, Bayer-Schering, Merck-Serono and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis.
FG served on scientific advisory boards for Biogen Idec, Novartis and Sanofi Aventis and received funding for travel and speaker honoraria from Biogen Idec, Merck Serono, and Almirall.
MS has participated in, but not received honoraria for, advisory board activity for Biogen, Merck Serono, Bayer Schering, Sanofi Aventis and Novartis.
DS received honoraria as a consultant on scientific advisory boards by Bayer-Schering, Novartis and Sanofi-Aventis and compensation for travel from Novartis, Biogen, Sanofi Aventis, Teva and Merck-Serono.
JO serves on scientific advisory boards for Biogen, Genzyme and Novartis; has received speaker honoraria from Biogen, Bayer-Schering, Genzyme, Merck-Serono, Novartis and Teva and research grants from Biogen, Merck Serono, Novartis and Teva.
RB received speaker honoraria from Bayer Schering, Biogen, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, Teva; research grants from Bayer Schering, Biogen, Merck Serono, Novartis, Sanofi-Aventis, Teva; congress and travel/accommodation expense compensations by Almirall, Bayer Schering, Biogen, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, Teva.
GI had travel/accommodations/meeting expenses funded by Bayer Schering, Biogen, Merck Serono, Novartis, Sanofi Aventis, and Teva.
FV is an advisory board member for Teva Biogen Merck Serono and Novartis.
SV did not declare any competing interests.
PM did not declare any competing interests.
SH received honoraria and consulting fees from Novartis, Bayer Schering and Sanofi, and travel grants from Novartis, Biogen Idec and Bayer Schering.
KK did not declare any competing interests.
JLSM accepted travel compensation from Novartis and Biogen, speaking honoraria from Biogen, Novartis, Sanofi, Merck Serono, Almirall, Bayer and Teva and has participated in a clinical trial by Biogen.
RA received conference travel support from Novartis, Teva, Biogen, Bayer and Merck Serono and has participated in a clinical trials by Biogen, Novartis, Teva and Actelion.
MS received speaker honoraria from Novartis, Biogen, Bayer Schering; congress/travel compensation from Teva, Biogen, Merck Serono, Bayer Schering.
TC received speaker honoraria/ conference travel support from Bayer Schering, Biogen, Merck Serono, Novartis and Teva.
CR received research funding, compensation for travel or speaker honoraria from Biogen, Novartis, Genzyme and Almirall.
EC received honoraria as consultant on scientific advisory boards by Biogen, Bayer-Schering, Merck-Serono, Genzyme and Novartis; has participated in clinical trials/other research projects by Merck-Serono, Roche and Novartis.
IP did not declare any competing interests.
MB served on scientific advisory boards for Biogen, Novartis and Genzyme and has received conference travel support from Biogen and Novartis. He serves on steering committees for trials conducted by Novartis. His institution has received research support from Biogen, Merck-Serono and Novartis.
HB served on scientific advisory boards for Biogen, Novartis and Sanofi-Aventis and has received conference travel support from Novartis, Biogen and Sanofi Aventis. He serves on steering committees for trials conducted by Biogen and Novartis, and has received research support from Merck Serono, Novartis and Biogen.
AC has received consulting and lecture fees from Genzyme-Sanofi, lecture fees from Merck Serono and research support paid to his institution from Genzyme-Sanofi.
Abstract: 251
Type: LB Oral
Abstract Category: Late Breaking News
Background: The efficacy of alemtuzumab, a highly effective anti-CD52 agent, was shown to be superior compared with interferon β in relapsing-remitting multiple sclerosis (MS). However, its efficacy relative to other potent therapies is unknown.
Objective: To compare treatment effectiveness of alemtuzumab vs natalizumab, fingolimod and interferon β.
Methods: 3936 patients (72% female, median follow-up 2.9 years, age 35, Expanded Disability Status Scale [EDSS] 2.5) from MSBase and MS centres in Cambridge, Cardiff, Bristol, Swansea, Dublin and Dresden were included. The inclusion criteria consisted of relapsing-remitting MS, on-treatment follow-up ≥6 months, 1 baseline and 2 follow-up EDSS scores and availability of the minimum dataset. Three pairwise comparisons of alemtuzumab vs natalizumab, fingolimod or interferon were carried out. Propensity score was used to match on demographic and clinical characteristics, using 1:2 variable matching and 0.1 caliper. Multivariable clustered weighted models were used to compare annualised relapse rates (ARR; negative binomial model) or cumulative hazard of relapses, and 6-month confirmed EDSS progression or regression events (Andersen-Gill survival models). Six sensitivity analyses for matching strategy, inclusion of secondary progressive MS, or high pre-treatment ARR or prior on-treatment relapses were carried out.
Results: The included cohort consisted of 189, 2155, 828 and 1160 patients treated with alemtuzumab, interferon, fingolimod or natalizumab, respectively. Compared to interferon, alemtuzumab was associated with lower ARR (0.5 vs 0.2, p=10-16) and lower risk of EDSS progression and more likely EDSS reduction in patients with previously highly active MS (hazard ratio(HR)=4, p=0.02). Compared to fingolimod, ARR was lower on alemtuzumab (0.3 vs 0.15, p=10-11). Importantly, no differences in ARR (0.2 both groups, p=0.8) and EDSS progression were found between alemtuzumab and natalizumab. The likelihood of EDSS reduction was higher on natalizumab (HR=2.9, p=10-4). Sensitivity analyses largely confirmed the above results. Statistical power was sufficient to demonstrate clinically meaningful effects.
Conclusion: We have replicated the outcomes of the pivotal trials, showing a superior efficacy of alemtuzumab vs interferon β. Alemtuzumab is superior to fingolimod in reducing ARR. Alemtuzumab and natalizumab show similar effects on relapse activity but natalizumab is associated with greater reduction in disability.
Disclosure: TK served on scientific advisory boards for Roche, Genzyme, Novartis, Merck and Biogen, has received conference travel support and/or speaker honoraria from WebMD Global, Novartis, Biogen, Sanofi, Genzyme, Teva, BioCSL and Merck and has received research support from Biogen.
JWLB has received travel expenses from Novartis and Sanofi-Genzyme.
NRn has received lecture honoraria and consultancy fees from Biogen, Genzyme, and Novartis and has received research funding from Novartis and Genzyme.
MW did not disclose any conflict of interests.
NS has received research support from Biogen, Sanofi-Genzyme, Merck-Serono and Teva.
OP received honoraria and support to attend scientific meetings, speakers" fees, and advisory boards from Biogen, Genzyme, Novartis, Teva, Merck Serono and Roche.
TZ has received compensation for consulting services from Almirall, Biogen Idec, Bayer, Genzyme, GlaxoSmithKline, MSD, Merck Serono, Novartis, Sanofi, Teva, and Synthon, and has received research support from Bayer, Biogen Idec, the Hertie Foundation, the Roland Ernst Foundation, the German Diabetes Foundation, Merck Serono, Novartis, Teva, and Sanofi Aventis. Further, he is a lead investigator in the PANGAEA and PEARL study.
MH served on a medical advisory board for the CONFIRM study [BG00012] for Biogen-Idec, serves on the editorial board of the Multiple Sclerosis journal, has received speaker"s honoraria from Novartis, Biogen Idec and Bayer-Schering and receives research support from Dystonia Ireland, the Health Research Board of Ireland and the European Dystonia Foundation.
CM has received research grants from Biogen, Genzyme, Novartis, Teva, Bayer and honoraria as a consultant from Biogen, Genzyme, Novartis and Roche.
VJ received conference travel support from Novartis and Merck Serono.
TS received honoraria for consultancy, funding for travel and compensation for serving on scientific advisory boards from Biogen and speaker honoraria from Novartis.
DHa received speaker honoraria and consulting fees from Biogen, Merck Serono, Teva and Novartis, as well as support for research activities from Biogen and research grants from Charles University in Prague (PRVOUK-P26/LF1/4 and Czech Ministry of Health (NT13237-4/2012).
EH received speaker honoraria and consultant fees from Biogen, Merck Serono, Novartis, Genzyme and Teva, as well as support for research activities from Biogen, Merck Serono and research grants from Charles University in Prague (PRVOUK-P26/LF1/4 and Czech Ministry of Health (NT13237-4/2012).
MT received speaker honoraria from Biogen-Idec, Bayer-Schering, Sanofi Aventis, Merck-Serono, Teva , Novartis and Almirall; has received research grants for her Institution from Biogen-Idec, Merck-Serono, and Novartis.
GI received speaking honoraria from Biogen, Novartis, Sanofi, Merck Serono and Teva.
AL is a Bayer, Biogen, Genzyme, Merck Advisory Board Member. She received travel grants and honoraria from Bayer, Biogen, Merck, Novartis, Sanofi, Teva and Fondazione Italiana Sclerosi Multipla (FISM). Her institution received research grants from Bayer, Biogen, Merck, Novartis, Sanofi , Teva and Fondazione Italiana Sclerosi Multipla (FISM).
AP did not declare any competing interests.
MG received consulting fees from Teva Canada Innovation, Biogen, Novartis and Genzyme Sanofi; lecture payments from Teva Canada Innovation, Novartis and EMD Serono. He has also received a research grant from Canadian Institutes of Health Research.
PD served on editorial boards and has been supported to attend meetings by EMDSerono, Biogen, Novartis, Genzyme, and TEVA Neuroscience. He holds grants from the CIHR and the MS Society of Canada and has received funding for investigator-initiated trials from Biogen, Novartis, and Genzyme.
PG is a Novartis, Teva-neuroscience, Biogen and Genzyme advisory board member, consultant for Merck Serono, received payments for lectures by Merck Serono, Teva-Neuroscience and Canadian Multiple sclerosis society, and received grants for travel from Teva-Neuroscience and Novartis.
RA received honororia from Biologix, Biogen, Bayer, Genpharm, Genzyme, Merck-Serono, GSK and Novartis, and served on advisory board for Biologix, Biogen, Bayer, Genpharm, Genzyme, Novartis, Genzyme, Merck-Serono and Novartis.
EP served on scientific advisory boards for Merck Serono, Genzyme and Biogen; he has received honoraria and travel grants from Sanofi Aventis, UCB, Lundbeck, Novartis, Bayer Schering, Biogen, Merck Serono, Genzyme and Teva; he has received travel grants and equipment from "Associazione Marchigiana Sclerosi Multipla e altre malattie neurologiche".
PS received travel grants and speaking honoraria from Bayer Schering, Biogen, Merck Serono, Novartis, Sanofi/Genzyme and Teva.
RH received honoraria as consultant on scientific advisory boards from Merck-Serono, Biogen, Genzyme-Sanofi and Teva, research funding from Merck-Serono and Biogen, and speaker honoraria from Sanofi-Genzyme and Novartis.
JLS accepted travel compensation from Novartis, Biogen and Merck Serono. Her institution receives the honoraria for talks and advisory board commitment and also clinic support from Bayer Health Care, Biogen, CSL, Genzyme Sanofi, Merck Serono, Novartis and Teva.
RFB received speaking honoraria from Biogen, Novartis, Merck Serono and Teva.
MT received travel grants from Merck Serono, Novartis, Bayer-Schering, Merck-Serono and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis.
VVP received travel grants and honoraria for consultancy and lectures from Biogen, Bayer Schering, Genzyme, Merck, Roche, Teva and Novartis Pharma.
Csilla Rozsa received speaker honoraria from Bayer Schering, Novartis and Biogen, congress and travel expense compensations from Biogen, Teva, Merck Serono and Bayer Schering.
FG received honoraria or research funding from Biogen, Genzyme, Novartis, Teva Neurosciences, Mitsubishi and ONO Pharmaceuticals.
CB received conference travel support from Biogen, Novartis, Bayer-Schering, Merck-Serono and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis.
FG served on scientific advisory boards for Biogen Idec, Novartis and Sanofi Aventis and received funding for travel and speaker honoraria from Biogen Idec, Merck Serono, and Almirall.
MS has participated in, but not received honoraria for, advisory board activity for Biogen, Merck Serono, Bayer Schering, Sanofi Aventis and Novartis.
DS received honoraria as a consultant on scientific advisory boards by Bayer-Schering, Novartis and Sanofi-Aventis and compensation for travel from Novartis, Biogen, Sanofi Aventis, Teva and Merck-Serono.
JO serves on scientific advisory boards for Biogen, Genzyme and Novartis; has received speaker honoraria from Biogen, Bayer-Schering, Genzyme, Merck-Serono, Novartis and Teva and research grants from Biogen, Merck Serono, Novartis and Teva.
RB received speaker honoraria from Bayer Schering, Biogen, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, Teva; research grants from Bayer Schering, Biogen, Merck Serono, Novartis, Sanofi-Aventis, Teva; congress and travel/accommodation expense compensations by Almirall, Bayer Schering, Biogen, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, Teva.
GI had travel/accommodations/meeting expenses funded by Bayer Schering, Biogen, Merck Serono, Novartis, Sanofi Aventis, and Teva.
FV is an advisory board member for Teva Biogen Merck Serono and Novartis.
SV did not declare any competing interests.
PM did not declare any competing interests.
SH received honoraria and consulting fees from Novartis, Bayer Schering and Sanofi, and travel grants from Novartis, Biogen Idec and Bayer Schering.
KK did not declare any competing interests.
JLSM accepted travel compensation from Novartis and Biogen, speaking honoraria from Biogen, Novartis, Sanofi, Merck Serono, Almirall, Bayer and Teva and has participated in a clinical trial by Biogen.
RA received conference travel support from Novartis, Teva, Biogen, Bayer and Merck Serono and has participated in a clinical trials by Biogen, Novartis, Teva and Actelion.
MS received speaker honoraria from Novartis, Biogen, Bayer Schering; congress/travel compensation from Teva, Biogen, Merck Serono, Bayer Schering.
TC received speaker honoraria/ conference travel support from Bayer Schering, Biogen, Merck Serono, Novartis and Teva.
CR received research funding, compensation for travel or speaker honoraria from Biogen, Novartis, Genzyme and Almirall.
EC received honoraria as consultant on scientific advisory boards by Biogen, Bayer-Schering, Merck-Serono, Genzyme and Novartis; has participated in clinical trials/other research projects by Merck-Serono, Roche and Novartis.
IP did not declare any competing interests.
MB served on scientific advisory boards for Biogen, Novartis and Genzyme and has received conference travel support from Biogen and Novartis. He serves on steering committees for trials conducted by Novartis. His institution has received research support from Biogen, Merck-Serono and Novartis.
HB served on scientific advisory boards for Biogen, Novartis and Sanofi-Aventis and has received conference travel support from Novartis, Biogen and Sanofi Aventis. He serves on steering committees for trials conducted by Biogen and Novartis, and has received research support from Merck Serono, Novartis and Biogen.
AC has received consulting and lecture fees from Genzyme-Sanofi, lecture fees from Merck Serono and research support paid to his institution from Genzyme-Sanofi.