Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting multiple sclerosis: a cohort study

Tomas Kalincik; J. William L. Brown; Neil Robertson; Mark Willis; Neil Scolding; Claire M. Rice; Alastair Wilkins; Owen Pearson; Tjalf Ziemssen; Michael Hutchinson; Christopher McGuigan; Vilija Jokubaitis; Tim Spelman; Dana Horakova; Eva Havrdova; Maria Trojano; Guillermo Izquierdo; Alessandra Lugaresi; Alexandre Prat; Marc Girard; Pierre Duquette; Pierre Grammond; Raed Alroughani; Eugenio Pucci; Patrizia Sola; Raymond Hupperts; Jeannette Lechner-Scott; Murat Terzi; Vincent Van Pesch; Csilla Rozsa; Francois Grand'Maison; Cavit Boz; Franco Granella; Mark Slee; Daniele Spitaleri; Javier Olascoaga; Roberto Bergamaschi; Freek Verheul; Steve Vucic; Pamela McCombe; Suzanne Hodgkinson; Jose Luis Sanchez-Menoyo; Radek Ampapa; Magdolna Simo; Tunde Csepany; Cristina Ramo; Edgardo Cristiano; Michael Barnett; Helmut Butzkueven; Alasdair Coles; MSBase Study Group

doi:10.1016/S1474-4422(17)30007-8

Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting multiple sclerosis: a cohort study

Tomas Kalincik^*, J. William L. Brown, Neil Robertson, Mark Willis, Neil Scolding, Claire M. Rice, Alastair Wilkins, Owen Pearson, Tjalf Ziemssen, Michael Hutchinson, Christopher McGuigan, Vilija Jokubaitis, Tim Spelman, Dana Horakova, Eva Havrdova, Maria Trojano, Guillermo Izquierdo, Alessandra Lugaresi, Alexandre Prat, Marc GirardPierre Duquette, Pierre Grammond, Raed Alroughani, Eugenio Pucci, Patrizia Sola, Raymond Hupperts, Jeannette Lechner-Scott, Murat Terzi, Vincent Van Pesch, Csilla Rozsa, Francois Grand'Maison, Cavit Boz, Franco Granella, Mark Slee, Daniele Spitaleri, Javier Olascoaga, Roberto Bergamaschi, Freek Verheul, Steve Vucic, Pamela McCombe, Suzanne Hodgkinson, Jose Luis Sanchez-Menoyo, Radek Ampapa, Magdolna Simo, Tunde Csepany, Cristina Ramo, Edgardo Cristiano, Michael Barnett, Helmut Butzkueven, Alasdair Coles, MSBase Study Group

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background Alemtuzumab, an anti-CD52 antibody, is proven to be more efficacious than interferon beta-1a in the treatment of relapsing-remitting multiple sclerosis, but its efficacy relative to more potent immunotherapies is unknown. We compared the effectiveness of alemtuzumab with natalizumab, fingolimod, and interferon beta in patients with relapsing-remitting multiple sclerosis treated for up to 5 years.

Methods In this international cohort study, we used data from propensity-matched patients with relapsing-remitting multiple sclerosis from the MSBase and six other cohorts. Longitudinal clinical data were obtained from 71 MSBase centres in 21 countries and from six non-MSBase centres in the UK and Germany between Nov 1, 2015, and June 30, 2016. Key inclusion criteria were a diagnosis of definite relapsing-remitting multiple sclerosis, exposure to one of the study therapies (alemtuzumab, interferon beta, fingolimod, or natalizumab), age 65 years or younger, Expanded Disability Status Scale (EDSS) score 6.5 or lower, and no more than 10 years since the first multiple sclerosis symptom. The primary endpoint was annualised relapse rate. The secondary endpoints were cumulative hazards of relapses, disability accumulation, and disability improvement events. We compared relapse rates with negative binomial models, and estimated cumulative hazards with conditional proportional hazards models.

Findings Patients were treated between Aug 1, 1994, and June 30, 2016. The cohorts consisted of 189 patients given alemtuzumab, 2155 patients given interferon beta, 828 patients given fingolimod, and 1160 patients given natalizumab. Alemtuzumab was associated with a lower annualised relapse rate than interferon beta (0.19 [95% CI 0.14-0.23] vs 0.53 [0.46-0.61], p

Interpretation Alemtuzumab and natalizumab seem to have similar effects on annualised relapse rates in relapsing-remitting multiple sclerosis. Alemtuzumab seems superior to fingolimod and interferon beta in mitigating relapse activity. Natalizumab seems superior to alemtuzumab in enabling recovery from disability. Both natalizumab and alemtuzumab seem highly effective and viable immunotherapies for multiple sclerosis. Treatment decisions between alemtuzumab and natalizumab should be primarily governed by their safety profiles.

Original language	English
Pages (from-to)	271-281
Number of pages	11
Journal	Lancet Neurology
Volume	16
Issue number	4
DOIs	https://doi.org/10.1016/S1474-4422(17)30007-8
Publication status	Published - Apr 2017

Keywords

PLACEBO-CONTROLLED TRIAL
CONTROLLED PHASE-3 TRIAL
REGRESSION-MODEL
ORAL FINGOLIMOD
SWITCH
MS

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10.1016/S1474-4422(17)30007-8

Cite this

Kalincik, T., Brown, J. W. L., Robertson, N., Willis, M., Scolding, N., Rice, C. M., Wilkins, A., Pearson, O., Ziemssen, T., Hutchinson, M., McGuigan, C., Jokubaitis, V., Spelman, T., Horakova, D., Havrdova, E., Trojano, M., Izquierdo, G., Lugaresi, A., Prat, A., ... MSBase Study Group (2017). Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting multiple sclerosis: a cohort study. Lancet Neurology, 16(4), 271-281. https://doi.org/10.1016/S1474-4422(17)30007-8

@article{376cf00f39024b00be045f60bab8803f,

title = "Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting multiple sclerosis: a cohort study",

abstract = "Background Alemtuzumab, an anti-CD52 antibody, is proven to be more efficacious than interferon beta-1a in the treatment of relapsing-remitting multiple sclerosis, but its efficacy relative to more potent immunotherapies is unknown. We compared the effectiveness of alemtuzumab with natalizumab, fingolimod, and interferon beta in patients with relapsing-remitting multiple sclerosis treated for up to 5 years.Methods In this international cohort study, we used data from propensity-matched patients with relapsing-remitting multiple sclerosis from the MSBase and six other cohorts. Longitudinal clinical data were obtained from 71 MSBase centres in 21 countries and from six non-MSBase centres in the UK and Germany between Nov 1, 2015, and June 30, 2016. Key inclusion criteria were a diagnosis of definite relapsing-remitting multiple sclerosis, exposure to one of the study therapies (alemtuzumab, interferon beta, fingolimod, or natalizumab), age 65 years or younger, Expanded Disability Status Scale (EDSS) score 6.5 or lower, and no more than 10 years since the first multiple sclerosis symptom. The primary endpoint was annualised relapse rate. The secondary endpoints were cumulative hazards of relapses, disability accumulation, and disability improvement events. We compared relapse rates with negative binomial models, and estimated cumulative hazards with conditional proportional hazards models.Findings Patients were treated between Aug 1, 1994, and June 30, 2016. The cohorts consisted of 189 patients given alemtuzumab, 2155 patients given interferon beta, 828 patients given fingolimod, and 1160 patients given natalizumab. Alemtuzumab was associated with a lower annualised relapse rate than interferon beta (0.19 [95% CI 0.14-0.23] vs 0.53 [0.46-0.61], pInterpretation Alemtuzumab and natalizumab seem to have similar effects on annualised relapse rates in relapsing-remitting multiple sclerosis. Alemtuzumab seems superior to fingolimod and interferon beta in mitigating relapse activity. Natalizumab seems superior to alemtuzumab in enabling recovery from disability. Both natalizumab and alemtuzumab seem highly effective and viable immunotherapies for multiple sclerosis. Treatment decisions between alemtuzumab and natalizumab should be primarily governed by their safety profiles.",

keywords = "PLACEBO-CONTROLLED TRIAL, CONTROLLED PHASE-3 TRIAL, REGRESSION-MODEL, ORAL FINGOLIMOD, SWITCH, MS",

author = "Tomas Kalincik and Brown, {J. William L.} and Neil Robertson and Mark Willis and Neil Scolding and Rice, {Claire M.} and Alastair Wilkins and Owen Pearson and Tjalf Ziemssen and Michael Hutchinson and Christopher McGuigan and Vilija Jokubaitis and Tim Spelman and Dana Horakova and Eva Havrdova and Maria Trojano and Guillermo Izquierdo and Alessandra Lugaresi and Alexandre Prat and Marc Girard and Pierre Duquette and Pierre Grammond and Raed Alroughani and Eugenio Pucci and Patrizia Sola and Raymond Hupperts and Jeannette Lechner-Scott and Murat Terzi and {Van Pesch}, Vincent and Csilla Rozsa and Francois Grand'Maison and Cavit Boz and Franco Granella and Mark Slee and Daniele Spitaleri and Javier Olascoaga and Roberto Bergamaschi and Freek Verheul and Steve Vucic and Pamela McCombe and Suzanne Hodgkinson and Sanchez-Menoyo, {Jose Luis} and Radek Ampapa and Magdolna Simo and Tunde Csepany and Cristina Ramo and Edgardo Cristiano and Michael Barnett and Helmut Butzkueven and Alasdair Coles and {MSBase Study Group}",

year = "2017",

month = apr,

doi = "10.1016/S1474-4422(17)30007-8",

language = "English",

volume = "16",

pages = "271--281",

journal = "Lancet Neurology",

issn = "1474-4422",

publisher = "Elsevier Science",

number = "4",

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Kalincik, T, Brown, JWL, Robertson, N, Willis, M, Scolding, N, Rice, CM, Wilkins, A, Pearson, O, Ziemssen, T, Hutchinson, M, McGuigan, C, Jokubaitis, V, Spelman, T, Horakova, D, Havrdova, E, Trojano, M, Izquierdo, G, Lugaresi, A, Prat, A, Girard, M, Duquette, P, Grammond, P, Alroughani, R, Pucci, E, Sola, P, Hupperts, R, Lechner-Scott, J, Terzi, M, Van Pesch, V, Rozsa, C, Grand'Maison, F, Boz, C, Granella, F, Slee, M, Spitaleri, D, Olascoaga, J, Bergamaschi, R, Verheul, F, Vucic, S, McCombe, P, Hodgkinson, S, Sanchez-Menoyo, JL, Ampapa, R, Simo, M, Csepany, T, Ramo, C, Cristiano, E, Barnett, M, Butzkueven, H, Coles, A & MSBase Study Group 2017, 'Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting multiple sclerosis: a cohort study', Lancet Neurology, vol. 16, no. 4, pp. 271-281. https://doi.org/10.1016/S1474-4422(17)30007-8

TY - JOUR

T1 - Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting multiple sclerosis

T2 - a cohort study

AU - Kalincik, Tomas

AU - Brown, J. William L.

AU - Robertson, Neil

AU - Willis, Mark

AU - Scolding, Neil

AU - Rice, Claire M.

AU - Wilkins, Alastair

AU - Pearson, Owen

AU - Ziemssen, Tjalf

AU - Hutchinson, Michael

AU - McGuigan, Christopher

AU - Jokubaitis, Vilija

AU - Spelman, Tim

AU - Horakova, Dana

AU - Havrdova, Eva

AU - Trojano, Maria

AU - Izquierdo, Guillermo

AU - Lugaresi, Alessandra

AU - Prat, Alexandre

AU - Girard, Marc

AU - Duquette, Pierre

AU - Grammond, Pierre

AU - Alroughani, Raed

AU - Pucci, Eugenio

AU - Sola, Patrizia

AU - Hupperts, Raymond

AU - Lechner-Scott, Jeannette

AU - Terzi, Murat

AU - Van Pesch, Vincent

AU - Rozsa, Csilla

AU - Grand'Maison, Francois

AU - Boz, Cavit

AU - Granella, Franco

AU - Slee, Mark

AU - Spitaleri, Daniele

AU - Olascoaga, Javier

AU - Bergamaschi, Roberto

AU - Verheul, Freek

AU - Vucic, Steve

AU - McCombe, Pamela

AU - Hodgkinson, Suzanne

AU - Sanchez-Menoyo, Jose Luis

AU - Ampapa, Radek

AU - Simo, Magdolna

AU - Csepany, Tunde

AU - Ramo, Cristina

AU - Cristiano, Edgardo

AU - Barnett, Michael

AU - Butzkueven, Helmut

AU - Coles, Alasdair

AU - MSBase Study Group

PY - 2017/4

Y1 - 2017/4

N2 - Background Alemtuzumab, an anti-CD52 antibody, is proven to be more efficacious than interferon beta-1a in the treatment of relapsing-remitting multiple sclerosis, but its efficacy relative to more potent immunotherapies is unknown. We compared the effectiveness of alemtuzumab with natalizumab, fingolimod, and interferon beta in patients with relapsing-remitting multiple sclerosis treated for up to 5 years.Methods In this international cohort study, we used data from propensity-matched patients with relapsing-remitting multiple sclerosis from the MSBase and six other cohorts. Longitudinal clinical data were obtained from 71 MSBase centres in 21 countries and from six non-MSBase centres in the UK and Germany between Nov 1, 2015, and June 30, 2016. Key inclusion criteria were a diagnosis of definite relapsing-remitting multiple sclerosis, exposure to one of the study therapies (alemtuzumab, interferon beta, fingolimod, or natalizumab), age 65 years or younger, Expanded Disability Status Scale (EDSS) score 6.5 or lower, and no more than 10 years since the first multiple sclerosis symptom. The primary endpoint was annualised relapse rate. The secondary endpoints were cumulative hazards of relapses, disability accumulation, and disability improvement events. We compared relapse rates with negative binomial models, and estimated cumulative hazards with conditional proportional hazards models.Findings Patients were treated between Aug 1, 1994, and June 30, 2016. The cohorts consisted of 189 patients given alemtuzumab, 2155 patients given interferon beta, 828 patients given fingolimod, and 1160 patients given natalizumab. Alemtuzumab was associated with a lower annualised relapse rate than interferon beta (0.19 [95% CI 0.14-0.23] vs 0.53 [0.46-0.61], pInterpretation Alemtuzumab and natalizumab seem to have similar effects on annualised relapse rates in relapsing-remitting multiple sclerosis. Alemtuzumab seems superior to fingolimod and interferon beta in mitigating relapse activity. Natalizumab seems superior to alemtuzumab in enabling recovery from disability. Both natalizumab and alemtuzumab seem highly effective and viable immunotherapies for multiple sclerosis. Treatment decisions between alemtuzumab and natalizumab should be primarily governed by their safety profiles.

AB - Background Alemtuzumab, an anti-CD52 antibody, is proven to be more efficacious than interferon beta-1a in the treatment of relapsing-remitting multiple sclerosis, but its efficacy relative to more potent immunotherapies is unknown. We compared the effectiveness of alemtuzumab with natalizumab, fingolimod, and interferon beta in patients with relapsing-remitting multiple sclerosis treated for up to 5 years.Methods In this international cohort study, we used data from propensity-matched patients with relapsing-remitting multiple sclerosis from the MSBase and six other cohorts. Longitudinal clinical data were obtained from 71 MSBase centres in 21 countries and from six non-MSBase centres in the UK and Germany between Nov 1, 2015, and June 30, 2016. Key inclusion criteria were a diagnosis of definite relapsing-remitting multiple sclerosis, exposure to one of the study therapies (alemtuzumab, interferon beta, fingolimod, or natalizumab), age 65 years or younger, Expanded Disability Status Scale (EDSS) score 6.5 or lower, and no more than 10 years since the first multiple sclerosis symptom. The primary endpoint was annualised relapse rate. The secondary endpoints were cumulative hazards of relapses, disability accumulation, and disability improvement events. We compared relapse rates with negative binomial models, and estimated cumulative hazards with conditional proportional hazards models.Findings Patients were treated between Aug 1, 1994, and June 30, 2016. The cohorts consisted of 189 patients given alemtuzumab, 2155 patients given interferon beta, 828 patients given fingolimod, and 1160 patients given natalizumab. Alemtuzumab was associated with a lower annualised relapse rate than interferon beta (0.19 [95% CI 0.14-0.23] vs 0.53 [0.46-0.61], pInterpretation Alemtuzumab and natalizumab seem to have similar effects on annualised relapse rates in relapsing-remitting multiple sclerosis. Alemtuzumab seems superior to fingolimod and interferon beta in mitigating relapse activity. Natalizumab seems superior to alemtuzumab in enabling recovery from disability. Both natalizumab and alemtuzumab seem highly effective and viable immunotherapies for multiple sclerosis. Treatment decisions between alemtuzumab and natalizumab should be primarily governed by their safety profiles.

KW - PLACEBO-CONTROLLED TRIAL

KW - CONTROLLED PHASE-3 TRIAL

KW - REGRESSION-MODEL

KW - ORAL FINGOLIMOD

KW - SWITCH

KW - MS

U2 - 10.1016/S1474-4422(17)30007-8

DO - 10.1016/S1474-4422(17)30007-8

M3 - Article

SN - 1474-4422

VL - 16

SP - 271

EP - 281

JO - Lancet Neurology

JF - Lancet Neurology

IS - 4

ER -