Association of Initial Disease-Modifying Therapy With Later Conversion to Secondary Progressive Multiple Sclerosis

MSBase Study Grp

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

IMPORTANCE Within 2 decades of onset, 80% of untreated patients with relapsing-remitting multiple sclerosis (MS) convert to a phase of irreversible disability accrual termed secondary progressiveMS. The association between disease-modifying treatments (DMTs), and this conversion has rarely been studied and never using a validated definition.

OBJECTIVE To determine the association between the use, the type of, and the timing of DMTs with the risk of conversion to secondary progressive MS diagnosed with a validated definition.

DESIGN, SETTING, AND PARTICIPANTS Cohort study with prospective data from 68 neurology centers in 21 countries examining patients with relapsing-remittingMS commencing DMTs (or clinical monitoring) between 1988-2012 with minimum 4 years' follow-up.

EXPOSURES The use, type, and timing of the following DMTs: interferon beta, glatiramer acetate, fingolimod, natalizumab, or alemtuzumab. After propensity-score matching, 1555 patients were included (last follow-up, February 14, 2017).

MAIN OUTCOME AND MEASURE Conversion to objectively defined secondary progressiveMS.

RESULTS Of the 1555 patients, 1123 were female (mean baseline age, 35 years [SD, 10]). Patients initially treated with glatiramer acetate or interferon beta had a lower hazard of conversion to secondary progressiveMS than matched untreated patients (HR, 0.71; 95% CI, 0.61-0.81; P

CONCLUSIONS AND RELEVANCE Among patients with relapsing-remittingMS, initial treatment with fingolimod, alemtuzumab, or natalizumab was associated with a lower risk of conversion to secondary progressiveMS vs initial treatment with glatiramer acetate or interferon beta. These findings, considered along with these therapies' risks, may help inform decisions about DMT selection.

Original languageEnglish
Pages (from-to)175-187
Number of pages13
JournalJAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
Volume321
Issue number2
DOIs
Publication statusPublished - 15 Jan 2019

Cite this

@article{1f84175cad3e4d20b2a0a2937d422d3a,
title = "Association of Initial Disease-Modifying Therapy With Later Conversion to Secondary Progressive Multiple Sclerosis",
abstract = "IMPORTANCE Within 2 decades of onset, 80{\%} of untreated patients with relapsing-remitting multiple sclerosis (MS) convert to a phase of irreversible disability accrual termed secondary progressiveMS. The association between disease-modifying treatments (DMTs), and this conversion has rarely been studied and never using a validated definition.OBJECTIVE To determine the association between the use, the type of, and the timing of DMTs with the risk of conversion to secondary progressive MS diagnosed with a validated definition.DESIGN, SETTING, AND PARTICIPANTS Cohort study with prospective data from 68 neurology centers in 21 countries examining patients with relapsing-remittingMS commencing DMTs (or clinical monitoring) between 1988-2012 with minimum 4 years' follow-up.EXPOSURES The use, type, and timing of the following DMTs: interferon beta, glatiramer acetate, fingolimod, natalizumab, or alemtuzumab. After propensity-score matching, 1555 patients were included (last follow-up, February 14, 2017).MAIN OUTCOME AND MEASURE Conversion to objectively defined secondary progressiveMS.RESULTS Of the 1555 patients, 1123 were female (mean baseline age, 35 years [SD, 10]). Patients initially treated with glatiramer acetate or interferon beta had a lower hazard of conversion to secondary progressiveMS than matched untreated patients (HR, 0.71; 95{\%} CI, 0.61-0.81; PCONCLUSIONS AND RELEVANCE Among patients with relapsing-remittingMS, initial treatment with fingolimod, alemtuzumab, or natalizumab was associated with a lower risk of conversion to secondary progressiveMS vs initial treatment with glatiramer acetate or interferon beta. These findings, considered along with these therapies' risks, may help inform decisions about DMT selection.",
keywords = "INTERFERON-BETA, GLATIRAMER ACETATE, ALEMTUZUMAB, NATALIZUMAB, FINGOLIMOD, DISABILITY, MULTICENTER, OUTCOMES, TIME",
author = "{MSBase Study Grp} and Brown, {J. William L.} and Alasdair Coles and Dana Horakova and Eva Havrdova and Guillermo Izquierdo and Alexandre Prat and Marc Girard and Pierre Duquette and Maria Trojano and Alessandra Lugaresi and Roberto Bergamaschi and Pierre Grammond and Raed Alroughani and Raymond Hupperts and Pamela McCombe and {Van Pesch}, Vincent and Patrizia Sola and Diana Ferraro and Francois Grand'Maison and Murat Terzi and Jeannette Lechner-Scott and Schlomo Flechter and Mark Slee and Vahid Shaygannejad and Eugenio Pucci and Franco Granella and Vilija Jokubaitis and Mark Willis and Claire Rice and Neil Scolding and Alastair Wilkins and Pearson, {Owen R.} and Tjalf Ziemssen and Michael Hutchinson and Katharine Harding and Joanne Jones and Christopher McGuigan and Helmut Butzkueven and Tomas Kalincik and Neil Robertson and Marco Onofrj and {De Luca}, Giovanna and {Di Tommaso}, Valeria and Daniela Travaglini and Erika Pietrolongo and {di Ioia}, Maria and Deborah Farina and Luca Mancinelli and Suzanne Hodgkinson and Celia Oreja-Guevara and Cavit Boz and Julie Prevost and Javier Olascoaga and {Van Wijmeersch}, Bart and Michael Barnett and Freek Verheul and Rojas, {Juan Ingacio} and Daniele Spitaleri and Rio, {Maria Edite} and {Luis Sanchez-Menoyo}, Jose and Cristina Ramo-Tello and Claudio Solaro and Tunde Csepany and Gerardo Iuliano and Olga Skibina and Thor Petersen and Bolanos, {Ricardo Fernandez} and Youssef Sidhom and Riadh and Steve Vucic and Richard Macdonell and Sempere, {Angel Perez} and Magdolna Simo and Ilya Kister and Neil Shuey and Renate Radek and Dominguez, {Jose Andres} and {Pia Amato}, Maria and Saladino, {Maria Laura} and Allan Kermode and Ernest Butler and Fraser Moore and Stella Hughes and Gavin McDonnell and Imre Piroska and Bassem Yamout and Aysun Soysal and Serkan Ozakbas and Cees Zwanikken",
year = "2019",
month = "1",
day = "15",
doi = "10.1001/jama.2018.20588",
language = "English",
volume = "321",
pages = "175--187",
journal = "JAMA: The Journal of the American Medical Association",
issn = "0098-7484",
publisher = "American Medical Association",
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}

Association of Initial Disease-Modifying Therapy With Later Conversion to Secondary Progressive Multiple Sclerosis. / MSBase Study Grp.

In: JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, Vol. 321, No. 2, 15.01.2019, p. 175-187.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Association of Initial Disease-Modifying Therapy With Later Conversion to Secondary Progressive Multiple Sclerosis

AU - MSBase Study Grp

AU - Brown, J. William L.

AU - Coles, Alasdair

AU - Horakova, Dana

AU - Havrdova, Eva

AU - Izquierdo, Guillermo

AU - Prat, Alexandre

AU - Girard, Marc

AU - Duquette, Pierre

AU - Trojano, Maria

AU - Lugaresi, Alessandra

AU - Bergamaschi, Roberto

AU - Grammond, Pierre

AU - Alroughani, Raed

AU - Hupperts, Raymond

AU - McCombe, Pamela

AU - Van Pesch, Vincent

AU - Sola, Patrizia

AU - Ferraro, Diana

AU - Grand'Maison, Francois

AU - Terzi, Murat

AU - Lechner-Scott, Jeannette

AU - Flechter, Schlomo

AU - Slee, Mark

AU - Shaygannejad, Vahid

AU - Pucci, Eugenio

AU - Granella, Franco

AU - Jokubaitis, Vilija

AU - Willis, Mark

AU - Rice, Claire

AU - Scolding, Neil

AU - Wilkins, Alastair

AU - Pearson, Owen R.

AU - Ziemssen, Tjalf

AU - Hutchinson, Michael

AU - Harding, Katharine

AU - Jones, Joanne

AU - McGuigan, Christopher

AU - Butzkueven, Helmut

AU - Kalincik, Tomas

AU - Robertson, Neil

AU - Onofrj, Marco

AU - De Luca, Giovanna

AU - Di Tommaso, Valeria

AU - Travaglini, Daniela

AU - Pietrolongo, Erika

AU - di Ioia, Maria

AU - Farina, Deborah

AU - Mancinelli, Luca

AU - Hodgkinson, Suzanne

AU - Oreja-Guevara, Celia

AU - Boz, Cavit

AU - Prevost, Julie

AU - Olascoaga, Javier

AU - Van Wijmeersch, Bart

AU - Barnett, Michael

AU - Verheul, Freek

AU - Rojas, Juan Ingacio

AU - Spitaleri, Daniele

AU - Rio, Maria Edite

AU - Luis Sanchez-Menoyo, Jose

AU - Ramo-Tello, Cristina

AU - Solaro, Claudio

AU - Csepany, Tunde

AU - Iuliano, Gerardo

AU - Skibina, Olga

AU - Petersen, Thor

AU - Bolanos, Ricardo Fernandez

AU - Sidhom, Youssef

AU - Riadh, null

AU - Vucic, Steve

AU - Macdonell, Richard

AU - Sempere, Angel Perez

AU - Simo, Magdolna

AU - Kister, Ilya

AU - Shuey, Neil

AU - Radek, Renate

AU - Dominguez, Jose Andres

AU - Pia Amato, Maria

AU - Saladino, Maria Laura

AU - Kermode, Allan

AU - Butler, Ernest

AU - Moore, Fraser

AU - Hughes, Stella

AU - McDonnell, Gavin

AU - Piroska, Imre

AU - Yamout, Bassem

AU - Soysal, Aysun

AU - Ozakbas, Serkan

AU - Zwanikken, Cees

PY - 2019/1/15

Y1 - 2019/1/15

N2 - IMPORTANCE Within 2 decades of onset, 80% of untreated patients with relapsing-remitting multiple sclerosis (MS) convert to a phase of irreversible disability accrual termed secondary progressiveMS. The association between disease-modifying treatments (DMTs), and this conversion has rarely been studied and never using a validated definition.OBJECTIVE To determine the association between the use, the type of, and the timing of DMTs with the risk of conversion to secondary progressive MS diagnosed with a validated definition.DESIGN, SETTING, AND PARTICIPANTS Cohort study with prospective data from 68 neurology centers in 21 countries examining patients with relapsing-remittingMS commencing DMTs (or clinical monitoring) between 1988-2012 with minimum 4 years' follow-up.EXPOSURES The use, type, and timing of the following DMTs: interferon beta, glatiramer acetate, fingolimod, natalizumab, or alemtuzumab. After propensity-score matching, 1555 patients were included (last follow-up, February 14, 2017).MAIN OUTCOME AND MEASURE Conversion to objectively defined secondary progressiveMS.RESULTS Of the 1555 patients, 1123 were female (mean baseline age, 35 years [SD, 10]). Patients initially treated with glatiramer acetate or interferon beta had a lower hazard of conversion to secondary progressiveMS than matched untreated patients (HR, 0.71; 95% CI, 0.61-0.81; PCONCLUSIONS AND RELEVANCE Among patients with relapsing-remittingMS, initial treatment with fingolimod, alemtuzumab, or natalizumab was associated with a lower risk of conversion to secondary progressiveMS vs initial treatment with glatiramer acetate or interferon beta. These findings, considered along with these therapies' risks, may help inform decisions about DMT selection.

AB - IMPORTANCE Within 2 decades of onset, 80% of untreated patients with relapsing-remitting multiple sclerosis (MS) convert to a phase of irreversible disability accrual termed secondary progressiveMS. The association between disease-modifying treatments (DMTs), and this conversion has rarely been studied and never using a validated definition.OBJECTIVE To determine the association between the use, the type of, and the timing of DMTs with the risk of conversion to secondary progressive MS diagnosed with a validated definition.DESIGN, SETTING, AND PARTICIPANTS Cohort study with prospective data from 68 neurology centers in 21 countries examining patients with relapsing-remittingMS commencing DMTs (or clinical monitoring) between 1988-2012 with minimum 4 years' follow-up.EXPOSURES The use, type, and timing of the following DMTs: interferon beta, glatiramer acetate, fingolimod, natalizumab, or alemtuzumab. After propensity-score matching, 1555 patients were included (last follow-up, February 14, 2017).MAIN OUTCOME AND MEASURE Conversion to objectively defined secondary progressiveMS.RESULTS Of the 1555 patients, 1123 were female (mean baseline age, 35 years [SD, 10]). Patients initially treated with glatiramer acetate or interferon beta had a lower hazard of conversion to secondary progressiveMS than matched untreated patients (HR, 0.71; 95% CI, 0.61-0.81; PCONCLUSIONS AND RELEVANCE Among patients with relapsing-remittingMS, initial treatment with fingolimod, alemtuzumab, or natalizumab was associated with a lower risk of conversion to secondary progressiveMS vs initial treatment with glatiramer acetate or interferon beta. These findings, considered along with these therapies' risks, may help inform decisions about DMT selection.

KW - INTERFERON-BETA

KW - GLATIRAMER ACETATE

KW - ALEMTUZUMAB

KW - NATALIZUMAB

KW - FINGOLIMOD

KW - DISABILITY

KW - MULTICENTER

KW - OUTCOMES

KW - TIME

U2 - 10.1001/jama.2018.20588

DO - 10.1001/jama.2018.20588

M3 - Article

VL - 321

SP - 175

EP - 187

JO - JAMA: The Journal of the American Medical Association

JF - JAMA: The Journal of the American Medical Association

SN - 0098-7484

IS - 2

ER -