Country, Sex, EDSS Change and Therapy Choice Independently Predict Treatment Discontinuation in Multiple Sclerosis and Clinically Isolated Syndrome
Identifieur interne : 000E85 ( Ncbi/Merge ); précédent : 000E84; suivant : 000E86Country, Sex, EDSS Change and Therapy Choice Independently Predict Treatment Discontinuation in Multiple Sclerosis and Clinically Isolated Syndrome
Auteurs : Claire Meyniel [Australie, France] ; Timothy Spelman [Australie] ; Vilija G. Jokubaitis [Australie] ; Maria Trojano [Italie] ; Guillermo Izquierdo [Espagne] ; François Grand Aison [Canada] ; Celia Oreja-Guevara [Espagne] ; Cavit Boz [Turquie] ; Alessandra Lugaresi [Italie] ; Marc Girard [Canada] ; Pierre Grammond [Canada] ; Gerardo Iuliano [Italie] ; Marcela Fiol [Argentine] ; Jose Antonio Cabrera-Gomez [Cuba] ; Ricardo Fernandez-Bolanos [Espagne] ; Giorgio Giuliani [Italie] ; Jeannette Lechner-Scott [Australie] ; Edgardo Cristiano [Argentine] ; Joseph Herbert [États-Unis] ; Tatjana Petkovska-Boskova [Macédoine (pays)] ; Roberto Bergamaschi [Italie] ; Vincent Van Pesch [Belgique] ; Fraser Moore [Canada] ; Norbert Vella [Malte] ; Mark Slee [Australie] ; Vetere Santiago [Argentine] ; Michael Barnett [Australie] ; Eva Havrdova [République tchèque] ; Carolyn Young [Royaume-Uni] ; Carmen-Adella Sirbu [Roumanie] ; Mary Tanner [Australie] ; Michelle Rutherford [Australie] ; Helmut Butzkueven [Australie]Source :
- PLoS ONE [ 1932-6203 ] ; 2012.
Abstract
We conducted a prospective study, MSBASIS, to assess factors leading to first treatment discontinuation in patients with a clinically isolated syndrome (CIS) and early relapsing-remitting multiple sclerosis (RRMS).
The MSBASIS Study, conducted by MSBase Study Group members, enrols patients seen from CIS onset, reporting baseline demographics, cerebral magnetic resonance imaging (MRI) features and Expanded Disability Status Scale (EDSS) scores. Follow-up visits report relapses, EDSS scores, and the start and end dates of MS-specific therapies. We performed a multivariable survival analysis to determine factors within this dataset that predict first treatment discontinuation.
A total of 2314 CIS patients from 44 centres were followed for a median of 2.7 years, during which time 1247 commenced immunomodulatory drug (IMD) treatment. Ninety percent initiated IMD after a diagnosis of MS was confirmed, and 10% while still in CIS status. Over 40% of these patients stopped their first IMD during the observation period. Females were more likely to cease medication than males (HR 1.36, p = 0.003). Patients treated in Australia were twice as likely to cease their first IMD than patients treated in Spain (HR 1.98, p = 0.001). Increasing EDSS was associated with higher rate of IMD cessation (HR 1.21 per EDSS unit, p<0.001), and intramuscular interferon-β-1a (HR 1.38, p = 0.028) and subcutaneous interferon-β-1a (HR 1.45, p = 0.012) had higher rates of discontinuation than glatiramer acetate, although this varied widely in different countries. Onset cerebral MRI features, age, time to treatment initiation or relapse on treatment were not associated with IMD cessation.
In this multivariable survival analysis, female sex, country of residence, EDSS change and IMD choice independently predicted time to first IMD cessation.
Url:
DOI: 10.1371/journal.pone.0038661
PubMed: 22768046
PubMed Central: 3387159
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Institute IRCCS Mondino, Pavia</wicri:regionArea><wicri:noRegion>Pavia</wicri:noRegion></affiliation></author><author><name sortKey="Van Pesch, Vincent" sort="Van Pesch, Vincent" uniqKey="Van Pesch V" first="Vincent" last="Van Pesch">Vincent Van Pesch</name><affiliation wicri:level="3"><nlm:aff id="aff20"><addr-line>Cliniques Universitaires Saint-Luc, Brussels, Belgium</addr-line></nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Cliniques Universitaires Saint-Luc, Brussels</wicri:regionArea><placeName><settlement type="city">Bruxelles</settlement><region nuts="2">Région de Bruxelles-Capitale</region></placeName></affiliation></author><author><name sortKey="Moore, Fraser" sort="Moore, Fraser" uniqKey="Moore F" first="Fraser" last="Moore">Fraser Moore</name><affiliation wicri:level="3"><nlm:aff id="aff21"><addr-line>Jewish General Hospital, Montreal, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Jewish General Hospital, Montreal</wicri:regionArea><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Vella, Norbert" sort="Vella, Norbert" uniqKey="Vella N" first="Norbert" last="Vella">Norbert Vella</name><affiliation wicri:level="1"><nlm:aff id="aff22"><addr-line>Mater Dei Hospital, Msida, Malta</addr-line></nlm:aff><country xml:lang="fr">Malte</country><wicri:regionArea>Mater Dei Hospital, Msida</wicri:regionArea><wicri:noRegion>Msida</wicri:noRegion></affiliation></author><author><name sortKey="Slee, Mark" sort="Slee, Mark" uniqKey="Slee M" first="Mark" last="Slee">Mark Slee</name><affiliation wicri:level="1"><nlm:aff id="aff23"><addr-line>Flinders University and Medical Centre, Adelaide, South Australia, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Flinders University and Medical Centre, Adelaide, South Australia</wicri:regionArea><wicri:noRegion>South Australia</wicri:noRegion></affiliation></author><author><name sortKey="Santiago, Vetere" sort="Santiago, Vetere" uniqKey="Santiago V" first="Vetere" last="Santiago">Vetere Santiago</name><affiliation wicri:level="1"><nlm:aff id="aff24"><addr-line>HIGA Gral, San Martin La Plata, Argentina</addr-line></nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea>HIGA Gral, San Martin La Plata</wicri:regionArea><wicri:noRegion>San Martin La Plata</wicri:noRegion></affiliation></author><author><name sortKey="Barnett, Michael" sort="Barnett, Michael" uniqKey="Barnett M" first="Michael" last="Barnett">Michael Barnett</name><affiliation wicri:level="1"><nlm:aff id="aff25"><addr-line>Brain Mind Research Institute, Camperdown, New South Wales, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Brain Mind Research Institute, Camperdown, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author><author><name sortKey="Havrdova, Eva" sort="Havrdova, Eva" uniqKey="Havrdova E" first="Eva" last="Havrdova">Eva Havrdova</name><affiliation wicri:level="3"><nlm:aff id="aff26"><addr-line>General Teaching Hospital, Prague, Czech Republic</addr-line></nlm:aff><country xml:lang="fr">République tchèque</country><wicri:regionArea>General Teaching Hospital, Prague</wicri:regionArea><placeName><settlement type="city">Prague</settlement><region type="région" nuts="2">Bohême centrale</region></placeName></affiliation></author><author><name sortKey="Young, Carolyn" sort="Young, Carolyn" uniqKey="Young C" first="Carolyn" last="Young">Carolyn Young</name><affiliation wicri:level="1"><nlm:aff id="aff27"><addr-line>The Walton Centre for Neurology and Neurosurgery, Liverpool, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The Walton Centre for Neurology and Neurosurgery, Liverpool</wicri:regionArea><wicri:noRegion>Liverpool</wicri:noRegion></affiliation></author><author><name sortKey="Sirbu, Carmen Adella" sort="Sirbu, Carmen Adella" uniqKey="Sirbu C" first="Carmen-Adella" last="Sirbu">Carmen-Adella Sirbu</name><affiliation wicri:level="1"><nlm:aff id="aff28"><addr-line>Central University Emergency Military Hospital, Bucharest, Romania</addr-line></nlm:aff><country xml:lang="fr">Roumanie</country><wicri:regionArea>Central University Emergency Military Hospital, Bucharest</wicri:regionArea><wicri:noRegion>Bucharest</wicri:noRegion></affiliation></author><author><name sortKey="Tanner, Mary" sort="Tanner, Mary" uniqKey="Tanner M" first="Mary" last="Tanner">Mary Tanner</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Neurology, Royal Melbourne Hospital, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Neurology, Royal Melbourne Hospital, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Rutherford, Michelle" sort="Rutherford, Michelle" uniqKey="Rutherford M" first="Michelle" last="Rutherford">Michelle Rutherford</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Neurology, Royal Melbourne Hospital, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Neurology, Royal Melbourne Hospital, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Butzkueven, Helmut" sort="Butzkueven, Helmut" uniqKey="Butzkueven H" first="Helmut" last="Butzkueven">Helmut Butzkueven</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Neurology, Royal Melbourne Hospital, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Neurology, Royal Melbourne Hospital, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff29"><addr-line>Department of Medicine, Melbourne Brain Centre, The University of Melbourne, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medicine, Melbourne Brain Centre, The University of Melbourne, Victoria</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff30"><addr-line>Department of Neurology, Box Hill Hospital, Monash University, Melbourne, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Neurology, Box Hill Hospital, Monash University, Melbourne, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22768046</idno><idno type="pmc">3387159</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387159</idno><idno type="RBID">PMC:3387159</idno><idno type="doi">10.1371/journal.pone.0038661</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">002A24</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002A24</idno><idno type="wicri:Area/Pmc/Curation">002874</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">002874</idno><idno type="wicri:Area/Pmc/Checkpoint">001F90</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">001F90</idno><idno type="wicri:Area/Ncbi/Merge">000E85</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Country, Sex, EDSS Change and Therapy Choice Independently Predict Treatment Discontinuation in Multiple Sclerosis and Clinically Isolated Syndrome</title><author><name sortKey="Meyniel, Claire" sort="Meyniel, Claire" uniqKey="Meyniel C" first="Claire" last="Meyniel">Claire Meyniel</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Neurology, Royal Melbourne Hospital, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Neurology, Royal Melbourne Hospital, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation><affiliation wicri:level="3"><nlm:aff id="aff2"><addr-line>CHU Nantes, CIC 0004, Nantes, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>CHU Nantes, CIC 0004, Nantes</wicri:regionArea><placeName><region type="region">Pays de la Loire</region><region type="old region">Pays de la Loire</region><settlement type="city">Nantes</settlement></placeName></affiliation></author><author><name sortKey="Spelman, Timothy" sort="Spelman, Timothy" uniqKey="Spelman T" first="Timothy" last="Spelman">Timothy Spelman</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Neurology, Royal Melbourne Hospital, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Neurology, Royal Melbourne Hospital, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Jokubaitis, Vilija G" sort="Jokubaitis, Vilija G" uniqKey="Jokubaitis V" first="Vilija G." last="Jokubaitis">Vilija G. Jokubaitis</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Neurology, Royal Melbourne Hospital, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Neurology, Royal Melbourne Hospital, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Trojano, Maria" sort="Trojano, Maria" uniqKey="Trojano M" first="Maria" last="Trojano">Maria Trojano</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>University of Bari, Bari, Italy</addr-line></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>University of Bari, Bari</wicri:regionArea><wicri:noRegion>Bari</wicri:noRegion></affiliation></author><author><name sortKey="Izquierdo, Guillermo" sort="Izquierdo, Guillermo" uniqKey="Izquierdo G" first="Guillermo" last="Izquierdo">Guillermo Izquierdo</name><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Hospital Universitario, Sevilla, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Hospital Universitario, Sevilla</wicri:regionArea><wicri:noRegion>Sevilla</wicri:noRegion></affiliation></author><author><name sortKey="Grand Aison, Francois" sort="Grand Aison, Francois" uniqKey="Grand Aison F" first="François" last="Grand Aison">François Grand Aison</name><affiliation wicri:level="1"><nlm:aff id="aff5"><addr-line>Clinique Neuro Rive-Sud, Greenfield Park, Quebec, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Clinique Neuro Rive-Sud, Greenfield Park, Quebec</wicri:regionArea><wicri:noRegion>Quebec</wicri:noRegion></affiliation></author><author><name sortKey="Oreja Guevara, Celia" sort="Oreja Guevara, Celia" uniqKey="Oreja Guevara C" first="Celia" last="Oreja-Guevara">Celia Oreja-Guevara</name><affiliation wicri:level="3"><nlm:aff id="aff6"><addr-line>University Hospital La Paz, IdiPAZ, Madrid, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>University Hospital La Paz, IdiPAZ, Madrid</wicri:regionArea><placeName><settlement type="city">Madrid</settlement><region nuts="2" type="region">Communauté de Madrid</region></placeName></affiliation></author><author><name sortKey="Boz, Cavit" sort="Boz, Cavit" uniqKey="Boz C" first="Cavit" last="Boz">Cavit Boz</name><affiliation wicri:level="1"><nlm:aff id="aff7"><addr-line>Karadeniz Technical University, Trabzon, Turkey</addr-line></nlm:aff><country xml:lang="fr">Turquie</country><wicri:regionArea>Karadeniz Technical University, Trabzon</wicri:regionArea><wicri:noRegion>Trabzon</wicri:noRegion></affiliation></author><author><name sortKey="Lugaresi, Alessandra" sort="Lugaresi, Alessandra" uniqKey="Lugaresi A" first="Alessandra" last="Lugaresi">Alessandra Lugaresi</name><affiliation wicri:level="1"><nlm:aff id="aff8"><addr-line>MS Center, Department of Neuroscience and Imaging, University “G. d’Annunzio”, Chieti, Italy</addr-line></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>MS Center, Department of Neuroscience and Imaging, University “G. d’Annunzio”, Chieti</wicri:regionArea><wicri:noRegion>Chieti</wicri:noRegion></affiliation></author><author><name sortKey="Girard, Marc" sort="Girard, Marc" uniqKey="Girard M" first="Marc" last="Girard">Marc Girard</name><affiliation wicri:level="1"><nlm:aff id="aff9"><addr-line>Hotel-Dieu de Levis, Department of Neurology, Levis, Quebec, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Hotel-Dieu de Levis, Department of Neurology, Levis, Quebec</wicri:regionArea><wicri:noRegion>Quebec</wicri:noRegion></affiliation></author><author><name sortKey="Grammond, Pierre" sort="Grammond, Pierre" uniqKey="Grammond P" first="Pierre" last="Grammond">Pierre Grammond</name><affiliation wicri:level="1"><nlm:aff id="aff9"><addr-line>Hotel-Dieu de Levis, Department of Neurology, Levis, Quebec, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Hotel-Dieu de Levis, Department of Neurology, Levis, Quebec</wicri:regionArea><wicri:noRegion>Quebec</wicri:noRegion></affiliation></author><author><name sortKey="Iuliano, Gerardo" sort="Iuliano, Gerardo" uniqKey="Iuliano G" first="Gerardo" last="Iuliano">Gerardo Iuliano</name><affiliation wicri:level="1"><nlm:aff id="aff10"><addr-line>Ospedali Riuniti di Salerno, Salerno, Italy</addr-line></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Ospedali Riuniti di Salerno, Salerno</wicri:regionArea><wicri:noRegion>Salerno</wicri:noRegion></affiliation></author><author><name sortKey="Fiol, Marcela" sort="Fiol, Marcela" uniqKey="Fiol M" first="Marcela" last="Fiol">Marcela Fiol</name><affiliation wicri:level="1"><nlm:aff id="aff11"><addr-line>FLENI, Buenos Aires, Argentina</addr-line></nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea>FLENI, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Cabrera Gomez, Jose Antonio" sort="Cabrera Gomez, Jose Antonio" uniqKey="Cabrera Gomez J" first="Jose Antonio" last="Cabrera-Gomez">Jose Antonio Cabrera-Gomez</name><affiliation wicri:level="1"><nlm:aff id="aff12"><addr-line>Centro Internacional de Restauracion Neurologica, Havana, Cuba</addr-line></nlm:aff><country xml:lang="fr">Cuba</country><wicri:regionArea>Centro Internacional de Restauracion Neurologica, Havana</wicri:regionArea><wicri:noRegion>Havana</wicri:noRegion></affiliation></author><author><name sortKey="Fernandez Bolanos, Ricardo" sort="Fernandez Bolanos, Ricardo" uniqKey="Fernandez Bolanos R" first="Ricardo" last="Fernandez-Bolanos">Ricardo Fernandez-Bolanos</name><affiliation wicri:level="1"><nlm:aff id="aff13"><addr-line>Hospital Universitario Virgen de Valme, Seville, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Hospital Universitario Virgen de Valme, Seville</wicri:regionArea><wicri:noRegion>Seville</wicri:noRegion></affiliation></author><author><name sortKey="Giuliani, Giorgio" sort="Giuliani, Giorgio" uniqKey="Giuliani G" first="Giorgio" last="Giuliani">Giorgio Giuliani</name><affiliation wicri:level="1"><nlm:aff id="aff14"><addr-line>Ospedale di Macerata, Macerata, Italy</addr-line></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Ospedale di Macerata, Macerata</wicri:regionArea><wicri:noRegion>Macerata</wicri:noRegion></affiliation></author><author><name sortKey="Lechner Scott, Jeannette" sort="Lechner Scott, Jeannette" uniqKey="Lechner Scott J" first="Jeannette" last="Lechner-Scott">Jeannette Lechner-Scott</name><affiliation wicri:level="1"><nlm:aff id="aff15"><addr-line>John Hunter Hospital, Newcastle, New South Wales, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>John Hunter Hospital, Newcastle, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author><author><name sortKey="Cristiano, Edgardo" sort="Cristiano, Edgardo" uniqKey="Cristiano E" first="Edgardo" last="Cristiano">Edgardo Cristiano</name><affiliation wicri:level="1"><nlm:aff id="aff16"><addr-line>Hospital Italiano, Buenos Aires, Argentina</addr-line></nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea>Hospital Italiano, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Herbert, Joseph" sort="Herbert, Joseph" uniqKey="Herbert J" first="Joseph" last="Herbert">Joseph Herbert</name><affiliation wicri:level="2"><nlm:aff id="aff17"><addr-line>New York University Hospital for Joint Diseases, New York, New York, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>New York University Hospital for Joint Diseases, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Petkovska Boskova, Tatjana" sort="Petkovska Boskova, Tatjana" uniqKey="Petkovska Boskova T" first="Tatjana" last="Petkovska-Boskova">Tatjana Petkovska-Boskova</name><affiliation wicri:level="1"><nlm:aff id="aff18"><addr-line>Clinic of Neurology Clinical Center, Skopje, Macedonia</addr-line></nlm:aff><country xml:lang="fr">Macédoine (pays)</country><wicri:regionArea>Clinic of Neurology Clinical Center, Skopje</wicri:regionArea><wicri:noRegion>Skopje</wicri:noRegion></affiliation></author><author><name sortKey="Bergamaschi, Roberto" sort="Bergamaschi, Roberto" uniqKey="Bergamaschi R" first="Roberto" last="Bergamaschi">Roberto Bergamaschi</name><affiliation wicri:level="1"><nlm:aff id="aff19"><addr-line>Neurological Institute IRCCS Mondino, Pavia, Italy</addr-line></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Neurological Institute IRCCS Mondino, Pavia</wicri:regionArea><wicri:noRegion>Pavia</wicri:noRegion></affiliation></author><author><name sortKey="Van Pesch, Vincent" sort="Van Pesch, Vincent" uniqKey="Van Pesch V" first="Vincent" last="Van Pesch">Vincent Van Pesch</name><affiliation wicri:level="3"><nlm:aff id="aff20"><addr-line>Cliniques Universitaires Saint-Luc, Brussels, Belgium</addr-line></nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Cliniques Universitaires Saint-Luc, Brussels</wicri:regionArea><placeName><settlement type="city">Bruxelles</settlement><region nuts="2">Région de Bruxelles-Capitale</region></placeName></affiliation></author><author><name sortKey="Moore, Fraser" sort="Moore, Fraser" uniqKey="Moore F" first="Fraser" last="Moore">Fraser Moore</name><affiliation wicri:level="3"><nlm:aff id="aff21"><addr-line>Jewish General Hospital, Montreal, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Jewish General Hospital, Montreal</wicri:regionArea><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Vella, Norbert" sort="Vella, Norbert" uniqKey="Vella N" first="Norbert" last="Vella">Norbert Vella</name><affiliation wicri:level="1"><nlm:aff id="aff22"><addr-line>Mater Dei Hospital, Msida, Malta</addr-line></nlm:aff><country xml:lang="fr">Malte</country><wicri:regionArea>Mater Dei Hospital, Msida</wicri:regionArea><wicri:noRegion>Msida</wicri:noRegion></affiliation></author><author><name sortKey="Slee, Mark" sort="Slee, Mark" uniqKey="Slee M" first="Mark" last="Slee">Mark Slee</name><affiliation wicri:level="1"><nlm:aff id="aff23"><addr-line>Flinders University and Medical Centre, Adelaide, South Australia, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Flinders University and Medical Centre, Adelaide, South Australia</wicri:regionArea><wicri:noRegion>South Australia</wicri:noRegion></affiliation></author><author><name sortKey="Santiago, Vetere" sort="Santiago, Vetere" uniqKey="Santiago V" first="Vetere" last="Santiago">Vetere Santiago</name><affiliation wicri:level="1"><nlm:aff id="aff24"><addr-line>HIGA Gral, San Martin La Plata, Argentina</addr-line></nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea>HIGA Gral, San Martin La Plata</wicri:regionArea><wicri:noRegion>San Martin La Plata</wicri:noRegion></affiliation></author><author><name sortKey="Barnett, Michael" sort="Barnett, Michael" uniqKey="Barnett M" first="Michael" last="Barnett">Michael Barnett</name><affiliation wicri:level="1"><nlm:aff id="aff25"><addr-line>Brain Mind Research Institute, Camperdown, New South Wales, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Brain Mind Research Institute, Camperdown, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author><author><name sortKey="Havrdova, Eva" sort="Havrdova, Eva" uniqKey="Havrdova E" first="Eva" last="Havrdova">Eva Havrdova</name><affiliation wicri:level="3"><nlm:aff id="aff26"><addr-line>General Teaching Hospital, Prague, Czech Republic</addr-line></nlm:aff><country xml:lang="fr">République tchèque</country><wicri:regionArea>General Teaching Hospital, Prague</wicri:regionArea><placeName><settlement type="city">Prague</settlement><region type="région" nuts="2">Bohême centrale</region></placeName></affiliation></author><author><name sortKey="Young, Carolyn" sort="Young, Carolyn" uniqKey="Young C" first="Carolyn" last="Young">Carolyn Young</name><affiliation wicri:level="1"><nlm:aff id="aff27"><addr-line>The Walton Centre for Neurology and Neurosurgery, Liverpool, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The Walton Centre for Neurology and Neurosurgery, Liverpool</wicri:regionArea><wicri:noRegion>Liverpool</wicri:noRegion></affiliation></author><author><name sortKey="Sirbu, Carmen Adella" sort="Sirbu, Carmen Adella" uniqKey="Sirbu C" first="Carmen-Adella" last="Sirbu">Carmen-Adella Sirbu</name><affiliation wicri:level="1"><nlm:aff id="aff28"><addr-line>Central University Emergency Military Hospital, Bucharest, Romania</addr-line></nlm:aff><country xml:lang="fr">Roumanie</country><wicri:regionArea>Central University Emergency Military Hospital, Bucharest</wicri:regionArea><wicri:noRegion>Bucharest</wicri:noRegion></affiliation></author><author><name sortKey="Tanner, Mary" sort="Tanner, Mary" uniqKey="Tanner M" first="Mary" last="Tanner">Mary Tanner</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Neurology, Royal Melbourne Hospital, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Neurology, Royal Melbourne Hospital, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Rutherford, Michelle" sort="Rutherford, Michelle" uniqKey="Rutherford M" first="Michelle" last="Rutherford">Michelle Rutherford</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Neurology, Royal Melbourne Hospital, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Neurology, Royal Melbourne Hospital, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Butzkueven, Helmut" sort="Butzkueven, Helmut" uniqKey="Butzkueven H" first="Helmut" last="Butzkueven">Helmut Butzkueven</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Neurology, Royal Melbourne Hospital, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Neurology, Royal Melbourne Hospital, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff29"><addr-line>Department of Medicine, Melbourne Brain Centre, The University of Melbourne, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medicine, Melbourne Brain Centre, The University of Melbourne, Victoria</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff30"><addr-line>Department of Neurology, Box Hill Hospital, Monash University, Melbourne, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Neurology, Box Hill Hospital, Monash University, Melbourne, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Objectives</title><p>We conducted a prospective study, MSBASIS, to assess factors leading to first treatment discontinuation in patients with a clinically isolated syndrome (CIS) and early relapsing-remitting multiple sclerosis (RRMS).</p></sec><sec><title>Methods</title><p>The MSBASIS Study, conducted by MSBase Study Group members, enrols patients seen from CIS onset, reporting baseline demographics, cerebral magnetic resonance imaging (MRI) features and Expanded Disability Status Scale (EDSS) scores. Follow-up visits report relapses, EDSS scores, and the start and end dates of MS-specific therapies. We performed a multivariable survival analysis to determine factors within this dataset that predict first treatment discontinuation.</p></sec><sec><title>Results</title><p>A total of 2314 CIS patients from 44 centres were followed for a median of 2.7 years, during which time 1247 commenced immunomodulatory drug (IMD) treatment. Ninety percent initiated IMD after a diagnosis of MS was confirmed, and 10% while still in CIS status. Over 40% of these patients stopped their first IMD during the observation period. Females were more likely to cease medication than males (HR 1.36, p = 0.003). Patients treated in Australia were twice as likely to cease their first IMD than patients treated in Spain (HR 1.98, p = 0.001). Increasing EDSS was associated with higher rate of IMD cessation (HR 1.21 per EDSS unit, p<0.001), and intramuscular interferon-β-1a (HR 1.38, p = 0.028) and subcutaneous interferon-β-1a (HR 1.45, p = 0.012) had higher rates of discontinuation than glatiramer acetate, although this varied widely in different countries. Onset cerebral MRI features, age, time to treatment initiation or relapse on treatment were not associated with IMD cessation.</p></sec><sec><title>Conclusion</title><p>In this multivariable survival analysis, female sex, country of residence, EDSS change and IMD choice independently predicted time to first IMD cessation.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Brodsky, M" uniqKey="Brodsky M">M Brodsky</name></author><author><name sortKey="Nazarian, S" uniqKey="Nazarian S">S Nazarian</name></author><author><name sortKey="Orengo Nania, S" uniqKey="Orengo Nania S">S Orengo-Nania</name></author><author><name sortKey="Hutton, Gj" uniqKey="Hutton G">GJ Hutton</name></author><author><name sortKey="Buckley, Eg" uniqKey="Buckley E">EG Buckley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Filippi, M" uniqKey="Filippi M">M Filippi</name></author><author><name sortKey="Rovaris, M" 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<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id><journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosone</journal-id><journal-title-group><journal-title>PLoS ONE</journal-title></journal-title-group><issn pub-type="epub">1932-6203</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">22768046</article-id><article-id pub-id-type="pmc">3387159</article-id><article-id pub-id-type="publisher-id">PONE-D-11-20113</article-id><article-id pub-id-type="doi">10.1371/journal.pone.0038661</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Medicine</subject><subj-group><subject>Neurology</subject><subj-group><subject>Demyelinating Disorders</subject><subj-group><subject>Multiple Sclerosis</subject></subj-group></subj-group></subj-group></subj-group></article-categories><title-group><article-title>Country, Sex, EDSS Change and Therapy Choice Independently Predict Treatment Discontinuation in Multiple Sclerosis and Clinically Isolated Syndrome</article-title><alt-title alt-title-type="running-head">Factors Predicting Treatment Discontinuation in MS</alt-title></title-group><contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Meyniel</surname><given-names>Claire</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Spelman</surname><given-names>Timothy</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Jokubaitis</surname><given-names>Vilija G.</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Trojano</surname><given-names>Maria</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Izquierdo</surname><given-names>Guillermo</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Grand’Maison</surname><given-names>François</given-names></name><xref ref-type="aff" rid="aff5"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Oreja-Guevara</surname><given-names>Celia</given-names></name><xref ref-type="aff" rid="aff6"><sup>6</sup></xref></contrib><contrib contrib-type="author"><name><surname>Boz</surname><given-names>Cavit</given-names></name><xref ref-type="aff" rid="aff7"><sup>7</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lugaresi</surname><given-names>Alessandra</given-names></name><xref ref-type="aff" rid="aff8"><sup>8</sup></xref></contrib><contrib contrib-type="author"><name><surname>Girard</surname><given-names>Marc</given-names></name><xref ref-type="aff" rid="aff9"><sup>9</sup></xref></contrib><contrib contrib-type="author"><name><surname>Grammond</surname><given-names>Pierre</given-names></name><xref ref-type="aff" rid="aff9"><sup>9</sup></xref></contrib><contrib contrib-type="author"><name><surname>Iuliano</surname><given-names>Gerardo</given-names></name><xref ref-type="aff" rid="aff10"><sup>10</sup></xref></contrib><contrib contrib-type="author"><name><surname>Fiol</surname><given-names>Marcela</given-names></name><xref ref-type="aff" rid="aff11"><sup>11</sup></xref></contrib><contrib contrib-type="author"><name><surname>Cabrera-Gomez</surname><given-names>Jose Antonio</given-names></name><xref ref-type="aff" rid="aff12"><sup>12</sup></xref></contrib><contrib contrib-type="author"><name><surname>Fernandez-Bolanos</surname><given-names>Ricardo</given-names></name><xref ref-type="aff" rid="aff13"><sup>13</sup></xref></contrib><contrib contrib-type="author"><name><surname>Giuliani</surname><given-names>Giorgio</given-names></name><xref ref-type="aff" rid="aff14"><sup>14</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lechner-Scott</surname><given-names>Jeannette</given-names></name><xref ref-type="aff" rid="aff15"><sup>15</sup></xref></contrib><contrib contrib-type="author"><name><surname>Cristiano</surname><given-names>Edgardo</given-names></name><xref ref-type="aff" rid="aff16"><sup>16</sup></xref></contrib><contrib contrib-type="author"><name><surname>Herbert</surname><given-names>Joseph</given-names></name><xref ref-type="aff" rid="aff17"><sup>17</sup></xref></contrib><contrib contrib-type="author"><name><surname>Petkovska-Boskova</surname><given-names>Tatjana</given-names></name><xref ref-type="aff" rid="aff18"><sup>18</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bergamaschi</surname><given-names>Roberto</given-names></name><xref ref-type="aff" rid="aff19"><sup>19</sup></xref></contrib><contrib contrib-type="author"><name><surname>van Pesch</surname><given-names>Vincent</given-names></name><xref ref-type="aff" rid="aff20"><sup>20</sup></xref></contrib><contrib contrib-type="author"><name><surname>Moore</surname><given-names>Fraser</given-names></name><xref ref-type="aff" rid="aff21"><sup>21</sup></xref></contrib><contrib contrib-type="author"><name><surname>Vella</surname><given-names>Norbert</given-names></name><xref ref-type="aff" rid="aff22"><sup>22</sup></xref></contrib><contrib contrib-type="author"><name><surname>Slee</surname><given-names>Mark</given-names></name><xref ref-type="aff" rid="aff23"><sup>23</sup></xref></contrib><contrib contrib-type="author"><name><surname>Santiago</surname><given-names>Vetere</given-names></name><xref ref-type="aff" rid="aff24"><sup>24</sup></xref></contrib><contrib contrib-type="author"><name><surname>Barnett</surname><given-names>Michael</given-names></name><xref ref-type="aff" rid="aff25"><sup>25</sup></xref></contrib><contrib contrib-type="author"><name><surname>Havrdova</surname><given-names>Eva</given-names></name><xref ref-type="aff" rid="aff26"><sup>26</sup></xref></contrib><contrib contrib-type="author"><name><surname>Young</surname><given-names>Carolyn</given-names></name><xref ref-type="aff" rid="aff27"><sup>27</sup></xref></contrib><contrib contrib-type="author"><name><surname>Sirbu</surname><given-names>Carmen-Adella</given-names></name><xref ref-type="aff" rid="aff28"><sup>28</sup></xref></contrib><contrib contrib-type="author"><name><surname>Tanner</surname><given-names>Mary</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rutherford</surname><given-names>Michelle</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Butzkueven</surname><given-names>Helmut</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff29"><sup>29</sup></xref><xref ref-type="aff" rid="aff30"><sup>30</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib><contrib contrib-type="author"><collab>on behalf of the MSBasis Study Group</collab><xref ref-type="author-notes" rid="fn1"><sup>¶</sup></xref></contrib></contrib-group><aff id="aff1"><label>1</label><addr-line>Department of Neurology, Royal Melbourne Hospital, Victoria, Australia</addr-line></aff><aff id="aff2"><label>2</label><addr-line>CHU Nantes, CIC 0004, Nantes, France</addr-line></aff><aff id="aff3"><label>3</label><addr-line>University of Bari, Bari, Italy</addr-line></aff><aff id="aff4"><label>4</label><addr-line>Hospital Universitario, Sevilla, Spain</addr-line></aff><aff id="aff5"><label>5</label><addr-line>Clinique Neuro Rive-Sud, Greenfield Park, Quebec, Canada</addr-line></aff><aff id="aff6"><label>6</label><addr-line>University Hospital La Paz, IdiPAZ, Madrid, Spain</addr-line></aff><aff id="aff7"><label>7</label><addr-line>Karadeniz Technical University, Trabzon, Turkey</addr-line></aff><aff id="aff8"><label>8</label><addr-line>MS Center, Department of Neuroscience and Imaging, University “G. d’Annunzio”, Chieti, Italy</addr-line></aff><aff id="aff9"><label>9</label><addr-line>Hotel-Dieu de Levis, Department of Neurology, Levis, Quebec, Canada</addr-line></aff><aff id="aff10"><label>10</label><addr-line>Ospedali Riuniti di Salerno, Salerno, Italy</addr-line></aff><aff id="aff11"><label>11</label><addr-line>FLENI, Buenos Aires, Argentina</addr-line></aff><aff id="aff12"><label>12</label><addr-line>Centro Internacional de Restauracion Neurologica, Havana, Cuba</addr-line></aff><aff id="aff13"><label>13</label><addr-line>Hospital Universitario Virgen de Valme, Seville, Spain</addr-line></aff><aff id="aff14"><label>14</label><addr-line>Ospedale di Macerata, Macerata, Italy</addr-line></aff><aff id="aff15"><label>15</label><addr-line>John Hunter Hospital, Newcastle, New South Wales, Australia</addr-line></aff><aff id="aff16"><label>16</label><addr-line>Hospital Italiano, Buenos Aires, Argentina</addr-line></aff><aff id="aff17"><label>17</label><addr-line>New York University Hospital for Joint Diseases, New York, New York, United States of America</addr-line></aff><aff id="aff18"><label>18</label><addr-line>Clinic of Neurology Clinical Center, Skopje, Macedonia</addr-line></aff><aff id="aff19"><label>19</label><addr-line>Neurological Institute IRCCS Mondino, Pavia, Italy</addr-line></aff><aff id="aff20"><label>20</label><addr-line>Cliniques Universitaires Saint-Luc, Brussels, Belgium</addr-line></aff><aff id="aff21"><label>21</label><addr-line>Jewish General Hospital, Montreal, Canada</addr-line></aff><aff id="aff22"><label>22</label><addr-line>Mater Dei Hospital, Msida, Malta</addr-line></aff><aff id="aff23"><label>23</label><addr-line>Flinders University and Medical Centre, Adelaide, South Australia, Australia</addr-line></aff><aff id="aff24"><label>24</label><addr-line>HIGA Gral, San Martin La Plata, Argentina</addr-line></aff><aff id="aff25"><label>25</label><addr-line>Brain Mind Research Institute, Camperdown, New South Wales, Australia</addr-line></aff><aff id="aff26"><label>26</label><addr-line>General Teaching Hospital, Prague, Czech Republic</addr-line></aff><aff id="aff27"><label>27</label><addr-line>The Walton Centre for Neurology and Neurosurgery, Liverpool, United Kingdom</addr-line></aff><aff id="aff28"><label>28</label><addr-line>Central University Emergency Military Hospital, Bucharest, Romania</addr-line></aff><aff id="aff29"><label>29</label><addr-line>Department of Medicine, Melbourne Brain Centre, The University of Melbourne, Victoria, Australia</addr-line></aff><aff id="aff30"><label>30</label><addr-line>Department of Neurology, Box Hill Hospital, Monash University, Melbourne, Victoria, Australia</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Kleinschnitz</surname><given-names>Christoph</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1">Julius-Maximilians-Universität Würzburg, Germany</aff><author-notes><corresp id="cor1">* E-mail: <email>butz@unimelb.edu.au</email></corresp><fn fn-type="con"><p>Conceived and designed the experiments: CM TS MT G. Izquierdo FG’M AL PG JLS MR HB. Performed the experiments: CM TS VGJ HB. Analyzed the data: CM TS VGJ HB. Contributed reagents/materials/analysis tools: MT G. Izquierdo FG’M COG CB AL MG PG G. Iuliano MF JACG RFB GG JLS EC JH TPB RB VvP FM NV MS VS MB EH CY CAS MT HB. Wrote the paper: CM TS VGJ HB.</p></fn><fn id="fn1" fn-type="other"><p>¶ Members of the MSBasis Study Group are listed in the acknowledgments</p></fn></author-notes><pub-date pub-type="collection"><year>2012</year></pub-date><pub-date pub-type="epub"><day>29</day><month>6</month><year>2012</year></pub-date><volume>7</volume><issue>6</issue><elocation-id>e38661</elocation-id><history><date date-type="received"><day>7</day><month>10</month><year>2011</year></date><date date-type="accepted"><day>9</day><month>5</month><year>2012</year></date></history><permissions><copyright-statement>Meyniel et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</copyright-statement><copyright-year>2012</copyright-year></permissions><abstract><sec><title>Objectives</title><p>We conducted a prospective study, MSBASIS, to assess factors leading to first treatment discontinuation in patients with a clinically isolated syndrome (CIS) and early relapsing-remitting multiple sclerosis (RRMS).</p></sec><sec><title>Methods</title><p>The MSBASIS Study, conducted by MSBase Study Group members, enrols patients seen from CIS onset, reporting baseline demographics, cerebral magnetic resonance imaging (MRI) features and Expanded Disability Status Scale (EDSS) scores. Follow-up visits report relapses, EDSS scores, and the start and end dates of MS-specific therapies. We performed a multivariable survival analysis to determine factors within this dataset that predict first treatment discontinuation.</p></sec><sec><title>Results</title><p>A total of 2314 CIS patients from 44 centres were followed for a median of 2.7 years, during which time 1247 commenced immunomodulatory drug (IMD) treatment. Ninety percent initiated IMD after a diagnosis of MS was confirmed, and 10% while still in CIS status. Over 40% of these patients stopped their first IMD during the observation period. Females were more likely to cease medication than males (HR 1.36, p = 0.003). Patients treated in Australia were twice as likely to cease their first IMD than patients treated in Spain (HR 1.98, p = 0.001). Increasing EDSS was associated with higher rate of IMD cessation (HR 1.21 per EDSS unit, p<0.001), and intramuscular interferon-β-1a (HR 1.38, p = 0.028) and subcutaneous interferon-β-1a (HR 1.45, p = 0.012) had higher rates of discontinuation than glatiramer acetate, although this varied widely in different countries. Onset cerebral MRI features, age, time to treatment initiation or relapse on treatment were not associated with IMD cessation.</p></sec><sec><title>Conclusion</title><p>In this multivariable survival analysis, female sex, country of residence, EDSS change and IMD choice independently predicted time to first IMD cessation.</p></sec></abstract><counts><page-count count="8"></page-count></counts></article-meta></front></pmc><affiliations><list><country><li>Argentine</li><li>Australie</li><li>Belgique</li><li>Canada</li><li>Cuba</li><li>Espagne</li><li>France</li><li>Italie</li><li>Macédoine (pays)</li><li>Malte</li><li>Roumanie</li><li>Royaume-Uni</li><li>République tchèque</li><li>Turquie</li><li>États-Unis</li></country><region><li>Bohême centrale</li><li>Communauté de Madrid</li><li>Pays de la Loire</li><li>Québec</li><li>Région de Bruxelles-Capitale</li><li>Victoria (État)</li><li>État de New York</li></region><settlement><li>Bruxelles</li><li>Madrid</li><li>Melbourne</li><li>Montréal</li><li>Nantes</li><li>Prague</li></settlement><orgName><li>Université de Melbourne</li></orgName></list><tree><country name="Australie"><noRegion><name sortKey="Meyniel, Claire" sort="Meyniel, Claire" uniqKey="Meyniel C" first="Claire" last="Meyniel">Claire Meyniel</name></noRegion><name sortKey="Barnett, Michael" sort="Barnett, Michael" uniqKey="Barnett M" first="Michael" last="Barnett">Michael Barnett</name><name sortKey="Butzkueven, Helmut" sort="Butzkueven, Helmut" uniqKey="Butzkueven H" first="Helmut" last="Butzkueven">Helmut Butzkueven</name><name sortKey="Butzkueven, Helmut" sort="Butzkueven, Helmut" uniqKey="Butzkueven H" first="Helmut" last="Butzkueven">Helmut Butzkueven</name><name sortKey="Butzkueven, Helmut" sort="Butzkueven, Helmut" uniqKey="Butzkueven H" first="Helmut" last="Butzkueven">Helmut Butzkueven</name><name sortKey="Jokubaitis, Vilija G" sort="Jokubaitis, Vilija G" uniqKey="Jokubaitis V" first="Vilija G." last="Jokubaitis">Vilija G. Jokubaitis</name><name sortKey="Lechner Scott, Jeannette" sort="Lechner Scott, Jeannette" uniqKey="Lechner Scott J" first="Jeannette" last="Lechner-Scott">Jeannette Lechner-Scott</name><name sortKey="Rutherford, Michelle" sort="Rutherford, Michelle" uniqKey="Rutherford M" first="Michelle" last="Rutherford">Michelle Rutherford</name><name sortKey="Slee, Mark" sort="Slee, Mark" uniqKey="Slee M" first="Mark" last="Slee">Mark Slee</name><name sortKey="Spelman, Timothy" sort="Spelman, Timothy" uniqKey="Spelman T" first="Timothy" last="Spelman">Timothy Spelman</name><name sortKey="Tanner, Mary" sort="Tanner, Mary" uniqKey="Tanner M" first="Mary" last="Tanner">Mary Tanner</name></country><country name="France"><region name="Pays de la Loire"><name sortKey="Meyniel, Claire" sort="Meyniel, Claire" uniqKey="Meyniel C" first="Claire" last="Meyniel">Claire Meyniel</name></region></country><country name="Italie"><noRegion><name sortKey="Trojano, Maria" sort="Trojano, Maria" uniqKey="Trojano M" first="Maria" last="Trojano">Maria Trojano</name></noRegion><name sortKey="Bergamaschi, Roberto" sort="Bergamaschi, Roberto" uniqKey="Bergamaschi R" first="Roberto" last="Bergamaschi">Roberto Bergamaschi</name><name sortKey="Giuliani, Giorgio" sort="Giuliani, Giorgio" uniqKey="Giuliani G" first="Giorgio" last="Giuliani">Giorgio Giuliani</name><name sortKey="Iuliano, Gerardo" sort="Iuliano, Gerardo" uniqKey="Iuliano G" first="Gerardo" last="Iuliano">Gerardo Iuliano</name><name sortKey="Lugaresi, Alessandra" sort="Lugaresi, Alessandra" uniqKey="Lugaresi A" first="Alessandra" last="Lugaresi">Alessandra Lugaresi</name></country><country name="Espagne"><noRegion><name sortKey="Izquierdo, Guillermo" sort="Izquierdo, Guillermo" uniqKey="Izquierdo G" first="Guillermo" last="Izquierdo">Guillermo Izquierdo</name></noRegion><name sortKey="Fernandez Bolanos, Ricardo" sort="Fernandez Bolanos, Ricardo" uniqKey="Fernandez Bolanos R" first="Ricardo" last="Fernandez-Bolanos">Ricardo 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uniqKey="Fiol M" first="Marcela" last="Fiol">Marcela Fiol</name></noRegion><name sortKey="Cristiano, Edgardo" sort="Cristiano, Edgardo" uniqKey="Cristiano E" first="Edgardo" last="Cristiano">Edgardo Cristiano</name><name sortKey="Santiago, Vetere" sort="Santiago, Vetere" uniqKey="Santiago V" first="Vetere" last="Santiago">Vetere Santiago</name></country><country name="Cuba"><noRegion><name sortKey="Cabrera Gomez, Jose Antonio" sort="Cabrera Gomez, Jose Antonio" uniqKey="Cabrera Gomez J" first="Jose Antonio" last="Cabrera-Gomez">Jose Antonio Cabrera-Gomez</name></noRegion></country><country name="États-Unis"><region name="État de New York"><name sortKey="Herbert, Joseph" sort="Herbert, Joseph" uniqKey="Herbert J" first="Joseph" last="Herbert">Joseph Herbert</name></region></country><country name="Macédoine (pays)"><noRegion><name sortKey="Petkovska Boskova, Tatjana" sort="Petkovska Boskova, Tatjana" uniqKey="Petkovska Boskova T" first="Tatjana" last="Petkovska-Boskova">Tatjana Petkovska-Boskova</name></noRegion></country><country name="Belgique"><region name="Région de Bruxelles-Capitale"><name sortKey="Van Pesch, Vincent" sort="Van Pesch, Vincent" uniqKey="Van Pesch V" first="Vincent" last="Van Pesch">Vincent Van Pesch</name></region></country><country name="Malte"><noRegion><name sortKey="Vella, Norbert" sort="Vella, Norbert" uniqKey="Vella N" first="Norbert" last="Vella">Norbert Vella</name></noRegion></country><country name="République tchèque"><region name="Bohême centrale"><name sortKey="Havrdova, Eva" sort="Havrdova, Eva" uniqKey="Havrdova E" first="Eva" last="Havrdova">Eva Havrdova</name></region></country><country name="Royaume-Uni"><noRegion><name sortKey="Young, Carolyn" sort="Young, Carolyn" uniqKey="Young C" first="Carolyn" last="Young">Carolyn Young</name></noRegion></country><country name="Roumanie"><noRegion><name sortKey="Sirbu, Carmen Adella" sort="Sirbu, Carmen Adella" uniqKey="Sirbu C" first="Carmen-Adella" last="Sirbu">Carmen-Adella Sirbu</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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