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Research Article| Volume 409, 116609, February 15, 2020

Consensus recommendations on the management of multiple sclerosis patients in Argentina

Published:December 02, 2019DOI:https://doi.org/10.1016/j.jns.2019.116609

      Highlights

      • The objective of these consensus was to review how MS should be managed in Argentina
      • Recommendations focused on diagnosis, tailored treatment, treatment failure and pharmacovigilance
      • An early and individualized specific treatment for MS should be used on every patient.
      • Neurologists who follow MS patients are responsible for the prescription of the specific treatment
      • Patients with suspected MS should be evaluated in an MS care unit and/or by trained MS neurologist

      Abstract

      Introduction

      During the last 20 years, multiple sclerosis (MS) disease has seen major changes with new diagnostic criteria, a better identification of disease phenotypes, individualization of disease prognosis and the appearance of new therapeutic options in relapsing remitting as well as progressive MS. As a result, the management of MS patients has become more complex and challenging. The objective of these consensus recommendations was to review how the disease should be managed in Argentina to improve long-term outcomes in MS patients.

      Methods

      A panel of 36 experts in neurology from Argentina, dedicated to the diagnosis and care of MS patients, gathered both virtually and in person during 2018 and 2019 to carry out a consensus recommendation on the management of MS patients in Argentina. To achieve consensus, the methodology of “formal consensus-RAND/UCLA method” was used.

      Results

      Recommendations focused on diagnosis, disease prognosis, tailored treatment, treatment failure identification and pharmacovigilance process.

      Conclusions

      The recommendations of these consensus guidelines attempt to optimize the health care and management of patients with MS in Argentina.

      Keywords

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      References

        • Rojas J.I.
        • Romano M.
        • Patrucco L.
        • Cristiano E.
        A systematic review about the epidemiology of primary progressive multiple sclerosis in Latin America and the Caribbean.
        Mult. Scler Relat. Disord. 2018; 22: 1-7
        • Cristiano E.
        • Patrucco L.
        • Miguez J.
        • Giunta D.
        • Correale J.
        • Fiol M.
        • Ysrraelit M.C.
        • Caceres F.
        • Liguori N.F.
        • Saladino M.L.
        • Garcea O.
        • Silva B.
        • Alonso R.
        • Carra A.
        • Curbelo M.C.
        • Martinez A.
        • Steinberg J.
        • Giachello S.
        • Melcom M.O.
        • Rojas J.I.
        Increasing prevalence of multiple sclerosis in Buenos Aires, Argentina.
        Mult. Scler Relat. Disord. 2016; 9: 91-94
        • Lublin F.D.
        • Reingold S.C.
        • Cohen J.A.
        • Cutter G.R.
        • Sorensen P.S.
        • Thompson A.J.
        • Wolinsky J.S.
        • Balcer L.J.
        • Banwell B.
        • Barkhof F.
        • Bebo Jr., B.
        • Calabresi P.A.
        • Clanet M.
        • Comi G.
        • Fox R.J.
        • Freedman M.S.
        • Goodman A.D.
        • Inglese M.
        • Kappos L.
        • Kieseier B.C.
        • Lincoln J.A.
        • Lubetzki C.
        • Miller A.E.
        • Montalban X.
        • O’Connor P.W.
        • Petkau J.
        • Pozzilli C.
        • Rudick R.A.
        • Sormani M.P.
        • Stuve O.
        • Waubant E.
        • Polman C.H.
        Defining the clinical course of multiple sclerosis: the 2013 revisions.
        Neurology. 2014; 83: 278-286
        • Comi G.
        • Radaelli M.
        • Soelberg Sorensen P.
        Evolving concepts in the treatment of relapsing multiple sclerosis.
        Lancet. 2017; 389: 1347-1356
        • Soelberg Sorensen P.
        • Giovannoni G.
        • Montalban X.
        • Thalheim C.
        • Zaratin P.
        • Comi G.
        The multiple sclerosis care unit.
        Mult. Scler. 2019; 25: 627-636
        • Bell B.G.
        • Spencer R.
        • Avery A.J.
        • Campbell S.M.
        Tools for measuring patient safety in primary care settings using the RAND/UCLA appropriateness method.
        BMC Fam. Pract. 2014; 15: 110
        • Santori G.
        • Fontana I.
        • Valente R.
        • Ghirelli R.
        • Valente U.
        Application of the RAND/UCLA Appropriateness Method to evaluate an information system for kidney/pancreas transplantation in adult recipients.
        Transplant. Proc. 2008; 40: 2021-2023
        • Thompson A.J.
        • Banwell B.L.
        • Barkhof F.
        • Carroll W.M.
        • Coetzee T.
        • Comi G.
        • Correale J.
        • Fazekas F.
        • Filippi M.
        • Freedman M.S.
        • Fujihara K.
        • Galetta S.L.
        • Hartung H.P.
        • Kappos L.
        • Lublin F.D.
        • Marrie R.A.
        • Miller A.E.
        • Miller D.H.
        • Montalban X.
        • Mowry E.M.
        • Sorensen P.S.
        • Tintore M.
        • Traboulsee A.L.
        • Trojano M.
        • Uitdehaag B.M.J.
        • Vukusic S.
        • Waubant E.
        • Weinshenker B.G.
        • Reingold S.C.
        • Cohen J.A.
        Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria.
        Lancet Neurol. 2018; 17: 162-173
        • Filippi M.
        • Preziosa P.
        • Meani A.
        • Ciccarelli O.
        • Mesaros S.
        • Rovira A.
        • Frederiksen J.
        • Enzinger C.
        • Barkhof F.
        • Gasperini C.
        • Brownlee W.
        • Drulovic J.
        • Montalban X.
        • Cramer S.P.
        • Pichler A.
        • Hagens M.
        • Ruggieri S.
        • Martinelli V.
        • Miszkiel K.
        • Tintore M.
        • Comi G.
        • Dekker I.
        • Uitdehaag B.
        • Dujmovic-Basuroski I.
        • Rocca M.A.
        Prediction of a multiple sclerosis diagnosis in patients with clinically isolated syndrome using the 2016 MAGNIMS and 2010 McDonald criteria: a retrospective study.
        Lancet Neurol. 2018; 17: 133-142
        • Hartung H.P.
        • Graf J.
        • Aktas O.
        • Mares J.
        • Barnett M.H.
        Diagnosis of multiple sclerosis: revisions of the McDonald criteria 2017 – continuity and change.
        Curr. Opin. Neurol. 2019; 32: 327-337
        • Rocha A.J.
        • Littig I.A.
        • Nunes R.H.
        • Tilbery C.P.
        Central nervous system infectious diseases mimicking multiple sclerosis: recognizing distinguishable features using MRI.
        Arq. Neuropsiquiatr. 2013; 71: 738-746
        • Miller D.H.
        • Weinshenker B.G.
        • Filippi M.
        • Banwell B.L.
        • Cohen J.A.
        • Freedman M.S.
        • Galetta S.L.
        • Hutchinson M.
        • Johnson R.T.
        • Kappos L.
        • Kira J.
        • Lublin F.D.
        • McFarland H.F.
        • Montalban X.
        • Panitch H.
        • Richert J.R.
        • Reingold S.C.
        • Polman C.H.
        Differential diagnosis of suspected multiple sclerosis: a consensus approach.
        Mult. Scler. 2008; 14: 1157-1174
        • Rovira A.
        • Wattjes M.P.
        • Tintore M.
        • Tur C.
        • Yousry T.A.
        • Sormani M.P.
        • De Stefano N.
        • Filippi M.
        • Auger C.
        • Rocca M.A.
        • Barkhof F.
        • Fazekas F.
        • Kappos L.
        • Polman C.
        • Miller D.
        • Montalban X.
        • M.s. group
        Evidence-based guidelines: MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis-clinical implementation in the diagnostic process.
        Nat. Rev. Neurol. 2015; 11: 471-482
        • Wattjes M.P.
        • Rovira A.
        • Miller D.
        • Yousry T.A.
        • Sormani M.P.
        • de Stefano M.P.
        • Tintore M.
        • Auger C.
        • Tur C.
        • Filippi M.
        • Rocca M.A.
        • Fazekas F.
        • Kappos L.
        • Polman C.
        • Frederik B.
        • Xavier M.
        • M.s. group
        Evidence-based guidelines: MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis--establishing disease prognosis and monitoring patients.
        Nat. Rev. Neurol. 2015; 11: 597-606
        • Solomon A.J.
        Diagnosis, differential diagnosis, and misdiagnosis of multiple sclerosis.
        Continuum (Minneap. Minn.). 2019; 25: 611-635
        • Fay A.J.
        • Mowry E.M.
        • Strober J.
        • Waubant E.
        Relapse severity and recovery in early pediatric multiple sclerosis.
        Mult. Scler. 2012; 18: 1008-1012
        • Vercellino M.
        • Romagnolo A.
        • Mattioda A.
        • Masera S.
        • Piacentino C.
        • Merola A.
        • Chio A.
        • Mutani R.
        • Cavalla P.
        Multiple sclerosis relapses: a multivariable analysis of residual disability determinants.
        Acta Neurol. Scand. 2009; 119: 126-130
        • Mowry E.M.
        • Pesic M.
        • Grimes B.
        • Deen S.
        • Bacchetti P.
        • Waubant E.
        Demyelinating events in early multiple sclerosis have inherent severity and recovery.
        Neurology. 2009; 72: 602-608
        • Weinshenker B.G.
        • Bass B.
        • Rice G.P.
        • Noseworthy J.
        • Carriere W.
        • Baskerville J.
        • Ebers G.C.
        The natural history of multiple sclerosis: a geographically based study. I. Clinical course and disability.
        Brain. 1989; 112: 133-146
        • Confavreux C.
        • Vukusic S.
        • Adeleine P.
        Early clinical predictors and progression of irreversible disability in multiple sclerosis: an amnesic process.
        Brain. 2003; 126: 770-782
        • Kremenchutzky M.
        • Rice G.P.
        • Baskerville J.
        • Wingerchuk D.M.
        • Ebers G.C.
        The natural history of multiple sclerosis: a geographically based study 9: observations on the progressive phase of the disease.
        Brain. 2006; 129: 584-594
        • Novotna M.
        • Paz Soldan M.M.
        • Abou Zeid N.
        • Kale N.
        • Tutuncu M.
        • Crusan D.J.
        • Atkinson E.J.
        • Siva A.
        • Keegan B.M.
        • Pirko I.
        • Pittock S.J.
        • Lucchinetti C.F.
        • Noseworthy J.H.
        • Weinshenker B.G.
        • Rodriguez M.
        • Kantarci O.H.
        Poor early relapse recovery affects onset of progressive disease course in multiple sclerosis.
        Neurology. 2015; 85: 722-729
        • Langer-Gould A.
        • Popat R.A.
        • Huang S.M.
        • Cobb K.
        • Fontoura P.
        • Gould M.K.
        • Nelson L.M.
        Clinical and demographic predictors of long-term disability in patients with relapsing-remitting multiple sclerosis: a systematic review.
        Arch. Neurol. 2006; 63: 1686-1691
        • Simone I.L.
        • Carrara D.
        • Tortorella C.
        • Liguori M.
        • Lepore V.
        • Pellegrini F.
        • Bellacosa A.
        • Ceccarelli A.
        • Pavone I.
        • Livrea P.
        Course and prognosis in early-onset MS: comparison with adult-onset forms.
        Neurology. 2002; 59: 1922-1928
        • Amato M.P.
        • Ponziani G.
        • Bartolozzi M.L.
        • Siracusa G.
        A prospective study on the natural history of multiple sclerosis: clues to the conduct and interpretation of clinical trials.
        J. Neurol. Sci. 1999; 168: 96-106
        • Bergamaschi R.
        • Berzuini C.
        • Romani A.
        • Cosi V.
        Predicting secondary progression in relapsing-remitting multiple sclerosis: a Bayesian analysis.
        J. Neurol. Sci. 2001; 189: 13-21
        • Damasceno A.
        • Von Glehn F.
        • Brandao C.O.
        • Damasceno B.P.
        • Cendes F.
        Prognostic indicators for long-term disability in multiple sclerosis patients.
        J. Neurol. Sci. 2013; 324: 29-33
        • Riise T.
        • Gronning M.
        • Fernandez O.
        • Lauer K.
        • Midgard R.
        • Minderhoud J.M.
        • Nyland H.
        • Palffy G.
        • Poser S.
        • Aarli J.A.
        Early prognostic factors for disability in multiple sclerosis, a European multicenter study.
        Acta Neurol. Scand. 1992; 85: 212-218
        • Scalfari A.
        • Neuhaus A.
        • Degenhardt A.
        • Rice G.P.
        • Muraro P.A.
        • Daumer M.
        • Ebers G.C.
        The natural history of multiple sclerosis: a geographically based study 10: relapses and long-term disability.
        Brain. 2010; 133: 1914-1929
        • Stewart T.
        • Spelman T.
        • Havrdova E.
        • Horakova D.
        • Trojano M.
        • Izquierdo G.
        • Duquette P.
        • Girard M.
        • Prat A.
        • Lugaresi A.
        • Grand'Maison F.
        • Grammond P.
        • Sola P.
        • Shaygannejad V.
        • Hupperts R.
        • Alroughani R.
        • Oreja-Guevara C.
        • Pucci E.
        • Boz C.
        • Lechner-Scott J.
        • Bergamaschi R.
        • Van Pesch V.
        • Iuliano G.
        • Ramo C.
        • Taylor B.
        • Slee M.
        • Spitaleri D.
        • Granella F.
        • Verheul F.
        • McCombe P.
        • Hodgkinson S.
        • Amato M.P.
        • Vucic S.
        • Gray O.
        • Cristiano E.
        • Barnett M.
        • Menoyo J.L. Sanchez
        • van Munster E.
        • Saladino M.L.
        • Olascoaga J.
        • Prevost J.
        • Deri N.
        • Shaw C.
        • Singhal B.
        • Moore F.
        • Rozsa C.
        • Shuey N.
        • Skibina O.
        • Kister I.
        • Petkovska-Boskova T.
        • Ampapa R.
        • Kermode A.
        • Butzkueven H.
        • Jokubaitis V.
        • Kalincik T.
        • M.S.S. Group
        Contribution of different relapse phenotypes to disability in multiple sclerosis.
        Mult. Scler. 2017; 23: 266-276
        • Tintore M.
        • Rovira A.
        • Rio J.
        • Otero-Romero S.
        • Arrambide G.
        • Tur C.
        • Comabella M.
        • Nos C.
        • Arevalo M.J.
        • Negrotto L.
        • Galan I.
        • Vidal-Jordana A.
        • Castillo J.
        • Palavra F.
        • Simon E.
        • Mitjana R.
        • Auger C.
        • Sastre-Garriga J.
        • Montalban X.
        Defining high, medium and low impact prognostic factors for developing multiple sclerosis.
        Brain. 2015; 138: 1863-1874
        • Kuhle J.
        • Disanto G.
        • Dobson R.
        • Adiutori R.
        • Bianchi L.
        • Topping J.
        • Bestwick J.P.
        • Meier U.C.
        • Marta M.
        • Costa G.D.
        • Runia T.
        • Evdoshenko E.
        • Lazareva N.
        • Thouvenot E.
        • Iaffaldano P.
        • Direnzo V.
        • Khademi M.
        • Piehl F.
        • Comabella M.
        • Sombekke M.
        • Killestein J.
        • Hegen H.
        • Rauch S.
        • D’Alfonso S.
        • Alvarez-Cermeno J.C.
        • Kleinova P.
        • Horakova D.
        • Roesler R.
        • Lauda F.
        • Llufriu S.
        • Avsar T.
        • Uygunoglu U.
        • Altintas A.
        • Saip S.
        • Menge T.
        • Rajda C.
        • Bergamaschi R.
        • Moll N.
        • Khalil M.
        • Marignier R.
        • Dujmovic I.
        • Larsson H.
        • Malmestrom C.
        • Scarpini E.
        • Fenoglio C.
        • Wergeland S.
        • Laroni A.
        • Annibali V.
        • Romano S.
        • Martinez A.D.
        • Carra A.
        • Salvetti M.
        • Uccelli A.
        • Torkildsen O.
        • Myhr K.M.
        • Galimberti D.
        • Rejdak K.
        • Lycke J.
        • Frederiksen J.L.
        • Drulovic J.
        • Confavreux C.
        • Brassat D.
        • Enzinger C.
        • Fuchs S.
        • Bosca I.
        • Pelletier J.
        • Picard C.
        • Colombo E.
        • Franciotta D.
        • Derfuss T.
        • Lindberg R.
        • Yaldizli O.
        • Vecsei L.
        • Kieseier B.C.
        • Hartung H.P.
        • Villoslada P.
        • Siva A.
        • Saiz A.
        • Tumani H.
        • Havrdova E.
        • Villar L.M.
        • Leone M.
        • Barizzone N.
        • Deisenhammer F.
        • Teunissen C.
        • Montalban X.
        • Tintore M.
        • Olsson T.
        • Trojano M.
        • Lehmann S.
        • Castelnovo G.
        • Lapin S.
        • Hintzen R.
        • Kappos L.
        • Furlan R.
        • Martinelli V.
        • Comi G.
        • Ramagopalan S.V.
        • Giovannoni G.
        Conversion from clinically isolated syndrome to multiple sclerosis: a large multicentre study.
        Mult. Scler. 2015; 21: 1013-1024
        • Fisniku L.K.
        • Brex P.A.
        • Altmann D.R.
        • Miszkiel K.A.
        • Benton C.E.
        • Lanyon R.
        • Thompson A.J.
        • Miller D.H.
        Disability and T2 MRI lesions: a 20-year follow-up of patients with relapse onset of multiple sclerosis.
        Brain. 2008; 131: 808-817
        • Giorgio A.
        • Battaglini M.
        • Rocca M.A.
        • De Leucio A.
        • Absinta M.
        • van Schijndel R.
        • Rovira A.
        • Tintore M.
        • Chard D.
        • Ciccarelli O.
        • Enzinger C.
        • Gasperini C.
        • Frederiksen J.
        • Filippi M.
        • Barkhof F.
        • De Stefano N.
        • M.S. Group
        Location of brain lesions predicts conversion of clinically isolated syndromes to multiple sclerosis.
        Neurology. 2013; 80: 234-241
        • Tintore M.
        • Rovira A.
        • Arrambide G.
        • Mitjana R.
        • Rio J.
        • Auger C.
        • Nos C.
        • Edo M.C.
        • Castillo J.
        • Horga A.
        • Perez-Miralles F.
        • Huerga E.
        • Comabella M.
        • Sastre-Garriga J.
        • Montalban X.
        Brainstem lesions in clinically isolated syndromes.
        Neurology. 2010; 75: 1933-1938
        • Swanton J.K.
        • Fernando K.T.
        • Dalton C.M.
        • Miszkiel K.A.
        • Altmann D.R.
        • Plant G.T.
        • Thompson A.J.
        • Miller D.H.
        Early MRI in optic neuritis: the risk for disability.
        Neurology. 2009; 72: 542-550
        • Minneboo A.
        • Barkhof F.
        • Polman C.H.
        • Uitdehaag B.M.
        • Knol D.L.
        • Castelijns J.A.
        Infratentorial lesions predict long-term disability in patients with initial findings suggestive of multiple sclerosis.
        Arch. Neurol. 2004; 61: 217-221
        • Kearney H.
        • Miller D.H.
        • Ciccarelli O.
        Spinal cord MRI in multiple sclerosis–diagnostic, prognostic and clinical value.
        Nat. Rev. Neurol. 2015; 11: 327-338
        • Sombekke M.H.
        • Wattjes M.P.
        • Balk L.J.
        • Nielsen J.M.
        • Vrenken H.
        • Uitdehaag B.M.
        • Polman C.H.
        • Barkhof F.
        Spinal cord lesions in patients with clinically isolated syndrome: a powerful tool in diagnosis and prognosis.
        Neurology. 2013; 80: 69-75
        • Cordonnier C.
        • de Seze J.
        • Breteau G.
        • Ferriby D.
        • Michelin E.
        • Stojkovic T.
        • Pruvo J.P.
        • Vermersch P.
        Prospective study of patients presenting with acute partial transverse myelopathy.
        J. Neurol. 2003; 250: 1447-1452
        • Bot J.C.
        • Barkhof F.
        • Polman C.H.
        • Lycklama a Nijeholt G.J.
        • de Groot V.
        • Bergers E.
        • Ader H.J.
        • Castelijns J.A.
        Spinal cord abnormalities in recently diagnosed MS patients: added value of spinal MRI examination.
        Neurology. 2004; 62: 226-233
        • Hoffman C.
        • Rice D.
        • Sung H.Y.
        Persons with chronic conditions. Their prevalence and costs.
        JAMA. 1996; 276: 1473-1479
        • Marrie R.
        • Horwitz R.
        • Cutter G.
        • Tyry T.
        • Campagnolo D.
        • Vollmer T.
        Comorbidity, socioeconomic status and multiple sclerosis.
        Mult. Scler. 2008; 14: 1091-1098
        • Marrie R.A.
        • Horwitz R.
        • Cutter G.
        • Tyry T.
        • Campagnolo D.
        • Vollmer T.
        Comorbidity delays diagnosis and increases disability at diagnosis in MS.
        Neurology. 2009; 72: 117-124
        • Marrie R.A.
        • Horwitz R.I.
        Emerging effects of comorbidities on multiple sclerosis.
        Lancet Neurol. 2010; 9: 820-828
        • Marrie R.A.
        • Rudick R.
        • Horwitz R.
        • Cutter G.
        • Tyry T.
        • Campagnolo D.
        • Vollmer T.
        Vascular comorbidity is associated with more rapid disability progression in multiple sclerosis.
        Neurology. 2010; 74: 1041-1047
        • Kessler R.C.
        • Berglund P.
        • Demler O.
        • Jin R.
        • Koretz D.
        • Merikangas K.R.
        • Rush A.J.
        • Walters E.E.
        • Wang P.S.
        • R. National Comorbidity Survey
        The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R).
        JAMA. 2003; 289: 3095-3105
        • Goldman Consensus G.
        The Goldman Consensus statement on depression in multiple sclerosis.
        Mult. Scler. 2005; 11: 328-337
        • Farez M.F.
        • Fiol M.P.
        • Gaitan M.I.
        • Quintana F.J.
        • Correale J.
        Sodium intake is associated with increased disease activity in multiple sclerosis.
        J. Neurol. Neurosurg. Psychiatry. 2015; 86: 26-31
        • Hernan M.A.
        • Jick S.S.
        • Logroscino G.
        • Olek M.J.
        • Ascherio A.
        • Jick H.
        Cigarette smoking and the progression of multiple sclerosis.
        Brain. 2005; 128: 1461-1465
        • Degelman M.L.
        • Herman K.M.
        Smoking and multiple sclerosis: a systematic review and meta-analysis using the Bradford Hill criteria for causation.
        Mult. Scler Relat. Disord. 2017; 17: 207-216
        • Manouchehrinia A.
        • Tench C.R.
        • Maxted J.
        • Bibani R.H.
        • Britton J.
        • Constantinescu C.S.
        Tobacco smoking and disability progression in multiple sclerosis: United Kingdom cohort study.
        Brain. 2013; 136: 2298-2304
        • Motl R.W.
        • Pilutti L.A.
        Is physical exercise a multiple sclerosis disease modifying treatment?.
        Expert. Rev. Neurother. 2016; 16: 951-960
        • Tallner A.
        • Waschbisch A.
        • Wenny I.
        • Schwab S.
        • Hentschke C.
        • Pfeifer K.
        • Maurer M.
        Multiple sclerosis relapses are not associated with exercise.
        Mult. Scler. 2012; 18: 232-235
        • Pilutti L.A.
        • Platta M.E.
        • Motl R.W.
        • Latimer-Cheung A.E.
        The safety of exercise training in multiple sclerosis: a systematic review.
        J. Neurol. Sci. 2014; 343: 3-7
        • Prakash R.S.
        • Snook E.M.
        • Motl R.W.
        • Kramer A.F.
        Aerobic fitness is associated with gray matter volume and white matter integrity in multiple sclerosis.
        Brain Res. 2010; 1341: 41-51
        • Grover S.A.
        • Aubert-Broche B.
        • Fetco D.
        • Collins D.L.
        • Arnold D.L.
        • Finlayson M.
        • Banwell B.L.
        • Motl R.W.
        • Yeh E.A.
        Lower physical activity is associated with higher disease burden in pediatric multiple sclerosis.
        Neurology. 2015; 85: 1663-1669
        • Snook E.M.
        • Motl R.W.
        Effect of exercise training on walking mobility in multiple sclerosis: a meta-analysis.
        Neurorehabil. Neural Repair. 2009; 23: 108-116
        • Motl R.W.
        • McAuley E.
        Association between change in physical activity and short-term disability progression in multiple sclerosis.
        J. Rehabil. Med. 2011; 43: 305-310
        • Pearson M.
        • Dieberg G.
        • Smart N.
        Exercise as a therapy for improvement of walking ability in adults with multiple sclerosis: a meta-analysis.
        Arch. Phys. Med. Rehabil. 2015; 96 (e7): 1339-1348
        • Fitzner B.
        • Hecker M.
        • Zettl U.K.
        Molecular biomarkers in cerebrospinal fluid of multiple sclerosis patients.
        Autoimmun. Rev. 2015; 14: 903-913
        • Link H.
        • Huang Y.M.
        Oligoclonal bands in multiple sclerosis cerebrospinal fluid: an update on methodology and clinical usefulness.
        J. Neuroimmunol. 2006; 180: 17-28
        • Tumani H.
        • Deisenhammer F.
        • Giovannoni G.
        • Gold R.
        • Hartung H.P.
        • Hemmer B.
        • Hohlfeld R.
        • Otto M.
        • Stangel M.
        • Wildemann B.
        • Zettl U.K.
        Revised McDonald criteria: the persisting importance of cerebrospinal fluid analysis.
        Ann. Neurol. 2011; 70 (author reply 521): 520
        • Dobson R.
        • Ramagopalan S.
        • Davis A.
        • Giovannoni G.
        Cerebrospinal fluid oligoclonal bands in multiple sclerosis and clinically isolated syndromes: a meta-analysis of prevalence, prognosis and effect of latitude.
        J. Neurol. Neurosurg. Psychiatry. 2013; 84: 909-914
        • Sormani M.P.
        • Arnold D.L.
        • De Stefano N.
        Treatment effect on brain atrophy correlates with treatment effect on disability in multiple sclerosis.
        Ann. Neurol. 2014; 75: 43-49
        • Zivadinov R.
        • Sepcic J.
        • Nasuelli D.
        • De Masi R.
        • Bragadin L.M.
        • Tommasi M.A.
        • Zambito-Marsala S.
        • Moretti R.
        • Bratina A.
        • Ukmar M.
        • Pozzi-Mucelli R.S.
        • Grop A.
        • Cazzato G.
        • Zorzon M.
        A longitudinal study of brain atrophy and cognitive disturbances in the early phase of relapsing-remitting multiple sclerosis.
        J. Neurol. Neurosurg. Psychiatry. 2001; 70: 773-780
        • Potagas C.
        • Giogkaraki E.
        • Koutsis G.
        • Mandellos D.
        • Tsirempolou E.
        • Sfagos C.
        • Vassilopoulos D.
        Cognitive impairment in different MS subtypes and clinically isolated syndromes.
        J. Neurol. Sci. 2008; 267: 100-106
        • Feuillet L.
        • Reuter F.
        • Audoin B.
        • Malikova I.
        • Barrau K.
        • Cherif A.A.
        • Pelletier J.
        Early cognitive impairment in patients with clinically isolated syndrome suggestive of multiple sclerosis.
        Mult. Scler. 2007; 13: 124-127
        • Glanz B.I.
        • Holland C.M.
        • Gauthier S.A.
        • Amunwa E.L.
        • Liptak Z.
        • Houtchens M.K.
        • Sperling R.A.
        • Khoury S.J.
        • Guttmann C.R.
        • Weiner H.L.
        Cognitive dysfunction in patients with clinically isolated syndromes or newly diagnosed multiple sclerosis.
        Mult. Scler. 2007; 13: 1004-1010
        • Freedman M.S.
        • Selchen D.
        • Arnold D.L.
        • Prat A.
        • Banwell B.
        • Yeung M.
        • Morgenthau D.
        • Lapierre Y.
        • G. Canadian Multiple Sclerosis Working
        Treatment optimization in MS: Canadian MS Working Group updated recommendations.
        Can. J. Neurol. Sci. 2013; 40: 307-323
        • Correale J.
        • Abad P.
        • Alvarenga R.
        • Alves-Leon S.
        • Armas E.
        • Barahona J.
        • Buzo R.
        • Corona T.
        • Cristiano E.
        • Gracia F.
        • Bonitto J.G.
        • Macias M.A.
        • Soto A.
        • Vizcarra D.
        • Freedman M.S.
        Management of relapsing-remitting multiple sclerosis in Latin America: practical recommendations for treatment optimization.
        J. Neurol. Sci. 2014; 339: 196-206
        • Trapp B.D.
        • Peterson J.
        • Ransohoff R.M.
        • Rudick R.
        • Mork S.
        • Bo L.
        Axonal transection in the lesions of multiple sclerosis.
        N. Engl. J. Med. 1998; 338: 278-285
        • Filippi M.
        • Rovaris M.
        • Inglese M.
        • Barkhof F.
        • De Stefano N.
        • Smith S.
        • Comi G.
        Interferon beta-1a for brain tissue loss in patients at presentation with syndromes suggestive of multiple sclerosis: a randomised, double-blind, placebo-controlled trial.
        Lancet. 2004; 364: 1489-1496
        • Rojas J.I.
        • Patrucco L.
        • Miguez J.
        • Besada C.
        • Cristiano E.
        Brain atrophy in radiologically isolated syndromes.
        J. Neuroimaging. 2015; 25: 68-71
        • Oberwahrenbrock T.
        • Ringelstein M.
        • Jentschke S.
        • Deuschle K.
        • Klumbies K.
        • Bellmann-Strobl J.
        • Harmel J.
        • Ruprecht K.
        • Schippling S.
        • Hartung H.P.
        • Aktas O.
        • Brandt A.U.
        • Paul F.
        Retinal ganglion cell and inner plexiform layer thinning in clinically isolated syndrome.
        Mult. Scler. 2013; 19: 1887-1895
        • Leocani L.
        • Rocca M.A.
        • Comi G.
        MRI and neurophysiological measures to predict course, disability and treatment response in multiple sclerosis.
        Curr. Opin. Neurol. 2016; 29: 243-253
        • Knier B.
        • Berthele A.
        • Buck D.
        • Schmidt P.
        • Zimmer C.
        • Muhlau M.
        • Hemmer B.
        • Korn T.
        Optical coherence tomography indicates disease activity prior to clinical onset of central nervous system demyelination.
        Mult. Scler. 2016; 22: 893-900
        • Jacobs L.D.
        • Beck R.W.
        • Simon J.H.
        • Kinkel R.P.
        • Brownscheidle C.M.
        • Murray T.J.
        • Simonian N.A.
        • Slasor P.J.
        • Sandrock A.W.
        • CHAMPS Study Group
        Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis.
        N. Engl. J. Med. 2000; 343: 898-904
        • Comi G.
        • Filippi M.
        • Barkhof F.
        • Durelli L.
        • Edan G.
        • Fernandez O.
        • Hartung H.
        • Seeldrayers P.
        • Sorensen P.S.
        • Rovaris M.
        • Martinelli V.
        • Hommes O.R.
        • G. Early Treatment of Multiple Sclerosis Study
        Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study.
        Lancet. 2001; 357: 1576-1582
        • Kappos L.
        • Traboulsee A.
        • Constantinescu C.
        • Eralinna J.P.
        • Forrestal F.
        • Jongen P.
        • Pollard J.
        • Sandberg-Wollheim M.
        • Sindic C.
        • Stubinski B.
        • Uitdehaag B.
        • Li D.
        Long-term subcutaneous interferon beta-1a therapy in patients with relapsing-remitting MS.
        Neurology. 2006; 67: 944-953
        • Comi G.
        • Martinelli V.
        • Rodegher M.
        • Moiola L.
        • Bajenaru O.
        • Carra A.
        • Elovaara I.
        • Fazekas F.
        • Hartung H.P.
        • Hillert J.
        • King J.
        • Komoly S.
        • Lubetzki C.
        • Montalban X.
        • Myhr K.M.
        • Ravnborg M.
        • Rieckmann P.
        • Wynn D.
        • Young C.
        • Filippi M.
        • C.s.g. Pre
        Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial.
        Lancet. 2009; 374: 1503-1511
        • Comi G.
        • Jeffery D.
        • Kappos L.
        • Montalban X.
        • Boyko A.
        • Rocca M.A.
        • Filippi M.
        • A.S. Group
        Placebo-controlled trial of oral laquinimod for multiple sclerosis.
        N. Engl. J. Med. 2012; 366: 1000-1009
        • Miller A.E.
        • Wolinsky J.S.
        • Kappos L.
        • Comi G.
        • Freedman M.S.
        • Olsson T.P.
        • Bauer D.
        • Benamor M.
        • Truffinet P.
        • O’Connor P.W.
        • T.S. Group
        Oral teriflunomide for patients with a first clinical episode suggestive of multiple sclerosis (TOPIC): a randomised, double-blind, placebo-controlled, phase 3 trial.
        Lancet Neurol. 2014; 13: 977-986
        • Freedman M.S.
        • Comi G.
        • De Stefano N.
        • Barkhof F.
        • Polman C.H.
        • Uitdehaag B.M.
        • Lehr L.
        • Stubinski B.
        • Kappos L.
        Moving toward earlier treatment of multiple sclerosis: findings from a decade of clinical trials and implications for clinical practice.
        Mult. Scler Relat. Disord. 2014; 3: 147-155
        • Trojano M.
        • Pellegrini F.
        • Fuiani A.
        • Paolicelli D.
        • Zipoli V.
        • Zimatore G.B.
        • Di Monte E.
        • Portaccio E.
        • Lepore V.
        • Livrea P.
        • Amato M.P.
        New natural history of interferon-beta-treated relapsing multiple sclerosis.
        Ann. Neurol. 2007; 61: 300-306
        • Trojano M.
        • Pellegrini F.
        • Paolicelli D.
        • Fuiani A.
        • Zimatore G.B.
        • Tortorella C.
        • Simone I.L.
        • Patti F.
        • Ghezzi A.
        • Zipoli V.
        • Rossi P.
        • Pozzilli C.
        • Salemi G.
        • Lugaresi A.
        • Bergamaschi R.
        • Millefiorini E.
        • Clerico M.
        • Lus G.
        • Vianello M.
        • Avolio C.
        • Cavalla P.
        • Lepore V.
        • Livrea P.
        • Comi G.
        • Amato M.P.
        • G. Italian Multiple Sclerosis Database Network
        Real-life impact of early interferon beta therapy in relapsing multiple sclerosis.
        Ann. Neurol. 2009; 66: 513-520
        • Comi G.
        Induction vs. escalating therapy in multiple sclerosis: practical implications.
        Neurol. Sci. 2008; 29: S253-S255
        • Freedman M.S.
        • Rush C.A.
        Severe, highly active, or aggressive multiple sclerosis.
        Continuum (Minneap. Minn.). 2016; 22: 761-784
        • Sormani M.P.
        • Gasperini C.
        • Romeo M.
        • Rio J.
        • Calabrese M.
        • Cocco E.
        • Enzingher C.
        • Fazekas F.
        • Filippi M.
        • Gallo A.
        • Kappos L.
        • Marrosu M.G.
        • Martinelli V.
        • Prosperini L.
        • Rocca M.A.
        • Rovira A.
        • Sprenger T.
        • Stromillo M.L.
        • Tedeschi G.
        • Tintore M.
        • Tortorella C.
        • Trojano M.
        • Montalban X.
        • Pozzilli C.
        • Comi G.
        • De Stefano N.
        • M.s. group
        Assessing response to interferon-beta in a multicenter dataset of patients with MS.
        Neurology. 2016; 87: 134-140
        • Rio J.
        • Auger C.
        • Rovira A.
        MR imaging in monitoring and predicting treatment response in multiple sclerosis.
        Neuroimaging Clin. N. Am. 2017; 27: 277-287
        • Cristiano E.
        • Alonso R.
        • Pinheiro A. Alvez
        • Bacile E.A.
        • Balbuena M.E.
        • Ballario C.
        • Barboza A.G.
        • Bestoso S.
        • Burgos M.
        • Caceres F.
        • Contentti E. Carnero
        • Carra A.
        • Crespo E.
        • Curbelo M.C.
        • Deri N.
        • Fernandez J.
        • Liguori N. Fernandez
        • Fiol M.
        • Gaitan M.I.
        • Garcea O.
        • Giunta D.
        • Halfon M.J.
        • Hryb J.P.
        • Jacobo M.
        • Kohler E.
        • Linares R.
        • Luetic G.G.
        • Martinez A.D.
        • Miguez J.
        • Nofal P.G.
        • Patrucco L.
        • Piedrabuena R.
        • Rojas J.I.
        • Escalante R. Rotta
        • Saladino M.L.
        • Silva B.A.
        • Sinay V.
        • Steinberg J.D.
        • Tarulla A.
        • Vetere S.A.
        • Villa A.
        • Vrech C.
        • Ysrraelit M.C.
        • Correale J.
        Corrigendum to "Argentinean recommendations on the identification of treatment failure in relapsing remitting multiple sclerosis patients" [J. Neurol. Sci. 385C (2018) 217-224].
        J. Neurol. Sci. 2018; 387: 231-232
        • Brownlee W.J.
        • Ciccarelli O.
        All relapsing multiple sclerosis patients should be managed at a specialist clinic – YES.
        Mult. Scler. 2016; 22: 873-875
        • Sorensen P.S.
        Balancing the benefits and risks of disease-modifying therapy in patients with multiple sclerosis.
        J. Neurol. Sci. 2011; 311: S29-S34
        • Trojano M.
        • Tintore M.
        • Montalban X.
        • Hillert J.
        • Kalincik T.
        • Iaffaldano P.
        • Spelman T.
        • Sormani M.P.
        • Butzkueven H.
        Treatment decisions in multiple sclerosis – insights from real-world observational studies.
        Nat. Rev. Neurol. 2017; 13: 105-118
        • Correale J.
        Follow-on products for treatment of multiple sclerosis in Latin America: an update.
        J. Neurol. Sci. 2017; 381: 153-159
        • Rivera V.M.
        • Macias M.A.
        Access and barriers to MS care in Latin America.
        Mult. Scler J. Exp. Transl. Clin. 2017; 3 (2055217317700668)
      1. US Food and Drug AdministrationScientific Considerations in Demonstrating Biosimilarity to a Reference Product Guidance for Industry.
        (Available from:)
      2. Guideline on Similar Biological Medicinal Products EMA, London.
        (Available from:)
        • World Health OrganizationExpert Committee on Biological Standarization
        Guidelines on Evaluation of Biosmilar Biotherapeutic Products (SBPs).
        (Available from:)