Optimizing treatment success in multiple sclerosis

Journal of Neurology

Volumn 263, Issue 6, 2016, Pages 1053-1065

  Ziemssen, Tjalf ^a   Derfuss, Tobias ^a   de Stefano, Nicola ^b   Giovannoni, Gavin ^c   Palavra, Filipe ^d   Tomic, Davorka ^e   Vollmer, Tim ^f   Schippling, Sven ^g  

^a UNIVERSITY HOSPITAL CARL GUSTAV CARUS   (Germany)

^b UNIVERSITY OF SIENA   (Italy)

^c QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

^d HOSPITAL UNIVERSITARI VALL D HEBRON   (Spain)

^e NOVARTIS PHARMA AG   (Switzerland)

^f UNIVERSITY OF COLORADO   (United States)

^g UNIVERSITY HOSPITAL ZURICH   (Switzerland)

Author keywords

Brain atrophy; Disability evaluation; Drug therapy; Multiple sclerosis

Indexed keywords

FINGOLIMOD; GADOLINIUM; PLACEBO;

BRAIN ATROPHY; BRAIN SIZE; DISABILITY; DISEASE ACTIVITY; DISEASE COURSE; EARLY DIAGNOSIS; EARLY INTERVENTION; HUMAN; MULTIPLE SCLEROSIS; NUCLEAR MAGNETIC RESONANCE IMAGING; OUTCOME ASSESSMENT; PATIENT MONITORING; PRIORITY JOURNAL; RELAPSE; REVIEW; SPAIN; TREATMENT INDICATION; TREATMENT OUTCOME;

HUMANS; MULTIPLE SCLEROSIS;

EID: 84951864477     PISSN: 03405354     EISSN: 14321459     Source Type: Journal    
DOI: 10.1007/s00415-015-7986-y     Document Type: Review

References (120)

1. Ziemssen T (2009) Multiple sclerosis beyond EDSS: depression and fatigue. J Neurol Sci 277(Suppl 1):S37–S41
2. Rao SM, Leo GJ, Bernardin L, Unverzagt F (2009) Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction. Neurology 41:685–691
3. Rao SM, Leo GJ, Ellington L, Nauertz T, Bernardin L, Unverzagt F (1991) Cognitive dysfunction in multiple sclerosis. II. Impact on employment and social functioning. Neurology 41:692–696
4. Potagas C, Giogkaraki E, Koutsis G, Mandellos D, Tsirempolou E, Sfagos C, Vassilopoulos D (2008) Cognitive impairment in different MS subtypes and clinically isolated syndromes. J Neurol Sci 267:100–106
5. Feuillet L, Reuter F, Audoin B, Malikova I, Barrau K, Cherif AA, Pelletier J (2007) Early cognitive impairment in patients with clinically isolated syndrome suggestive of multiple sclerosis. Mult Scler 13:124–127
6. Pfleger CC, Flachs EM, Koch-Henriksen N (2010) Social consequences of multiple sclerosis (1): early pension and temporary unemployment—a historical prospective cohort study. Mult Scler 16:121–126
7. Kobelt G, Berg J, Lindgren P, Fredrikson S, Jönsson B (2006) Costs and quality of life of patients with multiple sclerosis in Europe. J Neurol Neurosurg Psychiatry 77:918–926
8. Orme M, Kerrigan J, Tyas D, Russell N, Nixon R (2007) The effect of disease, functional status, and relapses on the utility of people with multiple sclerosis in the UK. Value Health 10:54–60
9. Zwibel HL, Smrtka J (2011) Improving quality of life in multiple sclerosis: an unmet need. Am J Manag Care 17(Suppl 5):S139–S145
10. Aronson KJ (1997) Quality of life among persons with multiple sclerosis and their caregivers. Neurology 48:74–80
11. Gustavsson A, Svensson M, Jacobi F et al (2011) Cost of disorders of the brain in Europe 2010. Eur Neuropsychopharmacol 21:718–779
12. Kobelt G, Berg J, Atherly D, Hadjimichael O (2006) Costs and quality of life in multiple sclerosis: a cross-sectional study in the United States. Neurology 66:1696–1702
13. Sadovnick AD, Ebers GC, Wilson RW, Paty DW (1992) Life expectancy in patients attending multiple sclerosis clinics. Neurology 42:991–994
14. Ebers GC (2001) Natural history of multiple sclerosis. J Neurol Neurosurg Psychiatry 71(Suppl 2):ii16–ii19
15. Kingwell E, van der Kop M, Zhao Y, Shirani A, Zhu F, Oger J, Tremlett H (2012) Relative mortality and survival in multiple sclerosis: findings from British Columbia, Canada. J Neurol Neurosurg Psychiatry 83:61–66
16. Torkildsen NG, Lie SA, Aarseth JH, Nyland H, Myhr KM (2008) Survival and cause of death in multiple sclerosis: results from a 50-year follow-up in Western Norway. Mult Scler 14:1191–1198
17. Sadovnick AD, Eisen K, Ebers GC, Paty DW (1991) Cause of death in patients attending multiple sclerosis clinics. Neurology 41:1193–1196
18. Koch-Henriksen N, Brønnum-Hansen H, Stenager E (1998) Underlying cause of death in Danish patients with multiple sclerosis: results from the Danish Multiple Sclerosis Registry. J Neurol Neurosurg Psychiatry 65:56–59
19. Goodin DS, Reder AT, Ebers GC, Cutter G, Kremenchutzky M, Oger J, Langdon D, Rametta M, Beckmann K, DeSimone TM, Knappertz V (2012) Survival in MS: a randomized cohort study 21 years after the start of the pivotal IFNβ-1b trial. Neurology 78:1315–1322
20. Río J, Comabella M, Montalban X (2011) Multiple sclerosis: current treatment algorithms. Curr Opin Neurol 24:230–237
21. Ziemssen T, de Stefano N, Sormani MP, Van Wijmeersch B, Wiendl H, Kieseier BC (2015) Optimizing therapy early in multiple sclerosis—an evidence-based view. Mult Scler Relat Disord 4:460–469
22. Tintoré M (2007) Early MS treatment. Int MS J 14:5–10
23. Trapp BD, Bö L, Mörk S, Chang A (1999) Pathogenesis of tissue injury in MS lesions. J Neuroimmunol 98:49–56
24. Trapp BD, Nave KA (2008) Multiple sclerosis: an immune or neurodegenerative disorder? Annu Rev Neurosci 31:247–269
25. Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mörk S, Bö L (1998) Axonal transection in the lesions of multiple sclerosis. N Engl J Med 338:278–285
26. Hauser SL, Oksenberg JR (2006) The neurobiology of multiple sclerosis: genes, inflammation, and neurodegeneration. Neuron 52:61–76
27. Kuhlmann T, Lingfeld G, Bitsch A, Schuchardt J, Brück W (2002) Acute axonal damage in multiple sclerosis is most extensive in early disease stages and decreases over time. Brain 125:2202–2212
28. Ziemssen T (2004) Neuroprotection and glatiramer acetate: the possible role in the treatment of multiple sclerosis. Adv Exp Med Biol 541:111–134
29. Filippi M, Rocca MA (2007) Conventional MRI in multiple sclerosis. J Neuroimaging 17(Suppl 1):3S–9S
30. Rocca MA, Mezzapesa DM, Falini A, Ghezzi A, Martinelli V, Scotti G, Comi G, Filippi M (2003) Evidence for axonal pathology and adaptive cortical reorganization in patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis. Neuroimage 18:847–855
31. Rovira A, Auger C, Alonso J (2013) Magnetic resonance monitoring of lesion evolution in multiple sclerosis. Ther Adv Neurol Disord 6:298–310
32. Scalfari A, Neuhaus A, Degenhardt A, Rice GP, Muraro PA, Daumer M, Ebers GC (2010) The natural history of multiple sclerosis: a geographically based study 10: relapses and long-term disability. Brain 133:1914–1929
33. Leray E, Yaouanq J, Le Page E, Coustans M, Laplaud D, Oger J, Edan G (2010) Evidence for a two-stage disability progression in multiple sclerosis. Brain 133:1900–1913
34. Zivadinov R, Stosic M, Cox JL, Ramasamy DP, Dwyer MG (2008) The place of conventional MRI and newly emerging MRI techniques in monitoring different aspects of treatment outcome. J Neurol 255(Suppl 1):61–74
35. Barkhof F, Calabresi PA, Miller DH, Reingold SC (2009) Imaging outcomes for neuroprotection and repair in multiple sclerosis trials. Nat Rev Neurol 5:256–266
36. Zivadinov R, Reder AT, Filippi M et al (2008) Mechanisms of action of disease-modifying agents and brain volume changes in multiple sclerosis. Neurology 71:136–144
37. Radue EW, Bendfeldt K, Mueller-Lenke N, Magon S, Sprenger T (2013) Brain atrophy: an in vivo measure of disease activity in multiple sclerosis. Swiss Med Wkly 143:w13887
38. De Stefano N, Giorgio A, Battaglini M et al (2010) Assessing brain atrophy rates in a large population of untreated multiple sclerosis subtypes. Neurology 74:1868–1876
39. Simon JH (2006) Brain atrophy in multiple sclerosis: what we know and would like to know. Mult Scler 12:679–687
40. Minneboo A, Jasperse B, Barkhof F, Uitdehaag BM, Knol DL, de Groot V, Polman CH, Castelijns JA (2008) Predicting short-term disability progression in early multiple sclerosis: added value of MRI parameters. J Neurol Neurosurg Psychiatry 79:917–923
41. Fisher E, Rudick RA, Simon JH, Cutter G, Baier M, Lee JC, Miller D, Weinstock-Guttman B, Mass MK, Dougherty DS, Simonian NA (2002) Eight-year follow-up study of brain atrophy in patients with MS. Neurology 59:1412–1420
42. Bermel RA, Bakshi R (2006) The measurement and clinical relevance of brain atrophy in multiple sclerosis. Lancet Neurol 5:158–170
43. Tedeschi G, Lavorgna L, Russo P et al (2005) Brain atrophy and lesion load in a large population of patients with multiple sclerosis. Neurology 65:280–285
44. Fisniku LK, Chard DT, Jackson JS, Anderson VM, Altmann DR, Miszkiel KA, Thompson AJ, Miller DH (2008) Gray matter atrophy is related to long-term disability in multiple sclerosis. Ann Neurol 64:247–254
45. Fischer MT, Wimmer I, Höftberger R et al (2013) Disease-specific molecular events in cortical multiple sclerosis lesions. Brain 136:1799–1815
46. Popescu V, Agosta F, Hulst HE et al (2013) Brain atrophy and lesion load predict long term disability in multiple sclerosis. J Neurol Neurosurg Psychiatry 84:1082–1091
47. Sormani MP, Arnold DL, De Stefano N (2014) Treatment effect on brain atrophy correlates with treatment effect on disability in multiple sclerosis. Ann Neurol 75:43–49
48. Vidal-Jordana A, Sastre-Garriga J, Rovira A, Montalban X (2015) Treating relapsing–remitting multiple sclerosis: therapy effects on brain atrophy. J Neurol 262(12):2617–26
49. Rudick RA, Fisher E, Lee JC, Duda JT, Simon J (2000) Brain atrophy in relapsing multiple sclerosis: relationship to relapses, EDSS, and treatment with interferon beta-1a. Mult Scler 6:365–372
50. Hardmeier M, Wagenpfeil S, Freitag P et al (2005) Rate of brain atrophy in relapsing MS decreases during treatment with IFNbeta-1a. Neurology 64:236–240
51. Kappos L, Traboulsee A, Constantinescu C et al (2006) Long-term subcutaneous interferon beta-1a therapy in patients with relapsing–remitting MS. Neurology 67:944–953
52. Ge Y, Grossman RI, Udupa JK et al (2000) Glatiramer acetate (Copaxone) treatment in relapsing–remitting MS: quantitative MR assessment. Neurology 54:813–817
53. Rovaris M, Comi G, Rocca MA et al (2001) Short-term brain volume change in relapsing–remitting multiple sclerosis: effect of glatiramer acetate and implications. Brain 124:1803–1812
54. Sormani MP, Rovaris M, Valsasina P, Wolinsky JS, Comi G, Filippi M (2004) Measurement error of two different techniques for brain atrophy assessment in multiple sclerosis. Neurology 62:1432–1434
55. Rovaris M, Comi G, Rocca MA et al (2007) Long-term follow-up of patients treated with glatiramer acetate: a multicentre, multinational extension of the European/Canadian double-blind, placebo-controlled, MRI-monitored trial. Mult Scler 13:502–508
56. Kappos L, Radue EW, O’Connor P et al (2010) A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med 362:387–401
57. Cohen JA, Barkhof F, Comi G et al (2010) Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 362:402–415
58. Calabresi PA, Radue EW, Goodin D et al (2014) Safety and efficacy of fingolimod in patients with relapsing–remitting multiple sclerosis (FREEDOMS II): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Neurol 13:545–556
59. Arnold DL, Gold R, Kappos L et al (2014) Effects of delayed-release dimethyl fumarate on MRI measures in the Phase 3 DEFINE study. J Neurol 261:1794–1802
60. Miller DH, Fox RJ, Phillips JT et al (2015) Effects of delayed-release dimethyl fumarate on MRI measures in the phase 3 CONFIRM study. Neurology 84:1145–1152
61. Miller DH, Soon D, Fernando KT et al (2007) MRI outcomes in a placebo-controlled trial of natalizumab in relapsing MS. Neurology 68:1390–1401
62. Radue EW, Stuart WH, Calabresi PA (2010) Natalizumab plus interferon beta-1a reduces lesion formation in relapsing multiple sclerosis. J Neurol Sci 292:28–35
63. O’Connor P, Wolinsky JS, Confavreux C et al (2011) Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med 365:1293–1303
64. Comi G, Jeffery D, Kappos L et al (2012) Placebo-controlled trial of oral laquinimod for multiple sclerosis. N Engl J Med 366:1000–1009
65. Vollmer TL, Sorensen PS, Selmaj K et al (2014) A randomized placebo-controlled phase III trial of oral laquinimod for multiple sclerosis. J Neurol 261:773–783
66. Mikol DD, Barkhof F, Chang P et al (2008) Comparison of subcutaneous interferon beta-1a with glatiramer acetate in patients with relapsing multiple sclerosis (the REbif vs Glatiramer Acetate in Relapsing MS Disease [REGARD] study): a multicentre, randomised, parallel, open-label trial. Lancet Neurol 7:903–914
67. O’Connor P, Filippi M, Arnason B et al (2009) 250 microg or 500 microg interferon beta-1b versus 20 mg glatiramer acetate in relapsing–remitting multiple sclerosis: a prospective, randomised, multicentre study. Lancet Neurol 8:889–897
68. Lublin FD, Cofield SS, Cutter GR et al (2013) Randomized study combining interferon and glatiramer acetate in multiple sclerosis. Ann Neurol 73:327–340
69. Cohen JA, Coles AJ, Arnold DL et al (2012) Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing–remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet 380:1819–1828
70. Coles AJ, Twyman CL, Arnold DL et al (2012) Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet 380:1829–1839
71. Rudick RA, Fisher E, Lee JC, Simon J, Jacobs L (1999) Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing–remitting MS. Multiple Sclerosis Collaborative Research Group. Neurology 53:1698–1704
72. Filippi M, Rovaris M, Inglese M, Barkhof F, De Stefano N, Smith S, Comi G (2004) 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 364:1489–1496
73. Kappos L, Freedman MS, Polman CH et al (2009) Long-term effect of early treatment with interferon beta-1b after a first clinical event suggestive of multiple sclerosis: 5-year active treatment extension of the phase 3 BENEFIT trial. Lancet Neurol 8:987–997
74. Molyneux PD, Kappos L, Polman C, Pozzilli C, Barkhof F, Filippi M, Yousry T, Hahn D, Wagner K, Ghazi M, Beckmann K, Dahlke F, Losseff N, Barker GJ, Thompson AJ, Miller DH (2000) The effect of interferon beta-1b treatment on MRI measures of cerebral atrophy in secondary progressive multiple sclerosis. European Study Group on Interferon beta-1b in secondary progressive multiple sclerosis. Brain 123:2256–2263
75. Comi G, Martinelli V, Rodegher M et al (2013) Effects of early treatment with glatiramer acetate in patients with clinically isolated syndrome. Mult Scler 19:1074–1083
76. Vidal-Jordana A, Sastre-Garriga J, Pérez-Miralles F et al (2013) Early brain pseudoatrophy while on natalizumab therapy is due to white matter volume changes. Mult Scler 19:1175–1181
77. Barkhof F, Hulst HE, Drulovic J, Uitdehaag BM, Matsuda K, Landin R, MN166-001 Investigators (2010) Ibudilast in relapsing–remitting multiple sclerosis: a neuroprotectant? Neurology 74:1033–1040
78. De Stefano N, Airas L, Grigoriadis N et al (2014) Clinical relevance of brain volume measures in multiple sclerosis. CNS Drugs 28:147–156
79. Barkhof F, Simon JH, Fazekas F et al (2011) MRI monitoring of immunomodulation in relapse-onset multiple sclerosis trials. Nat Rev Neurol 8:13–21
80. Zivadinov R, Havrdová E, Bergsland N et al (2013) Thalamic atrophy is associated with development of clinically definite multiple sclerosis. Radiology 268:831–841
81. Yaldizli Ö, Penner IK, Frontzek K (2014) The relationship between total and regional corpus callosum atrophy, cognitive impairment and fatigue in multiple sclerosis patients. Mult Scler 20:356–364
82. Carrá A, Onaha P, Luetic G et al (2008) Therapeutic outcome 3 years after switching of immunomodulatory therapies in patients with relapsing–remitting multiple sclerosis in Argentina. Eur J Neurol 15:386–393
83. Cohen JA, Reingold SC, Polman CH, Wolinsky JS, International Advisory Committee on Clinical Trials in Multiple Sclerosis (2012) Disability outcome measures in multiple sclerosis clinical trials: current status and future prospects. Lancet Neurol 11:467–476
84. Schäffler N, Schönberg P, Stephan J, Stellmann JP, Gold SM, Heesen C (2013) Comparison of patient-reported outcome measures in multiple sclerosis. Acta Neurol Scand 128:114–121
85. Multiple Sclerosis Therapy Consensus Group (MSTCG), Wiendl H, Toyka KV, Rieckmann P, Gold R, Hartung HP, Hohlfeld R (2008) Basic and escalating immunomodulatory treatments in multiple sclerosis: current therapeutic recommendations. J Neurol 255:1449–1463
86. ®))—2011. Neurologia 27:432–441
87. Kieseier BC, Stüve O (2011) A critical appraisal of treatment decisions in multiple sclerosis—old versus new. Nat Rev Neurol 7:255–262
88. Giovannoni G, Turner B, Gnanapavan S, Offiah C, Schmierer K, Marta M (2015) Is it time to target no evident disease activity (NEDA) in multiple sclerosis? Mult Scler Relat Disord 4:329–333
89. Rotstein DL, Healy BC, Malik MT, Chitnis T, Weiner HL (2015) Evaluation of no evidence of disease activity in a 7-year longitudinal multiple sclerosis cohort. JAMA Neurol 72:152–158
90. Stangel M, Penner IK, Kallmann BA, Lukas C, Kieseier BC (2015) Towards the implementation of ‘no evidence of disease activity’ in multiple sclerosis treatment: the multiple sclerosis decision model. Ther Adv Neurol Disord 8:3–13
91. Pérez-Miralles FC, Sastre-Garriga J, Vidal-Jordana A et al (2015) Predictive value of early brain atrophy on response in patients treated with interferon β. Neurol Neuroimmunol Neuroinflamm 2(4):e132
92. Kappos L, De Stefano N, Freedman MS et al (2015) Inclusion of brain volume loss in a revised measure of ‘no evidence of disease activity’ (NEDA-4) in relapsing–remitting multiple sclerosis. Mult Scler J (in press)
93. Arnold DL, Li D, Hohel M et al (2015) Evolving role of MRI in optimizing the treatment of multiple sclerosis: Canadian Consensus recommendations. Mult Scler J 1:1–9
94. Kappos L, Freedman MS, Polman CH et al (2007) Effect of early versus delayed interferon beta-1b treatment on disability after a first clinical event suggestive of multiple sclerosis: a 3-year follow-up analysis of the BENEFIT study. Lancet 370:389–397
95. Jacobs LD, Beck RW, Simon JH, Kinkel RP, Brownscheidle CM, Murray TJ, Simonian NA, Slasor PJ, Sandrock AW (2000) Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group. N Engl J Med 343:898–904
96. Kinkel RP, Kollman C, O’Connor P et al IM interferon beta-1a delays definite multiple sclerosis 5 years after a first demyelinating event. Neurology 66(5):678-684
97. Kinkel RP, Dontchev M, Kollman C, Skaramagas TT, O’Connor PW, Simon JH, Controlled High-Risk Avonex Multiple Sclerosis Prevention Study in Ongoing Neurological Surveillance Investigators (2012) Association between immediate initiation of intramuscular interferon beta-1a at the time of a clinically isolated syndrome and long-term outcomes: a 10-year follow-up of the Controlled High-Risk Avonex Multiple Sclerosis Prevention Study in Ongoing Neurological Surveillance. Arch Neurol 69:183–190
98. Comi G, De Stefano N, Freedman MS et al (2012) Comparison of two dosing frequencies of subcutaneous interferon beta-1a in patients with a first clinical demyelinating event suggestive of multiple sclerosis (REFLEX): a phase 3 randomised controlled trial. Lancet Neurol 11:33–41
99. De Stefano N, Comi G, Kappos L et al (2013) Efficacy of subcutaneous interferon β-1a on MRI outcomes in a randomised controlled trial of patients with clinically isolated syndromes. J Neurol Neurosurg Psychiatry 85:647–653
100. Comi G, Martinelli V, Rodegher M et al (2009) 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 374:1503–1511
101. Miller AE, Wolinsky JS, Kappos L, Comi G, Freedman MS, Olsson TP, Bauer D, Benamor M, Truffinet P, O’Connor PW, TOPIC Study Group (2014) 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 13:977–986
102. Coles AJ, Cox A, Le Page E, Jones J, Trip SA, Deans J, Seaman S, Miller DH, Hale G, Waldmann H, Compston DA (2006) The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy. J Neurol 253:98–108
103. Kappos L, O’Connor P, Radue EW, Polman C, Hohlfeld R, Selmaj K, Ritter S, Schlosshauer R, von Rosenstiel P, Zhang-Auberson L, Francis G (2015) Long-term effects of fingolimod in multiple sclerosis: the randomized FREEDOMS extension trial. Neurology 84:1582–1591
104. Bermel RA, You X, Foulds P, Hyde R, Simon JH, Fisher E, Rudick RA (2013) Predictors of long-term outcome in multiple sclerosis patients treated with interferon β. Ann Neurol 73:95–103
105. Río J, Castilló J, Rovira A et al (2009) Measures in the first year of therapy predict the response to interferon beta in MS. Mult Scler 15:848–853
106. Río J, Rovira A, Tintoré M, Huerga E, Nos C, Tellez N, Tur C, Comabella M, Montalban X (2008) Relationship between MRI lesion activity and response to IFN-beta in relapsing–remitting multiple sclerosis patients. Mult Scler 14:479–484
107. Prosperini L, Mancinelli CR, De Giglio L, De Angelis F, Barletta V, Pozzilli C (2014) Interferon beta failure predicted by EMA criteria or isolated MRI activity in multiple sclerosis. Mult Scler 20:566–576
108. Sormani MP, De Stefano N (2013) Defining and scoring response to IFN-β in multiple sclerosis. Nat Rev Neurol 9:504–512
109. Sormani MP, Rio J, Tintorè M, Signori A, Li D, Cornelisse P, Stubinski B, Stromillo M, Montalban X, De Stefano N (2013) Scoring treatment response in patients with relapsing multiple sclerosis. Mult Scler 19:605–612
110. Sormani M, Signori A, Stromillo M, De Stefano N (2013) Refining response to treatment as defined by the Modified Rio Score. Mult Scler 19:1246–1247
111. Goodin DS, Traboulsee A, Knappertz V, Reder AT, Li D, Langdon D, Wolf C, Beckmann K, Konieczny A, Ebers GC, 16-Year Long Term Follow-up Study Investigators (2012) Relationship between early clinical characteristics and long term disability outcomes: 16 year cohort study (follow-up) of the pivotal interferon β-1b trial in multiple sclerosis. J Neurol Neurosurg Psychiatry 83:282–287
112. Caon C (2009) Maximising therapeutic outcomes in patients failing on current therapy. J Neurol Sci 277(Suppl 1):S33–S36
113. Castillo-Trivino T, Mowry EM, Gajofatto A et al (2011) Switching multiple sclerosis patients with breakthrough disease to second-line therapy. PLoS One 6:e16664
114. Gajofatto A, Bacchetti P, Grimes B, High A, Waubant E (2009) Switching first-line disease-modifying therapy after failure: impact on the course of relapsing–remitting multiple sclerosis. Mult Scler 15:50–58
115. Limmroth V, Malessa R, Zettl UK et al (2007) Quality Assessment in Multiple Sclerosis Therapy (QUASIMS): a comparison of interferon beta therapies for relapsing–remitting multiple sclerosis. J Neurol 254:67–77
116. Prosperini L, Borriello G, De Giglio L, Leonardi L, Barletta V, Pozzilli C (2011) Management of breakthrough disease in patients with multiple sclerosis: when an increasing of Interferon beta dose should be effective? BMC Neurol 11:26
117. Coles AJ, Twyman CL, Arnold DL et al (2012) Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet 380:1829–1839
118. Khatri B, Barkhof F, Comi G et al (2011) Comparison of fingolimod with interferon beta-1a in relapsing–remitting multiple sclerosis: a randomised extension of the TRANSFORMS study. Lancet Neurol 10:520–529
119. Ziemssen T, Kern R, Cornelissen C (2015) The PANGAEA study design—a prospective, multicenter, non-interventional, long-term study on fingolimod for the treatment of multiple sclerosis in daily practice. BMC Neurol 15:93
120. Ziemssen T, Kempcke R, Eulitz M, Großmann L, Suhrbier A, Thomas K, Schultheiss T (2013) Multiple sclerosis documentation system (MSDS): moving from documentation to management of MS patients. J Neural Transm 120(Suppl 1):61–66