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Confirmed Disability Progression As a Marker of Permanent Disability in Multiple Sclerosis Publisher Pubmed



Sharmin S1 ; Bovis F2 ; Malpas C1, 3 ; Horakova D4 ; Havrdova E4 ; Izquierdo G5 ; Eichau S5 ; Trojano M6 ; Prat A7, 8 ; Girard M7, 8 ; Duquette P7, 8 ; Onofrj M9 ; Lugaresi A10, 11 ; Grandmaison F12 Show All Authors
Authors
  1. Sharmin S1
  2. Bovis F2
  3. Malpas C1, 3
  4. Horakova D4
  5. Havrdova E4
  6. Izquierdo G5
  7. Eichau S5
  8. Trojano M6
  9. Prat A7, 8
  10. Girard M7, 8
  11. Duquette P7, 8
  12. Onofrj M9
  13. Lugaresi A10, 11
  14. Grandmaison F12
  15. Grammond P13
  16. Sola P14
  17. Ferraro D14
  18. Terzi M15
  19. Gerlach O16
  20. Alroughani R17
  21. Boz C18
  22. Shaygannejad V19
  23. Van Pesch V20, 21
  24. Cartechini E22
  25. Kappos L23
  26. Lechnerscott J24, 25
  27. Bergamaschi R26
  28. Turkoglu R27
  29. Solaro C28
  30. Iuliano G29
  31. Granella F30, 31
  32. Van Wijmeersch B32
  33. Spitaleri D33
  34. Slee M34
  35. Mccombe P35, 36
  36. Prevost J37
  37. Ampapa R38
  38. Ozakbas S39
  39. Sanchezmenoyo J40
  40. Soysal A41
  41. Vucic S42
  42. Petersen T43
  43. De Gans K44
  44. Butler E45
  45. Hodgkinson S46
  46. Sidhom Y47
  47. Gouider R47
  48. Cristiano E48
  49. Castillotrivino T49
  50. Saladino M50
  51. Barnett M51
  52. Moore F52
  53. Rozsa C53
  54. Yamout B54
  55. Skibina O55, 56
  56. Van Der Walt A55, 56
  57. Buzzard K55, 56
  58. Gray O57
  59. Hughes S58
  60. Sempere AP59
  61. Singhal B60
  62. Fragoso Y61
  63. Shaw C62
  64. Kermode A63, 64, 65
  65. Taylor B66
  66. Simo M67
  67. Shuey N68
  68. Alharbi T69
  69. Macdonell R70
  70. Dominguez JA71
  71. Csepany T72
  72. Sirbu C73
  73. Sormani MP2
  74. Butzkueven H55, 56
  75. Kalincik T1, 3
Show Affiliations
Authors Affiliations
  1. 1. CORe, Department of Medicine, University of Melbourne, Melbourne, Australia
  2. 2. Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy
  3. 3. Melbourne MS Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia
  4. 4. Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic
  5. 5. Hospital Universitario Virgen Macarena, Sevilla, Spain
  6. 6. Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy
  7. 7. Hopital Notre Dame, Montreal, QC, Canada
  8. 8. CHUM and Universite de Montreal, Montreal, QC, Canada
  9. 9. Department of Neuroscience, Imaging, and Clinical Sciences, University G. d'Annunzio, Chieti, Italy
  10. 10. IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy
  11. 11. Dipartimento di Scienze Biomediche e Neuromotorie, Universita di Bologna, Bologna, Italy
  12. 12. Neuro Rive-Sud, Greenfield Park, QC, Canada
  13. 13. CISSS Chaudiere-Appalache, Levis, QC, Canada
  14. 14. Department of Neuroscience, Azienda Ospedaliera Universitaria, Modena, Italy
  15. 15. Medical Faculty, 19 Mayis University, Samsun, Turkey
  16. 16. Department of Neurology, Zuyderland Medical Center, Sittard-Geleen, Netherlands
  17. 17. Division of Neurology, Department of Medicine, Amiri Hospital, Sharq, Kuwait
  18. 18. KTU Medical Faculty Farabi Hospital, Trabzon, Turkey
  19. 19. Isfahan University of Medical Sciences, Isfahan, Iran
  20. 20. Cliniques Universitaires Saint-Luc, Brussels, Belgium
  21. 21. Universite Catholique de Louvain, Louvain-la-Neuve, Belgium
  22. 22. UOC Neurologia, Azienda Sanitaria Unica Regionale Marche - AV3, Macerata, Italy
  23. 23. Neurologic Clinic and Policlinic, Departments of Medicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland
  24. 24. School of Medicine and Public Health, University Newcastle, Newcastle, NSW, Australia
  25. 25. Department of Neurology, John Hunter Hospital, Hunter New England Health, Newcastle, NSW, Australia
  26. 26. IRCCS Mondino Foundation, Pavia, Italy
  27. 27. Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey
  28. 28. Department of Rehabilitaiton, ML Novarese Hospital, Moncrivello, Italy
  29. 29. Ospedali Riuniti di Salerno, Salerno, Italy
  30. 30. Department of Medicine and Surgery, University of Parma, Parma, Italy
  31. 31. Department of General Medicine, Parma University Hospital, Parma, Italy
  32. 32. Rehabilitation and MS-Centre Overpelt and Hasselt University, Hasselt, Belgium
  33. 33. Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino, Avellino, Italy
  34. 34. Flinders University, Adelaide, SA, Australia
  35. 35. University of Queensland, Brisbane, QLD, Australia
  36. 36. Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia
  37. 37. CSSS Saint-Jerome, Saint-Jerome, QC, Canada
  38. 38. Nemocnice Jihlava, Jihlava, Czech Republic
  39. 39. Dokuz Eylul University, Konak/Izmir, Turkey
  40. 40. Hospital de Galdakao-Usansolo, Galdakao, Spain
  41. 41. Bakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases, Istanbul, Turkey
  42. 42. Westmead Hospital, Sydney, NSW, Australia
  43. 43. University hospital Aarhus, Aarhus, Denmark
  44. 44. Groene Hart Ziekenhuis, Gouda, Netherlands
  45. 45. Monash Medical Centre, Melbourne, VIC, Australia
  46. 46. Liverpool Hospital, Sydney, NSW, Australia
  47. 47. Department of Neurology, Razi Hospital, Manouba, Tunisia
  48. 48. Hospital Italiano, Buenos Aires, Argentina
  49. 49. Instituto de Investigacion Sanitaria Biodonostia, Department of Neurology, Hospital Universitario Donostia, San Sebastian, Spain
  50. 50. INEBA - Institute of Neuroscience Buenos Aires, Buenos Aires, Argentina
  51. 51. Brain and Mind Centre, Sydney, NSW, Australia
  52. 52. Jewish General Hospital, Montreal, QC, Canada
  53. 53. Jahn Ferenc Teaching Hospital, Budapest, Hungary
  54. 54. Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center, Beirut, Lebanon
  55. 55. Central Clinical School, Monash University, Melbourne, VIC, Australia
  56. 56. Department of Neurology, The Alfred Hospital, Melbourne, VIC, Australia
  57. 57. South East Trust, Belfast, United Kingdom
  58. 58. Craigavon Area Hospital, Craigavon, United Kingdom
  59. 59. Hospital General Universitario de Alicante, Alicante, Spain
  60. 60. Bombay Hospital Institute of Medical Sciences, Mumbai, India
  61. 61. Universidade Metropolitana de Santos, Santos, Brazil
  62. 62. Geelong Hospital, Geelong, VIC, Australia
  63. 63. Perron Institute, University of Western Australia, Nedlands, WA, Australia
  64. 64. Institute of Immunology and Infectious Diseases, Murdoch University, Perth, WA, Australia
  65. 65. Sir Charles Gairdner Hospital, Nedlands, WA, Australia
  66. 66. Royal Hobart Hospital, Hobart, TAS, Australia
  67. 67. Semmelweis University Budapest, Budapest, Hungary
  68. 68. St Vincents Hospital, Fitzroy, Melbourne, VIC, Australia
  69. 69. Neurology Department, King Fahad Specialist Hospital-Dammam, Dammam, Saudi Arabia
  70. 70. Austin Health, Melbourne, VIC, Australia
  71. 71. Hospital Universitario de la Ribera, Alzira, Spain
  72. 72. Department of Neurology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
  73. 73. Central Military Emergency University Hospital, Titu Maiorescu University, Bucharest, Romania

Source: European Journal of Neurology Published:2022


Abstract

Background and purpose: The prevention of disability over the long term is the main treatment goal in multiple sclerosis (MS); however, randomized clinical trials evaluate only short-term treatment effects on disability. This study aimed to define criteria for 6-month confirmed disability progression events of MS with a high probability of resulting in sustained long-term disability worsening. Methods: In total, 14,802 6-month confirmed disability progression events were identified in 8741 patients from the global MSBase registry. For each 6-month confirmed progression event (13,321 in the development and 1481 in the validation cohort), a sustained progression score was calculated based on the demographic and clinical characteristics at the time of progression that were predictive of long-term disability worsening. The score was externally validated in the Cladribine Tablets Treating Multiple Sclerosis Orally (CLARITY) trial. Results: The score was based on age, sex, MS phenotype, relapse activity, disability score and its change from baseline, number of affected functional system domains and worsening in six of the domains. In the internal validation cohort, a 61% lower chance of improvement was estimated with each unit increase in the score (hazard ratio 0.39, 95% confidence interval 0.29–0.52; discriminatory index 0.89). The proportions of progression events sustained at 5 years stratified by the score were 1: 72%; 2: 88%; 3: 94%; 4: 100%. The results of the CLARITY trial were confirmed for reduction of disability progression that was >88% likely to be sustained (events with score ˃1.5). Conclusions: Clinicodemographic characteristics of 6-month confirmed disability progression events identify those at high risk of sustained long-term disability. This knowledge will allow future trials to better assess the effect of therapy on long-term disability accrual. © 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.
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