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Early Non-Disabling Relapses Are Important Predictors of Disability Accumulation in People With Relapsing-Remitting Multiple Sclerosis Publisher Pubmed



Daruwalla C1 ; Shaygannejad V2 ; Ozakbas S3 ; Havrdova EK4 ; Horakova D4 ; Alroughani R5 ; Boz C6 ; Patti F7, 80 ; Onofrj M8 ; Lugaresi A9, 99 ; Eichau S10 ; Girard M11 ; Prat A11 ; Duquette P11 Show All Authors
Authors
  1. Daruwalla C1
  2. Shaygannejad V2
  3. Ozakbas S3
  4. Havrdova EK4
  5. Horakova D4
  6. Alroughani R5
  7. Boz C6
  8. Patti F7, 80
  9. Onofrj M8
  10. Lugaresi A9, 99
  11. Eichau S10
  12. Girard M11
  13. Prat A11
  14. Duquette P11
  15. Yamout B12
  16. Khoury SJ12
  17. Sajedi SA13
  18. Turkoglu R14
  19. Altintas A15
  20. Skibina O16, 19, 87
  21. Buzzard K16, 19, 92
  22. Grammond P17
  23. Karabudak R18
  24. Van Der Walt A19, 87
  25. Butzkueven H19
  26. Maimone D20
  27. Lechnerscott J21, 86
  28. Soysal A22
  29. John N23, 91
  30. Prevost J24
  31. Spitaleri D25
  32. Ramotello C26
  33. Gerlach O27, 95
  34. Iuliano G28
  35. Foschi M29
  36. Ampapa R30
  37. Van Pesch V31, 90
  38. Barnett M32
  39. Shalaby N33
  40. Dhooghe M34
  41. Kuhle J35
  42. Sa MJ36, 84
  43. Fabispedrini M37, 89
  44. Kermode A37, 96, 97
  45. Mrabet S38, 94
  46. Gouider R38
  47. Hodgkinson S39
  48. Laureys G40
  49. Van Hijfte L40
  50. Macdonell R41
  51. Orejaguevara C42
  52. Cristiano E43
  53. Mccombe P44, 85
  54. Sanchezmenoyo JL45
  55. Singhal B46
  56. Blanco Y47
  57. Hughes S48
  58. Garber J49
  59. Solaro C50, 88
  60. Mcguigan C51
  61. Taylor B52
  62. De Gans K53
  63. Habek M54, 98
  64. Alasmi A55
  65. Mihaela S56
  66. Castillo Trivino T57
  67. Alharbi T58
  68. Rojas JI59
  69. Gray O60
  70. Khurana D61
  71. Van Wijmeersch B62, 93
  72. Grigoriadis N63
  73. Inshasi J64
  74. Oh J65
  75. Agueramorales E66
  76. Fragoso Y67
  77. Moore F68
  78. Shaw C69
  79. Baghbanian SM70
  80. Shuey N71
  81. Willekens B72, 79
  82. Hardy TA73
  83. Decoo D74
  84. Sempere AP75
  85. Field D76
  86. Wynfordthomas R77, 83
  87. Cunniffe NG1
  88. Roos I78, 81
  89. Malpas CB78, 81, 82
  90. Coles AJ1
  91. Kalincik T78, 81
  92. Brown JWL1
Show Affiliations
Authors Affiliations
  1. 1. Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
  2. 2. Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Dokuz Eylul University, Izmir, Turkey
  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. Division of Neurology, Department of Medicine, Amiri Hospital, Sharq, Kuwait
  6. 6. KTU Medical Faculty Farabi Hospital, Trabzon, Turkey
  7. 7. Department of Medical and Surgical Sciences and Advanced Technologies, GF Ingrassia, Catania, Italy
  8. 8. Department of Neuroscience, Imaging and Clinical Sciences, University G. D’Annunzio, Chieti, Italy
  9. 9. Dipartimento di Scienze Biomediche e Neuromotorie, Universita di Bologna, Bologna, Italy
  10. 10. Hospital Universitario Virgen Macarena, Sevilla, Spain
  11. 11. CHUM and Universite de Montreal, Montreal, QC, Canada
  12. 12. Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center, Beirut, Lebanon
  13. 13. Department of Neurology, Neuroscience Research Center, Golestan University of Medical Sciences, Gorgan, Iran
  14. 14. Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey
  15. 15. Department of Neurology, School of Medicine, Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey
  16. 16. Department of Neurology, Box Hill Hospital, Melbourne, VIC, Australia
  17. 17. CISSS Chaudiere-Appalache, Levis, QC, Canada
  18. 18. Hacettepe University, Ankara, Turkey
  19. 19. Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia
  20. 20. Centro Sclerosi Multipla, UOC Neurologia, ARNAS Garibaldi, Catania, Italy
  21. 21. School of Medicine and Public Health, University Newcastle, Newcastle, NSW, Australia
  22. 22. Bakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases, Istanbul, Turkey
  23. 23. Monash Medical Centre, Melbourne, VIC, Australia
  24. 24. CSSS Saint-Jerome, Saint-Jerome, QC, Canada
  25. 25. Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino, Avellino, Italy
  26. 26. Hospital Germans Trias i Pujol, Badalona, Spain
  27. 27. Academic MS Center Zuyderland, Department of Neurology, Zuyderland Medical Center, Sittard-Geleen, Netherlands
  28. 28. Ospedali Riuniti di Salerno, Salerno, Italy
  29. 29. Department of Neuroscience, Neurology Unit, S. Maria delle Croci Hospital of Ravenna, AUSL Romagna, Ravenna, Italy
  30. 30. Nemocnice Jihlava, Jihlava, Czech Republic
  31. 31. Cliniques Universitaires Saint-Luc, Brussels, Belgium
  32. 32. Brain and Mind Centre, Sydney, NSW, Australia
  33. 33. Kasr Al Ainy MS Research Unit (KAMSU), Cairo, Egypt
  34. 34. Department of Neurology, National MS Center, Melsbroek, Belgium
  35. 35. MS Center, Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Departments of Head, Spine and Neuromedicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland
  36. 36. Department of Neurology, Centro Hospitalar Universitario de Sao Joao, Porto, Portugal
  37. 37. Perron Institute for Neurological and Translational Science, University of Western Australia, Nedlands, WA, Australia
  38. 38. Department of Neurology, University Hospital Razi – Manouba, Tunis, Tunisia
  39. 39. Immune Tolerance Laboratory, Ingham Institute, Department of Medicine, University of New South Wales (UNSW), Sydney, NSW, Australia
  40. 40. Department of Neurology, University Hospital Ghent, Ghent, Belgium
  41. 41. Austin Health, Melbourne, VIC, Australia
  42. 42. Department of Neurology, Hospital Clinico San Carlos, Madrid, Spain
  43. 43. Centro de Esclerosis Multiple de Buenos Aires (CEMBA), Buenos Aires, Argentina
  44. 44. The University of Queensland, Brisbane, QLD, Australia
  45. 45. Hospital de Galdakao-Usansolo, Galdakao, Spain
  46. 46. Bombay Hospital Institute of Medical Sciences, Mumbai, India
  47. 47. Center of Neuroimmunology, Service of Neurology, Hospital Clinic de Barcelona, Barcelona, Spain
  48. 48. Royal Victoria Hospital, Belfast, United Kingdom
  49. 49. Westmead Hospital, Sydney, NSW, Australia
  50. 50. Department of Neurology, ASL3 Genovese, Genova, Italy
  51. 51. St. Vincent’s University Hospital, Dublin, Ireland
  52. 52. Royal Hobart Hospital, Hobart, TAS, Australia
  53. 53. Groene Hart Ziekenhuis, Gouda, Netherlands
  54. 54. Department of Neurology, University Hospital Center Zagreb, Zagreb, Croatia
  55. 55. College of Medicine & Health Sciences and Sultan Qaboos University Hospital, Sultan Qaboos University, Seeb, Oman
  56. 56. Department of Neurology, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania
  57. 57. Hospital Universitario Donostia and IIS Biodonostia, San Sebastian, Spain
  58. 58. Neurology Department, King Fahad Specialist Hospital-Dammam, Khobar, Saudi Arabia
  59. 59. Hospital Universitario de CEMIC, Buenos Aires, Argentina
  60. 60. South Eastern HSC Trust, Belfast, United Kingdom
  61. 61. Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
  62. 62. University MS Centre, Pelt, Hasselt, Belgium
  63. 63. AHEPA University Hospital, Thessaloniki, Greece
  64. 64. Rashid Hospital, Dubai, United Arab Emirates
  65. 65. St. Michael’s Hospital, Toronto, ON, Canada
  66. 66. University Hospital Reina Sofia, Cordoba, Spain
  67. 67. Universidade Metropolitana de Santos, Santos, Brazil
  68. 68. Jewish General Hospital, Montreal, QC, Canada
  69. 69. Geelong Hospital, Geelong, VIC, Australia
  70. 70. Booali Sina Hospital, Neurology Department, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
  71. 71. St. Vincent’s Hospital, Fitzroy, Melbourne, VIC, Australia
  72. 72. Department of Neurology, Antwerp University Hospital, Edegem, Belgium
  73. 73. Concord Repatriation General Hospital, Sydney, NSW, Australia
  74. 74. AZ Alma Ziekenhuis, Damme, Belgium
  75. 75. Hospital General Universitario de Alicante, Alicante, Spain
  76. 76. Lyell McEwin Hospital, Elizabeth Vale, SA, Australia
  77. 77. Division of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff, United Kingdom
  78. 78. MS Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia
  79. 79. Translational Neurosciences Research Group, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
  80. 80. Multiple Sclerosis Center, University of Catania, Catania, Italy
  81. 81. CORe, Department of Medicine, University of Melbourne, Melbourne, VIC, Australia
  82. 82. Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, VIC, Australia
  83. 83. Helen Durham Centre for Neuroinflammation, University Hospital of Wales, Cardiff, United Kingdom
  84. 84. Faculty of Health Sciences, University Fernando Pessoa, Porto, Portugal
  85. 85. Royal Brisbane and Women’s Hospital, Herston, QLD, Australia
  86. 86. Department of Neurology, John Hunter Hospital, Hunter New England Health, Newcastle, NSW, Australia
  87. 87. Department of Neurology, The Alfred Hospital, Melbourne, VIC, Australia
  88. 88. Department of Rehabilitation, M.L. Novarese Hospital, Moncrivello, Italy
  89. 89. Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth, WA, Australia
  90. 90. Universite Catholique de Louvain, Ottignies-Louvain-la-Neuve, Belgium
  91. 91. Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, VIC, Australia
  92. 92. MS Centre, Royal Melbourne Hospital, Melbourne, VIC, Australia
  93. 93. Noorderhart Rehabilitation & MS Center, Pelt and Hasselt University, Hasselt, Belgium
  94. 94. Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
  95. 95. School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands
  96. 96. Institute of Immunology and Infectious Diseases, Murdoch University, Perth, WA, Australia
  97. 97. Sir Charles Gairdner Hospital, Nedlands, WA, Australia
  98. 98. University of Zagreb, School of Medicine, Zagreb, Croatia
  99. 99. IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy

Source: Multiple Sclerosis Journal Published:2023


Abstract

Background: The prognostic significance of non-disabling relapses in people with relapsing-remitting multiple sclerosis (RRMS) is unclear. Objective: To determine whether early non-disabling relapses predict disability accumulation in RRMS. Methods: We redefined mild relapses in MSBase as ‘non-disabling’, and moderate or severe relapses as ‘disabling’. We used mixed-effects Cox models to compare 90-day confirmed disability accumulation events in people with exclusively non-disabling relapses within 2 years of RRMS diagnosis to those with no early relapses; and any early disabling relapses. Analyses were stratified by disease-modifying therapy (DMT) efficacy during follow-up. Results: People who experienced non-disabling relapses within 2 years of RRMS diagnosis accumulated more disability than those with no early relapses if they were untreated (n = 285 vs 4717; hazard ratio (HR) = 1.29, 95% confidence interval (CI) = 1.00–1.68) or given platform DMTs (n = 1074 vs 7262; HR = 1.33, 95% CI = 1.15–1.54), but not if given high-efficacy DMTs (n = 572 vs 3534; HR = 0.90, 95% CI = 0.71–1.13) during follow-up. Differences in disability accumulation between those with early non-disabling relapses and those with early disabling relapses were not confirmed statistically. Conclusion: This study suggests that early non-disabling relapses are associated with a higher risk of disability accumulation than no early relapses in RRMS. This risk may be mitigated by high-efficacy DMTs. Therefore, non-disabling relapses should be considered when making treatment decisions. © The Author(s), 2023.
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