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Disability Accrual in Primary and Secondary Progressive Multiple Sclerosis Publisher Pubmed



Hardingforrester S1 ; Roos I1, 2 ; Nguyen AL1, 2 ; Malpas CB1, 2 ; Diouf I1, 2 ; Moradi N1, 2 ; Sharmin S1, 2 ; Izquierdo G3 ; Eichau S3 ; Patti F4 ; Horakova D5 ; Kubala Havrdova E5 ; Prat A6, 7 ; Girard M6, 8 Show All Authors
Authors
  1. Hardingforrester S1
  2. Roos I1, 2
  3. Nguyen AL1, 2
  4. Malpas CB1, 2
  5. Diouf I1, 2
  6. Moradi N1, 2
  7. Sharmin S1, 2
  8. Izquierdo G3
  9. Eichau S3
  10. Patti F4
  11. Horakova D5
  12. Kubala Havrdova E5
  13. Prat A6, 7
  14. Girard M6, 8
  15. Duquette P6, 8
  16. Grandmaison F9
  17. Onofrj M10
  18. Lugaresi A11, 12
  19. Grammond P13
  20. Ozakbas S14
  21. Amato MP15, 16
  22. Gerlach O17
  23. Sola P18
  24. Ferraro D19, 20
  25. Buzzard K21
  26. Skibina O21
  27. Lechnerscott J22, 23
  28. Alroughani R24
  29. Boz C25
  30. Van Pesch V26
  31. Cartechini E27
  32. Terzi M28
  33. Maimone D29
  34. Ramotello C30
  35. Yamout B31, 32
  36. Khoury SJ31, 33
  37. La Spitaleri D34
  38. Sa MJ35, 36
  39. Blanco Y37
  40. Granella F38
  41. Slee M39
  42. Butler E40
  43. Sidhom Y41
  44. Gouider R42
  45. Bergamaschi R43
  46. Karabudak R44
  47. Ampapa R45
  48. Sanchezmenoyo JL46
  49. Prevost J47
  50. Castillotrivino T48
  51. Mccombe PA49
  52. Macdonell R50
  53. Laureys G51
  54. Van Hijfte L51
  55. Oh J52
  56. Altintas A53, 54
  57. De Gans K55
  58. Turkoglu R56
  59. Van Der Walt A57
  60. Butzkueven H58, 59
  61. Vucic S60
  62. Barnett M61
  63. Cristiano E62
  64. Hodgkinson S63
  65. Iuliano G64
  66. Kappos L65, 66
  67. Kuhle J65, 66
  68. Shaygannejad V67
  69. Soysal A68
  70. Weinstockguttman B69
  71. Van Wijmeersch B70, 71
  72. Kalincik T1, 2
Show Affiliations
Authors Affiliations
  1. 1. CORe, Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia
  2. 2. Neuroimmunology Centre, Department of Neurology, The Royal Melbourne Hospital, Parkville, VIC, Australia
  3. 3. Multiple Sclerosis Unit, Hospital Universitario Virgen Macarena, Andalucia, Sevilla, Spain
  4. 4. Neuroscience, Department of Surgical and Medical Sciences and Advanced Technologies 'G.f. Ingrassia', University of Catania, Catania, Italy
  5. 5. Department of Neurology and Centre of Clinical Neuroscience, Charles University, First Faculty of Medicine, Praha, Czech Republic
  6. 6. Centre Hospitalier, Universite de Montreal, Montreal, QC, Canada
  7. 7. Department of Neuroscience, Universite de Montreal, Montreal, QC, Canada
  8. 8. Faculte de Medecine, Universite de Montreal, Montreal, QC, Canada
  9. 9. Neuro Rive-Sud, Longueuil, QC, Canada
  10. 10. Department of Neurosciences Imaging and Clinical Sciences, Gabriele d'Annunzio University of Chieti-Pescara, Chieti, Italy
  11. 11. UOSI Riabilitazione Sclerosi Multipla, IRCCS, Istituto Delle Scienze Neurologiche di Bologna, Bologna, Italy
  12. 12. Dipartimento di Scienze Biomediche e Neuromotorie, Universita di Bologna, Bologna, Italy
  13. 13. Centre Integre de Sante, De Services Sociaux de Chaudiere-Appalaches, Quebec Centre de Recherche, Levis, QC, Canada
  14. 14. Department of Neurology, Dokuz Eylul University, Izmir, Turkey
  15. 15. Department of Neurological Siences, University of Florence, Florence, Italy
  16. 16. IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy
  17. 17. Department of Neurology, Zuyderland Medical Centre, Sittard-Geleen, Netherlands
  18. 18. Neurology Unit, Azienda Ospedaliero-Universitaria of Modena, Modena, Italy
  19. 19. Department of Neuroscience, Azienda Ospedaliero-Universitaria di Modena, Emilia-Romagna, Modena, Italy
  20. 20. Department of Biomedical Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
  21. 21. Department of Neurology, Box Hill Hospital, Box Hill, VIC, Australia
  22. 22. School of Medicine and Public Health, The University of Newcastle, Callaghan, NSW, Australia
  23. 23. Department of Neurology, John Hunter Hospital, Newcastle, NSW, Australia
  24. 24. Department of Medicine, Al-Amiri Hospital, Kuwait City, Kuwait
  25. 25. Department of Neurology, Karadeniz Technical University, Trabzon, Turkey
  26. 26. Department of Neurology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
  27. 27. UOC Neurologia, Azienda Sanitaria Unica Regionale Marche - AV3, Macerata, Italy
  28. 28. Ondokuz Mayis Universitesi, Samsun, Turkey
  29. 29. UO Neurologia, Ospedale Garibaldi, Catania, Italy
  30. 30. Department of Neurosciences, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain
  31. 31. Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut, Medical Center, Beirut, Lebanon
  32. 32. Department of Neurology, American University of Beirut, Beirut, Lebanon
  33. 33. American University of Beirut, Beirut, Lebanon
  34. 34. UOC Neurologia e Stroke, AORN San Giuseppe Moscati, Avellino, Italy
  35. 35. Department of Neurology, Centro Hospitalar de Sao Joao, Porto, Portugal
  36. 36. Health Sciences Faculty, Fernando Pessoa University, Porto, Portugal
  37. 37. Hospital Clinic de Barcelona, Catalunya, Barcelona, Spain
  38. 38. Multiple Sclerosis Centre, Neurosciences, University of Parma, Parma, Italy
  39. 39. Department of Neurology, Flinders Medical Centre, Adelaide, SA, Australia
  40. 40. Department of Neurology, Monash Medical Centre Clayton, Clayton, VIC, Australia
  41. 41. Department of Neurology, Hopital Razi, La Manouba, Tunisia
  42. 42. Department of Neurology, Razi Hospital, Gilan, Rasht, Iran
  43. 43. Multiple Sclerosis Centre, Neurological Institute C.Mondino, Pavia, Italy
  44. 44. Department of Neurology, Hacettepe University, Faculty of Medicine, Ankara, Turkey
  45. 45. Department of Neurology, Nemocnice Jihlava, Jihlava, Czech Republic
  46. 46. Department of Neurology, Hospital Galdakao-Usansolo, Pais Vasco, Galdakao, Spain
  47. 47. Centre Integre de Sante et de Services, Sociaux des Laurentides Point de Service de Saint-Jerome, Saint-Jerome, QC, Canada
  48. 48. Department of Neurology, Donostia University Hospital, San Sebastian, Spain
  49. 49. UQCCR, The University of Queensland, Saint Lucia, QLD, Australia
  50. 50. Department of Neurology, Austin Health, Heidelberg, VIC, Australia
  51. 51. Department of Neurology, University Hospital Ghent, Oost-Vlaanderen, Gent, Belgium
  52. 52. Division of Neurology, Department of Medicine, St Michael's Hospital, Toronto, ON, Canada
  53. 53. Department of Neurology, Koc Universitesi, Istanbul, Turkey
  54. 54. Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey
  55. 55. Department of Neurology, Groene Hart Ziekenhuis, Zuid-Holland, Gouda, Netherlands
  56. 56. Department of Neurology, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey
  57. 57. Multiple Sclerosis and Neuroimmunology Unit, Monash University, Central Clinical School, Melbourne, VIC, Australia
  58. 58. Department of Neuroscience, Monash University, Central Clinical School, Melbourne, VIC, Australia
  59. 59. Department of Neurology, The Alfred, Melbourne, VIC, Australia
  60. 60. Department of Neurology, Westmead Hospital, Westmead, NSW, Australia
  61. 61. Brain and Mind Centre, The University of Sydney, Sydney, NSW, Australia
  62. 62. Centro de Esclerosis Multiple de Buenos Aires, Hospital Italiano de Buenos Aires, Federal District, Buenos Aires, Argentina
  63. 63. Department of Neurology, Liverpool Hospital, Liverpool, NSW, Australia
  64. 64. Ospedali Riuniti di Salerno, Salerno, Italy
  65. 65. Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, Basel, Switzerland
  66. 66. Research Centre for Clinical Neuroimmunology and Neuroscience, University Hospital Basel, Basel, Switzerland
  67. 67. Department of Neurology, Isfahan University of Medical Sciences, Isfahan, Iran
  68. 68. Department of Neurology, Bakirkoy Research and Training Hospital for Psychiatry, Neurology and Neurosurgery, Istanbul, Turkey
  69. 69. Department of Neurology, University at Buffalo, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, United States
  70. 70. Universitair MS Centrum, Hasselt University, Pelt, Hasselt, Belgium
  71. 71. Rehabilitation & MS Centre, Pelt, Belgium

Source: Journal of Neurology, Neurosurgery and Psychiatry Published:2023


Abstract

Background Some studies comparing primary and secondary progressive multiple sclerosis (PPMS, SPMS) report similar ages at onset of the progressive phase and similar rates of subsequent disability accrual. Others report later onset and/or faster accrual in SPMS. Comparisons have been complicated by regional cohort effects, phenotypic differences in sex ratio and management and variable diagnostic criteria for SPMS. Methods We compared disability accrual in PPMS and operationally diagnosed SPMS in the international, clinic-based MSBase cohort. Inclusion required PPMS or SPMS with onset at age ≥18 years since 1995. We estimated Andersen-Gill hazard ratios for disability accrual on the Expanded Disability Status Scale (EDSS), adjusted for sex, age, baseline disability, EDSS score frequency and drug therapies, with centre and patient as random effects. We also estimated ages at onset of the progressive phase (Kaplan-Meier) and at EDSS milestones (Turnbull). Analyses were replicated with physician-diagnosed SPMS. Results Included patients comprised 1872 with PPMS (47% men; 50% with activity) and 2575 with SPMS (32% men; 40% with activity). Relative to PPMS, SPMS had older age at onset of the progressive phase (median 46.7 years (95% CI 46.2-47.3) vs 43.9 (43.3-44.4); p<0.001), greater baseline disability, slower disability accrual (HR 0.86 (0.78-0.94); p<0.001) and similar age at wheelchair dependence. Conclusions We demonstrate later onset of the progressive phase and slower disability accrual in SPMS versus PPMS. This may balance greater baseline disability in SPMS, yielding convergent disability trajectories across phenotypes. The different rates of disability accrual should be considered before amalgamating PPMS and SPMS in clinical trials. © 2023 BMJ Publishing Group. All rights reserved.
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