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Effect of Disease-Modifying Therapy on Disability in Relapsing-Remitting Multiple Sclerosis Over 15 Years Publisher Pubmed



Kalincik T1, 2 ; Diouf I2 ; Sharmin S2 ; Malpas C2 ; Spelman T3, 4, 5 ; Horakova D5 ; Havrdova EK6 ; Trojano M7 ; Izquierdo G8 ; Lugaresi A9, 10 ; Prat A11, 12 ; Girard M11, 12 ; Duquette P11, 12 ; Grammond P1 Show All Authors
Authors
  1. Kalincik T1, 2
  2. Diouf I2
  3. Sharmin S2
  4. Malpas C2
  5. Spelman T3, 4, 5
  6. Horakova D5
  7. Havrdova EK6
  8. Trojano M7
  9. Izquierdo G8
  10. Lugaresi A9, 10
  11. Prat A11, 12
  12. Girard M11, 12
  13. Duquette P11, 12
  14. Grammond P1
  15. Jokubaitis V3, 13
  16. Van Der Walt A3, 13
  17. Grandmaison F14
  18. Sola P15, 16
  19. Ferraro D16
  20. Shaygannejad V17
  21. Alroughani R18
  22. Hupperts R19
  23. Terzi M20
  24. Boz C21
  25. Lechnerscott J22, 23
  26. Pucci E24
  27. Van Pesch V25
  28. Granella F26
  29. Bergamaschi R27
  30. Spitaleri D28
  31. Slee M29
  32. Vucic S30
  33. Ampapa R31
  34. Mccombe P32, 33
  35. Ramotello C34, 35
  36. Prevost J36
  37. Olascoaga J37
  38. Cristiano E38
  39. Barnett M39
  40. Saladino ML40
  41. Sanchezmenoyo JL41
  42. Hodgkinson S41
  43. Rozsa C42
  44. Hughes S43
  45. Moore F44
  46. Shaw C45
  47. Butler E46
  48. Skibina O3, 13
  49. Gray O47, 48
  50. Kermode A49, 50, 51, 52, 53, 54
  51. Csepany T55
  52. Singhal B56
  53. Shuey N57
  54. Piroska I58
  55. Taylor B59
  56. Simo M60
  57. Sirbu CA60
  58. Sas A60
  59. Butzkueven H3, 13, 60
Show Affiliations
Authors Affiliations
  1. 1. Department of Medicine, University of Melbourne, Australia
  2. 2. Ms Centre, Department of Neurology, Royal Melbourne Hospital, Australia
  3. 3. Karolinska Institute, Stockholm, Sweden
  4. 4. Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia
  5. 5. Burnet Institute, Melbourne, Australia
  6. 6. Department of Neurology, Center of Clinical Neuroscience, General University Hospital, Charles University in Prague, Czech Republic
  7. 7. Department of Basic Medical Sciences Neuroscience and Sense Organs, University of Bari, Italy
  8. 8. Hospital Universitario Virgen Macarena, Sevilla, Spain
  9. 9. Department of Neuroscience Imaging and Clinical Sciences, University g. d'Annunzio, Chieti, Italy
  10. 10. Department of Biomedical and Neuromotor Sciences, University of Bologna, Irccs Istituto Delle Scienze Neurologiche di Bologna, Italy
  11. 11. Hopital Notre Dame, Montreal, Canada
  12. 12. Chum, Universite de Montreal, Canada
  13. 13. Cisss Chaudiere-Appalache, Levis, Canada
  14. 14. Department of Neurology, Alfred Hospital, Melbourne, Australia
  15. 15. Neuro Rive-Sud, Quebec, Canada
  16. 16. Department of Neuroscience, Azienda Ospedaliera Universitaria, Modena, Italy
  17. 17. Isfahan University of Medical Sciences, Isfahan, Iran
  18. 18. Amiri Hospital, Kuwait City, Kuwait
  19. 19. Zuyderland Ziekenhuis, Sittard, Netherlands
  20. 20. Medical Faculty, 19 Mayis University, Samsun, Turkey
  21. 21. Ktu Medical Faculty Farabi Hospital, Karadeniz Technical University, Trabzon, Turkey
  22. 22. School of Medicine and Public Health, University Newcastle, United Kingdom
  23. 23. Department of Neurology, John Hunter Hospital, Newcastle, Australia
  24. 24. Uoc Neurologia, Azienda Sanitaria Unica Regionale Marche-AV3, Macerata, Italy
  25. 25. Cliniques Universitaires Saint-Luc, Brussels, Belgium
  26. 26. University of Parma, Italy
  27. 27. C. Mondino National Neurological Institute, Pavia, Italy
  28. 28. Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino, Italy
  29. 29. Flinders University, Adelaide, Australia
  30. 30. Westmead Hospital, Sydney, Australia
  31. 31. Nemocnice Jihlava, Czech Republic
  32. 32. University of Queensland, Brisbane, Australia
  33. 33. Royal Brisbane and Women's Hospital, Brisbane, Australia
  34. 34. Hospital Germans Trias i Pujol, Badalona, Spain
  35. 35. Csss Saint-Jerome, Canada
  36. 36. Hospital Universitario Donostia, Paseo de Begiristain, San Sebastian, Spain
  37. 37. Hospital Italiano, Buenos Aires, Argentina
  38. 38. Brain and Mind Centre, University of Sydney, Australia
  39. 39. INEBA-Institute of Neuroscience Buenos Aires, Argentina
  40. 40. Hospital de Galdakao-Usansolo, Galdakao, Spain
  41. 41. Liverpool Hospital, Sydney, Australia
  42. 42. Jahn Ferenc Teaching Hospital, Budapest, Hungary
  43. 43. Craigavon Area Hospital, United Kingdom
  44. 44. Jewish General Hospital, Montreal, Canada
  45. 45. Deakin University, Geelong, Australia
  46. 46. Monash Medical Centre, Melbourne, Australia
  47. 47. South East Trust, Belfast, United Kingdom
  48. 48. Perron Institute, University of Western Australia, Nedlands, Australia
  49. 49. Institute of Immunology and Infectious Diseases, Murdoch University, Australia
  50. 50. Sir Charles Gairdner Hospital, Perth, Australia
  51. 51. Department of Neurology, Faculty of Medicine, University of Debrecen, Hungary
  52. 52. Bombay Hospital Institute of Medical Sciences, Mumbai, India
  53. 53. St Vincents Hospital, Fitzroy, Melbourne, Australia
  54. 54. Veszprem Megyei Csolnoky Ferenc Korhaz Zrt, Veszprem, Hungary
  55. 55. Royal Hobart Hospital, Australia
  56. 56. Semmelweis University Budapest, Hungary
  57. 57. Central Military Emergency University Hospital, Bucharest, Romania
  58. 58. Titu Maiorescu University, Bucharest, Romania
  59. 59. Baz County Hospital, Miskolc, Hungary
  60. 60. Box Hill Hospital, Melbourne, Australia

Source: Neurology Published:2021


Abstract

Objective To test the hypothesis that immunotherapy prevents long-term disability in relapsing-remitting multiple sclerosis (MS), we modeled disability outcomes in 14,717 patients. Methods We studied patients from MSBase followed for ≥1 year, with ≥3 visits, ≥1 visit per year, and exposed to MS therapy, and a subset of patients with ≥15-year follow-up. Marginal structural models were used to compare the cumulative hazards of 12-month confirmed increase and decrease in disability, Expanded Disability Status Scale (EDSS) step 6, and the incidence of relapses between treated and untreated periods. Marginal structural models were continuously readjusted for patient age, sex, pregnancy, date, disease course, time from first symptom, prior relapse history, disability, and MRI activity. Results A total of 14,717 patients were studied. During the treated periods, patients were less likely to experience relapses (hazard ratio 0.60, 95% confidence interval [CI] 0.43-0.82, p = 0.0016), worsening of disability (0.56, 0.38-0.82, p = 0.0026), and progress to EDSS step 6 (0.33, 0.19-0.59, p = 0.00019). Among 1,085 patients with ≥15-year follow-up, the treated patients were less likely to experience relapses (0.59, 0.50-0.70, p = 10-9) and worsening of disability (0.81, 0.67-0.99, p = 0.043). Conclusion Continued treatment with MS immunotherapies reduces disability accrual by 19%-44% (95% CI 1%-62%), the risk of need of a walking aid by 67% (95% CI 41%-81%), and the frequency of relapses by 40-41% (95% CI 18%-57%) over 15 years. This study provides evidence that disease-modifying therapies are effective in improving disability outcomes in relapsing-remitting MS over the long term. Classification of Evidence This study provides Class IV evidence that, for patients with relapsing-remitting MS, long-term exposure to immunotherapy prevents neurologic disability. © American Academy of Neurology.
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