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The Effectiveness of Natalizumab Vs Fingolimod–A Comparison of International Registry Studies Publisher Pubmed



Andersen JB1, 95 ; Sharmin S2, 93 ; Lefort M4, 86 ; Kochhenriksen N6 ; Sellebjerg F7 ; Sorensen PS8, 13, 96 ; Hilt Christensen CC9 ; Rasmussen PV10 ; Jensen MB11 ; Frederiksen JL12 ; Bramow S7 ; Mathiesen HK8, 13, 96 ; Schreiber KI7 ; Horakova D14, 15 Show All Authors
Authors
  1. Andersen JB1, 95
  2. Sharmin S2, 93
  3. Lefort M4, 86
  4. Kochhenriksen N6
  5. Sellebjerg F7
  6. Sorensen PS8, 13, 96
  7. Hilt Christensen CC9
  8. Rasmussen PV10
  9. Jensen MB11
  10. Frederiksen JL12
  11. Bramow S7
  12. Mathiesen HK8, 13, 96
  13. Schreiber KI7
  14. Horakova D14, 15
  15. Havrdova EK14, 15
  16. Alroughani R16
  17. Izquierdo G17, 18
  18. Eichau S17, 18
  19. Ozakbas S19
  20. Patti F20
  21. Onofrj M21
  22. Lugaresi A22
  23. Terzi M23
  24. Grammond P24
  25. Grand Maison F25
  26. Yamout B26
  27. Prat A27, 28, 29
  28. Girard M27, 28, 29
  29. Duquette P27, 28, 29
  30. Boz C30
  31. Trojano M31
  32. Mccombe P32
  33. Slee M33
  34. Lechnerscott J34
  35. Turkoglu R36
  36. Sola P37, 38
  37. Ferraro D37, 38
  38. Granella F39
  39. Shaygannejad V41
  40. Prevost J42
  41. Skibina O43
  42. Solaro C44
  43. Karabudak R46
  44. Wijmeersch BV47
  45. Csepany T48
  46. Spitaleri D49
  47. Vucic S50
  48. Casey R51
  49. Debouverie M54
  50. Edan G55
  51. Ciron J56
  52. Ruet A57
  53. Seze JD58
  54. Maillart E59
  55. Zephir H60
  56. Labauge P61
  57. Defer G62
  58. Lebrun C63
  59. Moreau T64
  60. Berger E65
  61. Clavelou P66
  62. Pelletier J67
  63. Stankoff B68
  64. Gout O69
  65. Thouvenot E70
  66. Heinzlef O71
  67. Alkhedr A72
  68. Bourre B73
  69. Casez O74
  70. Cabre P75
  71. Montcuquet A76
  72. Wahab A77
  73. Camdessanche JP78
  74. Marousset A79
  75. Patry I80
  76. Hankiewicz K81
  77. Pottier C82
  78. Maubeuge N83
  79. Labeyrie C84
  80. Nifle C85
  81. Leray E4, 86
  82. Laplaud DA88
  83. Butzkueven H90
  84. Kalincik T2, 93
  85. Vukusic S1, 95
  86. Magyari M1, 7, 95
Show Affiliations
Authors Affiliations
  1. 1. The Danish Multiple Sclerosis Registry, Department of Neurology, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark
  2. 2. CORe, Department of Medicine, University of Melbourne, Melbourne, Australia
  3. 3. Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia
  4. 4. Rennes University, EHESP, REPERES – EA 7449, F-35000 Rennes, France
  5. 5. Univ Rennes, CHU Rennes, Inserm, CIC 1414 (Centre d'Investigation Clinique de Rennes), Rennes, F-35000, France
  6. 6. Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
  7. 7. The Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet Glostrup, Denmark
  8. 8. The Danish Multiple Sclerosis Center, Department of Neurology, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark
  9. 9. Department of Neurology Aalborg University Hospital, Multiple Sclerosis Unit
  10. 10. Aarhus University Hospital, Neurology, PPJ Boulevard, Aarhus N, DK-8200
  11. 11. Department of Neurology, University Hospital of Northern Sealand
  12. 12. Danish Multiple Sclerosis Centre, Dept. of Neurology, Copenhagen University Hospital, Rigshospitalet in Glostrup, Glostrup, 2600, Denmark
  13. 13. The Danish Multiple Sclerosis Center, Department of Neurology, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark
  14. 14. Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic
  15. 15. Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic
  16. 16. Division of Neurology, Department of Medicine, Amiri Hospital, Sharq, Kuwait
  17. 17. Hospital Universitario Virgen Macarena, Sevilla, Spain
  18. 18. Hospital Universitario Virgen Macarena, Sevilla, Spain
  19. 19. Dokuz Eylul University, Konak/Izmir, Turkiye
  20. 20. GF Ingrassia Department, University of Catania, Catania, Policlinico G Rodolico, Italy
  21. 21. Department of Neuroscience, Imaging, and Clinical Sciences, University G. d'Annunzio, Chieti, Italy
  22. 22. Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy
  23. 23. Medical Faculty, 19 Mayis University, Samsun, Turkiye
  24. 24. CISSS Chaudiere-Appalache, Levis, Canada
  25. 25. Neuro Rive-Sud, Quebec, Canada
  26. 26. Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center, Beirut, Lebanon
  27. 27. Hopital Notre Dame, Montreal, Canada, CHUM and Universite de Montreal, Montreal, Canada
  28. 28. Hopital Notre Dame, Montreal, Canada, CHUM and Universite de Montreal, Montreal, Canada
  29. 29. Hopital Notre Dame, Montreal, Canada, CHUM and Universite de Montreal, Montreal, Canada
  30. 30. KTU Medical Faculty Farabi Hospital, Trabzon, Turkiye
  31. 31. Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy
  32. 32. University of Queensland, Brisbane, Australia, Royal Brisbane and Women's Hospital
  33. 33. Flinders University, Adelaide, Australia
  34. 34. School of Medicine and Public Health, University Newcastle, Newcastle, Australia
  35. 35. Department of Neurology, John Hunter Hospital, Hunter New England Health, Newcastle, Australia
  36. 36. Haydarpasa Numune Training and Research Hospital, Istanbul, Turkiye
  37. 37. Department of Neuroscience, Azienda Ospedaliera Universitaria, Modena, Italy
  38. 38. Department of Neuroscience, Azienda Ospedaliera Universitaria, Modena, Italy
  39. 39. Department of Medicine and Surgery, University of Parma, Parma, Italy
  40. 40. Department of Emergency and General Medicine, Parma University Hospital, Parma, Italy
  41. 41. Isfahan University of Medical Sciences, Isfahan, Iran
  42. 42. CSSS Saint-Jerome, Saint-Jerome, Canada
  43. 43. Monash University, Melbourne, Australia
  44. 44. Department of Neurology, ASL3 Genovese, Genova, Italy
  45. 45. Department of Rehabilitaiton, ML Novarese Hospital Moncrivello
  46. 46. Hacettepe University, Ankara, Turkiye
  47. 47. Rehabilitation and MS-Centre Overpelt and Hasselt University, Hasselt, Belgium
  48. 48. Department of Neurology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
  49. 49. Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino, Avellino, Italy
  50. 50. Westmead Hospital, Sydney, Australia
  51. 51. Service de neurologie, sclerose en plaques, pathologies de la myeline et neuro-inflammation, Hopital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, 69677 Lyon/Bron, France
  52. 52. Centre des Neurosciences de Lyon, Observatoire Francais de la Sclerose en Plaques, INSERM 1028 et CNRS UMR5292, 69003 Lyon, France
  53. 53. Universite Claude Bernard Lyon 1, Faculte de medecine Lyon Est, F-69000 Lyon, France, Eugene Devic EDMUS Foundation, Lyon/Bron, 69677, France
  54. 54. Centre hospitalier regional universitaire de Nancy, Hopital central, Service de neurologie, Nancy, France
  55. 55. Centre hospitalier universitaire de Rennes, Hopital Pontchaillou, Service de neurologie, Rennes, France
  56. 56. Centre hospitalier universitaire de Toulouse, Hopital Purpan, Service de neurologie inflammatoire et neuro-oncologie, Toulouse, France
  57. 57. Centre hospitalier universitaire de Bordeaux, Hopital Pellegrin, Service de neurologie, Bordeaux, France
  58. 58. Hopitaux universitaire de Strasbourg, Hopital de Hautepierre, Service des maladies inflammatoires du systeme nerveux – neurologie, Strasbourg, France
  59. 59. Assistance publique des hopitaux de Paris, Hopital de la Pitie-Salpetriere, Service de neurologie, Paris, France
  60. 60. Centre hospitalier universitaire de Lille, Hopital Salengro, Service de neurologie D, Lille, France
  61. 61. Centre hospitalier universitaire de Montpellier, Hopital Gui de Chauliac, Service de neurologie, Montpellier, France
  62. 62. Centre hospitalier universitaire de Caen Normandie, Service de neurologie, Hopital Cote de Nacre, Caen, France
  63. 63. Centre hospitalier universitaire de Nice, Universite Nice Cote d'Azur, Hopital Pasteur, Service de neurologie, Nice, France
  64. 64. Centre hospitalier universitaire Dijon Bourgogne, Hopital Francois Mitterrand, Service de neurologie, maladies inflammatoires du systeme nerveux et neurologie generale, Dijon, France
  65. 65. Centre hospitalier regional universitaire de Besancon, Hopital Jean Minjoz, Service de neurologie, Besancon, France
  66. 66. Centre hospitalier universitaire de Clermont-Ferrand, Hopital Gabriel-Montpied, Service de neurologie, Clermont-Ferrand, France
  67. 67. Assistance publique des hopitaux de Marseille, Centre hospitalier de la Timone, Service de neurologie et unite neuro-vasculaire, Marseille, France
  68. 68. Assistance publique des hopitaux de Paris, Hopital Saint-Antoine, Service de neurologie, Paris, France
  69. 69. Fondation Adolphe de Rothschild de l’oeil et du cerveau, Service de neurologie, Paris, France
  70. 70. Centre hospitalier universitaire de Nimes, Hopital Caremeau, Service de neurologie, Nimes, France
  71. 71. Centre hospitalier intercommunal de Poissy Saint-Germain-en-Laye, Service de neurologie, Poissy, France
  72. 72. Centre hospitalier universitaire d'Amiens Picardie, Site sud, Service de neurologie, Amiens, France
  73. 73. Centre hospitalier universitaire Rouen Normandie, Hopital Charles-Nicolle, Service de neurologie, Rouen, France
  74. 74. Centre hospitalier universitaire Grenoble-Alpes, Site nord, Service de neurologie, Grenoble/La Tronche, France
  75. 75. Centre hospitalier universitaire de Martinique, Hopital Pierre Zobda-Quitman, Service de Neurologie, Fort-de-France, France
  76. 76. Centre hospitalier universitaire Limoges, Hopital Dupuytren, Service de neurologie, Limoges, France
  77. 77. Hopital Henri Mondor, Department of Neurology, Creteil, F-94000, France
  78. 78. Centre hospitalier universitaire de Saint-Etienne, Hopital Nord, Service de neurologie, Saint-Etienne, France
  79. 79. Centre hospitalier regional universitaire de Tours, Hopital Bretonneau, Service de neurologie, Tours, France
  80. 80. Centre hospitalier sud francilien, Service de neurologie, Corbeil-Essonnes, France
  81. 81. Centre hospitalier de Saint-Denis, Hopital Casanova, Service de neurologie, Saint-Denis, France
  82. 82. Centre hospitalier de Pontoise, Service de neurologie, Pontoise, France
  83. 83. Centre hospitalier universitaire de Poitiers, Site de la Miletrie, Service de neurologie, Poitiers, France
  84. 84. Assistance publique des hopitaux de Paris, Hopital Bicetre, Service de neurologie, Le Kremlin-Bicetre, France
  85. 85. Centre hospitalier de Versailles, Hopital Andre-Mignot, Service de neurologie, Le Chesnay, France
  86. 86. Rennes University, EHESP, REPERES – EA 7449, F-35000 Rennes, France
  87. 87. Univ Rennes, CHU Rennes, Inserm, CIC 1414 (Centre d'Investigation Clinique de Rennes), Rennes, F-35000, France
  88. 88. CHU de Nantes, Service de Neurologie & CIC015 INSERM, F-44093 Nantes, France
  89. 89. INSERM CR1064, Nantes, F-44000, France
  90. 90. Central Clinical School, Monash University, Melbourne, Australia
  91. 91. Department of Neurology, The Alfred Hospital, Melbourne, Australia
  92. 92. Department of Neurology, Box Hill Hospital, Monash University, Melbourne, Australia
  93. 93. CORe, Department of Medicine, University of Melbourne, Melbourne, Australia
  94. 94. Melbourne MS Centre, Department of Neurology, Melbourne, Royal Melbourne Hospital, Australia
  95. 95. The Danish Multiple Sclerosis Registry, Department of Neurology, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark
  96. 96. The Danish Multiple Sclerosis Center, Department of Neurology, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark

Source: Multiple Sclerosis and Related Disorders Published:2021


Abstract

Background: Natalizumab and fingolimod were the first preparations recommended for disease breakthrough in priorly treated relapsing-remitting multiple sclerosis. Of three published head-to-head studies two showed that natalizumab is the more effective to prevent relapses and EDSS worsening. Methods: By re-analyzing original published results from MSBase, France, and Denmark using uniform methodologies, we aimed at identifying the effects of differences in methodology, in the MS-populations, and at re-evaluating the differences in effectiveness between the two drugs. We gained access to copies of the individual amended databases and pooled all data. We used uniform inclusion/exclusion criteria and statistical methods with Inverse Probability Treatment Weighting. Results: The pooled analyses comprised 968 natalizumab- and 1479 fingolimod treated patients. The on-treatment natalizumab/fingolimod relapse rate ratio was 0.77 (p=0.004). The hazard ratio (HR) for a first relapse was 0.82 (p=0.030), and the HR for sustained EDSS improvement was 1.4 (p=0.009). There were modest differences between each of the original published studies and the replication study, but the conclusions of the three original studies remained unchanged: in two of them natalizumab was more effective, but in the third there was no difference between natalizumab and fingolimod. Conclusion: The results were largely invariant to the epidemiological and statistical methods but differed between the MS populations. Generally, the advantage of natalizumab was confirmed. © 2021 Elsevier B.V.
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