Variability of the response to immunotherapy among subgroups of patients with multiple sclerosis

Author:

Diouf Ibrahima1,Malpas Charles B.12,Sharmin Sifat1,Roos Izanne12ORCID,Horakova Dana3,Havrdova Eva Kubala3,Patti Francesco4ORCID,Shaygannejad Vahid5,Ozakbas Serkan6,Izquierdo Guillermo7,Eichau Sara7,Onofrj Marco8,Lugaresi Alessandra910,Alroughani Raed11,Prat Alexandre12,Girard Marc12,Duquette Pierre12,Terzi Murat13ORCID,Boz Cavit14,Grand'Maison Francois15,Hamdy Sherif16,Sola Patrizia17,Ferraro Diana17ORCID,Grammond Pierre18,Turkoglu Recai19,Buzzard Katherine20,Skibina Olga20,Yamout Bassem21ORCID,Altintas Ayse2223,Gerlach Oliver24,van Pesch Vincent25ORCID,Blanco Yolanda26ORCID,Maimone Davide27,Lechner‐Scott Jeannette28,Bergamaschi Roberto29,Karabudak Rana30,Iuliano Gerardo31,McGuigan Chris32,Cartechini Elisabetta33,Barnett Michael34,Hughes Stella35,Sa Maria José36,Solaro Claudio3738,Kappos Ludwig39,Ramo‐Tello Cristina40,Cristiano Edgardo41,Hodgkinson Suzanne42,Spitaleri Daniele43,Soysal Aysun44,Petersen Thor45,Slee Mark46,Butler Ernest47,Granella Franco48,de Gans Koen49,McCombe Pamela50,Ampapa Radek51,Van Wijmeersch Bart52,van der Walt Anneke2053,Butzkueven Helmut54,Prevost Julie55,Sinnige L. G. F.56,Sanchez‐Menoyo Jose Luis57ORCID,Vucic Steve58ORCID,Laureys Guy59,Van Hijfte Liesbeth59,Khurana Dheeraj60,Macdonell Richard54,Gouider Riadh61,Castillo‐Triviño Tamara62,Gray Orla63,Aguera‐Morales Eduardo64,Al‐Asmi Abdullah65,Shaw Cameron66,Deri Norma67,Al‐Harbi Talal68,Fragoso Yara69ORCID,Csepany Tunde70ORCID,Perez Sempere Angel71,Trevino‐Frenk Irene72,Schepel Jan73,Moore Fraser74,Kalincik Tomas12ORCID

Affiliation:

1. Department of Medicine CORe, University of Melbourne Melbourne Victoria Australia

2. Department of Neurology Neuroimmunology Centre, Royal Melbourne Hospital Melbourne Victoria Australia

3. Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine Charles University in Prague and General University Hospital Prague Czech Republic

4. Department of Medical and Surgical Sciences and Advanced Technologies GF Ingrassia Catania Italy

5. Isfahan University of Medical Sciences Isfahan Iran

6. Dokuz Eylul University Konak/Izmir Turkey

7. Hospital Universitario Virgen Macarena Seville Spain

8. Department of Neuroscience, Imaging, and Clinical Sciences D'Annunzio University Chieti Italy

9. IRCCS Istituto delle Scienze Neurologiche di Bologna Bologna Italy

10. Dipartimento di Scienze Biomediche e Neuromotorie Università di Bologna Bologna Italy

11. Division of Neurology, Department of Medicine Amiri Hospital Sharq Kuwait

12. CHUM Mississippi Center and University of Montreal Montreal Quebec Canada

13. School of Medicine Ondokuz Mayis University Samsun Turkey

14. KTU Medical Faculty, Farabi Hospital Trabzon Turkey

15. Neuro Rive‐Sud Quebec City Quebec Canada

16. Neurology Kasr Al Ainy MS Research Unit Cairo Egypt

17. Department of Neuroscience Azienda Ospedaliera Universitaria Modena Italy

18. CISSS Chaudière‐Appalache, Levis Sainte‐Marie Quebec Canada

19. Haydarpasa Numune Training and Research Hospital Istanbul Turkey

20. Central Clinical School Monash University Melbourne Victoria Australia

21. Nehme and Therese Tohme Multiple Sclerosis Center American University of Beirut Medical Center Beirut Lebanon

22. Department of Neurology, School of Medicine Koc University Istanbul Turkey

23. Koc University Research Center for Translational Medicine Istanbul Turkey

24. Zuyderland Medical Center Sittard‐Geleen the Netherlands

25. Cliniques Universitaires Saint‐Luc, Louvain Brussels Belgium

26. Center of Neuroimmunology, Service of Neurology, Hospital Clinic of Barcelona Barcelona Spain

27. Garibaldi Hospital Catania Italy

28. School of Medicine and Public Health University of Newcastle Newcastle New South Wales Australia

29. IRCCS Mondino Foundation Pavia Italy

30. Hacettepe University Ankara Turkey

31. Ospedali Riuniti di Salerno Salerno Italy

32. St Vincent's University Hospital Dublin Ireland

33. UOC Neurologia, Azienda Sanitaria Unica Regionale Marche–AV3 Macerata Italy

34. Brain and Mind Centre Sydney New South Wales Australia

35. Royal Victoria Hospital Belfast UK

36. Department of Neurology Centro Hospitalar Universitário de São João Porto Portugal

37. Department of Neurology ASL3 Genovese Genoa Italy

38. Department of Rehabilitation ML Novarese Hospital Moncrivello Genoa Italy

39. Departments of Medicine and Clinical Research, Neurologic Clinic and Policlinic University Hospital and University of Basel Basel Switzerland

40. Trias and Pujol Brothers University Hospital Badalona Spain

41. Hospital Italiano Buenos Aires Argentina

42. Liverpool Hospital Sydney New South Wales Australia

43. Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino Avellino Italy

44. Bakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases Istanbul Turkey

45. Aarhus University Hospital Aarhus Denmark

46. Flinders University Adelaide South Australia Australia

47. Monash Medical Centre Melbourne Victoria Australia

48. Department of Medicine and Surgery University of Parma Parma Italy

49. Groene Hart Ziekenhuis Gouda the Netherlands

50. University of Queensland Brisbane Queensland Australia

51. Nemocnice Jihlava Jihlava Czech Republic

52. Rehabilitation and MS Center Overpelt and Hasselt University Hasselt Belgium

53. Department of Neurology Alfred Hospital Melbourne Victoria Australia

54. Austin Health Melbourne Victoria Australia

55. CSSS Saint‐Jerome Saint‐Jerome Quebec Canada

56. Medical Center Leeuwarden Leeuwarden the Netherlands

57. Hospital de Galdakao‐Usansolo Galdakao Spain

58. Westmead Hospital Sydney New South Wales Australia

59. University Hospital Ghent Ghent Belgium

60. Postgraduate Institute of Medical Education and Research Chandigarh India

61. Department of Neurology Razi Hospital Manouba Tunisia

62. Instituto de Investigacion Sanitaria Biodonostia, Hospital Universitario Donostia San Sebastian Spain

63. South East Trust Belfast UK

64. University Hospital Reina Sofia Cordoba Spain

65. Department of Medicine Sultan Qaboos University Hospital Seeb Oman

66. University Hospital Geelong Geelong Victoria Australia

67. Hospital Fernandez Buenos Aires Argentina

68. Neurology Department King Fahad Specialist Hospital–Dammam Dammam Saudi Arabia

69. Universidade Metropolitana de Santos Santos Brazil

70. Department of Neurology, Faculty of Medicine University of Debrecen Debrecen Hungary

71. Hospital General Universitario de Alicante Alicante Spain

72. Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran Mexico City Mexico

73. Waikato Hospital Hamilton New Zealand

74. Jewish General Hospital Montreal Quebec Canada

Abstract

AbstractBackground and purposeThis study assessed the effect of patient characteristics on the response to disease‐modifying therapy (DMT) in multiple sclerosis (MS).MethodsWe extracted data from 61,810 patients from 135 centers across 35 countries from the MSBase registry. The selection criteria were: clinically isolated syndrome or definite MS, follow‐up ≥ 1 year, and Expanded Disability Status Scale (EDSS) score ≥ 3, with ≥1 score recorded per year. Marginal structural models with interaction terms were used to compare the hazards of 12‐month confirmed worsening and improvement of disability, and the incidence of relapses between treated and untreated patients stratified by their characteristics.ResultsAmong 24,344 patients with relapsing MS, those on DMTs experienced 48% reduction in relapse incidence (hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.45–0.60), 46% lower risk of disability worsening (HR = 0.54, 95% CI = 0.41–0.71), and 32% greater chance of disability improvement (HR = 1.32, 95% CI = 1.09–1.59). The effect of DMTs on EDSS worsening and improvement and the risk of relapses was attenuated with more severe disability. The magnitude of the effect of DMT on suppressing relapses declined with higher prior relapse rate and prior cerebral magnetic resonance imaging activity. We did not find any evidence for the effect of age on the effectiveness of DMT. After inclusion of 1985 participants with progressive MS, the effect of DMT on disability mostly depended on MS phenotype, whereas its effect on relapses was driven mainly by prior relapse activity.ConclusionsDMT is generally most effective among patients with lower disability and in relapsing MS phenotypes. There is no evidence of attenuation of the effect of DMT with age.

Funder

National Health and Medical Research Council

Roche

Publisher

Wiley

Subject

Neurology (clinical),Neurology

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