Comparative Effectiveness of Autologous Hematopoietic Stem Cell Transplant vs Fingolimod, Natalizumab, and Ocrelizumab in Highly Active Relapsing-Remitting Multiple Sclerosis-Reference-Cited by-同舟云学术

Comparative Effectiveness of Autologous Hematopoietic Stem Cell Transplant vs Fingolimod, Natalizumab, and Ocrelizumab in Highly Active Relapsing-Remitting Multiple Sclerosis

Published:2023-07-01 Issue:7 Volume:80 Page:702
ISSN:2168-6149
Container-title:JAMA Neurology
language:en
Short-container-title:JAMA Neurol

Author:

Kalincik Tomas¹²,Sharmin Sifat¹²,Roos Izanne¹²,Freedman Mark S.³,Atkins Harold⁴,Burman Joachim⁵,Massey Jennifer⁶⁷,Sutton Ian⁶⁸,Withers Barbara⁷⁹,Macdonell Richard¹⁰¹¹,Grigg Andrew¹¹¹²,Torkildsen Øivind¹³,Bo Lars¹³,Lehmann Anne Kristine¹⁴,Havrdova Eva Kubala¹⁵,Krasulova Eva¹⁵,Trněný Marek¹⁶,Kozak Tomas¹⁷,van der Walt Anneke¹⁸¹⁹,Butzkueven Helmut¹⁸¹⁹,McCombe Pamela²⁰²¹,Skibina Olga¹⁸²²²³,Lechner-Scott Jeannette²⁴²⁵,Willekens Barbara²⁶²⁷,Cartechini Elisabetta²⁸,Ozakbas Serkan²⁹,Alroughani Raed³⁰,Kuhle Jens³¹,Patti Francesco³²³³,Duquette Pierre³⁴,Lugaresi Alessandra³⁵³⁶,Khoury Samia J.³⁷,Slee Mark³⁸,Turkoglu Recai³⁹,Hodgkinson Suzanne⁴⁰,John Nevin⁴¹⁴²,Maimone Davide⁴³,Sa Maria Jose⁴⁴,van Pesch Vincent⁴⁵⁴⁶,Gerlach Oliver⁴⁷⁴⁸,Laureys Guy⁴⁹,Van Hijfte Liesbeth⁴⁹,Karabudak Rana⁵⁰,Spitaleri Daniele⁵¹,Csepany Tunde⁵²,Gouider Riadh⁵³⁵⁴,Castillo-Triviño Tamara⁵⁵,Taylor Bruce⁵⁶⁵⁷,Sharrack Basil⁵⁸,Snowden John A.⁵⁹,Horakova Dana⁶⁰,Buzzard Katherine⁶⁰,Terzi Murat⁶⁰,Prat Alexandre⁶⁰,Girard Marc⁶⁰,Grammond Pierre⁶⁰,Barnett Michael⁶⁰,Stewart Grace⁶⁰,Onofrj Marco⁶⁰,Izquierdo Guillermo⁶⁰,Eichau Sara⁶⁰,Grand'Maison Francois⁶⁰,Prevost Julie⁶⁰,Van Wijmeersch Bart⁶⁰,Amato Maria Pia⁶⁰,Shaygannejad Vahid⁶⁰,Boz Cavit⁶⁰,Bolaños Ricardo Fernandez⁶⁰,Soysal Aysun⁶⁰,Ramo-Tello Cristina⁶⁰,Solaro Claudio⁶⁰,Gobbi Claudio⁶⁰,Cabrera-Gomez Jose Antonio⁶⁰,Roullet Etienne⁶⁰,Zwanikken Cees⁶⁰,Den braber-Moerland Leontien⁶⁰,Deri Norma⁶⁰,Saladino Maria Laura⁶⁰,Cristiano Edgardo⁶⁰,Rojas Juan Ignacio⁶⁰,Vrech Carlos⁶⁰,Shaw Cameron⁶⁰,Shuey Neil⁶⁰,Boggild Mike⁶⁰,Tan Ik Lin⁶⁰,Hardy Todd⁶⁰,Decoo Danny⁶⁰,Moore Fraser⁶⁰,Oh Jiwon⁶⁰,Lalive Patrice⁶⁰,Ampapa Radek⁶⁰,Petersen Thor⁶⁰,Oreja-Guevara Celia⁶⁰,Perez Sempere Angel⁶⁰,Dominguez Jose Andres⁶⁰,Besora Sarah⁶⁰,Hughes Stella⁶⁰,Gray Orla⁶⁰,Grigoriadis Nikolaos⁶⁰,Piroska Imre⁶⁰,Rozsa Csilla⁶⁰,Kasa Krisztian⁶⁰,Simo Magdolna⁶⁰,Kovacs Krisztina⁶⁰,Sas Attila⁶⁰,Dobos Eniko⁶⁰,Rajda Cecilia⁶⁰,McGuigan Chris⁶⁰,Mason Deborah⁶⁰,Schepel Jan⁶⁰,Alkhaboori Jabir⁶⁰,Rio Maria Edite⁶⁰,Mihaela Simu⁶⁰,Al-Harbi Talal⁶⁰,Altintas Ayse⁶⁰,Kister Ilya⁶⁰,Marriott Mark⁶⁰,Kilpatrick Trevor⁶⁰,King John⁶⁰,Nguyen Ai-Lan⁶⁰,Dwyer Chris⁶⁰,Monif Mastura⁶⁰,Roos Izanne⁶⁰,Taylor Lisa⁶⁰,Diamanti Matteo⁶⁰,Chisari Clara⁶⁰,Toscano Simona⁶⁰,Salvatore Lo Fermo⁶⁰,Larochelle Catherine⁶⁰,De Luca Giovanna⁶⁰,Di Tommaso Valeria⁶⁰,Travaglini Daniela⁶⁰,Pietrolongo Erika⁶⁰,di Ioia Maria⁶⁰,Farina Deborah⁶⁰,Mancinelli Luca⁶⁰,Hupperts Raymond⁶⁰,Olascoaga Javier⁶⁰,Saiz Albert⁶⁰,Zivadinov Robert⁶⁰,Benedict Ralph⁶⁰,Verheul Freek⁶⁰,Fabis-Pedrini Marzena⁶⁰,Mrabet Saloua⁵³⁵⁴,Garber Justin⁶¹,Sanchez-Menoyo Jose Luis⁶²,Aguera-Morales Eduardo⁶³,Blanco Yolanda⁶⁴,Al-Asmi Abdullah⁶⁵,Weinstock-Guttman Bianca⁶⁶,Fragoso Yara⁶⁷,de Gans Koen⁶⁸,Kermode Allan⁶⁹⁷⁰, ,

Affiliation:

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

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

3. University of Ottawa, Department of Medicine, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada

4. Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada

5. Department of Medical Sciences, Neurology, Uppsala University, Uppsala, Sweden

6. Department of Neurology, St Vincent's Hospital Sydney, Sydney, New South Wales, Australia

7. St Vincent’s Clinical School, University of New South Wales, Sydney, New South Wales, Australia

8. University of Sydney, Sydney, New South Wales, Australia

9. Department of Haematology, St Vincent's Hospital Sydney, Sydney, New South Wales, Australia

10. Department of Neurology, Austin Health, Melbourne, Victoria, Australia

11. University of Melbourne, Melbourne, Victoria, Australia

12. Department of Haematology, Austin Health, Melbourne, Victoria, Australia

13. Department of Neurology, Haukeland University Hospital, Bergen, Norway

14. Department of Haematology, Haukeland University Hospital, Bergen, Norway

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. Department of Haematology, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic

17. Department of Haematology, 3rd Faculty of Medicine, Charles University in Prague, and University Hospital Kralovske Vinohrady, Prague, Czech Republic

18. Department of Neurology, The Alfred Hospital, Melbourne, Victoria, Australia

19. Central Clinical School, Monash University, Melbourne, Victoria, Australia

20. University of Queensland, Brisbane, Queensland, Australia

21. Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia

22. Department of Neurology, Box Hill Hospital, Melbourne, Victoria, Australia

23. Monash University, Melbourne, Victoria, Australia

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

25. Department of Neurology, John Hunter Hospital, Hunter New England Health, Newcastle, New South Wales, Australia

26. Department of Neurology, Antwerp University Hospital, Edegem, Belgium

27. Translational Neurosciences Research Group, Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk, Belgium

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

29. Dokuz Eylul University, Konak, Izmir, Turkey

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

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

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

33. Multiple Sclerosis Center, University of Catania, Catania, Italy

34. CHUM MS Center and Universite de Montreal, Montreal, Quebec, Canada

35. IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy

36. Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy

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

38. Flinders University, Adelaide, South Australia, Australia

39. Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey

40. Liverpool Hospital, Sydney, New South Wales, Australia

41. Monash Medical Centre, Melbourne, Victoria, Australia

42. Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia

43. Garibaldi Hospital, Catania, Italy

44. Department of Neurology, Centro Hospitalar Universitario de Sao Joao, Porto, Portugal

45. Cliniques Universitaires Saint-Luc, Brussels, Belgium

46. Université Catholique de Louvain, Ottignies-Louvain-la-Neuve, Belgium

47. Academic MS Center Zuyderland, Department of Neurology, Zuyderland Medical Center, Sittard-Geleen, the Netherlands

48. School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands

49. Department of Neurology, University Hospital Ghent, Ghent, Belgium

50. Department of Neurology, Hacettepe University Hospitals, Ankara, Turkey

51. Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino, Avellino, Italy

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

53. Department of Neurology, Razi University Hospital, Manouba, Tunis, Tunisia

54. Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia

55. Hospital Universitario Donostia, San Sebastián, Spain

56. Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia

57. Royal Hobart Hospital, Hobart, Tasmania, Australia

58. Department of Neurology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom

59. Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom

60. and the MSBase Study Group Authors

61. Westmead Hospital, Sydney, New South Wales, Australia

62. Hospital de Galdakao-Usansolo, Galdakao, Spain

63. University Hospital Reina Sofia, Cordoba, Spain

64. Center of Neuroimmunology, Service of Neurology, Hospital Clinic de Barcelona, Barcelona, Spain

65. Department of Medicine, Sultan Qaboos University Hospital, Al-Khodh, Oman

66. Department of Neurology, Buffalo General Medical Center, Buffalo, New York

67. Universidade Metropolitana de Santos, Santos, Brazil

68. Groene Hart Ziekenhuis, Gouda, the Netherlands

69. Perron Institute, University of Western Australia, Nedlands, Western Australia, Australia

70. Institute of Immunology and Infectious Diseases, Sir Charles Gairdner Hospital, Murdoch University, Perth, Western Australia, Australia

Abstract

ImportanceAutologous hematopoietic stem cell transplant (AHSCT) is available for treatment of highly active multiple sclerosis (MS).ObjectiveTo compare the effectiveness of AHSCT vs fingolimod, natalizumab, and ocrelizumab in relapsing-remitting MS by emulating pairwise trials.Design, Setting, and ParticipantsThis comparative treatment effectiveness study included 6 specialist MS centers with AHSCT programs and international MSBase registry between 2006 and 2021. The study included patients with relapsing-remitting MS treated with AHSCT, fingolimod, natalizumab, or ocrelizumab with 2 or more years study follow-up including 2 or more disability assessments. Patients were matched on a propensity score derived from clinical and demographic characteristics.ExposureAHSCT vs fingolimod, natalizumab, or ocrelizumab.Main outcomesPairwise-censored groups were compared on annualized relapse rates (ARR) and freedom from relapses and 6-month confirmed Expanded Disability Status Scale (EDSS) score worsening and improvement.ResultsOf 4915 individuals, 167 were treated with AHSCT; 2558, fingolimod; 1490, natalizumab; and 700, ocrelizumab. The prematch AHSCT cohort was younger and with greater disability than the fingolimod, natalizumab, and ocrelizumab cohorts; the matched groups were closely aligned. The proportion of women ranged from 65% to 70%, and the mean (SD) age ranged from 35.3 (9.4) to 37.1 (10.6) years. The mean (SD) disease duration ranged from 7.9 (5.6) to 8.7 (5.4) years, EDSS score ranged from 3.5 (1.6) to 3.9 (1.9), and frequency of relapses ranged from 0.77 (0.94) to 0.86 (0.89) in the preceding year. Compared with the fingolimod group (769 [30.0%]), AHSCT (144 [86.2%]) was associated with fewer relapses (ARR: mean [SD], 0.09 [0.30] vs 0.20 [0.44]), similar risk of disability worsening (hazard ratio [HR], 1.70; 95% CI, 0.91-3.17), and higher chance of disability improvement (HR, 2.70; 95% CI, 1.71-4.26) over 5 years. Compared with natalizumab (730 [49.0%]), AHSCT (146 [87.4%]) was associated with marginally lower ARR (mean [SD], 0.08 [0.31] vs 0.10 [0.34]), similar risk of disability worsening (HR, 1.06; 95% CI, 0.54-2.09), and higher chance of disability improvement (HR, 2.68; 95% CI, 1.72-4.18) over 5 years. AHSCT (110 [65.9%]) and ocrelizumab (343 [49.0%]) were associated with similar ARR (mean [SD], 0.09 [0.34] vs 0.06 [0.32]), disability worsening (HR, 1.77; 95% CI, 0.61-5.08), and disability improvement (HR, 1.37; 95% CI, 0.66-2.82) over 3 years. AHSCT-related mortality occurred in 1 of 159 patients (0.6%).ConclusionIn this study, the association of AHSCT with preventing relapses and facilitating recovery from disability was considerably superior to fingolimod and marginally superior to natalizumab. This study did not find evidence for difference in the effectiveness of AHSCT and ocrelizumab over a shorter available follow-up time.

Publisher

American Medical Association (AMA)

Subject

Neurology (clinical)

Link

https://jamanetwork.com/journals/jamaneurology/articlepdf/2805036/jamaneurology_kalincik_2023_oi_230026_1688145198.64284.pdf

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