Isfahan University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Effectiveness of Multiple Disease-Modifying Therapies in Relapsing-Remitting Multiple Sclerosis: Causal Inference to Emulate a Multiarm Randomised Trial Publisher Pubmed



Diouf I1, 2 ; Malpas CB1, 3 ; Sharmin S1 ; Roos I1 ; Horakova D4, 5 ; Kubala Havrdova E4, 5 ; Patti F6 ; Shaygannejad V7 ; Ozakbas S8 ; Eichau S9 ; Onofrj M10 ; Lugaresi A11, 12 ; Alroughani R13 ; Prat A14, 15 Show All Authors
Authors
  1. Diouf I1, 2
  2. Malpas CB1, 3
  3. Sharmin S1
  4. Roos I1
  5. Horakova D4, 5
  6. Kubala Havrdova E4, 5
  7. Patti F6
  8. Shaygannejad V7
  9. Ozakbas S8
  10. Eichau S9
  11. Onofrj M10
  12. Lugaresi A11, 12
  13. Alroughani R13
  14. Prat A14, 15
  15. Duquette P14, 15
  16. Terzi M14, 15
  17. Boz C16, 17
  18. Grandmaison F18
  19. Sola P19
  20. Ferraro D19
  21. Grammond P20
  22. Yamout B21, 22
  23. Altintas A23, 24
  24. Gerlach O25, 26
  25. Lechnerscott J27, 28
  26. Bergamaschi R29
  27. Karabudak R30
  28. Iuliano G31
  29. Mcguigan C32
  30. Cartechini E33
  31. Hughes S34
  32. Sa MJ35
  33. Solaro C36, 37
  34. Kappos L38, 39
  35. Hodgkinson S40
  36. Slee M41
  37. Granella F42
  38. De Gans K43
  39. Mccombe PA44
  40. Ampapa R45
  41. Van Der Walt A46, 47
  42. Butzkueven H46, 47
  43. Sanchezmenoyo JL48
  44. Vucic S49
  45. Laureys G50
  46. Sidhom Y51, 52
  47. Gouider R52
  48. Castillotrivino T53
  49. Gray O54
  50. Agueramorales E55
  51. Alasmi A56, 57
  52. Shaw C58
  53. Alharbi TM59
  54. Csepany T60
  55. Sempere AP61
  56. Trevino Frenk I62
  57. Stuart EA63
  58. Kalincik T1, 3
Show Affiliations
Authors Affiliations
  1. 1. CORe, Department of Medicine, University of Melbourne, Melbourne, VIC, Australia
  2. 2. Health and Biosecurity Unit, Commonwealth Scientific and Industrial Research Organisation, Melbourne, VIC, Australia
  3. 3. Neuroimmunology Centre, Department of Neurology, Royal Melbourne Hospital City Campus, Parkville, 3050, VIC, Australia
  4. 4. Department of Neurology, Center of Clinical Neuroscience, Charles University, Praha, Czech Republic
  5. 5. General University Hospital in Prague, Praha, Czech Republic
  6. 6. Department of Medical and Surgical Sciences and Advanced Technologies, University of Catania 'G.F. Ingrassia', Catania, Italy
  7. 7. Department of Neurology, Isfahan University of Medical Sciences, (the Islamic Republic of), Isfahan, Iran
  8. 8. Dokuz Eylul University, Izmir, Turkey
  9. 9. Neurology, Hospital Universitario Virgen Macarena, Sevilla, Spain
  10. 10. Deptartment of Neuroscience Imaging, and Clinical Sciences, Gabriele d'Annunzio University of Chieti and 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. Division of Neurology, Department of Medicine, Amiri Hospital, Kuwait City, Kuwait
  14. 14. CHUM MS Center, Montreal, QC, Canada
  15. 15. Universite de Montreal, Montreal, QC, Canada
  16. 16. School of Medicine, Ondokuz Mayis Universitesi, Samsun, Turkey
  17. 17. KTU Medical Faculty Farabi Hospital, Trabzon, Turkey
  18. 18. Neuro Rive-Sud, Greenfield Park, QC, Canada
  19. 19. Department of Neuroscience, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy
  20. 20. CISSS de Chaudiere-Appalaches, Levis, QC, Canada
  21. 21. Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center, Beirut, Lebanon
  22. 22. Department of Neurology, American University of Beirut, Beirut, Lebanon
  23. 23. Department of Neurology, Koc Universitesi, Istanbul, Turkey
  24. 24. Koc University Research Center for Translational Medicine, Istanbul, Turkey
  25. 25. Department of Neurology, Zuyderland Medical Centre Sittard-Geleen, Sittard-Geleen, Netherlands
  26. 26. School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands
  27. 27. University of Newcastle Hunter Medical Research Institute, Newcastle, NSW, Australia
  28. 28. Department of Neurology, John Hunter Hospital, Newcastle, NSW, Australia
  29. 29. Foundation National Neurological Institute, C Mondino Institute for Hospitalization and Care Scientific, Pavia, Italy
  30. 30. Department of Neurology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
  31. 31. Ospedali Riuniti di Salerno, Salerno, Italy
  32. 32. Department of Neurology, St Vincent's University Hospital, Dublin, Ireland
  33. 33. UOC Neurologia, Azienda Sanitaria Unica Regionale Marche - AV3, Macerata, Italy
  34. 34. Royal Victoria Hospital, Belfast, United Kingdom
  35. 35. Department of Neurology, Centro Hospitalar de Sao Joao, Porto, Portugal
  36. 36. Department of Neurology, ASL3 Genovese, Genova, Italy
  37. 37. Department of Rehabilitaiton, Casa di Cura Centro di Recupero e Rieducazione Funzionale Mons Luigi Novarese, Moncrivello, Italy
  38. 38. Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), MS Center, Neurologic Clinic and Policlinic, Departments of Head, Spine and Neuromedicine and Clinical Research, University Hospital Basel, Basel, Switzerland
  39. 39. University of Basel, Basel, Switzerland
  40. 40. Liverpool Hospital, Sydney, NSW, Australia
  41. 41. Flinders University, Adelaide, SA, Australia
  42. 42. Department of Medicine and Surgery, University of Parma, Parma, Italy
  43. 43. Groene Hart Ziekenhuis, Gouda, Netherlands
  44. 44. UQCCR, University of Queensland, Brisbane, QLD, Australia
  45. 45. Nemocnice Jihlava, Jihlava, Czech Republic
  46. 46. Department of Neurology, Alfred Hospital, Melbourne, VIC, Australia
  47. 47. Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia
  48. 48. Department of Neurology, Galdakao-Usansolo Hospital, Galdakao, Spain
  49. 49. Westmead Hospital, Westmead, NSW, Australia
  50. 50. Universitair Ziekenhuis Gent, Gent, Belgium
  51. 51. Department of Neurology, Razi University Hospital, Tunis, Tunisia
  52. 52. Department of Neurology, University of Tunis El Manar, Tunis, Tunisia
  53. 53. Instituto de Investigacion Sanitaria Biodonostia, Hospital Universitario de Donostia, San Sebastian, Spain
  54. 54. South and East Belfast Health and Social Services Trust, Belfast, United Kingdom
  55. 55. Neurology, Hospital Universitario Reina Sofia, Cordoba, Spain
  56. 56. Department of Medicine, Sultan Qaboos University Hospital, Seeb, Oman
  57. 57. Sultan Qaboos University, Muscat, Oman
  58. 58. University Hospital Geelong, Geelong, VIC, Australia
  59. 59. Department of Neurology, King Fahad Specialist Hospital-Dammam, Khobar, Saudi Arabia
  60. 60. Department of Neurology, University of Debrecen, Debrecen, Hungary
  61. 61. Department of Neurology, Hospital General de Alicante, Alicante, Spain
  62. 62. Department of Neurology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico
  63. 63. Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, United States

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


Abstract

Background Simultaneous comparisons of multiple disease-modifying therapies for relapsing-remitting multiple sclerosis (RRMS) over an extended follow-up are lacking. Here we emulate a randomised trial simultaneously comparing the effectiveness of six commonly used therapies over 5 years. Methods Data from 74 centres in 35 countries were sourced from MSBase. For each patient, the first eligible intervention was analysed, censoring at change/discontinuation of treatment. The compared interventions included natalizumab, fingolimod, dimethyl fumarate, teriflunomide, interferon beta, glatiramer acetate and no treatment. Marginal structural Cox models (MSMs) were used to estimate the average treatment effects (ATEs) and the average treatment effects among the treated (ATT), rebalancing the compared groups at 6-monthly intervals on age, sex, birth-year, pregnancy status, treatment, relapses, disease duration, disability and disease course. The outcomes analysed were incidence of relapses, 12-month confirmed disability worsening and improvement. Results 23 236 eligible patients were diagnosed with RRMS or clinically isolated syndrome. Compared with glatiramer acetate (reference), several therapies showed a superior ATE in reducing relapses: natalizumab (HR=0.44, 95% CI=0.40 to 0.50), fingolimod (HR=0.60, 95% CI=0.54 to 0.66) and dimethyl fumarate (HR=0.78, 95% CI=0.66 to 0.92). Further, natalizumab (HR=0.43, 95% CI=0.32 to 0.56) showed a superior ATE in reducing disability worsening and in disability improvement (HR=1.32, 95% CI=1.08 to 1.60). The pairwise ATT comparisons also showed superior effects of natalizumab followed by fingolimod on relapses and disability. Conclusions The effectiveness of natalizumab and fingolimod in active RRMS is superior to dimethyl fumarate, teriflunomide, glatiramer acetate and interferon beta. This study demonstrates the utility of MSM in emulating trials to compare clinical effectiveness among multiple interventions simultaneously. © 2023 Author(s). Published by BMJ.
Other Related Docs
31. Disability Accrual in Primary and Secondary Progressive Multiple Sclerosis, Journal of Neurology, Neurosurgery and Psychiatry (2023)
42. Diagnosis and Management of Multiple Sclerosis in Children, Iranian Journal of Child Neurology (2016)
47. Early Predictors of Conversion to Secondary Progressive Multiple Sclerosis, Multiple Sclerosis and Related Disorders (2021)
49. Concurrent Glioma and Multiple Sclerosis: A Systematic Review of Case Reports, Multiple Sclerosis and Related Disorders (2024)