Safety and effectiveness of disease-modifying therapies after switching from natalizumab.

Journal: Multiple sclerosis (Houndmills, Basingstoke, England)

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Affiliated Institutions:  Inserm U, IRD U, Univ. Limoges, CHU Limoges, EpiMaCT-Epidemiology of chronic diseases in tropical zone, Institute of Epidemiology and Tropical Neurology, Omega Health, Limoges, France. Al-Amiri Hospital, Kuwait City, Kuwait. Ibn Sina Hospital, Kuwait City, Kuwait. American University of Beirut Medical Center, Nehme and Therese Tohme Multiple Sclerosis Center, Beirut, Lebanon. Baghdad Medical City Teaching Hospital, Baghdad, Iraq. Department of Neurology, The Royal Hospital, Muscat, Oman. Neurology Unit, Department of Medicine, College of Medicine and Health Sciences and Sultan Qaboos University Hospital, Sultan Qaboos University, Muscat, Oman. Neurology Department, University Hospital Center, Oran, Algeria. MS Department, Rashid Hospital and Dubai Medical College, Dubai Health Authority, Dubai, United Arab Emirates. Department of Neurology, LRSP, Clinical Investigation Center "Neurosciences and Mental Health," Razi University Hospital-Manouba, Tunis, Tunisia. Neurology Department, Kasr Alainy School of Medicine, Cairo University, Cairo, Egypt. Neurology Institute and MS Center, Harley Street Medical Center, Abu Dhabi, United Arab Emirates. Faculty of Pharmacy, Lebanese University, Beirut, Lebanon.

Abstract summary 

One strategy to mitigate progressive multifocal leukoencephalopathy (PML) risk is to switch to other highly effective disease-modifying therapies (DMTs). However, the optimal switch DMT following natalizumab (NTZ) discontinuation is yet to be determined.The objective of the study is to determine the most effective and tolerable DMTs to switch to following NTZ discontinuation due to John Cunningham virus (JCV) antibody positivity.This is a multicenter observational cohort study that included all stable relapsing-remitting multiple sclerosis (MS) patients who were treated with NTZ for at least 6 months before switching therapy due to JCV antibody positivity.Of 321 patients, 255 switched from NTZ to rituximab/ocrelizumab, 52 to fingolimod, and 14 to alemtuzumab, with higher annualized relapse rate (ARR) in fingolimod switchers (0.193) compared with rituximab/ocrelizumab or alemtuzumab (0.028 and 0.032, respectively). Fingolimod switchers also had increased disability progression ( = 0.014) and a higher proportion developed magnetic resonance imaging (MRI) lesions compared with rituximab/ocrelizumab (62.9% vs. 13.0%, < 0.001, and 66.6% vs. 24.0%, < 0.001, respectively). Mean drug survival favored rituximab/ocrelizumab or alemtuzumab over fingolimod ( < 0.001).Our study shows superior effectiveness of rituximab/ocrelizumab and alemtuzumab compared with fingolimod in stable patients switching from NTZ due to JC virus antibody positivity.

Authors & Co-authors:  Zeineddine Maya M Al-Roughani Raed R Farouk Ahmed Samar S Khoury Samia S El-Ayoubi Nabil N Al-Mahdawi Akram A Al-Khabouri Jaber J Al-Asmi Abdullah A Chentouf Amina A Inshasi Jihad J Gouider Riadh R Mrabet Saloua S Shalaby Nevin N Massouh Joelle J Mohamed Ramzy Hasan Mohamed Farah F Al-Hajje Amal A Salameh Pascale P Dimassi Hani H Boumediene Farid F Yamout Bassem B

Study Outcome 

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Citations : 
Authors :  20
Identifiers
Doi : 10.1177/13524585241261565
SSN : 1477-0970
Study Population
Male,Female
Mesh Terms
Other Terms
Natalizumab;PML;effectiveness;fingolimod;multiple sclerosis;rituximab;switching
Study Design
Cohort Study
Study Approach
Country of Study
Publication Country
England