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

• Published in: Multiple sclerosis 2024-07, Vol.30 (8), p.1026-1035
• Main Authors: Zeineddine, Maya, Al-Roughani, Raed, Farouk Ahmed, Samar, Khoury, Samia, El-Ayoubi, Nabil, Al-Mahdawi, Akram, Al-Khabouri, Jaber, Al-Asmi, Abdullah, Chentouf, Amina, Inshasi, Jihad, Gouider, Riadh, Mrabet, Saloua, Shalaby, Nevin, Massouh, Joelle, Mohamed Ramzy Hasan Mohamed, Farah, Al-Hajje, Amal, Salameh, Pascale, Dimassi, Hani, Boumediene, Farid, Yamout, Bassem
• Format: Article
• Language: English
• Subjects: Adult; Alemtuzumab - adverse effects; Alemtuzumab - therapeutic use; Antibodies; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Drug Substitution; Female; Fingolimod Hydrochloride - therapeutic use; Humans; Immunologic Factors - adverse effects; JC Virus - immunology; Leukoencephalopathy; Leukoencephalopathy, Progressive Multifocal - chemically induced; Life Sciences; Magnetic resonance imaging; Male; Middle Aged; Monoclonal antibodies; Multiple sclerosis; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Natalizumab - adverse effects; Natalizumab - therapeutic use; Progressive multifocal leukoencephalopathy; Rituximab; Rituximab - adverse effects; Rituximab - therapeutic use; Santé publique et épidémiologie
• ISSN: 1352-4585; 1477-0970; 1477-0970
• DOI: 10.1177/13524585241261565

Introduction: 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. Objective: 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. Methods: 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. Results: 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 (p = 0.014) and a higher proportion developed magnetic resonance imaging (MRI) lesions compared with rituximab/ocrelizumab (62.9% vs. 13.0%, p < 0.001, and 66.6% vs. 24.0%, p < 0.001, respectively). Mean drug survival favored rituximab/ocrelizumab or alemtuzumab over fingolimod (p < 0.001). Conclusion: 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.