Helmut Butzkueven1, Maria Trojano2, Ludwig Kappos3, Tim Spelman4, Heinz Wiendl5, Karen Rosales6, Ray Su6, Stephanie Licata6, Pei-Ran Ho6, Nolan Campbell6. 1. Department of Neuroscience, Central Clinical School, Alfred Campus, Monash University, Melbourne, VIC, Australia/Department of Neurology, Box Hill Hospital, Monash University, Box Hill, VIC, Australia. 2. Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, Italy. 3. Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital, University of Basel, Basel, Switzerland. 4. Department of Medicine and Melbourne Brain Centre, Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC, Australia. 5. Department of Neurology-Inflammatory Disorders of the Nervous System and Neuro-Oncology, University of Münster, Münster, Germany. 6. Biogen, Cambridge, MA, USA.
Abstract
BACKGROUND: Natalizumab is a highly efficacious therapy for relapsing-remitting multiple sclerosis (RRMS). Patients who discontinue natalizumab may experience return of MS disease activity. OBJECTIVE: The aim of this study was to analyze predictors of post-natalizumab disease activity return. METHODS: The Tysabri® Observational Program (TOP) is an ongoing observational study of natalizumab-treated RRMS patients. Patients discontinuing natalizumab are encouraged to remain in TOP. RESULTS: Analyses included 3221 TOP patients. After ⩾2 years on natalizumab, relapse risk was twice as high for patients who switched to an oral therapy (n = 660, hazard ratio (HR) = 2.18, p < 0.001) and three times as high for patients who switched to an injectable therapy (n = 95, HR = 3.02, p < 0.001) as for those who stayed on natalizumab (n = 2466). Relapse rates after switching remained below pre-natalizumab rates. In patients who switched to an oral therapy, higher relapse risk was predicted by longer washout time, more pre-natalizumab relapses, higher Expanded Disability Status Scale score at natalizumab initiation, and shorter natalizumab treatment duration. CONCLUSION: Patients who stayed on natalizumab had better clinical outcomes than those who switched to an oral or injectable therapy after ⩾2 years on natalizumab. These results highlight modifiable risk factors for disease activity return (e.g. natalizumab treatment duration and washout duration) to consider when making treatment decisions.
BACKGROUND:Natalizumab is a highly efficacious therapy for relapsing-remitting multiple sclerosis (RRMS). Patients who discontinue natalizumab may experience return of MS disease activity. OBJECTIVE: The aim of this study was to analyze predictors of post-natalizumab disease activity return. METHODS: The Tysabri® Observational Program (TOP) is an ongoing observational study of natalizumab-treated RRMS patients. Patients discontinuing natalizumab are encouraged to remain in TOP. RESULTS: Analyses included 3221 TOP patients. After ⩾2 years on natalizumab, relapse risk was twice as high for patients who switched to an oral therapy (n = 660, hazard ratio (HR) = 2.18, p < 0.001) and three times as high for patients who switched to an injectable therapy (n = 95, HR = 3.02, p < 0.001) as for those who stayed on natalizumab (n = 2466). Relapse rates after switching remained below pre-natalizumab rates. In patients who switched to an oral therapy, higher relapse risk was predicted by longer washout time, more pre-natalizumab relapses, higher Expanded Disability Status Scale score at natalizumab initiation, and shorter natalizumab treatment duration. CONCLUSION:Patients who stayed on natalizumab had better clinical outcomes than those who switched to an oral or injectable therapy after ⩾2 years on natalizumab. These results highlight modifiable risk factors for disease activity return (e.g. natalizumab treatment duration and washout duration) to consider when making treatment decisions.
Authors: Michael Auer; Anne Zinganell; Harald Hegen; Gabriel Bsteh; Franziska Di Pauli; Klaus Berek; Elena Fava; Sebastian Wurth; Thomas Berger; Florian Deisenhammer Journal: Sci Rep Date: 2021-12-02 Impact factor: 4.379
Authors: Michael Guger; Christian Enzinger; Fritz Leutmezer; Franziska Di Pauli; Jörg Kraus; Stefan Kalcher; Erich Kvas; Thomas Berger Journal: J Neurol Date: 2021-04-22 Impact factor: 4.849