Steffen Pfeuffer1, Rene Schmidt2, Frederike Anne Straeten1, Refik Pul3, Christoph Kleinschnitz3, Marinus Wieshuber4, De-Hyung Lee4, Ralf A Linker4, Sebastian Doerck5, Vera Straeten6, Susanne Windhagen7, Marc Pawlitzki8, Christoph Aufenberg9, Michael Lang10, Christian Eienbroeker11, Björn Tackenberg11, Volker Limmroth12, Brigitte Wildemann13, Jürgen Haas13, Luisa Klotz1, Heinz Wiendl1, Tobias Ruck1, Sven G Meuth14. 1. Department of Neurology and Institute for Translational Neurology, University Hospital Muenster, University of Muenster, Albert-Schweitzer-Campus 1, 48149, Muenster, Germany. 2. Institute of Biostatistics and Clinical Research, University of Muenster, Muenster, Germany. 3. Department of Neurology, University Duisburg-Essen, Duisburg, Germany. 4. Department of Neurology, Friedrich-Alexander-University, Erlangen-Nuremberg, Germany. 5. Department of Neurology, University of Wuerzburg, Wuerzburg, Germany. 6. Department of Neurology, Johannes-Wesling-Hospital Minden, Minden, Germany. 7. Department of Neurology, Clinics Osnabrueck, Osnabrueck, Germany. 8. Department of Neurology, University Medical Center Magdeburg, Magdeburg, Germany. 9. Department of Neurology, Herz-Jesu-Hospital Muenster-Hiltrup, Muenster, Germany. 10. Center for Neurology, Ulm, Germany. 11. Department of Neurology, University of Giessen-Marburg, Marburg, Germany. 12. Department of Neurology, Cologne General Hospitals, University of Cologne, Cologne, Germany. 13. Department of Neurology, University Hospital of Heidelberg, Heidelberg, Germany. 14. Department of Neurology and Institute for Translational Neurology, University Hospital Muenster, University of Muenster, Albert-Schweitzer-Campus 1, 48149, Muenster, Germany. sven.meuth@ukmuenster.de.
Abstract
BACKGROUND: Natalizumab (NTZ) was the first approved monoclonal antibody for the treatment of relapsing-remitting multiple sclerosis (RRMS). Despite proven and sustained efficacy, its use is limited by the risk of progressive multifocal leukoencephalopathy (PML). Moreover, some patients show ongoing disease activity under NTZ, requiring a switch to another disease-modifying treatment (DMT). However, evidence regarding the optimal DMT for treatment of active RRMS after NTZ-cessation is still scarce. OBJECTIVE: To evaluate efficacy and safety outcomes of ALEM vs FTY treatment after cessation of NTZ. METHODS: We retrospectively identified patients at 12 German neurology centers and analyzed risks for disease activity, adverse events, disability progression, and treatment discontinuation. RESULTS: 195 patients were identified and 144 underwent final analysis (FTY: 101; ALEM: 42). The hazard ratio for clinical relapses was 2.24 favoring ALEM (95% CI 1.12-4.50; p = 0.015). The hazard ratio for adverse events was 7.78 (95% CI 1.04-57.95; p = 0.006) and 2.41 for MRI progression (95% CI 1.26-4.60; p = 0.004). The odds ratio for disability progression after 12 months was 4.84 (95% CI 1.74-13.47, p = 0.003). Differences remained after adjusting for possible confounders (e.g., age, sex, baseline disability, NTZ treatment duration, washout time). CONCLUSION: Our findings indicated particular advantages of ALEM compared to FTY in patients stopping NTZ.
BACKGROUND: Natalizumab (NTZ) was the first approved monoclonal antibody for the treatment of relapsing-remitting multiple sclerosis (RRMS). Despite proven and sustained efficacy, its use is limited by the risk of progressive multifocal leukoencephalopathy (PML). Moreover, some patients show ongoing disease activity under NTZ, requiring a switch to another disease-modifying treatment (DMT). However, evidence regarding the optimal DMT for treatment of active RRMS after NTZ-cessation is still scarce. OBJECTIVE: To evaluate efficacy and safety outcomes of ALEM vs FTY treatment after cessation of NTZ. METHODS: We retrospectively identified patients at 12 German neurology centers and analyzed risks for disease activity, adverse events, disability progression, and treatment discontinuation. RESULTS: 195 patients were identified and 144 underwent final analysis (FTY: 101; ALEM: 42). The hazard ratio for clinical relapses was 2.24 favoring ALEM (95% CI 1.12-4.50; p = 0.015). The hazard ratio for adverse events was 7.78 (95% CI 1.04-57.95; p = 0.006) and 2.41 for MRI progression (95% CI 1.26-4.60; p = 0.004). The odds ratio for disability progression after 12 months was 4.84 (95% CI 1.74-13.47, p = 0.003). Differences remained after adjusting for possible confounders (e.g., age, sex, baseline disability, NTZ treatment duration, washout time). CONCLUSION: Our findings indicated particular advantages of ALEM compared to FTY in patients stopping NTZ.
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