Fabien Rollot1, Romain Casey1, Emmanuelle Leray2, Marc Debouverie3, Gilles Edan4, Sandrine Wiertlewski5, Sandra Vukusic1, David-Axel Laplaud6. 1. Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France; Service de Neurologie, sclérose en plaques, pathologies de la myéline et neuro-inflammation, Hospices Civils de Lyon, Bron, France; Observatoire Français de la Sclérose en Plaques, Centre de Recherche en Neurosciences de Lyon, INSERM 1028 et CNRS UMR 5292, Lyon, France; EUGENE DEVIC EDMUS Foundation, Bron, France. 2. Univ Rennes/EHESP, REPERES - EA 7449, Rennes, France; CIC-P 1414, CHU Rennes, Rennes, France. 3. Département de Neurologie, CHU Nancy, Nancy, France; EA 4360 APEMAC, Université Lorraine, Nancy, France. 4. CIC-P 1414, CHU Rennes, Rennes, France; Département de Neurologie, CHU Rennes, Rennes, France. 5. Département de Neurologie, CHU Nantes, Nantes, France; CIC Inserm 1415, CHU Nantes, Nantes, France. 6. Département de Neurologie, CHU Nantes, Nantes, France; CIC Inserm 1415, CHU Nantes, Nantes, France; Centre de Recherche en Transplantation et Immunologie, Inserm U1064, Nantes, France.
Abstract
BACKGROUND: Long-term effectiveness of treatment remains a key question in multiple sclerosis (MS) and the cumulative effects of past treatment have not been investigated so far. OBJECTIVE: Explore the relationship between treatment exposure and disability risk in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: A total of 2285 adult patients from the French nationwide cohort were included. Outcomes were irreversible EDSS4, and conversion to secondary progression of multiple sclerosis (SPMS). Associations between treatments and risk of disability were assessed using a novel weighted cumulative exposure model, assuming a 3-year lag to account for reverse causality. This flexible approach accounts for past exposure in a multivariate Cox proportional hazards model by computing a weight function. RESULTS: At baseline, mean ± standard deviation age of patients was 33.4 ± 8.9 years and 75.0% were women. A 15-year continuous treatment starting 20 years ago was associated with a decrease in risk of 26% for irreversible EDSS4, and 34% for SPMS compared to a 5-year treatment starting 10 years ago. The risk of disability decreased with increasing duration of exposure to disease-modifying treatment (DMT). CONCLUSION: Long-term use of treatments in RRMS has a stronger beneficial cumulative impact than only early uses and delays the occurrence of moderate disability and conversion to SPMS.
BACKGROUND: Long-term effectiveness of treatment remains a key question in multiple sclerosis (MS) and the cumulative effects of past treatment have not been investigated so far. OBJECTIVE: Explore the relationship between treatment exposure and disability risk in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: A total of 2285 adult patients from the French nationwide cohort were included. Outcomes were irreversible EDSS4, and conversion to secondary progression of multiple sclerosis (SPMS). Associations between treatments and risk of disability were assessed using a novel weighted cumulative exposure model, assuming a 3-year lag to account for reverse causality. This flexible approach accounts for past exposure in a multivariate Cox proportional hazards model by computing a weight function. RESULTS: At baseline, mean ± standard deviation age of patients was 33.4 ± 8.9 years and 75.0% were women. A 15-year continuous treatment starting 20 years ago was associated with a decrease in risk of 26% for irreversible EDSS4, and 34% for SPMS compared to a 5-year treatment starting 10 years ago. The risk of disability decreased with increasing duration of exposure to disease-modifying treatment (DMT). CONCLUSION: Long-term use of treatments in RRMS has a stronger beneficial cumulative impact than only early uses and delays the occurrence of moderate disability and conversion to SPMS.
Authors: Laura Bierhansl; Hans-Peter Hartung; Orhan Aktas; Tobias Ruck; Michael Roden; Sven G Meuth Journal: Nat Rev Drug Discov Date: 2022-06-06 Impact factor: 112.288