Ilya Kister1, Tim Spelman2, Francesco Patti3, Pierre Duquette4, Maria Trojano5, Guillermo Izquierdo6, Alessandra Lugaresi7, Pierre Grammond8, Patrizia Sola9, Diana Ferraro9, Francois Grand'Maison10, Raed Alroughani11, Murat Terzi12, Cavit Boz13, Raymond Hupperts14, Jeannette Lechner-Scott15, Ludwig Kappos16, Eugenio Pucci17, Suzanne Hodgkinson18, Claudio Solaro19, Helmut Butzkueven20. 1. NYU School of Medicine, New York, NY, USA. Electronic address: ilya.kister@nyumc.org. 2. Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia; Department of Neurology, Alfred Hospital, Melbourne, VIC, Australia. 3. Department of Neurological Sciences, Centro Sclerosi Multipla, Policlinico Universitario di Catania, Catania, Italy. 4. Hôpital Notre Dame, Montreal, QC, Canada. 5. Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy. 6. Hospital Universitario Virgen Macarena, Sevilla, Spain. 7. University "Alma Mater Studiorum", Bologna, Italy; IRCCS "Istituto delle Scienze Neurologiche di Bologna", Bologna, Italy. 8. Hotel-Dieu de Levis, Lévis, QC, Canada. 9. Nuovo Ospedale Civile Sant'Agostino-Estense, Modena, Italy. 10. Hopital Charles LeMoyne, QC, Canada. 11. Amiri Hospital, Kuwait City, Kuwait. 12. Medical Faculty, 19 Mayis University, Samsun, Turkey. 13. Karadeniz Technical University, Trabzon, Turkey. 14. Orbis Medical Center, Sittard-Geleen, the Netherlands. 15. Hunter Medical Research Institute, University Newcastle, Newcastle, NSW, Australia. 16. University Hospital Basel, Neurology, Departments of Medicine, Clinical Research and Biomedicine, Basel, Switzerland. 17. Azienda Sanitaria Unica Regionale Marche, Macerata, Italy. 18. Liverpool Hospital, Sydney, NSW, Australia. 19. Dept of Rehabilitation Mons L Novarese Hospital, Moncrivello, Italy. 20. Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia; Department of Neurology, Alfred Hospital, Melbourne, VIC, Australia; Box Hill Hospital, Melbourne, VIC, Australia.
Abstract
BACKGROUND: Discontinuation of disease-modifying therapies (DMTs) for MS is common. MSBase, a large global observational registry, affords a unique opportunity to investigate predictors of 'post-DMT' relapses and confirmed disability progression (CDP) in a diverse group of patients exposed to different DMTs. MATERIALS/ METHODS: Main inclusion criteria: clinician-confirmed MS diagnosis (2010 McDonald criteria); age ≥ 18 at index DMT start; ≥12 months on index DMT prior to discontinuation; ≥24 months of follow-up post-discontinuation; did not restart DMT for ≥6 months. Predictors of time to first relapse and 3-month CDP were analyzed using Cox proportional hazards regression adjusted for age, gender, baseline EDSS, EDSS stability and relapse-free period for ≥1 year prior to discontinuation, calendar epoch, index DMT and reason for discontinuation. RESULTS: 4842 patients (74.2% female) from 20 MSBase Centers met our inclusion criteria. 3556 (73%) discontinued one of IFNβ preparations, 849 (18%) - glatiramer acetate, 308 (6%) - natalizumab and 129 (3%) - fingolimod; other DMTs were excluded because too few records were available. Overall post-discontinuation annualized relapse rate (95% CI) was 0.224 (0.219, 0.229) and CDP rate was 8.23 (7.72, 8.76) per 100 person-years. Risk of post-DMT relapse was higher in younger patients, female patients, those with moderate disability and a relapse within 1 year of discontinuation. Hazard of CDP increased with increasing disability at baseline and disease progression within 3 years prior to stopping DMT. Of all the DMTs, only natalizumab was associated with increased risk of both post-DMT relapse and CDP. CONCLUSIONS: Knowledge of post-DMT relapse and disability progression rates and predictors of post-DMT disease activity allows for a more informed discussion of DMT discontinuation in those patients who are considering this option.
BACKGROUND: Discontinuation of disease-modifying therapies (DMTs) for MS is common. MSBase, a large global observational registry, affords a unique opportunity to investigate predictors of 'post-DMT' relapses and confirmed disability progression (CDP) in a diverse group of patients exposed to different DMTs. MATERIALS/ METHODS: Main inclusion criteria: clinician-confirmed MS diagnosis (2010 McDonald criteria); age ≥ 18 at index DMT start; ≥12 months on index DMT prior to discontinuation; ≥24 months of follow-up post-discontinuation; did not restart DMT for ≥6 months. Predictors of time to first relapse and 3-month CDP were analyzed using Cox proportional hazards regression adjusted for age, gender, baseline EDSS, EDSS stability and relapse-free period for ≥1 year prior to discontinuation, calendar epoch, index DMT and reason for discontinuation. RESULTS: 4842 patients (74.2% female) from 20 MSBase Centers met our inclusion criteria. 3556 (73%) discontinued one of IFNβ preparations, 849 (18%) - glatiramer acetate, 308 (6%) - natalizumab and 129 (3%) - fingolimod; other DMTs were excluded because too few records were available. Overall post-discontinuation annualized relapse rate (95% CI) was 0.224 (0.219, 0.229) and CDP rate was 8.23 (7.72, 8.76) per 100 person-years. Risk of post-DMT relapse was higher in younger patients, female patients, those with moderate disability and a relapse within 1 year of discontinuation. Hazard of CDP increased with increasing disability at baseline and disease progression within 3 years prior to stopping DMT. Of all the DMTs, only natalizumab was associated with increased risk of both post-DMT relapse and CDP. CONCLUSIONS: Knowledge of post-DMT relapse and disability progression rates and predictors of post-DMT disease activity allows for a more informed discussion of DMT discontinuation in those patients who are considering this option.
Authors: Massimiliano Mirabella; Pietro Annovazzi; Wallace Brownlee; Jeffrey A Cohen; Christoph Kleinschnitz; Christian Wolf Journal: Front Neurol Date: 2022-04-15 Impact factor: 4.086