Michael Zhong1, Anneke van der Walt1, Jim Stankovich2, Tomas Kalincik3, Katherine Buzzard4, Olga Skibina5, Cavit Boz6, Suzanne Hodgkinson7, Mark Slee8, Jeannette Lechner-Scott9, Richard Macdonell10, Julie Prevost11, Jens Kuhle12, Guy Laureys13, Liesbeth Van Hijfte13, Raed Alroughani14, Allan G Kermode15, Ernest Butler16, Michael Barnett17, Sara Eichau18, Vincent van Pesch19, Pierre Grammond20, Pamela McCombe21, Rana Karabudak22, Pierre Duquette23, Marc Girard23, Bruce Taylor24, Wei Yeh1, Mastura Monif25, Melissa Gresle2, Helmut Butzkueven1, Vilija G Jokubaitis1. 1. Central Clinical School, Monash University, Melbourne, VIC, Australia/Department of Neurology, The Alfred Hospital, Melbourne, VIC, Australia. 2. Central Clinical School, Monash University, Melbourne, VIC, Australia. 3. CORe, Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia/MS Centre, Department of Neurology, The Royal Melbourne Hospital, Melbourne, VIC, Australia. 4. MS Centre, Department of Neurology, The Royal Melbourne Hospital, Melbourne, VIC, Australia/Department of Neurology, Box Hill Hospital, Melbourne, VIC, Australia/Monash University, Melbourne, VIC, Australia. 5. Department of Neurology, The Alfred Hospital, Melbourne, VIC, Australia/Department of Neurology, Box Hill Hospital, Melbourne, VIC, Australia/Monash University, Melbourne, VIC, Australia. 6. KTU Medical Faculty, Farabi Hospital, Trabzon, Turkey. 7. Liverpool Hospital, Sydney, NSW, Australia. 8. Flinders University, Adelaide, SA, Australia. 9. School of Medicine and Public Health, The University of Newcastle, Newcastle, NSW, Australia/Department of Neurology, John Hunter Hospital, Hunter New England Health, Newcastle, NSW, Australia. 10. Department of Neurology, Austin Health, Melbourne, VIC, Australia. 11. CSSS Saint-Jérôme, Saint-Jérôme, QC, Canada. 12. Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland. 13. Department of Neurology, University Hospital Ghent, Ghent, Belgium. 14. Division of Neurology, Department of Medicine, Amiri Hospital, Sharq, Kuwait. 15. Perron Institute, The University of Western Australia, Perth, WA, Australia/Institute of Immunology and Infectious Diseases, Murdoch University, Perth, WA, Australia. 16. Monash Medical Centre, Melbourne, VIC, Australia. 17. Brain and Mind Centre, Sydney, NSW, Australia. 18. Hospital Universitario Virgen Macarena, Sevilla, Spain. 19. Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, Belgium. 20. CISSS Chaudière-Appalache, Levis, QC, Canada. 21. Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia. 22. Department of Neurology, Hacettepe University, Ankara, Turkey. 23. CHUM and Universite de Montreal, Montreal, QC, Canada. 24. Royal Hobart Hospital, Hobart, TAS, Australia. 25. Central Clinical School, Monash University, Melbourne, VIC, Australia/Department of Neurology, The Alfred Hospital, Melbourne, VIC, Australia/MS Centre, Department of Neurology, The Royal Melbourne Hospital, Melbourne, VIC, Australia.
Abstract
BACKGROUND: Increasingly, people with relapsing-remitting multiple sclerosis (RRMS) are switched to highly effective disease-modifying therapies (DMTs) such as ocrelizumab. OBJECTIVE: To determine predictors of relapse and disability progression when switching from another DMT to ocrelizumab. METHODS: Patients with RRMS who switched to ocrelizumab were identified from the MSBase Registry and grouped by prior disease-modifying therapy (pDMT; interferon-β/glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod or natalizumab) and washout duration (<1 month, 1-2 months or 2-6 months). Survival analyses including multivariable Cox proportional hazard regression models were used to identify predictors of on-ocrelizumab relapse within 1 year, and 6-month confirmed disability progression (CDP). RESULTS: After adjustment, relapse hazard when switching from fingolimod was greater than other pDMTs, but only in the first 3 months of ocrelizumab therapy (hazard ratio (HR) = 3.98, 95% confidence interval (CI) = 1.57-11.11, p = 0.004). The adjusted hazard for CDP was significantly higher with longer washout (2-6 m compared to <1 m: HR = 9.57, 95% CI = 1.92-47.64, p = 0.006). CONCLUSION: The risk of disability worsening during switch to ocrelizumab is reduced by short treatment gaps. Patients who cease fingolimod are at heightened relapse risk in the first 3 months on ocrelizumab. Prospective evaluation of strategies such as washout reduction may help optimise this switch.
BACKGROUND: Increasingly, people with relapsing-remitting multiple sclerosis (RRMS) are switched to highly effective disease-modifying therapies (DMTs) such as ocrelizumab. OBJECTIVE: To determine predictors of relapse and disability progression when switching from another DMT to ocrelizumab. METHODS: Patients with RRMS who switched to ocrelizumab were identified from the MSBase Registry and grouped by prior disease-modifying therapy (pDMT; interferon-β/glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod or natalizumab) and washout duration (<1 month, 1-2 months or 2-6 months). Survival analyses including multivariable Cox proportional hazard regression models were used to identify predictors of on-ocrelizumab relapse within 1 year, and 6-month confirmed disability progression (CDP). RESULTS: After adjustment, relapse hazard when switching from fingolimod was greater than other pDMTs, but only in the first 3 months of ocrelizumab therapy (hazard ratio (HR) = 3.98, 95% confidence interval (CI) = 1.57-11.11, p = 0.004). The adjusted hazard for CDP was significantly higher with longer washout (2-6 m compared to <1 m: HR = 9.57, 95% CI = 1.92-47.64, p = 0.006). CONCLUSION: The risk of disability worsening during switch to ocrelizumab is reduced by short treatment gaps. Patients who cease fingolimod are at heightened relapse risk in the first 3 months on ocrelizumab. Prospective evaluation of strategies such as washout reduction may help optimise this switch.