Prediction of multiple sclerosis outcomes when switching to ocrelizumab

Author:

Zhong Michael1,van der Walt Anneke1ORCID,Stankovich Jim2,Kalincik Tomas3ORCID,Buzzard Katherine4,Skibina Olga5,Boz Cavit6,Hodgkinson Suzanne7,Slee Mark8,Lechner-Scott Jeannette9ORCID,Macdonell Richard10,Prevost Julie11,Kuhle Jens12,Laureys Guy13,Van Hijfte Liesbeth13,Alroughani Raed14ORCID,Kermode Allan G15ORCID,Butler Ernest16,Barnett Michael17ORCID,Eichau Sara18ORCID,van Pesch Vincent19,Grammond Pierre20,McCombe Pamela21,Karabudak Rana22,Duquette Pierre23,Girard Marc23,Taylor Bruce24,Yeh Wei1,Monif Mastura25ORCID,Gresle Melissa2,Butzkueven Helmut1,Jokubaitis Vilija G1ORCID

Affiliation:

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.

Publisher

SAGE Publications

Subject

Clinical Neurology,Neurology

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