Prediction of multiple sclerosis outcomes when switching to ocrelizumab

Michael Zhong; Anneke van der Walt; Jim Stankovich; Tomas Kalincik; Katherine Buzzard; Olga Skibina; Cavit Boz; Suzanne Hodgkinson; Mark Slee; Jeannette Lechner-Scott; Richard Macdonell; Julie Prevost; Jens Kuhle; Guy Laureys; Liesbeth Van Hijfte; Raed Alroughani; Allan G. Kermode; Ernest Butler; Michael Barnett; Sara Eichau; Vincent van Pesch; Pierre Grammond; Pamela McCombe; Rana Karabudak; Pierre Duquette; Marc Girard; Bruce Taylor; Wei Yeh; Mastura Monif; Melissa Gresle; Helmut Butzkueven; Vilija G. Jokubaitis

doi:10.1177/13524585211049986

Prediction of multiple sclerosis outcomes when switching to ocrelizumab

Michael Zhong, Anneke van der Walt, Jim Stankovich, Tomas Kalincik, Katherine Buzzard, Olga Skibina, Cavit Boz, Suzanne Hodgkinson, Mark Slee, Jeannette Lechner-Scott, Richard Macdonell, Julie Prevost, Jens Kuhle, Guy Laureys, Liesbeth Van Hijfte, Raed Alroughani, Allan G. Kermode, Ernest Butler, Michael Barnett, Sara EichauVincent van Pesch, Pierre Grammond, Pamela McCombe, Rana Karabudak, Pierre Duquette, Marc Girard, Bruce Taylor, Wei Yeh, Mastura Monif, Melissa Gresle, Helmut Butzkueven, Vilija G. Jokubaitis

Research output: Contribution to journal › Article › Research › peer-review

10 Citations (Scopus)

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.

Original language	English
Pages (from-to)	958-969
Number of pages	12
Journal	Multiple Sclerosis Journal
Volume	28
Issue number	6
DOIs	https://doi.org/10.1177/13524585211049986
Publication status	Published - May 2022

Keywords

fingolimod
Ocrelizumab
switch
washout

Access to Document

10.1177/13524585211049986

Cite this

Zhong, M., van der Walt, A., Stankovich, J., Kalincik, T., Buzzard, K., Skibina, O., Boz, C., Hodgkinson, S., Slee, M., Lechner-Scott, J., Macdonell, R., Prevost, J., Kuhle, J., Laureys, G., Van Hijfte, L., Alroughani, R., Kermode, A. G., Butler, E., Barnett, M., ... Jokubaitis, V. G. (2022). Prediction of multiple sclerosis outcomes when switching to ocrelizumab. Multiple Sclerosis Journal, 28(6), 958-969. https://doi.org/10.1177/13524585211049986

@article{53405e4d4fb74e8780d4916941f001b7,

title = "Prediction of multiple sclerosis outcomes when switching to ocrelizumab",

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.",

keywords = "fingolimod, Ocrelizumab, switch, washout",

author = "Michael Zhong and {van der Walt}, Anneke and Jim Stankovich and Tomas Kalincik and Katherine Buzzard and Olga Skibina and Cavit Boz and Suzanne Hodgkinson and Mark Slee and Jeannette Lechner-Scott and Richard Macdonell and Julie Prevost and Jens Kuhle and Guy Laureys and {Van Hijfte}, Liesbeth and Raed Alroughani and Kermode, {Allan G.} and Ernest Butler and Michael Barnett and Sara Eichau and {van Pesch}, Vincent and Pierre Grammond and Pamela McCombe and Rana Karabudak and Pierre Duquette and Marc Girard and Bruce Taylor and Wei Yeh and Mastura Monif and Melissa Gresle and Helmut Butzkueven and Jokubaitis, {Vilija G.}",

note = "Funding Information: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: M.Z. received conference attendance support from Roche. A.v.d.W. reports no disclosures relevant to the manuscript. J.S. reports no disclosures relevant to the manuscript. T.K. served on scientific advisory boards for Roche, Sanofi Genzyme, Novartis, Merck and Biogen, steering committee for Brain Atrophy Initiative by Sanofi Genzyme, received conference travel support and/or speaker honoraria from WebMD Global, Novartis, Biogen, Sanofi Genzyme, Teva, bioCSL and Merck, and received research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene and Merck. K.B. received honoraria and consulting fees from Biogen, Teva, Novartis, Sanofi Genzyme, Roche, Merck, CSL and Grifols. O.S. has worked on advisory boards of Roche, Merck and Sanofi Genzyme, received travel grants from Roche, Sanofi Genzyme and Merck, and speaker honoraria from Sanofi Genzyme, Merck and Novartis. C.B. received conference travel support from Biogen, Novartis, Bayer Schering, Merck and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis. S.H. received honoraria and consulting fees from Novartis, Bayer Schering and Sanofi, and travel grants from Novartis, Biogen Idec and Bayer Schering. M.S. has participated in, but not received honoraria for, advisory board activity for Biogen, Merck, Bayer Schering, Sanofi Aventis and Novartis. J.L-S. received travel compensation from Novartis, Biogen, Roche and Merck. Her institution receives the honoraria for talks and advisory board commitment as well as research grants from Biogen, Merck, Roche, Teva and Novartis. R.M. reports no disclosures relevant to the manuscript. J.P. accepted travel compensation from Novartis, Biogen, Genzyme, Teva, and speaking honoraria from Biogen, Novartis, Genzyme and Teva. J.K. reports no disclosures relevant to the manuscript. G.L. received travel and/or consultancy compensation from Sanofi Genzyme, Roche, Teva, Merck, Novartis, Celgene and Biogen. L.V.H. reports no disclosures relevant to the manuscript. R.A. received honoraria as a speaker and for serving on scientific advisory boards from Bayer, Biogen, GSK, Merck, Novartis, Roche and Sanofi Genzyme. A.G.K. received speaker honoraria and scientific advisory board fees from Bayer, bioCSL, Biogen, Genzyme, Innate Immunotherapeutics, Merck, Novartis, Sanofi, Sanofi Aventis and Teva. E.B. reports no disclosures relevant to the manuscript. M.B. served on scientific advisory boards for Biogen, Novartis and Genzyme, and has received conference travel support from Biogen and Novartis. He serves on steering committees for trials conducted by Novartis. His institution has received research support from Biogen, Merck and Novartis. S.E. received speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck, Bayer, Sanofi Genzyme, Roche and Teva. V.v.P. received travel grants from Merck, Biogen, Sanofi, Celgene, Almirall and Roche. His institution has received research grants and consultancy fees from Roche, Biogen, Sanofi, Celgene, Merck and Novartis Pharma. P.G. has served in advisory boards for Novartis, EMD Serono, Roche, Biogen Idec, Sanofi Genzyme and Pendopharm; has received grant support from Genzyme and Roche; has received research grants for his institution from Biogen Idec, Sanofi Genzyme and EMD Serono. P.M. received honoraria and consulting fees from Novartis, Bayer Schering and Sanofi and travel grants from Novartis, Biogen and Bayer Schering. R.K. reports no disclosures relevant to the manuscript. P.D. served on editorial boards and has been supported to attend meetings by EMD, Biogen, Novartis, Genzyme and Teva Neuroscience. He holds grants from the CIHR and the MS Society of Canada and has received funding for investigator-initiated trials from Biogen, Novartis and Genzyme. M.G. received consulting fees from Teva Canada Innovation, Biogen, Novartis and Genzyme Sanofi; lecture payments from Teva Canada Innovation, Novartis and EMD. He has also received a research grant from Canadian Institutes of Health Research. B.T. received funding for travel and speaker honoraria from Bayer Schering Pharma, CSL Australia, Biogen and Novartis, and has served on advisory boards for Biogen, Novartis, Roche and CSL Australia. W.Y. received research support from Multiple Sclerosis Research Australia and the Australian Government Research Training Program, speaker honoraria and conference attendance support from Biogen, and travel support from Merck. M.M. has received funding from the National Medical Research Council Medical Research Future Fund (MRFF); her institution also has received funding from Brain Foundation, Charles and Sylvia Viertel Foundation, and Merck Industry funding. M.G. reports no disclosures relevant to the manuscript. H.B.{\textquoteright}s institution received compensation for Advisory Board, Steering Committee and Educational activities from Biogen, Roche, Merck and Novartis. His institution received research support from Roche, Novartis, Biogen, NHMRC and MRFF Australia and MS Research Australia. He received personal compensation from Oxford HPF for serving on the steering group of MS Brain Health. V.G.J. received conference travel support from Merck and Roche, and speakers honoraria from Biogen and Roche outside of the submitted work. She receives research support from the Australian National Health and Medical Research Grant and MS Research Australia. Publisher Copyright: {\textcopyright} The Author(s), 2021. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2022",

month = may,

doi = "10.1177/13524585211049986",

language = "English",

volume = "28",

pages = "958--969",

journal = "Multiple Sclerosis Journal",

issn = "1352-4585",

publisher = "SAGE Publications Ltd",

number = "6",

}

Zhong, M, van der Walt, A, Stankovich, J, Kalincik, T, Buzzard, K , Skibina, O, Boz, C, Hodgkinson, S, Slee, M, Lechner-Scott, J, Macdonell, R, Prevost, J, Kuhle, J, Laureys, G, Van Hijfte, L, Alroughani, R, Kermode, AG, Butler, E, Barnett, M, Eichau, S, van Pesch, V, Grammond, P, McCombe, P, Karabudak, R, Duquette, P, Girard, M, Taylor, B, Yeh, W , Monif, M , Gresle, M , Butzkueven, H & Jokubaitis, VG 2022, 'Prediction of multiple sclerosis outcomes when switching to ocrelizumab', Multiple Sclerosis Journal, vol. 28, no. 6, pp. 958-969. https://doi.org/10.1177/13524585211049986

TY - JOUR

T1 - Prediction of multiple sclerosis outcomes when switching to ocrelizumab

AU - Zhong, Michael

AU - van der Walt, Anneke

AU - Stankovich, Jim

AU - Kalincik, Tomas

AU - Buzzard, Katherine

AU - Skibina, Olga

AU - Boz, Cavit

AU - Hodgkinson, Suzanne

AU - Slee, Mark

AU - Lechner-Scott, Jeannette

AU - Macdonell, Richard

AU - Prevost, Julie

AU - Kuhle, Jens

AU - Laureys, Guy

AU - Van Hijfte, Liesbeth

AU - Alroughani, Raed

AU - Kermode, Allan G.

AU - Butler, Ernest

AU - Barnett, Michael

AU - Eichau, Sara

AU - van Pesch, Vincent

AU - Grammond, Pierre

AU - McCombe, Pamela

AU - Karabudak, Rana

AU - Duquette, Pierre

AU - Girard, Marc

AU - Taylor, Bruce

AU - Yeh, Wei

AU - Monif, Mastura

AU - Gresle, Melissa

AU - Butzkueven, Helmut

AU - Jokubaitis, Vilija G.

N1 - Funding Information: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: M.Z. received conference attendance support from Roche. A.v.d.W. reports no disclosures relevant to the manuscript. J.S. reports no disclosures relevant to the manuscript. T.K. served on scientific advisory boards for Roche, Sanofi Genzyme, Novartis, Merck and Biogen, steering committee for Brain Atrophy Initiative by Sanofi Genzyme, received conference travel support and/or speaker honoraria from WebMD Global, Novartis, Biogen, Sanofi Genzyme, Teva, bioCSL and Merck, and received research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene and Merck. K.B. received honoraria and consulting fees from Biogen, Teva, Novartis, Sanofi Genzyme, Roche, Merck, CSL and Grifols. O.S. has worked on advisory boards of Roche, Merck and Sanofi Genzyme, received travel grants from Roche, Sanofi Genzyme and Merck, and speaker honoraria from Sanofi Genzyme, Merck and Novartis. C.B. received conference travel support from Biogen, Novartis, Bayer Schering, Merck and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis. S.H. received honoraria and consulting fees from Novartis, Bayer Schering and Sanofi, and travel grants from Novartis, Biogen Idec and Bayer Schering. M.S. has participated in, but not received honoraria for, advisory board activity for Biogen, Merck, Bayer Schering, Sanofi Aventis and Novartis. J.L-S. received travel compensation from Novartis, Biogen, Roche and Merck. Her institution receives the honoraria for talks and advisory board commitment as well as research grants from Biogen, Merck, Roche, Teva and Novartis. R.M. reports no disclosures relevant to the manuscript. J.P. accepted travel compensation from Novartis, Biogen, Genzyme, Teva, and speaking honoraria from Biogen, Novartis, Genzyme and Teva. J.K. reports no disclosures relevant to the manuscript. G.L. received travel and/or consultancy compensation from Sanofi Genzyme, Roche, Teva, Merck, Novartis, Celgene and Biogen. L.V.H. reports no disclosures relevant to the manuscript. R.A. received honoraria as a speaker and for serving on scientific advisory boards from Bayer, Biogen, GSK, Merck, Novartis, Roche and Sanofi Genzyme. A.G.K. received speaker honoraria and scientific advisory board fees from Bayer, bioCSL, Biogen, Genzyme, Innate Immunotherapeutics, Merck, Novartis, Sanofi, Sanofi Aventis and Teva. E.B. reports no disclosures relevant to the manuscript. M.B. served on scientific advisory boards for Biogen, Novartis and Genzyme, and has received conference travel support from Biogen and Novartis. He serves on steering committees for trials conducted by Novartis. His institution has received research support from Biogen, Merck and Novartis. S.E. received speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck, Bayer, Sanofi Genzyme, Roche and Teva. V.v.P. received travel grants from Merck, Biogen, Sanofi, Celgene, Almirall and Roche. His institution has received research grants and consultancy fees from Roche, Biogen, Sanofi, Celgene, Merck and Novartis Pharma. P.G. has served in advisory boards for Novartis, EMD Serono, Roche, Biogen Idec, Sanofi Genzyme and Pendopharm; has received grant support from Genzyme and Roche; has received research grants for his institution from Biogen Idec, Sanofi Genzyme and EMD Serono. P.M. received honoraria and consulting fees from Novartis, Bayer Schering and Sanofi and travel grants from Novartis, Biogen and Bayer Schering. R.K. reports no disclosures relevant to the manuscript. P.D. served on editorial boards and has been supported to attend meetings by EMD, Biogen, Novartis, Genzyme and Teva Neuroscience. He holds grants from the CIHR and the MS Society of Canada and has received funding for investigator-initiated trials from Biogen, Novartis and Genzyme. M.G. received consulting fees from Teva Canada Innovation, Biogen, Novartis and Genzyme Sanofi; lecture payments from Teva Canada Innovation, Novartis and EMD. He has also received a research grant from Canadian Institutes of Health Research. B.T. received funding for travel and speaker honoraria from Bayer Schering Pharma, CSL Australia, Biogen and Novartis, and has served on advisory boards for Biogen, Novartis, Roche and CSL Australia. W.Y. received research support from Multiple Sclerosis Research Australia and the Australian Government Research Training Program, speaker honoraria and conference attendance support from Biogen, and travel support from Merck. M.M. has received funding from the National Medical Research Council Medical Research Future Fund (MRFF); her institution also has received funding from Brain Foundation, Charles and Sylvia Viertel Foundation, and Merck Industry funding. M.G. reports no disclosures relevant to the manuscript. H.B.’s institution received compensation for Advisory Board, Steering Committee and Educational activities from Biogen, Roche, Merck and Novartis. His institution received research support from Roche, Novartis, Biogen, NHMRC and MRFF Australia and MS Research Australia. He received personal compensation from Oxford HPF for serving on the steering group of MS Brain Health. V.G.J. received conference travel support from Merck and Roche, and speakers honoraria from Biogen and Roche outside of the submitted work. She receives research support from the Australian National Health and Medical Research Grant and MS Research Australia. Publisher Copyright: © The Author(s), 2021. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2022/5

Y1 - 2022/5

N2 - 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.

AB - 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.

KW - fingolimod

KW - Ocrelizumab

KW - switch

KW - washout

UR - http://www.scopus.com/inward/record.url?scp=85116675811&partnerID=8YFLogxK

U2 - 10.1177/13524585211049986

DO - 10.1177/13524585211049986

M3 - Article

C2 - 34623947

AN - SCOPUS:85116675811

SN - 1352-4585

VL - 28

SP - 958

EP - 969

JO - Multiple Sclerosis Journal

JF - Multiple Sclerosis Journal

IS - 6

ER -

Prediction of multiple sclerosis outcomes when switching to ocrelizumab

Abstract

Keywords

Access to Document

Other files and links

Cite this