Prediction of multiple sclerosis outcomes when switching to ocrelizumab

• Published in: Multiple sclerosis Vol. 28; no. 6; pp. 958 - 969
• Main Authors: Zhong, Michael, van der Walt, Anneke, Stankovich, Jim, Kalincik, Tomas, Buzzard, Katherine, Skibina, Olga, Boz, Cavit, Hodgkinson, Suzanne, Slee, Mark, Lechner-Scott, Jeannette, Macdonell, Richard, Prevost, Julie, Kuhle, Jens, Laureys, Guy, Van Hijfte, Liesbeth, Alroughani, Raed, Kermode, Allan G, Butler, Ernest, Barnett, Michael, Eichau, Sara, van Pesch, Vincent, Grammond, Pierre, McCombe, Pamela, Karabudak, Rana, Duquette, Pierre, Girard, Marc, Taylor, Bruce, Yeh, Wei, Monif, Mastura, Gresle, Melissa, Butzkueven, Helmut, Jokubaitis, Vilija G
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01-05-2022; Sage Publications Ltd
• Subjects: Antibodies, Monoclonal, Humanized; Copolymer 1; Fingolimod Hydrochloride - therapeutic use; Humans; Immunosuppressive Agents - therapeutic use; Interferon; Monoclonal antibodies; Multiple sclerosis; Multiple Sclerosis - chemically induced; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Patients; Recurrence; Regression analysis; β-Interferon; Ocrelizumab; fingolimod; washout; switch
• ISSN: 1352-4585; 1477-0970
• DOI: 10.1177/13524585211049986

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.