De-escalation of Disease-Modifying Therapy for People with Multiple Sclerosis Due to Safety Considerations: Characterizing 1-Year Outcomes in 25 People Who Switched from Ocrelizumab to Diroximel Fumarate

Abstract

Introduction: Switching disease-modifying therapy (DMT) may be considered for relapsing-remitting multiple sclerosis (RRMS) if a patient's current therapy is no longer optimal. This was particularly important during the recent COVID-19 pandemic because of considerations around immune deficiency and impaired vaccine response associated with B cell-depleting DMTs. This real-world, single-center study aimed to evaluate change or decline in functional ability and overall disease stability in people with RRMS who were switched from B cell-depleting ocrelizumab (OCRE) to diroximel fumarate (DRF) because of safety concern related to the COVID-19 pandemic.

Methods: Adults with RRMS were included if they had been clinically stable for ≥ 1 year on OCRE. Data collected at baseline and 1 year post switch included relapse rate, magnetic resonance imaging (MRI), blood work for assessment of peripheral immune parameters, the Cognitive Assessment Battery (CAB), optical coherence tomography (OCT), and patient-reported outcomes (PROs).

Results: Participants (N = 25) had a mean (SD) age of 52 (9) years, and a mean (SD) duration of 26 (8) months' treatment with OCRE before the switch to DRF. Median washout duration since the last OCRE infusion was 7 months (range 4-18 months). No participants relapsed on DRF during follow-up, and all remained persistent on DRF after 1 year. There were no significant changes in peripheral immune parameters, other than an increase in the percentage of CD19⁺ cells 1 year after switching (p < 0.05). Similarly, there were no significant changes in CAB, OCT, and PROs.

Conclusion: These preliminary findings suggest that transition to DRF from OCRE may be an effective treatment option for people with RRMS who are clinically stable but may need to switch for reasons unrelated to effectiveness. Longer follow-up times on larger samples are needed to confirm these observations.

Keywords: Cognitive Assessment Battery; Diroximel fumarate; Ocrelizumab; Ocular tomography; Patient-reported outcomes; Relapsing–remitting multiple sclerosis.

Fig. 1

Median PRO scores at baseline on OCRE and 1 year post switch to DRF. Median and interquartile range is shown. Higher scores indicate worse outcome for PROs, except for PROMIS Social Roles. DRF diroximel fumarate, HADS-A Hospital Anxiety and Depression Scale—Anxiety, HADS-D Hospital Anxiety and Depression Scale—Depression, MFES Modified Falls Efficacy Scale, MSWS-12 12-Item Multiple Sclerosis Walking Scale, OCRE ocrelizumab, PDSS Patient Determined Disease Steps, PRO patient-reported outcome, PROMIS Patient-Reported Outcome Measurement Information System

Fig. 2

Mean CAB parameters at baseline on OCRE and 1 year post switch to DRF. Error bars represent SD. Cognitive Assessment Domain Scores: > 115 = above average; 115–100 = average; 99–85 = below average; < 85 = abnormal. CAB Cognitive Assessment Battery, DRF diroximel fumarate, OCRE ocrelizumab, SD standard deviation