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Introduction: Ocrelizumab is an often used and effective anti- CD20 therapy for patients with multiple sclerosis. The disease course of coronavirus disease 2019 (COVID-19) might be more severe in patients using anti-CD20 therapies, since B-cell depletion is associated with an increased risk of severe infections. Consequently, international MS experts have advised neurologists to consider interval extension between ocrelizumab doses based on B-cell count. Objectives: To assess the safety and efficacy of B-cell tailored personalized dosing of ocrelizumab in patients with multiple sclerosis. Aims: To provide knowledge on personalized dosing of ocrelizumab in multiple sclerosis in a large, closely monitored cohort and share the B-cell tailored personalized dosing protocol as implemented at our center during the COVID-19 pandemic. Methods: We conducted an observational study of all patients who received personalized dosing of ocrelizumab at our center since March 15th 2020. The personalized dosing protocol was based on serum CD19 B-cell count measured every 4 weeks, starting 24 weeks after a 600 mg dose or 12 weeks after a 300 mg dose. The next ocrelizumab dose was scheduled as soon as CD19 B-cell count re-emerged to ≥10 cells/μL. Clinical and radiological disease activity parameters and serum neurofilament light (sNfL) levels were collected until November 1st 2020. We applied linear regression (correcting for age and BMI) and mixed models (correcting for within-subjects correlations) to assess the effect of extended intervals on log-transformed sNfL levels. Results: A total of 159 patients received personalized dosing of ocrelizumab after a 600 mg dose and 6 patients after a 300 mg dose. Median CD19 B-cell count was 2 [1-7] cells/μL at the start of the personalized dosing protocol and 15 [4-27] cells/μL prior to re-dosing. After a 600 mg dose, median interval until re-dosing or until the last available CD19 B-cell count was 34 [30-38] weeks. No clinical relapses were reported and monthly sNfL levels during extended intervals remained stable. Of the 107 patients with a follow-up MRI-scan, only 2 (1.9%) showed radiological disease activity. Conclusions: Personalized dosing of ocrelizumab based on CD19 B-cell count led to an interval extension in the majority of patients with a low short-term incidence of disease activity, encouraging future studies to confirm safety and efficacy of this protocol beyond the COVID-19 pandemic.
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BACKGROUND: Patients with multiple sclerosis (MS) who are treated with monoclonal antibodies frequently report an increase of MS-related symptoms prior to the next dose known as the wearing-off phenomenon. The objective of this study was to assess the prevalence and predicting factors of the wearing-off phenomenon in patients with MS using ocrelizumab. METHODS: This was a prospective cohort study in patients with MS receiving ocrelizumab ≥1 year. Most participants received B-cell guided personalized extended interval dosing to limit ocrelizumab exposure and hospital visits during the COVID-19 pandemic (cut-off ≥ 10 cells/µL). Participants completed questionnaires during ocrelizumab infusion and 2 weeks thereafter. Demographics, clinical and radiological characteristics, CD19 B-cell counts, and serum neurofilament light (sNfL) levels were collected. Data were analyzed using logistic regression analyses. RESULTS: Seventy-one (61%) out of 117 participants reported the wearing-off phenomenon during ocrelizumab treatment. The most frequently reported symptoms were fatigue, cognitive disability and sensory symptoms. Wearing-off symptoms started < 1 week (11%), 1-4 weeks (49%) or more than 4 weeks (37%) before ocrelizumab infusion. Fifty participants (43%) reported a current wearing-off phenomenon at the first questionnaire. Higher body mass index (threshold BMI ≥ 25) increased the odds of reporting a current wearing-off phenomenon (OR 2.70, 95% CI 1.26 to 5.80, p = .011). Infusion interval, EDSS score, MRI disease activity, clinical relapses, CD19 B-cell counts, and sNfL levels were no predictors. Disappearance of the wearing-off phenomenon occurred in the first week after ocrelizumab infusion in most participants. Participants with a current wearing-off phenomenon significantly improved in self-reported physical and psychological functioning after ocrelizumab infusion. Reporting the wearing-off phenomenon did not influence treatment satisfaction. Forty of 109 participants (37%) reported post-infusion symptoms, such as fatigue, flu-like symptoms or walking difficulties. These post-infusion symptoms started directly or in the first week after ocrelizumab infusion and disappeared within 2 weeks. CONCLUSIONS: The wearing-off phenomenon is reported by more than half of patients with MS using ocrelizumab. Only BMI was identified as a predicting factor. The wearing-off phenomenon was not elicited by extending infusion intervals or higher B-cell counts. The wearing-off phenomenon of ocrelizumab therefore does not seem to reflect suboptimal control of MS disease activity.