Disease activity and CD19+ B-cell counts with extended interval dosing of ocrelizumab

ABSTRACT

Introduction: Ocrelizumab is licenced for a fixed treatment interval of six-monthly infusions to treat multiple sclerosis (MS). Disruption in clinical services, triggered by the COVID-19 pandemic, has led to extended intervals between treatments for some patients. Increasing evidence suggests that extended interval dosing of another anti-CD20 medicine, rituximab, maintains its efficacy while reducing the risks of immunosuppression. Objectives: To assess for evidence of clinical or radiological MS disease activity with extended interval dosing of ocrelizumab. To assess the rates of developing low immunoglobulin levels and timing of CD19+ B-cell count repopulation in a real-world clinical population. Methods: We audited the clinical, radiological and immunological data of 301 patients given ocrelizumab by our clinical services. Baseline demographics included age, sex, previous disease modifying treatment (DMT), phase of MS, and Expanded Disability Status Scale (EDSS). Dates of ocrelizumab administration were recorded. Disease activity was defined as on treatment EDSS progression, radiological activity or clinical relapse. All monitoring of CD19+ cell counts and immunoglobulin levels were recorded. Results: 301 participants were included in the analysis, among whom 62% were women, the mean age was 43 years and the median baseline EDSS was 3 (IQR 1-6). Half had previously used other DMTs and six (2%) had low immunoglobulin levels at baseline. They received 966 treatment cycles, of which 70 were administered with a treatment interval of 7-8 months, 45 with an interval of 8-9 months and 14 with an interval of more than nine months. In total, 131 (44%) participants had extended interval dosing. Disease activity included 33 (11%) with EDSS progression, 16 (5%) with new MRI lesions and 4 (1%) participants had clinical relapses. The odds ratio for rates of disease activity comparing extended to standard interval dosing was 0.97. Low immunoglobulin levels developed in 22 (7%). The longest recorded suppression of CD19+ B-cells was 405 days. We will present our mixed effects linear regression model of the factors that influence CD19+ count repopulation. Conclusions: This real-world data of extended interval dosing of ocrelizumab indicates no detrimental effect on short-term treatment efficacy. Our CD19+ dataset, could inform the design of a prospective trial of individualised retreatment intervals in ocrelizumab.