B-cell depleting therapies like ocrelizumab are very effective in the treatment of relapsing remitting multiple sclerosis (RRMS). As B cell repopulation varies extensively between individuals (ranging from 27-175 weeks), using a treatment scheme with a fixed infusion interval may be suboptimal.
Evaluating the efficacy, safety and cost-effectiveness of ocrelizumab when administered in personalized B cell tailored intervals.
This is a multicenter non-inferiority randomized controlled trial with 96 weeks follow-up.
The study population consists of 280 adult RRMS patients who received ocrelizumab treatment for a minimum of 24 weeks.
INVESTIGATIONAL PRODUCT & COMPARATOR
Patients will be randomized into the standard interval group or the personalized interval group in which the ocrelizumab infusions will be extended until the first sign of B cell repopulation.
The primary outcome is the percentage of relapse-free patients. Secondary study parameters include MRI activity, disability progression, serum neurofilament light, quality of life, burden of treatment, immunoglobulin levels and adverse events.
We will report a 90% confidence interval for the difference in the percentage of relapse-free patients and conclude non-inferiority when the lower limit of the confidence interval is >-10%.
We will use an absolute non-inferiority margin of 10% for the difference in proportions. Non-inferiority testing at a one-sided significance level of 5% requires 112 patients to be included in each arm. Taking into account 20% drop out or missing data, the total sample size needed for this study is 280 patients.
We estimate that minimal repopulation of B-cells will occur after a median of 34 weeks. Healthcare costs can decrease with 10 million euros annually when personalized treatment of ocrelizumab is implemented in the Netherlands.