Serum ocrelizumab concentrations in patients with multiple sclerosis: A cross-sectional study from routine healthcare

Ocrelizumab is a humanised monoclonal antibody used to treat multiple sclerosis. In this cross-sectional study, the serum concentrations of ocrelizumab obtained during routine healthcare of patients with multiple sclerosis were measured using ultra-performance liquid chromatography with tandem mass spectrometry.

The study group included 180 patients who received either an initial dose of 300 mg or at least one complete dose of 600 mg intravenously administered ocrelizumab. Patients were stratified into two subgroups according to the time of blood collection (≤ 28 weeks and > 28 weeks post-dose). Blood counts and immunoglobulin A, G, and M concentrations were also recorded.

Serum ocrelizumab concentrations ranged between 20.5-62.4 mg/L in patients with the initial dose of 300 mg and between 0.3-21.8 mg/L in patients with at least one complete 600 mg dose. A significant inverse correlation was observed between serum ocrelizumab concentration and body weight, height, body surface area, and body mass index. Significantly lower ocrelizumab concentrations were observed in patients with a collection time > 28 weeks compared to ≤ 28 weeks. An inverse correlation was observed between ocrelizumab concentrations and haematological parameters (leukocyte count, absolute lymphocyte, neutrophil and eosinophil counts, and differential eosinophil count), and immunoglobulin A and G concentrations.

Wide interindividual variability in serum concentrations was observed in both the group of patients who received an initial intravenous dose of 300 mg ocrelizumab and in patients who received at least one complete dose of 600 mg. This variability in ocrelizumab pharmacokinetics was also evident when samples were collected at similar time after dosing and may lead to both toxicity and the risk of suboptimal drug concentrations.