Natalizumab in cerebrospinal fluid and breastmilk of patients with multiple sclerosis

Ilaria Callegari; Mika Schneider; Vera Aebischer; Margarete M Voortman; Undine Proschmann; Tjalf Ziemssen; Raija Lindberg; Bettina Fischer-Barnicol; Michael Khalil; Ludwig Kappos; Jens Kuhle; Nicholas S R Sanderson; Tobias Derfuss

doi:10.1177/17562864221150040

Natalizumab in cerebrospinal fluid and breastmilk of patients with multiple sclerosis

Ther Adv Neurol Disord. 2023 Jan 30:16:17562864221150040. doi: 10.1177/17562864221150040. eCollection 2023.

Authors

Affiliations

¹ Department of Biomedicine, University of Basel and University Hospital Basel, Basel, Switzerland.
² Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland.
³ Department of Neurology, Medical University of Graz, Graz, Austria.
⁴ Neuroimmunological Lab, Center of Clinical Neuroscience, Department of Neurology, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany.
⁵ Department of Biomedicine, University of Basel and University Hospital Basel, Neurologic Clinic and Policlinic, MS Center Petersgraben 4, 4031 Basel, Switzerland.

Abstract

Background: Natalizumab is a highly effective monoclonal antibody for the treatment of multiple sclerosis (MS), which can diffuse in different anatomical compartments, including cerebrospinal fluid (CSF) and milk.

Objectives: Starting from incidental detection of natalizumab in the CSF of MS patients, the objective of this study was to develope a flow-cytometry-based assay and apply it to quantify natalizumab in body fluids, including milk collected from nursing patients over 180 days and in patients with neutralizing antibodies against natalizumab.

Methods: CSF, milk and sera samples from patients with multiple sclerosis were tested by flow-cytometry for binding to a VLA-4 expressing cell line or to a control cell line. A standard curve was prepared by incubating the same cells with natalizumab at 50 μg/ml and serially diluted to 0.005 ng/ml. Binding specificity was confirmed using an anti-natalizumab neutralizing antibody.

Results: Our assay was sensitive enough to detect natalizumab in CSF, with a lower detection limit of 1.5 ng/ml. Neutralizing antibodies against natalizumab inhibited binding to the cell line. In breastmilk, the peak concentration was observed during the first 2 weeks after infusion and the average concentration over the observation time was 173.3 ng/ml, with a trend toward increased average milk concentration over subsequent administrations.

Conclusion: Routine use of such an assay would enable a better understanding of the safety of therapeutic antibody administration during pregnancy and lactation.

Keywords: Natalizumab; breastfeeding; cerebrospinal fluid; milk; multiple sclerosis.