Monitoring CD49d Receptor Occupancy: A Method to Optimize and Personalize Natalizumab Therapy in Multiple Sclerosis Patients

Joan Puñet-Ortiz, José Vicente Hervás-García, Aina Teniente-Serra, Antonio Cano-Orgaz, Maria José Mansilla, Bibiana Quirant-Sánchez, Juan Navarro-Barriuso, Marco A. Fernández-Sanmartín, Silvia Presas-Rodríguez, Cristina Ramo-Tello, Eva María Martínez-Cáceres

Research output: Contribution to journalArticleResearchpeer-review

10 Citations (Scopus)

Abstract

© 2017 International Clinical Cytometry Society Background: In natalizumab-treated relapsing-remitting MS (RRMS) patients, various extended interval dosing strategies are under evaluation to minimize severe treatment-associated side effects, mainly progressive multifocal leukoencephalopathy development. Up to now, it has not been presented any approach, even in form of assay design, to determine the optimal percentage of CD49d receptor occupancy (RO) associated with a favorable clinical, radiological, and immunological response. Methods: A multiparametric quantitative flow cytometry method was settled to measure CD49d RO on peripheral blood lymphocytes. The analytical protocol was tested in a 6-month follow-up from 19 RRMS patients treated with the natalizumab standard dosing of every 4 weeks or an extended-interval dosing of every 6 weeks. Results: Extended natalizumab dose schedule promoted an increase of CD49d molecules per cell surface and a reduction of CD49d RO levels. The reduction observed on CD49d RO was not only depending on dose schedule but also on individual parameters such as body mass. Interestingly, individual clinical outcome was apparently the same between the different dose schedules or even better with the extended interval dosing. Conclusions: Following up CD49d RO levels with a well-regulated monitoring work scheme is crucial to further identify over-/under-treated patients and to define a safe, personalized natalizumab regimen. © 2017 International Clinical Cytometry Society.
Original languageEnglish
Pages (from-to)327-333
JournalCytometry Part B - Clinical Cytometry
Volume94
Issue number2
DOIs
Publication statusPublished - 1 Mar 2018

Keywords

  • extended interval dosing
  • multiple sclerosis
  • natalizumab
  • quantitative flow cytometry
  • receptor occupancy
  • standard dose

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