Nicola Capasso1, Raffaele Palladino2, Vincenza Cerbone3, Antonio Luca Spiezia1,4, Bianca Covelli5, Antonia Fiore3, Roberta Lanzillo1,4, Antonio Carotenuto1,4, Maria Petracca1,6, Lucia Stanziola5, Giulia Scalia3, Vincenzo Brescia Morra1, Marcello Moccia7,8. 1. Multiple Sclerosis Unit, Federico II University Hospital, Via Sergio Pansini 5, 80131, Naples, Italy. 2. Department of Public Health, Federico II University of Naples, Naples, Italy. 3. Centre for Advanced Biotechnology (CEINGE), Naples, Italy. 4. Department of Neuroscience, Reproductive Sciences and Odontostomatology, Federico II University of Naples, Naples, Italy. 5. Department of Translational Medical Sciences, Federico II University of Naples, Naples, Italy. 6. Department of Human Neuroscience, Sapienza University of Rome, Rome, Italy. 7. Multiple Sclerosis Unit, Federico II University Hospital, Via Sergio Pansini 5, 80131, Naples, Italy. moccia.marcello@gmail.com. 8. Department of Molecular Medicine and Medical Biotechnology, Federico II University of Naples, Via Sergio Pansini 5, 80131, Naples, Italy. moccia.marcello@gmail.com.
Abstract
OBJECTIVE: We aim to evaluate 3-year effects of ocrelizumab (humanized anti-CD20 monoclonal antibody for the treatment of multiple sclerosis (MS)) on lymphocytes, neutrophils and immunoglobulins: (1) when compared with pre-infusion assessment; (2) over the course of treatment; and (3) possible clinical correlates of the observed immunological modifications. METHODS: This real-world observational cohort study has been conducted on prospectively collected data from 78 MS patients (mean age 47.8 ± 10.5 years; females 48.7%) commencing on ocrelizumab from 2018, with mean follow-up of 36.5 ± 6.8 months. Clinical data and blood samples were collected every three months. Total lymphocyte count and subpopulations were assessed on peripheral blood using flow cytometry. Serum immunoglobulins were evaluated with nephelometry. RESULTS: When compared with pre-infusion values, we observed reduction of total, CD19 and CD20 lymphocyte counts; however, after the first infusion, their levels remained substantially stable. Over time we observed a progressive reduction of CD8 lymphocytes, while no changes were observed for CD4, CD27, CD3CD27, and CD19CD27. After the first infusion, we observed reduction in IgG, which further decreased during the follow-up. Higher probability of EDSS progression was associated with reduced modulation of CD8 lymphocytes. INTERPRETATION: Ocrelizumab affects both humoral and cellular immune responses. Disability progression over the follow-up was associated with lower CD8 cytotoxic T-lymphocyte reduction. Changes in humoral response are immediate and sustained, while modulation of cellular immunity occurs progressively through regular re-treatment, and is related to clinical stability.
OBJECTIVE: We aim to evaluate 3-year effects of ocrelizumab (humanized anti-CD20 monoclonal antibody for the treatment of multiple sclerosis (MS)) on lymphocytes, neutrophils and immunoglobulins: (1) when compared with pre-infusion assessment; (2) over the course of treatment; and (3) possible clinical correlates of the observed immunological modifications. METHODS: This real-world observational cohort study has been conducted on prospectively collected data from 78 MS patients (mean age 47.8 ± 10.5 years; females 48.7%) commencing on ocrelizumab from 2018, with mean follow-up of 36.5 ± 6.8 months. Clinical data and blood samples were collected every three months. Total lymphocyte count and subpopulations were assessed on peripheral blood using flow cytometry. Serum immunoglobulins were evaluated with nephelometry. RESULTS: When compared with pre-infusion values, we observed reduction of total, CD19 and CD20 lymphocyte counts; however, after the first infusion, their levels remained substantially stable. Over time we observed a progressive reduction of CD8 lymphocytes, while no changes were observed for CD4, CD27, CD3CD27, and CD19CD27. After the first infusion, we observed reduction in IgG, which further decreased during the follow-up. Higher probability of EDSS progression was associated with reduced modulation of CD8 lymphocytes. INTERPRETATION: Ocrelizumab affects both humoral and cellular immune responses. Disability progression over the follow-up was associated with lower CD8 cytotoxic T-lymphocyte reduction. Changes in humoral response are immediate and sustained, while modulation of cellular immunity occurs progressively through regular re-treatment, and is related to clinical stability.
Authors: Amit Bar-Or; Lama Fawaz; Boli Fan; Peter J Darlington; Aja Rieger; Christine Ghorayeb; Peter A Calabresi; Emmanuelle Waubant; Stephen L Hauser; Jiameng Zhang; Craig H Smith Journal: Ann Neurol Date: 2010-04 Impact factor: 10.422
Authors: Stephen L Hauser; Amit Bar-Or; Giancarlo Comi; Gavin Giovannoni; Hans-Peter Hartung; Bernhard Hemmer; Fred Lublin; Xavier Montalban; Kottil W Rammohan; Krzysztof Selmaj; Anthony Traboulsee; Jerry S Wolinsky; Douglas L Arnold; Gaelle Klingelschmitt; Donna Masterman; Paulo Fontoura; Shibeshih Belachew; Peter Chin; Nicole Mairon; Hideki Garren; Ludwig Kappos Journal: N Engl J Med Date: 2016-12-21 Impact factor: 91.245
Authors: Xavier Montalban; Stephen L Hauser; Ludwig Kappos; Douglas L Arnold; Amit Bar-Or; Giancarlo Comi; Jérôme de Seze; Gavin Giovannoni; Hans-Peter Hartung; Bernhard Hemmer; Fred Lublin; Kottil W Rammohan; Krzysztof Selmaj; Anthony Traboulsee; Annette Sauter; Donna Masterman; Paulo Fontoura; Shibeshih Belachew; Hideki Garren; Nicole Mairon; Peter Chin; Jerry S Wolinsky Journal: N Engl J Med Date: 2016-12-21 Impact factor: 91.245