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      ECTRIMS/EAN consensus on vaccination in people with multiple sclerosis: Improving immunization strategies in the era of highly active immunotherapeutic drugs

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          Abstract

          Background:

          With the new highly active drugs available for people with multiple sclerosis (pwMS), vaccination becomes an essential part of the risk management strategy

          Objective:

          To develop a European evidence-based consensus for the vaccination strategy of pwMS who are candidates for disease-modifying therapies (DMTs).

          Methods:

          This work was conducted by a multidisciplinary working group using formal consensus methodology. Clinical questions (defined as population, interventions, and outcomes) considered all authorized DMTs and vaccines. A systematic literature search was conducted and quality of evidence was defined according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. The recommendations were formulated based on the quality of evidence and the risk–benefit balance.

          Results:

          Seven questions, encompassing vaccine safety, vaccine effectiveness, global vaccination strategy and vaccination in sub-populations (pediatric, pregnant women, elderly and international travelers) were considered. A narrative description of the evidence considering published studies, guidelines, and position statements is presented. A total of 53 recommendations were agreed by the working group after three rounds of consensus.

          Conclusion:

          This first European consensus on vaccination in pwMS proposes the best vaccination strategy according to current evidence and expert knowledge, with the goal of homogenizing the immunization practices in pwMS.

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          Most cited references102

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          How to use the nominal group and Delphi techniques

          Introduction The Nominal Group Technique (NGT) and Delphi Technique are consensus methods used in research that is directed at problem-solving, idea-generation, or determining priorities. While consensus methods are commonly used in health services literature, few studies in pharmacy practice use these methods. This paper provides an overview of the NGT and Delphi technique, including the steps involved and the types of research questions best suited to each method, with examples from the pharmacy literature. Methodology The NGT entails face-to-face discussion in small groups, and provides a prompt result for researchers. The classic NGT involves four key stages: silent generation, round robin, clarification and voting (ranking). Variations have occurred in relation to generating ideas, and how ‘consensus’ is obtained from participants. The Delphi technique uses a multistage self-completed questionnaire with individual feedback, to determine consensus from a larger group of ‘experts.’ Questionnaires have been mailed, or more recently, e-mailed to participants. When to use The NGT has been used to explore consumer and stakeholder views, while the Delphi technique is commonly used to develop guidelines with health professionals. Method choice is influenced by various factors, including the research question, the perception of consensus required, and associated practicalities such as time and geography. Limitations The NGT requires participants to personally attend a meeting. This may prove difficult to organise and geography may limit attendance. The Delphi technique can take weeks or months to conclude, especially if multiple rounds are required, and may be complex for lay people to complete.
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            Correlates of protection induced by vaccination.

            This paper attempts to summarize current knowledge about immune responses to vaccines that correlate with protection. Although the immune system is redundant, almost all current vaccines work through antibodies in serum or on mucosa that block infection or bacteremia/viremia and thus provide a correlate of protection. The functional characteristics of antibodies, as well as quantity, are important. Antibody may be highly correlated with protection or synergistic with other functions. Immune memory is a critical correlate: effector memory for short-incubation diseases and central memory for long-incubation diseases. Cellular immunity acts to kill or suppress intracellular pathogens and may also synergize with antibody. For some vaccines, we have no true correlates, but only useful surrogates, for an unknown protective response.
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              Cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy

              SARS-CoV-2 messenger RNA vaccination in healthy individuals generates immune protection against COVID-19. However, little is known about SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed patients. We investigated induction of antigen-specific antibody, B cell and T cell responses longitudinally in patients with multiple sclerosis (MS) on anti-CD20 antibody monotherapy (n = 20) compared with healthy controls (n = 10) after BNT162b2 or mRNA-1273 mRNA vaccination. Treatment with anti-CD20 monoclonal antibody (aCD20) significantly reduced spike-specific and receptor-binding domain (RBD)-specific antibody and memory B cell responses in most patients, an effect ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. By contrast, all patients with MS treated with aCD20 generated antigen-specific CD4 and CD8 T cell responses after vaccination. Treatment with aCD20 skewed responses, compromising circulating follicular helper T (TFH) cell responses and augmenting CD8 T cell induction, while preserving type 1 helper T (TH1) cell priming. Patients with MS treated with aCD20 lacking anti-RBD IgG had the most severe defect in circulating TFH responses and more robust CD8 T cell responses. These data define the nature of the SARS-CoV-2 vaccine-induced immune landscape in aCD20-treated patients and provide insights into coordinated mRNA vaccine-induced immune responses in humans. Our findings have implications for clinical decision-making and public health policy for immunosuppressed patients including those treated with aCD20.
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                Author and article information

                Contributors
                Journal
                Mult Scler
                Mult Scler
                MSJ
                spmsj
                Multiple Sclerosis (Houndmills, Basingstoke, England)
                SAGE Publications (Sage UK: London, England )
                1352-4585
                1477-0970
                9 June 2023
                July 2023
                : 29
                : 8
                : 904-925
                Affiliations
                [1-13524585231168043]Department of Preventive Medicine and Epidemiology, Vall d’Hebron Barcelona Hospital, Barcelona, Spain Multiple Sclerosis Centre of Catalonia (Cemcat), Vall d’Hebron Barcelona Hospital, Barcelona, Spain
                [2-13524585231168043]CRC-SEP Nice, CHU de Nice, Universite Nice Cote d’Azur UR2CA-URRIS, Nice, France
                [3-13524585231168043]Fundación Santa Fe de Bogotá, Bogotá, Colombia School of Medicine, Universidad de los Andes, Bogotá, Colombia Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
                [4-13524585231168043]Department NEUROFARBA, University of Florence, Florence, Italy IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy
                [5-13524585231168043]Department of Preventive Medicine and Epidemiology, Vall d’Hebron Barcelona Hospital, Barcelona, Spain
                [6-13524585231168043]Centro para la Investigación de Enfermedades Neuroinmunológicas (CIEN), FLENI, Buenos Aires, Argentina
                [7-13524585231168043]Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy Neurology Unit, Neurorehabilitation Unit, and Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan, Italy Vita-Salute San Raffaele University, Milan, Italy
                [8-13524585231168043]Department of Paediatric Neurology, Great Ormond Street Hospital for Children, London, UK Department of Neuroinflammation, Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, London, UK
                [9-13524585231168043]Department of Neurology, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
                [10-13524585231168043]Multiple Sclerosis International Federation, London, UK
                [11-13524585231168043]Department of Neurology, Danish Multiple Sclerosis Center and the Danish Multiple Sclerosis Registry, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark
                [12-13524585231168043]Department of Neurology, Hospital Clínico San Carlos, IdISSC, Departamento de Medicina, Universidad Complutense, Madrid, Spain
                [13-13524585231168043]Department of Neurology, School of Medicine, Istanbul University Cerrahpasa, Cerrahpasa, Istanbul, Turkey
                [14-13524585231168043]Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation, Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Lyon, France
                [15-13524585231168043]Centre des Neurosciences de Lyon, Observatoire Français de la Sclérose en Plaques, INSERM 1028 et CNRS UMR5292, Lyon, France Université Claude Bernard Lyon 1, Faculté de Médecine Lyon Est, Lyon, France
                [16-13524585231168043]Multiple Sclerosis Centre of Catalonia (Cemcat), Vall d’Hebron Barcelona Hospital, Barcelona, Spain
                Author notes
                [*]S Otero-Romero Department of Preventive Medicine and Epidemiology, Vall d’Hebron Barcelona Hospital, Pg. de la Vall d’Hebron 119-129, 08035 Barcelona, Spain. sotero@ 123456cem-cat.org
                [*]

                These authors gave equal contribution to this study.

                Author information
                https://orcid.org/0000-0002-3713-2416
                https://orcid.org/0000-0003-3325-3760
                https://orcid.org/0000-0002-5485-0479
                https://orcid.org/0000-0001-5985-6784
                https://orcid.org/0000-0002-0972-5222
                https://orcid.org/0000-0002-9221-5716
                https://orcid.org/0000-0002-8340-6641
                https://orcid.org/0000-0001-7337-7122
                https://orcid.org/0000-0001-9999-5359
                Article
                10.1177_13524585231168043
                10.1177/13524585231168043
                10338708
                37293841
                7ac53c6f-7806-4df7-900b-b8bef0f9d5cd
                © The Author(s), 2023

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 4 November 2022
                : 30 January 2023
                : 19 March 2023
                Funding
                Funded by: ECTRIMS executive committee, ;
                Award ID: Grant awarded by the ECTRIMS executive committee
                Categories
                Review
                Custom metadata
                ts1

                Immunology
                multiple sclerosis,vaccination,consensus,infections,disease-modifying therapy
                Immunology
                multiple sclerosis, vaccination, consensus, infections, disease-modifying therapy

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