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Galota F, Marcheselli S, De Biasi S, Gibellini L, Vitetta F, Fiore A, Smolik K, De Napoli G, Cardi M, Cossarizza A, Ferraro D. Impact of High-Efficacy Therapies for Multiple Sclerosis on B Cells. Cells 2025; 14:606. [PMID: 40277931 PMCID: PMC12025603 DOI: 10.3390/cells14080606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2025] [Revised: 04/09/2025] [Accepted: 04/10/2025] [Indexed: 04/26/2025] Open
Abstract
Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative autoimmune disorder of the central nervous system characterized by demyelination and neurodegeneration. Traditionally considered a T-cell-mediated disease, the crucial role of B lymphocytes in its pathogenesis, through different mechanisms contributing to inflammation and autoreactivity, is increasingly recognized. The risk of long-term disability in MS patients can be reduced by an early treatment initiation, in particular with high-efficacy therapies. The aim of this review is to provide an overview of the mechanisms of action of high-efficacy therapies for MS, with a focus on their impact on B cells and how this contributes to the drugs' efficacy and safety profiles. Anti-CD20 monoclonal antibodies, Alemtuzumab, Cladribine and sequestering therapies encompassing Natalizumab and S1P receptors modulators will be discussed and emerging therapies, including Bruton's Tyrosine Kinase inhibitors, will be presented.
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Affiliation(s)
- Federica Galota
- Department of Biomedical, Metabolic and Neurosciences, University of Modena and Reggio Emilia, 41121 Modena, Italy; (F.G.); (S.M.); (K.S.); (M.C.)
| | - Simone Marcheselli
- Department of Biomedical, Metabolic and Neurosciences, University of Modena and Reggio Emilia, 41121 Modena, Italy; (F.G.); (S.M.); (K.S.); (M.C.)
| | - Sara De Biasi
- Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia School of Medicine, 41125 Modena, Italy; (S.D.B.); (L.G.); (A.C.)
| | - Lara Gibellini
- Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia School of Medicine, 41125 Modena, Italy; (S.D.B.); (L.G.); (A.C.)
| | - Francesca Vitetta
- Neurology Unit, Department of Neurosciences, Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria di Modena, 41126 Modena, Italy; (F.V.); (A.F.)
| | - Alessia Fiore
- Neurology Unit, Department of Neurosciences, Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria di Modena, 41126 Modena, Italy; (F.V.); (A.F.)
| | - Krzysztof Smolik
- Department of Biomedical, Metabolic and Neurosciences, University of Modena and Reggio Emilia, 41121 Modena, Italy; (F.G.); (S.M.); (K.S.); (M.C.)
| | - Giulia De Napoli
- Department of Biomedical, Metabolic and Neurosciences, University of Modena and Reggio Emilia, 41121 Modena, Italy; (F.G.); (S.M.); (K.S.); (M.C.)
| | - Martina Cardi
- Department of Biomedical, Metabolic and Neurosciences, University of Modena and Reggio Emilia, 41121 Modena, Italy; (F.G.); (S.M.); (K.S.); (M.C.)
| | - Andrea Cossarizza
- Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia School of Medicine, 41125 Modena, Italy; (S.D.B.); (L.G.); (A.C.)
- National Institute for Cardiovascular Research, 40126 Bologna, Italy
| | - Diana Ferraro
- Department of Biomedical, Metabolic and Neurosciences, University of Modena and Reggio Emilia, 41121 Modena, Italy; (F.G.); (S.M.); (K.S.); (M.C.)
- Neurology Unit, Department of Neurosciences, Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria di Modena, 41126 Modena, Italy; (F.V.); (A.F.)
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Otani IM, Ballow M. If and When to Consider Prophylactic Immunoglobulin Replacement Therapy in Secondary Hypogammaglobulinemia. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2025; 13:511-521. [PMID: 39725313 DOI: 10.1016/j.jaip.2024.12.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/09/2024] [Revised: 12/11/2024] [Accepted: 12/12/2024] [Indexed: 12/28/2024]
Abstract
Secondary hypogammaglobulinemia (SHG), or decreased IgG levels due to reduced production or increased loss caused by medications or underlying conditions, can be associated with increased infection risk. Although immunoglobulin replacement therapy (IgRT) is generally accepted as a strategy to help prevent recurrent bacterial infections in SHG, controversy exists as to whether it should be initiated to prevent the first occurrence of infection. This question has been raised particularly in the setting of anti-CD20 therapy, solid organ transplant, and B-cell malignancies and their treatments once IgG levels fall below 300 to 400 mg/dL. This article reviews the evidence for and against initiating IgRT in these settings, as well as associated considerations for evaluation and monitoring. Although it is relatively clear that infection risk increases with decreasing IgG levels, the exact contribution of SHG to overall infection risk and the protective benefit of IgRT in the absence of infections remain unclear. In the absence of clear consensus, shared decision-making is often needed to determine if and when to initiate IgRT.
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Affiliation(s)
- Iris M Otani
- Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, UCSF Medical Center, San Francisco, Calif.
| | - Mark Ballow
- Division of Pediatric Allergy and Immunology, Department of Pediatrics, Morsani College of Medicine, University of South Florida at Johns Hopkins All Children's Hospital, St Petersburg, Fla
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Iwabuchi R, Harada M, Yamada A, Aomura D, Yamada Y, Sonoda K, Nakazawa H, Sakai K, Mizukami E, Hashimoto K, Kamijo Y. Anti-SARS-CoV-2 IgG antibody titer after BNT162b2 mRNA COVID-19 vaccination in Japanese patients who underwent renal replacement therapy, hemodialysis, peritoneal dialysis, and kidney transplantation. Clin Exp Nephrol 2023; 27:660-671. [PMID: 37095343 PMCID: PMC10124692 DOI: 10.1007/s10157-023-02348-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Accepted: 04/05/2023] [Indexed: 04/26/2023]
Abstract
BACKGROUND Coronavirus disease (COVID-19) vaccination is recommended for patients undergoing renal replacement therapy (RRT), including hemodialysis (HD), peritoneal dialysis (PD), and kidney transplantation (KT). However, the difference in the immune response between RRT patients and healthy individuals after mRNA vaccines remains uncertain. METHODS This retrospective observational study evaluated the anti-severe-acute-respiratory-syndrome-coronavirus-2 (anti-SARS-CoV-2) IgG antibody acquisition, titers and their changes, normal response rate (reaching titers of healthy individuals), factors associated with a normal response, and effectiveness of booster vaccination in Japanese RRT patients. RESULTS Most HD and PD patients acquired anti-SARS-CoV-2 IgG antibodies after the second vaccination; however, their antibody titers and normal response rates (62-75%) were low compared with those of healthy subjects. Approximately 62% of KT recipients acquired antibodies, but the normal response rate was low (23%). Anti-SARS-CoV-2 IgG antibody waning occurred in the control, HD, and PD groups, while negative or very low titers remained in KT recipients. Third booster vaccination was effective in most HD and PD patients. However, the effect was mild in KT recipients - only 58% reached a normal response level. Multivariate logistic regression analyses demonstrated that younger age, higher serum albumin level, and RRT other than KT were significantly associated with a normal response after the second vaccination. CONCLUSIONS RRT patients, particularly KT recipients, exhibited poor vaccine responses. Booster vaccination would be beneficial for HD and PD patients; however, its effect in KT recipients was mild. Further COVID-19 vaccinations using the latest vaccine or alternative procedures should be considered in RRT patients.
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Affiliation(s)
- Ryohei Iwabuchi
- Department of Nephrology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan
- Kashiwabara Clinic, 4565-1 Hotaka Kashiwabara, Azumino, 399-8304, Japan
| | - Makoto Harada
- Department of Nephrology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan
- Kashiwabara Clinic, 4565-1 Hotaka Kashiwabara, Azumino, 399-8304, Japan
| | - Aiko Yamada
- Department of Nephrology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan
- Kashiwabara Clinic, 4565-1 Hotaka Kashiwabara, Azumino, 399-8304, Japan
| | - Daiki Aomura
- Department of Nephrology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan
| | - Yosuke Yamada
- Department of Nephrology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan
| | - Kosuke Sonoda
- Department of Nephrology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan
| | - Hideyuki Nakazawa
- Department of Hematology and Oncology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan
| | - Kaoko Sakai
- Department of Hematology and Oncology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan
| | - Etsuko Mizukami
- Kashiwabara Clinic, 4565-1 Hotaka Kashiwabara, Azumino, 399-8304, Japan
| | - Koji Hashimoto
- Department of Nephrology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan
| | - Yuji Kamijo
- Department of Nephrology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
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Otero-Romero S, Lebrun-Frénay C, Reyes S, Amato MP, Campins M, Farez M, Filippi M, Hacohen Y, Hemmer B, Juuti R, Magyari M, Oreja-Guevara C, Siva A, Vukusic S, Tintoré M. ECTRIMS/EAN consensus on vaccination in people with multiple sclerosis: Improving immunization strategies in the era of highly active immunotherapeutic drugs. Mult Scler 2023; 29:904-925. [PMID: 37293841 PMCID: PMC10338708 DOI: 10.1177/13524585231168043] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 01/30/2023] [Accepted: 03/19/2023] [Indexed: 06/10/2023]
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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Affiliation(s)
- Susana Otero-Romero
- 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
| | | | - Saúl Reyes
- 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
| | - Maria Pia Amato
- Department NEUROFARBA, University of Florence, Florence, Italy IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy
| | - Magda Campins
- Department of Preventive Medicine and Epidemiology, Vall d’Hebron Barcelona Hospital, Barcelona, Spain
| | - Mauricio Farez
- Centro para la Investigación de Enfermedades Neuroinmunológicas (CIEN), FLENI, Buenos Aires, Argentina
| | - Massimo Filippi
- 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
| | - Yael Hacohen
- 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
| | - Bernhard Hemmer
- Department of Neurology, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
| | - Rosa Juuti
- Multiple Sclerosis International Federation, London, UK
| | - Melinda Magyari
- Department of Neurology, Danish Multiple Sclerosis Center and the Danish Multiple Sclerosis Registry, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark
| | - Celia Oreja-Guevara
- Department of Neurology, Hospital Clínico San Carlos, IdISSC, Departamento de Medicina, Universidad Complutense, Madrid, Spain
| | - Aksel Siva
- Department of Neurology, School of Medicine, Istanbul University Cerrahpasa, Cerrahpasa, Istanbul, Turkey
| | - Sandra Vukusic
- 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
- 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
| | - Mar Tintoré
- Multiple Sclerosis Centre of Catalonia (Cemcat), Vall d’Hebron Barcelona Hospital, Barcelona, Spain
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Silva PBR, Silva GD. Risk and characteristics of attacks occurring after vaccination in patients with neuromyelitis optica spectrum disorders: A systematic review and meta-analysis. Mult Scler Relat Disord 2023; 75:104741. [PMID: 37182477 DOI: 10.1016/j.msard.2023.104741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 03/25/2023] [Accepted: 04/30/2023] [Indexed: 05/16/2023]
Abstract
BACKGROUND Vaccination in patients with neuromyelitis optica spectrum disorders (NMOSD) is challenging because there is a concern that vaccines can lead to clinical attacks. However, little is known about the risk and the characteristics of attacks occurring after vaccination. METHODS We performed a systematic review and meta-analysis using PubMed and Embase databases to estimate a summary frequency of attacks occurring after vaccination and describe the clinical features of theses attacks. We defined attacks occurring after vaccination as typical NMOSD attacks that occurred up to 30 days after vaccine administration. For the frequency of attacks occurring after vaccination, we selected observational studies that reported the number of attacks and total number of patients that received vaccines; for the clinical description of the attacks, case reports and case series were also included. RESULTS We included 377 participants from 5 studies to estimate the frequency of NMOSD attacks occurring after vaccination. We found a summary frequency of of 2% (95% CI 1-4%, I2 = 0%). We evaluated 17 studies to identify that 13 different vaccines were associated with NMOSD attacks. A higher-than-expected proportion of males, simultaneous optic neuritis and transverse myelitis attacks, and anti-aquaporin 4 antibody negative cases were identified in vaccine-associated attacks from 24 participants from 17 studies. Nearly two-thirds of attacks occurring after vaccination were an initial event of NMOSD. CONCLUSION The frequency of NMOSD attacks occurring after vaccination is low and non-specific to different vaccine technologies. Our work reinforces the safety of vaccine recommendations in patients with NMOSD.
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Affiliation(s)
| | - Guilherme Diogo Silva
- Neuroimmunology group, Hospital das Clínicas da Universidade de São Paulo, São Paulo, Brazil.
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Rolfes L, Pfeuffer S, Skuljec J, He X, Su C, Oezalp SH, Pawlitzki M, Ruck T, Korsen M, Kleinschnitz K, Aslan D, Hagenacker T, Kleinschnitz C, Meuth SG, Pul R. Immune Response to Seasonal Influenza Vaccination in Multiple Sclerosis Patients Receiving Cladribine. Cells 2023; 12:cells12091243. [PMID: 37174643 PMCID: PMC10177067 DOI: 10.3390/cells12091243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 04/17/2023] [Accepted: 04/22/2023] [Indexed: 05/15/2023] Open
Abstract
Cladribine has been approved for the treatment of multiple sclerosis (MS) and its administration results in a long-lasting depletion of lymphocytes. As lymphopenia is known to hamper immune responses to vaccination, we evaluated the immunogenicity of the influenza vaccine in patients undergoing cladribine treatment at different stages vs. controls. The antibody response in 90 cladribine-treated MS patients was prospectively compared with 10 control subjects receiving platform immunotherapy (NCT05019248). Serum samples were collected before and six months after vaccination. Response to vaccination was determined by the hemagglutination-inhibition test. Postvaccination seroprotection rates against influenza A were comparable in cladribine-treated patients and controls (H1N1: 94.4% vs. 100%; H3N2: 92.2% vs. 90.0%). Influenza B response was lower in the cladribine cohort (61.1% vs. 80%). The increase in geometric mean titers was lower in the cladribine group vs. controls (H1N1: +98.5 vs. +188.1; H3N2: +225.3 vs. +300.0; influenza B: +40.0 vs. +78.4); however, titers increased in both groups for all strains. Seroprotection was achieved irrespective of vaccination timing and lymphocyte subset counts at the time of vaccination in the cladribine cohort. To conclude, cladribine-treated MS patients can mount an adequate immune response to influenza independently of treatment duration and time interval to the last cladribine administration.
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Affiliation(s)
- Leoni Rolfes
- Department of Neurology, HeinrichHeine University Düsseldorf, 40225 Duesseldorf, Germany
| | - Steffen Pfeuffer
- Department of Neurology, University Hospital Giessen and Marburg, Justus-Liebig-University Giessen, 35392 Giessen, Germany
| | - Jelena Skuljec
- Department of Neurology and Center for Translational Neuro and Behavioral Science, University Medicine Essen, 45127 Essen, Germany
- Center for Translational Neuro and Behavioral Sciences (C-TNBS), University Medicine Essen, 45127 Essen, Germany
| | - Xia He
- Department of Neurology and Center for Translational Neuro and Behavioral Science, University Medicine Essen, 45127 Essen, Germany
- Center for Translational Neuro and Behavioral Sciences (C-TNBS), University Medicine Essen, 45127 Essen, Germany
| | - Chuanxin Su
- Department of Neurology and Center for Translational Neuro and Behavioral Science, University Medicine Essen, 45127 Essen, Germany
- Center for Translational Neuro and Behavioral Sciences (C-TNBS), University Medicine Essen, 45127 Essen, Germany
| | - Sinem-Hilal Oezalp
- Department of Neurology and Center for Translational Neuro and Behavioral Science, University Medicine Essen, 45127 Essen, Germany
- Center for Translational Neuro and Behavioral Sciences (C-TNBS), University Medicine Essen, 45127 Essen, Germany
| | - Marc Pawlitzki
- Department of Neurology, HeinrichHeine University Düsseldorf, 40225 Duesseldorf, Germany
| | - Tobias Ruck
- Department of Neurology, HeinrichHeine University Düsseldorf, 40225 Duesseldorf, Germany
| | - Melanie Korsen
- Department of Neurology, HeinrichHeine University Düsseldorf, 40225 Duesseldorf, Germany
| | - Konstanze Kleinschnitz
- Department of Neurology and Center for Translational Neuro and Behavioral Science, University Medicine Essen, 45127 Essen, Germany
- Center for Translational Neuro and Behavioral Sciences (C-TNBS), University Medicine Essen, 45127 Essen, Germany
| | - Derya Aslan
- Department of Neurology and Center for Translational Neuro and Behavioral Science, University Medicine Essen, 45127 Essen, Germany
- Center for Translational Neuro and Behavioral Sciences (C-TNBS), University Medicine Essen, 45127 Essen, Germany
| | - Tim Hagenacker
- Department of Neurology and Center for Translational Neuro and Behavioral Science, University Medicine Essen, 45127 Essen, Germany
- Center for Translational Neuro and Behavioral Sciences (C-TNBS), University Medicine Essen, 45127 Essen, Germany
| | - Christoph Kleinschnitz
- Department of Neurology and Center for Translational Neuro and Behavioral Science, University Medicine Essen, 45127 Essen, Germany
- Center for Translational Neuro and Behavioral Sciences (C-TNBS), University Medicine Essen, 45127 Essen, Germany
| | - Sven G Meuth
- Department of Neurology, HeinrichHeine University Düsseldorf, 40225 Duesseldorf, Germany
| | - Refik Pul
- Department of Neurology and Center for Translational Neuro and Behavioral Science, University Medicine Essen, 45127 Essen, Germany
- Center for Translational Neuro and Behavioral Sciences (C-TNBS), University Medicine Essen, 45127 Essen, Germany
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de Sèze J, Maillart E, Gueguen A, Laplaud DA, Michel L, Thouvenot E, Zephir H, Zimmer L, Biotti D, Liblau R. Anti-CD20 therapies in multiple sclerosis: From pathology to the clinic. Front Immunol 2023; 14:1004795. [PMID: 37033984 PMCID: PMC10076836 DOI: 10.3389/fimmu.2023.1004795] [Citation(s) in RCA: 49] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 02/13/2023] [Indexed: 04/11/2023] Open
Abstract
The immune system plays a significant role in multiple sclerosis. While MS was historically thought to be T cell-mediated, multiple pieces of evidence now support the view that B cells are essential players in multiple sclerosis pathogenic processes. High-efficacy disease-modifying therapies that target the immune system have emerged over the past two decades. Anti-CD20 monoclonal antibodies selectively deplete CD20+ B and CD20+ T cells and efficiently suppress inflammatory disease activity. These monotherapies prevent relapses, reduce new or active magnetic resonance imaging brain lesions, and lessen disability progression in patients with relapsing multiple sclerosis. Rituximab, ocrelizumab, and ofatumumab are currently used in clinical practice, while phase III clinical trials for ublituximab have been recently completed. In this review, we compare the four anti-CD20 antibodies in terms of their mechanisms of action, routes of administration, immunological targets, and pharmacokinetic properties. A deeper understanding of the individual properties of these molecules in relation to their efficacy and safety profiles is critical for their use in clinical practice.
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Affiliation(s)
- Jérôme de Sèze
- Department of Neurology, Hôpital de Hautepierre, Clinical Investigation Center, Institut National de la Santé et de la Recherche Médicale (INSERM), Strasbourg, France
- Fédération de Médecine Translationelle, Institut National de la Santé et de la Recherche Médicale (INSERM), Strasbourg, France
- *Correspondence: Jérôme de Sèze,
| | - Elisabeth Maillart
- Department of Neurology, Pitié Salpêtrière Hospital, Paris, France
- Centre de Ressources et de Compétences Sclérose en Plaques, Paris, France
| | - Antoine Gueguen
- Department of Neurology, Rothschild Ophthalmologic Foundation, Paris, France
| | - David A. Laplaud
- Department of Neurology, Centre Hospitalier Universitaire (CHU) Nantes, Nantes Université, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d’Investigation Clinique (CIC), Center for Research in Transplantation and Translational Immunology, UMR, UMR1064, Nantes, France
| | - Laure Michel
- Clinical Neuroscience Centre, CIC_P1414 Institut National de la Santé et de la Recherche Médicale (INSERM), Rennes University Hospital, Rennes University, Rennes, France
- Microenvironment, Cell Differentiation, Immunology and Cancer Unit, Institut National de la Santé et de la Recherche Médicale (INSERM), Rennes I University, French Blood Agency, Rennes, France
- Neurology Department, Rennes University Hospital, Rennes, France
| | - Eric Thouvenot
- Department of Neurology, Centre Hospitalier Universitaire (CHU) Nîmes, University of Montpellier, Nîmes, France
- Institut de Génomique Fonctionnelle, UMR, Institut National de la Santé et de la Recherche Médicale (INSERM), University of Montpellier, Montpellier, France
| | - Hélène Zephir
- University of Lille, Institut National de la Santé et de la Recherche Médicale (INSERM) U1172, Centre Hospitalier Universitaire (CHU), Lille, France
| | - Luc Zimmer
- Université Claude Bernard Lyon 1, Hospices Civils de Lyon, Institut National de la Santé et de la Recherche Médicale (INSERM), CNRS, Lyon Neuroscience Research Center, Lyon, France
| | - Damien Biotti
- Centre Ressources et Compétences Sclérose En Plaques (CRC-SEP) and Department of Neurology, Centre Hospitalier Universitaire (CHU) Toulouse Purpan – Hôpital Pierre-Paul Riquet, Toulouse, France
| | - Roland Liblau
- Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), University of Toulouse, CNRS, Institut National de la Santé et de la Recherche Médicale (INSERM), UPS, Toulouse, France
- Department of Immunology, Toulouse University Hospital, Toulouse, France
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8
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Gomes ABAGR, Feo LB, Silva GD, Disserol CCD, Paolilo RB, Lara AN, Tonácio AC, Mendes MF, Pereira SLA, Callegaro D. Reducing infection risk in multiple sclerosis and neuromyelitis optica spectrum disorders: a Brazilian reference center's approach. ARQUIVOS DE NEURO-PSIQUIATRIA 2022; 80:1057-1066. [PMID: 36261129 PMCID: PMC9770084 DOI: 10.1055/s-0042-1754348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) are the most common autoimmune diseases of the central nervous system (CNS). They present chronic relapsing courses that demand treatment with disease-modifying drugs (DMDs) to prevent inflammatory activity. Disease-modifying drugs lead to immunomodulation or immunosuppression through diverse mechanisms (e.g., shifting lymphocyte and cytokine profile, suppressing specific lymphocyte subpopulations). Thus, patients are more prone to infectious complications and associated worsening of disease. OBJECTIVE To present feasible strategies for mitigating the infection risk of MS and NMOSD treated patients. METHODS Targeted literature review concerning the management of infection risk with an emphasis on vaccination, therapy-specific measures, and particularities of the Brazilian endemic infectious diseases' scenario. CONCLUSION We propose a vaccination schedule, infectious screening routine, and prophylactic measures based on the current scientific evidence. Awareness of emergent tropical diseases is necessary due to evidence of demyelinating events and possible parainfectious cases of MS and NMOSD.
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Affiliation(s)
| | - Lucas Bueno Feo
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Divisão de Neurologia,, São Paulo SP, Brazil
| | - Guilherme Diogo Silva
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Divisão de Neurologia,, São Paulo SP, Brazil
| | - Caio César Diniz Disserol
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Divisão de Neurologia,, São Paulo SP, Brazil
| | - Renata Barbosa Paolilo
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Divisão de Neurologia,, São Paulo SP, Brazil
| | - Amanda Nazareth Lara
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Divisão de Doenças Infecciosas e Parasitárias, São Paulo SP, Brazil
| | - Adriana Coracini Tonácio
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Divisão de Doenças Infecciosas e Parasitárias, São Paulo SP, Brazil
| | - Maria Fernanda Mendes
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Divisão de Neurologia,, São Paulo SP, Brazil,Faculdade de Ciências Mídicas, Santa Casa de São Paulo, Divisão de Neurologia, São Paulo SP, Brazil,Address for correspondence Maria Fernanda Mendes
| | | | - Dagoberto Callegaro
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Divisão de Neurologia,, São Paulo SP, Brazil
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9
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Kim E, Haag A, Nguyen J, Kesselman MM, Demory Beckler M. Vaccination of multiple sclerosis patients during the COVID-19 era: Novel insights into vaccine safety and immunogenicity. Mult Scler Relat Disord 2022; 67:104172. [PMID: 36116380 PMCID: PMC9462931 DOI: 10.1016/j.msard.2022.104172] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 07/13/2022] [Accepted: 09/08/2022] [Indexed: 11/15/2022]
Abstract
Multiple sclerosis (MS) is an incurable autoimmune disease known to cause widespread demyelinating lesions in the central nervous system (CNS) and a host of debilitating symptoms in patients. The development of MS is believed to be driven by the breakdown of the blood brain barrier, subsequent infiltration by CD4+ and CD8+ T cells, and widespread CNS inflammation and demyelination. Disease modifying therapies (DMTs) profoundly disrupt these processes and therefore compose an essential component of disease management. However, the effects of these therapeutic agents on vaccine safety and immunogenicity in individuals with MS are not yet fully understood. As such, the primary objective of this review article was to summarize the findings of recently conducted studies on vaccine safety and immunogenicity in MS patients treated with DMTs, particularly in the context of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Discussed in this review are vaccinations against influenza, yellow fever, human papillomavirus, measles, mumps, rubella, Streptococcus pneumoniae, hepatitis B, and COVID-19. This article additionally reviews our current understanding of COVID-19 severity and incidence in this patient population, the risks and benefits of vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and vaccination guidelines set forth by MS societies and organizations.
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Affiliation(s)
- Enoch Kim
- Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States of America.
| | - Alyssa Haag
- Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States of America.
| | - Jackie Nguyen
- Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States of America.
| | - Marc M Kesselman
- Division of Rheumatology, Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States of America.
| | - Michelle Demory Beckler
- Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States of America.
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10
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Otani IM, Lehman HK, Jongco AM, Tsao LR, Azar AE, Tarrant TK, Engel E, Walter JE, Truong TQ, Khan DA, Ballow M, Cunningham-Rundles C, Lu H, Kwan M, Barmettler S. Practical guidance for the diagnosis and management of secondary hypogammaglobulinemia: A Work Group Report of the AAAAI Primary Immunodeficiency and Altered Immune Response Committees. J Allergy Clin Immunol 2022; 149:1525-1560. [PMID: 35176351 DOI: 10.1016/j.jaci.2022.01.025] [Citation(s) in RCA: 88] [Impact Index Per Article: 29.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 12/31/2021] [Accepted: 01/21/2022] [Indexed: 11/17/2022]
Abstract
Secondary hypogammaglobulinemia (SHG) is characterized by reduced immunoglobulin levels due to acquired causes of decreased antibody production or increased antibody loss. Clarification regarding whether the hypogammaglobulinemia is secondary or primary is important because this has implications for evaluation and management. Prior receipt of immunosuppressive medications and/or presence of conditions associated with SHG development, including protein loss syndromes, are histories that raise suspicion for SHG. In patients with these histories, a thorough investigation of potential etiologies of SHG reviewed in this report is needed to devise an effective treatment plan focused on removal of iatrogenic causes (eg, discontinuation of an offending drug) or treatment of the underlying condition (eg, management of nephrotic syndrome). When iatrogenic causes cannot be removed or underlying conditions cannot be reversed, therapeutic options are not clearly delineated but include heightened monitoring for clinical infections, supportive antimicrobials, and in some cases, immunoglobulin replacement therapy. This report serves to summarize the existing literature regarding immunosuppressive medications and populations (autoimmune, neurologic, hematologic/oncologic, pulmonary, posttransplant, protein-losing) associated with SHG and highlights key areas for future investigation.
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Affiliation(s)
- Iris M Otani
- Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, UCSF Medical Center, San Francisco, Calif.
| | - Heather K Lehman
- Division of Allergy, Immunology, and Rheumatology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY
| | - Artemio M Jongco
- Division of Allergy and Immunology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY
| | - Lulu R Tsao
- Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, UCSF Medical Center, San Francisco, Calif
| | - Antoine E Azar
- Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore
| | - Teresa K Tarrant
- Division of Rheumatology and Immunology, Duke University, Durham, NC
| | - Elissa Engel
- Division of Hematology and Oncology, Cincinnati Children's Hospital, Cincinnati, Ohio
| | - Jolan E Walter
- Division of Allergy and Immunology, Johns Hopkins All Children's Hospital, St Petersburg, Fla; Division of Allergy and Immunology, Morsani College of Medicine, University of South Florida, Tampa; Division of Allergy and Immunology, Massachusetts General Hospital for Children, Boston
| | - Tho Q Truong
- Divisions of Rheumatology, Allergy and Clinical Immunology, National Jewish Health, Denver
| | - David A Khan
- Division of Allergy and Immunology, University of Texas Southwestern Medical Center, Dallas
| | - Mark Ballow
- Division of Allergy and Immunology, Morsani College of Medicine, Johns Hopkins All Children's Hospital, St Petersburg
| | | | - Huifang Lu
- Department of General Internal Medicine, Section of Rheumatology and Clinical Immunology, The University of Texas MD Anderson Cancer Center, Houston
| | - Mildred Kwan
- Division of Rheumatology, Allergy, and Immunology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill
| | - Sara Barmettler
- Allergy and Immunology, Massachusetts General Hospital, Boston.
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11
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Zanetta C, Rocca MA, Filippi M. Impact of immunotherapies on COVID-19 outcomes in multiple sclerosis patients. Expert Rev Clin Immunol 2022; 18:495-512. [PMID: 35395927 DOI: 10.1080/1744666x.2022.2064845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
INTRODUCTION SARS-CoV-2 pandemic has led the scientific community to maximize efforts to prevent infections and disease severity in patients with multiple sclerosis (pwMS). We analyze the impact of immunotherapies on COVID-19 outcomes in pwMS, providing our interpretation of data. AREAS COVERED Infections, hospitalizations, intensive care unit admissions and death rates in COVID-19 pwMS are comparable to general population. Severity of disability, MS clinical phenotype, age and comorbidities, along with the use of intravenous methylprednisolone and anti-CD20 treatments, are risk factors for COVID-19 severity. Disease modifying treatments (DMTs) can be safely started and continued during the pandemic. Benefit-risk evaluation is mandatory when managing second-line therapies, to balance risk of worse COVID-19 outcomes and MS reactivation. COVID-19 vaccination is safe in MS and its efficacy could be reduced in fingolimod and ocrelizumab-treated patients. EXPERT OPINION Rate of (re)-infection and outcomes with SARS-CoV-2 variants in pwMS and antiviral properties of DMTs need to be further explored. Data on COVID-19 in pregnant MS women, children and elderly pwMS are limited. Evidence on long-term effects of infection is needed. Impact of emerging DMTs on COVID-19 should be investigated. More data and longer follow-up are needed to characterize long-term efficacy and safety profile of vaccinations in pwMS.
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Affiliation(s)
| | - Maria A Rocca
- Neurology Unit.,Neuroimaging Research Unit, Division of Neuroscience.,Vita-Salute San Raffaele University, Milan, Italy
| | - Massimo Filippi
- Neurology Unit.,Neurorehabilitation Unit.,Neuroimaging Research Unit, Division of Neuroscience.,Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan, Italy.,Vita-Salute San Raffaele University, Milan, Italy
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12
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Abstract
Neuroimmunological diseases and their treatment compromise the immune system, thereby increasing the risk of infections and serious illness. Consequently, vaccinations to protect against infections are an important part of the clinical management of these diseases. However, the wide variety of immunotherapies that are currently used to treat neuroimmunological disease — particularly multiple sclerosis and neuromyelitis optica spectrum disorders — can also impair immunological responses to vaccinations. In this Review, we discuss what is known about the effects of various immunotherapies on immunological responses to vaccines and what these effects mean for the safe and effective use of vaccines in patients with a neuroimmunological disease. The success of vaccination in patients receiving immunotherapy largely depends on the specific mode of action of the immunotherapy. To minimize the risk of infection when using immunotherapy, assessment of immune status and exclusion of underlying chronic infections before initiation of therapy are essential. Selection of the required vaccinations and leaving appropriate time intervals between vaccination and administration of immunotherapy can help to safeguard patients. We also discuss the rapidly evolving knowledge of how immunotherapies affect responses to SARS-CoV-2 vaccines and how these effects should influence the management of patients on these therapies during the COVID-19 pandemic. In this Review, the authors discuss how various immunotherapies for neuroimmunological diseases interact with vaccination responses, including responses to SARS-CoV-2 vaccinations, and the implications for the safe and effective use of vaccines in patients with these diseases.
Vaccination against infection is an essential part of the management of neuroimmunological diseases. All indicated vaccinations should be administered before initiation of immunotherapy whenever possible; appropriate intervals between vaccination and treatment vary with treatment and vaccination. Inactivated vaccines are considered safe in neuroimmunological diseases but live vaccines are generally contraindicated during immunotherapy. Vaccination responses during immunotherapy can be diminished or abrogated, depending on the treatment and vaccination; antibody titre testing to monitor responses can be considered where appropriate. Vaccinations must be avoided during relapses or exacerbations of neuroimmunological diseases. Vaccination against SARS-CoV-2 is recommended for patients with neuroimmunological disease but some immunotherapies limit the immune response; therefore, timing should be considered carefully.
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13
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Bemben NM, Berg ML. Efficacy of inactivated vaccines in patients treated with immunosuppressive drug therapy. Pharmacotherapy 2022; 42:334-342. [PMID: 35146780 PMCID: PMC9088666 DOI: 10.1002/phar.2671] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Revised: 01/28/2022] [Accepted: 01/28/2022] [Indexed: 12/17/2022]
Affiliation(s)
- Nina M. Bemben
- Wolters Kluwer Clinical Effectiveness Chicago Illinois USA
| | - Melody L. Berg
- American Society of Health‐System Pharmacists Bethesda Maryland USA
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14
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Law MF, Ho R, Law KWT, Cheung CKM. Gastrointestinal and hepatic side effects of potential treatment for COVID-19 and vaccination in patients with chronic liver diseases. World J Hepatol 2021; 13:1850-1874. [PMID: 35069994 PMCID: PMC8727202 DOI: 10.4254/wjh.v13.i12.1850] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 07/20/2021] [Accepted: 11/15/2021] [Indexed: 02/06/2023] Open
Abstract
The outbreak of coronavirus disease 2019 (COVID-19) is a global pandemic. Many clinical trials have been performed to investigate potential treatments or vaccines for this disease to reduce the high morbidity and mortality. The drugs of higher interest include umifenovir, bromhexine, remdesivir, lopinavir/ritonavir, steroid, tocilizumab, interferon alpha or beta, ribavirin, fivapiravir, nitazoxanide, ivermectin, molnupiravir, hydroxychloroquine/chloroquine alone or in combination with azithromycin, and baricitinib. Gastrointestinal (GI) symptoms and liver dysfunction are frequently seen in patients with COVID-19, which can make it difficult to differentiate disease manifestations from treatment adverse effects. GI symptoms of COVID-19 include anorexia, dyspepsia, nausea, vomiting, diarrhea and abdominal pain. Liver injury can be a result of systemic inflammation or cytokine storm, or due to the adverse drug effects in patients who have been receiving different treatments. Regular monitoring of liver function should be performed. COVID-19 vaccines have been rapidly developed with different technologies including mRNA, viral vectors, inactivated viruses, recombinant DNA, protein subunits and live attenuated viruses. Patients with chronic liver disease or inflammatory bowel disease and liver transplant recipients are encouraged to receive vaccination as the benefits outweigh the risks. Vaccination against COVID-19 is also recommended to family members and healthcare professionals caring for these patients to reduce exposure to the severe acute respiratory syndrome coronavirus 2 virus.
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Affiliation(s)
- Man Fai Law
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
| | - Rita Ho
- Department of Medicine, North District Hospital, Hong Kong, China
| | | | - Carmen Ka Man Cheung
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
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15
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Becker J, Ferreira LC, Damasceno A, Bichuetti DB, Christo PP, Callegaro D, Peixoto MAL, Sousa NADC, Almeida SMD, Adoni T, Santiago-Amaral J, Junqueira T, Pereira SLA, Gomes ABAGR, Pitombeira M, Paolilo RB, Grzesiuk AK, Piccolo AC, D Almeida JAC, Gomes Neto AP, Oliveira ACPD, Oliveira BSD, Tauil CB, Vasconcelos CF, Kaimen-Maciel D, Varela D, Diniz DS, Oliveira EMLD, Malfetano FR, Borges FE, Figueira FFA, Gondim FDAA, Passos GRD, Silva GD, Olival GSD, Santos GACD, Ruocco HH, Sato HK, Soares Neto HR, Cortoni Calia L, Gonçalves MVM, Vecino MCAD, Pimentel MLV, Ribeiro MDC, Boaventura M, Parolin MKF, Melo RBDS, Lázaro R, Thomaz RB, Kleinpaul R, Dias RM, Gomes S, Lucatto SA, Alves-Leon SV, Fukuda T, Ribeiro TAGJ, Winckler TCD, Fragoso YD, Nascimento OJMD, Ferreira MLB, Mendes MF, Brum DG, Glehn FV. Recommendations by the Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology (DCNI/ABN) and the Brazilian Committee for Treatment and Research in Multiple Sclerosis and Neuroimmunological Diseases (BCTRIMS) on vaccination in general and specifically against SARS-CoV-2 for patients with demyelinating diseases of the central nervous system. ARQUIVOS DE NEURO-PSIQUIATRIA 2021; 79:1049-1061. [PMID: 34816999 DOI: 10.1590/0004-282x-anp-2021-0162] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Accepted: 05/30/2021] [Indexed: 11/22/2022]
Abstract
The Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology (DCNI/ABN) and Brazilian Committee for Treatment and Research in Multiple Sclerosis and Neuroimmunological Diseases (BCTRIMS) provide recommendations in this document for vaccination of the population with demyelinating diseases of the central nervous system (CNS) against infections in general and against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19. We emphasize the seriousness of the current situation in view of the spread of COVID-19 in our country. Therefore, reference guides on vaccination for clinicians, patients, and public health authorities are particularly important to prevent some infectious diseases. The DCNI/ABN and BCTRIMS recommend that patients with CNS demyelinating diseases (e.g., MS and NMOSD) be continually monitored for updates to their vaccination schedule, especially at the beginning or before a change in treatment with a disease modifying drug (DMD). It is also important to note that vaccines are safe, and physicians should encourage their use in all patients. Clearly, special care should be taken when live attenuated viruses are involved. Finally, it is important for physicians to verify which DMD the patient is receiving and when the last dose was taken, as each drug may affect the induction of immune response differently.
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Affiliation(s)
- Jefferson Becker
- Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre RS, Brazil
| | - Lis Campos Ferreira
- Universidade Federal de Sergipe, Aracaju SE, Brazil.,Universidade Tiradentes, Aracaju SE, Brazil
| | - Alfredo Damasceno
- Universidade de Campinas, Faculdade de Ciências Médicas, Campinas SP, Brazil
| | | | | | - Dagoberto Callegaro
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo SP, Brazil
| | | | | | | | - Tarso Adoni
- Hospital Sírio Libanês, São Paulo SP, Brazil
| | | | | | | | | | | | - Renata Barbosa Paolilo
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo SP, Brazil
| | | | | | | | | | | | | | | | | | | | - Daniel Varela
- Hospital de Clínicas de Passo Fundo, Passo Fundo RS, Brazil
| | | | | | | | | | | | | | | | - Guilherme Diogo Silva
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo SP, Brazil
| | | | | | - Heloisa Helena Ruocco
- Universidade Federal Fluminense, Niterói RJ, Brazil.,Pontifícia Universidade Católica, Campina SP, Brazil
| | | | | | | | | | | | | | | | - Mateus Boaventura
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo SP, Brazil
| | | | | | - Robson Lázaro
- Faculdade de Medicina de Jundiaí, Jundiaí SP, Brazil
| | | | | | | | - Sidney Gomes
- Hospital Beneficiência Portuguesa, São Paulo SP, Brazil
| | | | | | - Thiago Fukuda
- Hospital Universitário Prof. Edgar Santos, Salvador BA, Brazil
| | | | | | | | | | | | | | | | - Felipe Von Glehn
- Universidade de Campinas, Faculdade de Ciências Médicas, Campinas SP, Brazil.,Universidade de Brasília, Faculdade de Medicina, Brasília DF, Brazil
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16
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Smets I, Giovannoni G. Derisking CD20-therapies for long-term use. Mult Scler Relat Disord 2021; 57:103418. [PMID: 34902761 DOI: 10.1016/j.msard.2021.103418] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Revised: 09/15/2021] [Accepted: 11/20/2021] [Indexed: 11/16/2022]
Abstract
Anti-CD20 have quickly become the mainstay in the treatment of multiple sclerosis (MS) and other neuroinflammatory conditions. However, when they are used as a maintenance therapy the balance between risks and benefits changes. In this review, we suggested six steps to derisk anti-CD20. Firstly and secondly, adequate infectious screening followed by vaccinations before starting anti-CD20 are paramount. Third, family planning needs to be discussed upfront with every woman of childbearing age. Fourth, infusion reactions should be adequately managed to avoid treatment interruption. After repeated infusions, it becomes important to detect and prevent anti-CD20-related adverse events. Fifth, we recommended measuring immunoglobulin levels and reviewing vaccinations annually as well as counselling adequate fever management. For female patients, we emphasised the importance to engage with the local breast cancer screening programs. Sixth, to fundamentally derisk anti-CD20 therapies, we need evidence-based approaches to reduce dosing intervals and guide retreatment.
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Affiliation(s)
- Ide Smets
- Blizard Institute, Centre for Neuroscience, Surgery and Trauma, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark St, Whitechapel, London E1 2AT, United Kingdom; Clinical Board Medicine (Neuroscience), Royal London Hospital, Barts Health NHS Trust, Whitechapel Road, London E1 1FR, United Kingdom
| | - Gavin Giovannoni
- Blizard Institute, Centre for Neuroscience, Surgery and Trauma, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark St, Whitechapel, London E1 2AT, United Kingdom; Clinical Board Medicine (Neuroscience), Royal London Hospital, Barts Health NHS Trust, Whitechapel Road, London E1 1FR, United Kingdom.
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17
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Yarahmadi P, Alirezaei M, Forouzannia SM, Naser Moghadasi A. The Outcome of COVID-19 in Patients with a History of Taking Rituximab: A Narrative Review. IRANIAN JOURNAL OF MEDICAL SCIENCES 2021; 46:411-419. [PMID: 34840381 PMCID: PMC8611224 DOI: 10.30476/ijms.2021.88717.1946] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 01/26/2021] [Accepted: 03/13/2021] [Indexed: 01/16/2023]
Abstract
Coronavirus disease 2019 (COVID-19) is a recently emerging disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Notably, the safety of immunosuppressive medications is a major concern during an infectious disease pandemic. Rituximab (RTX), as a monoclonal antibody against CD20 molecule, is widely used for the treatment of various diseases, mostly autoimmune diseases and some malignancies. Previous studies indicated that RTX, as an immunosuppressive medication, may be associated with the increased risk of infections. Moreover, given the wide use of RTX, a necessity of determining the different aspects of RTX use in the COVID-19 era is strongly felt. We reviewed current studies on the clinical courses of patients with SARS-CoV-2 infection. It appears that the use of RTX does not increase morbidity and mortality in most patients. However, underlying diseases and other concomitant medications may play a role in the disease course, while the concerns of vaccine efficacy in patients receiving RTX still need to be addressed. Therefore, more controlled studies are needed for a better conclusion.
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Affiliation(s)
- Pourya Yarahmadi
- Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Alirezaei
- Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyed Mohammad Forouzannia
- Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Abdorreza Naser Moghadasi
- Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
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18
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Yeaman MR. Immunosuppression in Glomerular Diseases: Implications for SARS-CoV-2 Vaccines and COVID-19. GLOMERULAR DISEASES 2021; 1:277-293. [PMID: 34935004 PMCID: PMC8678218 DOI: 10.1159/000519182] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Accepted: 08/19/2021] [Indexed: 01/13/2023]
Abstract
BACKGROUND Glomerular diseases (GD) are chronic conditions that often involve immune dysfunction and require immunosuppressive therapy (IST) to control underlying pathogenesis. Unfortunately, such diseases appear to heighten risks of severe outcomes in COVID-19 and predispose to other infections that may be life-threatening. Thus, averting preventable infections is imperative in GD patients. SUMMARY The advent of vaccines demonstrated to be safe and efficacious against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has favorably impacted the COVID-19 pandemic epidemiology. However, patients on ISTs were excluded from initial vaccine clinical trials. Thus, only limited and incomplete data are available currently regarding the potential impact of immunosuppression on immune response to or efficacy of the SARS-CoV-2 vaccines. However, new insights are emerging from SARS-CoV-2 vaccine studies, and impacts of ISTs on conventional vaccines are useful to consider. Mechanisms of immunosuppressive agents commonly used in the treatment of GD are reviewed with respect to implications for immune responses induced by SARS-CoV-2 vaccines. ISTs discussed include corticosteroids; alkylating agents; antimetabolites; calcineurin or mammalian target of rapamycin inhibitors; CD38+, CD20+, or CD19+ cell depletion; and complement protein C5 inhibition. KEY MESSAGES Many immunosuppressive therapies may potentially attenuate or impair protective immunity of the SARS-CoV-2 vaccines. However, as vaccines currently in use employ mRNA or nonreplicative viral vectors, they appear to be safe in patients on immunosuppression, further favoring vaccination. Moreover, predominant SARS-CoV-2 vaccines are likely to afford at least partial protective immunity through one or more immune mechanisms even in patients on IST. Guidelines and emerging strategies are also considered to optimize vaccine protection from COVID-19.
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Affiliation(s)
- Michael R. Yeaman
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
- Divisions of Molecular Medicine & Infectious Diseases, Harbor-UCLA Medical Center, Torrance, California, USA
- The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California, USA
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19
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Landtblom A, Berntsson SG, Boström I, Iacobaeus E. Multiple sclerosis and COVID-19: The Swedish experience. Acta Neurol Scand 2021; 144:229-235. [PMID: 34028810 PMCID: PMC8222873 DOI: 10.1111/ane.13453] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 04/16/2021] [Accepted: 04/22/2021] [Indexed: 12/13/2022]
Abstract
The COVID-19 pandemic has brought challenges for healthcare management of patients with multiple sclerosis (MS). Concerns regarding vulnerability to infections and disease-modifying therapies (DMTs) and their complications have been raised. Recent published guidelines on the use of DMTs in relation to COVID-19 in MS patients have been diverse between countries with lack of evidence-based facts. In Sweden, there exists a particular interest in anti-CD20 therapy as a possible risk factor for severe COVID-19 due to the large number of rituximab-treated patients off-label in the country. Rapid responses from the Swedish MS Association (SMSS) and the Swedish MS registry (SMSreg) have resulted in national guidelines on DMT use for MS patients and implementation of a COVID-19 module in the SMSreg. Recently updated guidelines also included recommendations on COVID-19 vaccination with regard to the different DMTs. Social distancing policies forced implementation of telemedicine consultation to replace in-person consultations as part of regular MS health care. Patient-reported outcome measures (PROMs) in SMSreg have been useful in this respect. This paper reports our experiences on the progress of national MS health care during the COVID-19 pandemic, in addition to offering an overview of the present scientific context.
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Affiliation(s)
- Anne‐Marie Landtblom
- Department of NeuroscienceUppsala UniversityUppsalaSweden
- Department of Biomedical and Clinical SciencesLinköping UniversityLinköpingSweden
| | | | - Inger Boström
- Department of Biomedical and Clinical SciencesLinköping UniversityLinköpingSweden
| | - Ellen Iacobaeus
- Department of Clinical NeuroscienceDivision of NeurologyKarolinska Institute and Karolinska University HospitalStockholmSweden
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20
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Pawlitzki M, Meuth SG. Immunmodulatorische Therapien bei Multipler Sklerose in der Pandemie. INFO NEUROLOGIE + PSYCHIATRIE 2021. [PMCID: PMC8373422 DOI: 10.1007/s15005-021-2009-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Affiliation(s)
- Marc Pawlitzki
- des UniversitätsklinikumMünster, Institut für translationale Neurologie, Albert-Schweitzer-Campus1, 48149 Münster, Germany
| | - Sven G. Meuth
- Klinik für Neurologie, Universitätsklinikum Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany
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Rolfes L, Pawlitzki M, Pfeuffer S, Nelke C, Lux A, Pul R, Kleinschnitz C, Kleinschnitz K, Rogall R, Pape K, Bittner S, Zipp F, Warnke C, Goereci Y, Schroeter M, Ingwersen J, Aktas O, Klotz L, Ruck T, Wiendl H, Meuth SG. Ocrelizumab Extended Interval Dosing in Multiple Sclerosis in Times of COVID-19. NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION 2021; 8:8/5/e1035. [PMID: 34261812 PMCID: PMC8362352 DOI: 10.1212/nxi.0000000000001035] [Citation(s) in RCA: 77] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Accepted: 04/22/2021] [Indexed: 12/26/2022]
Abstract
Objective To evaluate the clinical consequences of extended interval dosing (EID) of ocrelizumab in relapsing-remitting multiple sclerosis (RRMS) during the coronavirus disease 2019 (COVID-19) pandemic. Methods In our retrospective, multicenter cohort study, we compared patients with RRMS on EID (defined as ≥4-week delay of dose interval) with a control group on standard interval dosing (SID) at the same period (January to December 2020). Results Three hundred eighteen patients with RRMS were longitudinally evaluated in 5 German centers. One hundred sixteen patients received ocrelizumab on EID (median delay [interquartile range 8.68 [5.09–13.07] weeks). Three months after the last ocrelizumab infusion, 182 (90.1%) patients following SID and 105 (90.5%) EID patients remained relapse free (p = 0.903). Three-month confirmed progression of disability was observed in 18 SID patients (8.9%) and 11 EID patients (9.5%, p = 0.433). MRI progression was documented in 9 SID patients (4.5%) and 8 EID patients (6.9%) at 3-month follow-up (p = 0.232). Multivariate logistic regression showed no association between treatment regimen and no evidence of disease activity status at follow-up (OR: 1.266 [95% CI: 0.695–2.305]; p = 0.441). Clinical stability was accompanied by persistent peripheral CD19+ B-cell depletion in both groups (SID vs EID: 82.6% vs 83.3%, p = 0.463). Disease activity in our cohort was not associated with CD19+ B-cell repopulation. Conclusion Our data support EID of ocrelizumab as potential risk mitigation strategy in times of the COVID-19 pandemic. Classification of Evidence This study provides Class IV evidence that for patients with RRMS, an EID of at least 4 weeks does not diminish effectiveness of ocrelizumab.
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Affiliation(s)
- Leoni Rolfes
- From the Department of Neurology with Institute of Translational Neurology (L.R., M.P., S.P., C.N., L.K., H.W.), University Hospital Muenster, Germany; Institute for Biometrics and Bioinformatic (A.L.), Otto-von-Guericke University, Magdeburg, Germany; Department for Neurology (R.P., C.K., K.K., R.R.), University Hospital Essen, Germany; Focus Program Translational Neurosciences (FTN) and Immunology (FZI) (K.P., S.B., F.Z.), Rhine Main Neuroscience Network (rmn2), Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Germany; Department of Neurology (C.W., Y.G., M.S.), University Hospital Cologne, Germany; and Department of Neurology (J.I., O.A., T.R., S.G.M.), Heinrich-Heine University, Duesseldorf, Germany
| | - Marc Pawlitzki
- From the Department of Neurology with Institute of Translational Neurology (L.R., M.P., S.P., C.N., L.K., H.W.), University Hospital Muenster, Germany; Institute for Biometrics and Bioinformatic (A.L.), Otto-von-Guericke University, Magdeburg, Germany; Department for Neurology (R.P., C.K., K.K., R.R.), University Hospital Essen, Germany; Focus Program Translational Neurosciences (FTN) and Immunology (FZI) (K.P., S.B., F.Z.), Rhine Main Neuroscience Network (rmn2), Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Germany; Department of Neurology (C.W., Y.G., M.S.), University Hospital Cologne, Germany; and Department of Neurology (J.I., O.A., T.R., S.G.M.), Heinrich-Heine University, Duesseldorf, Germany
| | - Steffen Pfeuffer
- From the Department of Neurology with Institute of Translational Neurology (L.R., M.P., S.P., C.N., L.K., H.W.), University Hospital Muenster, Germany; Institute for Biometrics and Bioinformatic (A.L.), Otto-von-Guericke University, Magdeburg, Germany; Department for Neurology (R.P., C.K., K.K., R.R.), University Hospital Essen, Germany; Focus Program Translational Neurosciences (FTN) and Immunology (FZI) (K.P., S.B., F.Z.), Rhine Main Neuroscience Network (rmn2), Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Germany; Department of Neurology (C.W., Y.G., M.S.), University Hospital Cologne, Germany; and Department of Neurology (J.I., O.A., T.R., S.G.M.), Heinrich-Heine University, Duesseldorf, Germany
| | - Christopher Nelke
- From the Department of Neurology with Institute of Translational Neurology (L.R., M.P., S.P., C.N., L.K., H.W.), University Hospital Muenster, Germany; Institute for Biometrics and Bioinformatic (A.L.), Otto-von-Guericke University, Magdeburg, Germany; Department for Neurology (R.P., C.K., K.K., R.R.), University Hospital Essen, Germany; Focus Program Translational Neurosciences (FTN) and Immunology (FZI) (K.P., S.B., F.Z.), Rhine Main Neuroscience Network (rmn2), Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Germany; Department of Neurology (C.W., Y.G., M.S.), University Hospital Cologne, Germany; and Department of Neurology (J.I., O.A., T.R., S.G.M.), Heinrich-Heine University, Duesseldorf, Germany
| | - Anke Lux
- From the Department of Neurology with Institute of Translational Neurology (L.R., M.P., S.P., C.N., L.K., H.W.), University Hospital Muenster, Germany; Institute for Biometrics and Bioinformatic (A.L.), Otto-von-Guericke University, Magdeburg, Germany; Department for Neurology (R.P., C.K., K.K., R.R.), University Hospital Essen, Germany; Focus Program Translational Neurosciences (FTN) and Immunology (FZI) (K.P., S.B., F.Z.), Rhine Main Neuroscience Network (rmn2), Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Germany; Department of Neurology (C.W., Y.G., M.S.), University Hospital Cologne, Germany; and Department of Neurology (J.I., O.A., T.R., S.G.M.), Heinrich-Heine University, Duesseldorf, Germany
| | - Refik Pul
- From the Department of Neurology with Institute of Translational Neurology (L.R., M.P., S.P., C.N., L.K., H.W.), University Hospital Muenster, Germany; Institute for Biometrics and Bioinformatic (A.L.), Otto-von-Guericke University, Magdeburg, Germany; Department for Neurology (R.P., C.K., K.K., R.R.), University Hospital Essen, Germany; Focus Program Translational Neurosciences (FTN) and Immunology (FZI) (K.P., S.B., F.Z.), Rhine Main Neuroscience Network (rmn2), Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Germany; Department of Neurology (C.W., Y.G., M.S.), University Hospital Cologne, Germany; and Department of Neurology (J.I., O.A., T.R., S.G.M.), Heinrich-Heine University, Duesseldorf, Germany
| | - Christoph Kleinschnitz
- From the Department of Neurology with Institute of Translational Neurology (L.R., M.P., S.P., C.N., L.K., H.W.), University Hospital Muenster, Germany; Institute for Biometrics and Bioinformatic (A.L.), Otto-von-Guericke University, Magdeburg, Germany; Department for Neurology (R.P., C.K., K.K., R.R.), University Hospital Essen, Germany; Focus Program Translational Neurosciences (FTN) and Immunology (FZI) (K.P., S.B., F.Z.), Rhine Main Neuroscience Network (rmn2), Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Germany; Department of Neurology (C.W., Y.G., M.S.), University Hospital Cologne, Germany; and Department of Neurology (J.I., O.A., T.R., S.G.M.), Heinrich-Heine University, Duesseldorf, Germany
| | - Konstanze Kleinschnitz
- From the Department of Neurology with Institute of Translational Neurology (L.R., M.P., S.P., C.N., L.K., H.W.), University Hospital Muenster, Germany; Institute for Biometrics and Bioinformatic (A.L.), Otto-von-Guericke University, Magdeburg, Germany; Department for Neurology (R.P., C.K., K.K., R.R.), University Hospital Essen, Germany; Focus Program Translational Neurosciences (FTN) and Immunology (FZI) (K.P., S.B., F.Z.), Rhine Main Neuroscience Network (rmn2), Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Germany; Department of Neurology (C.W., Y.G., M.S.), University Hospital Cologne, Germany; and Department of Neurology (J.I., O.A., T.R., S.G.M.), Heinrich-Heine University, Duesseldorf, Germany
| | - Rebeca Rogall
- From the Department of Neurology with Institute of Translational Neurology (L.R., M.P., S.P., C.N., L.K., H.W.), University Hospital Muenster, Germany; Institute for Biometrics and Bioinformatic (A.L.), Otto-von-Guericke University, Magdeburg, Germany; Department for Neurology (R.P., C.K., K.K., R.R.), University Hospital Essen, Germany; Focus Program Translational Neurosciences (FTN) and Immunology (FZI) (K.P., S.B., F.Z.), Rhine Main Neuroscience Network (rmn2), Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Germany; Department of Neurology (C.W., Y.G., M.S.), University Hospital Cologne, Germany; and Department of Neurology (J.I., O.A., T.R., S.G.M.), Heinrich-Heine University, Duesseldorf, Germany
| | - Katrin Pape
- From the Department of Neurology with Institute of Translational Neurology (L.R., M.P., S.P., C.N., L.K., H.W.), University Hospital Muenster, Germany; Institute for Biometrics and Bioinformatic (A.L.), Otto-von-Guericke University, Magdeburg, Germany; Department for Neurology (R.P., C.K., K.K., R.R.), University Hospital Essen, Germany; Focus Program Translational Neurosciences (FTN) and Immunology (FZI) (K.P., S.B., F.Z.), Rhine Main Neuroscience Network (rmn2), Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Germany; Department of Neurology (C.W., Y.G., M.S.), University Hospital Cologne, Germany; and Department of Neurology (J.I., O.A., T.R., S.G.M.), Heinrich-Heine University, Duesseldorf, Germany
| | - Stefan Bittner
- From the Department of Neurology with Institute of Translational Neurology (L.R., M.P., S.P., C.N., L.K., H.W.), University Hospital Muenster, Germany; Institute for Biometrics and Bioinformatic (A.L.), Otto-von-Guericke University, Magdeburg, Germany; Department for Neurology (R.P., C.K., K.K., R.R.), University Hospital Essen, Germany; Focus Program Translational Neurosciences (FTN) and Immunology (FZI) (K.P., S.B., F.Z.), Rhine Main Neuroscience Network (rmn2), Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Germany; Department of Neurology (C.W., Y.G., M.S.), University Hospital Cologne, Germany; and Department of Neurology (J.I., O.A., T.R., S.G.M.), Heinrich-Heine University, Duesseldorf, Germany
| | - Frauke Zipp
- From the Department of Neurology with Institute of Translational Neurology (L.R., M.P., S.P., C.N., L.K., H.W.), University Hospital Muenster, Germany; Institute for Biometrics and Bioinformatic (A.L.), Otto-von-Guericke University, Magdeburg, Germany; Department for Neurology (R.P., C.K., K.K., R.R.), University Hospital Essen, Germany; Focus Program Translational Neurosciences (FTN) and Immunology (FZI) (K.P., S.B., F.Z.), Rhine Main Neuroscience Network (rmn2), Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Germany; Department of Neurology (C.W., Y.G., M.S.), University Hospital Cologne, Germany; and Department of Neurology (J.I., O.A., T.R., S.G.M.), Heinrich-Heine University, Duesseldorf, Germany
| | - Clemens Warnke
- From the Department of Neurology with Institute of Translational Neurology (L.R., M.P., S.P., C.N., L.K., H.W.), University Hospital Muenster, Germany; Institute for Biometrics and Bioinformatic (A.L.), Otto-von-Guericke University, Magdeburg, Germany; Department for Neurology (R.P., C.K., K.K., R.R.), University Hospital Essen, Germany; Focus Program Translational Neurosciences (FTN) and Immunology (FZI) (K.P., S.B., F.Z.), Rhine Main Neuroscience Network (rmn2), Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Germany; Department of Neurology (C.W., Y.G., M.S.), University Hospital Cologne, Germany; and Department of Neurology (J.I., O.A., T.R., S.G.M.), Heinrich-Heine University, Duesseldorf, Germany
| | - Yasemin Goereci
- From the Department of Neurology with Institute of Translational Neurology (L.R., M.P., S.P., C.N., L.K., H.W.), University Hospital Muenster, Germany; Institute for Biometrics and Bioinformatic (A.L.), Otto-von-Guericke University, Magdeburg, Germany; Department for Neurology (R.P., C.K., K.K., R.R.), University Hospital Essen, Germany; Focus Program Translational Neurosciences (FTN) and Immunology (FZI) (K.P., S.B., F.Z.), Rhine Main Neuroscience Network (rmn2), Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Germany; Department of Neurology (C.W., Y.G., M.S.), University Hospital Cologne, Germany; and Department of Neurology (J.I., O.A., T.R., S.G.M.), Heinrich-Heine University, Duesseldorf, Germany
| | - Michael Schroeter
- From the Department of Neurology with Institute of Translational Neurology (L.R., M.P., S.P., C.N., L.K., H.W.), University Hospital Muenster, Germany; Institute for Biometrics and Bioinformatic (A.L.), Otto-von-Guericke University, Magdeburg, Germany; Department for Neurology (R.P., C.K., K.K., R.R.), University Hospital Essen, Germany; Focus Program Translational Neurosciences (FTN) and Immunology (FZI) (K.P., S.B., F.Z.), Rhine Main Neuroscience Network (rmn2), Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Germany; Department of Neurology (C.W., Y.G., M.S.), University Hospital Cologne, Germany; and Department of Neurology (J.I., O.A., T.R., S.G.M.), Heinrich-Heine University, Duesseldorf, Germany
| | - Jens Ingwersen
- From the Department of Neurology with Institute of Translational Neurology (L.R., M.P., S.P., C.N., L.K., H.W.), University Hospital Muenster, Germany; Institute for Biometrics and Bioinformatic (A.L.), Otto-von-Guericke University, Magdeburg, Germany; Department for Neurology (R.P., C.K., K.K., R.R.), University Hospital Essen, Germany; Focus Program Translational Neurosciences (FTN) and Immunology (FZI) (K.P., S.B., F.Z.), Rhine Main Neuroscience Network (rmn2), Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Germany; Department of Neurology (C.W., Y.G., M.S.), University Hospital Cologne, Germany; and Department of Neurology (J.I., O.A., T.R., S.G.M.), Heinrich-Heine University, Duesseldorf, Germany
| | - Orhan Aktas
- From the Department of Neurology with Institute of Translational Neurology (L.R., M.P., S.P., C.N., L.K., H.W.), University Hospital Muenster, Germany; Institute for Biometrics and Bioinformatic (A.L.), Otto-von-Guericke University, Magdeburg, Germany; Department for Neurology (R.P., C.K., K.K., R.R.), University Hospital Essen, Germany; Focus Program Translational Neurosciences (FTN) and Immunology (FZI) (K.P., S.B., F.Z.), Rhine Main Neuroscience Network (rmn2), Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Germany; Department of Neurology (C.W., Y.G., M.S.), University Hospital Cologne, Germany; and Department of Neurology (J.I., O.A., T.R., S.G.M.), Heinrich-Heine University, Duesseldorf, Germany
| | - Luisa Klotz
- From the Department of Neurology with Institute of Translational Neurology (L.R., M.P., S.P., C.N., L.K., H.W.), University Hospital Muenster, Germany; Institute for Biometrics and Bioinformatic (A.L.), Otto-von-Guericke University, Magdeburg, Germany; Department for Neurology (R.P., C.K., K.K., R.R.), University Hospital Essen, Germany; Focus Program Translational Neurosciences (FTN) and Immunology (FZI) (K.P., S.B., F.Z.), Rhine Main Neuroscience Network (rmn2), Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Germany; Department of Neurology (C.W., Y.G., M.S.), University Hospital Cologne, Germany; and Department of Neurology (J.I., O.A., T.R., S.G.M.), Heinrich-Heine University, Duesseldorf, Germany
| | - Tobias Ruck
- From the Department of Neurology with Institute of Translational Neurology (L.R., M.P., S.P., C.N., L.K., H.W.), University Hospital Muenster, Germany; Institute for Biometrics and Bioinformatic (A.L.), Otto-von-Guericke University, Magdeburg, Germany; Department for Neurology (R.P., C.K., K.K., R.R.), University Hospital Essen, Germany; Focus Program Translational Neurosciences (FTN) and Immunology (FZI) (K.P., S.B., F.Z.), Rhine Main Neuroscience Network (rmn2), Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Germany; Department of Neurology (C.W., Y.G., M.S.), University Hospital Cologne, Germany; and Department of Neurology (J.I., O.A., T.R., S.G.M.), Heinrich-Heine University, Duesseldorf, Germany
| | - Heinz Wiendl
- From the Department of Neurology with Institute of Translational Neurology (L.R., M.P., S.P., C.N., L.K., H.W.), University Hospital Muenster, Germany; Institute for Biometrics and Bioinformatic (A.L.), Otto-von-Guericke University, Magdeburg, Germany; Department for Neurology (R.P., C.K., K.K., R.R.), University Hospital Essen, Germany; Focus Program Translational Neurosciences (FTN) and Immunology (FZI) (K.P., S.B., F.Z.), Rhine Main Neuroscience Network (rmn2), Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Germany; Department of Neurology (C.W., Y.G., M.S.), University Hospital Cologne, Germany; and Department of Neurology (J.I., O.A., T.R., S.G.M.), Heinrich-Heine University, Duesseldorf, Germany
| | - Sven G Meuth
- From the Department of Neurology with Institute of Translational Neurology (L.R., M.P., S.P., C.N., L.K., H.W.), University Hospital Muenster, Germany; Institute for Biometrics and Bioinformatic (A.L.), Otto-von-Guericke University, Magdeburg, Germany; Department for Neurology (R.P., C.K., K.K., R.R.), University Hospital Essen, Germany; Focus Program Translational Neurosciences (FTN) and Immunology (FZI) (K.P., S.B., F.Z.), Rhine Main Neuroscience Network (rmn2), Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Germany; Department of Neurology (C.W., Y.G., M.S.), University Hospital Cologne, Germany; and Department of Neurology (J.I., O.A., T.R., S.G.M.), Heinrich-Heine University, Duesseldorf, Germany.
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Vaccine response following anti-CD20 therapy: a systematic review and meta-analysis of 905 patients. Blood Adv 2021; 5:2624-2643. [PMID: 34152403 PMCID: PMC8216656 DOI: 10.1182/bloodadvances.2021004629] [Citation(s) in RCA: 72] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Accepted: 04/23/2021] [Indexed: 11/20/2022] Open
Abstract
The objective of this study was to perform a systematic review of the literature on vaccine responsiveness in patients who have received anti-CD20 therapy. PubMed and EMBASE were searched up to 4 January 2021 to identify studies of vaccine immunogenicity in patients treated with anti-CD20 therapy, including patients with hematologic malignancy or autoimmune disease. The primary outcomes were seroprotection (SP), seroconversion (SC), and/or seroresponse rates for each type of vaccine reported. As the pandemic influenza vaccine (2009 H1N1) has standardized definitions for SP and SC, and represented a novel primary antigen similar to the COVID-19 vaccine, meta-analysis was conducted for SC of studies of this vaccine. Pooled estimates, relative benefit ratios (RBs), and 95% confidence intervals (CIs) were calculated using a random-effects model. Thirty-eight studies (905 patients treated with anti-CD20 therapy) were included (19 studies of patients with hematologic malignancies). Patients on active (<3 months since last dose) anti-CD20 therapy had poor responses to all types of vaccines. The pooled estimate for SC after 1 pandemic influenza vaccine dose in these patients was 3% (95% CI, 0% to 9%), with an RB of 0.05 (95% CI, 0-0.73) compared with healthy controls and 0.22 (95% CI, 0.09-0.56) compared with disease controls. SC compared with controls seems abrogated for at least 6 months following treatment (3-6 months post anti-CD20 therapy with an RB of 0.50 [95% CI, 0.24-1.06] compared with healthy and of 0.44 [95% CI, 0.23-0.84] compared with disease controls). For all vaccine types, response to vaccination improves incrementally over time, but may not reach the level of healthy controls even 12 months after therapy.
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Abstract
PURPOSE OF REVIEW This review focuses on new evidence supporting the global immunization strategy for multiple sclerosis (MS) patients receiving disease-modifying drugs (DMDs), including the recently available vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. RECENT FINDINGS New data strengthen the evidence against a causal link between MS and vaccination. Recent consensus statements agree on the need to start vaccination early. Timings for vaccine administration should be adjusted to ensure safety and optimize vaccine responses, given the potential interference of DMDs. Patients treated with Ocrelizumab (and potentially other B-cell depleting therapies) are at risk of diminished immunogenicity to vaccines. This has relevant implications for the upcoming vaccination against SARS-CoV-2. SUMMARY An early assessment and immunization of MS patients allows optimizing vaccine responses and avoiding potential interference with treatment plans. Vaccinations are safe and effective but some specific considerations should be followed when vaccinating before, during, and after receiving immunotherapy. A time-window for vaccination taking into account the kinetics of B cell repopulation could potentially improve vaccine responses. Further understanding of SARS-CoV-2 vaccine response dynamics in MS patients under specific therapies will be key for defining the best vaccination strategy.
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Kant S, Kronbichler A, Salas A, Bruchfeld A, Geetha D. Timing of COVID-19 Vaccine in the Setting of Anti-CD20 Therapy: A Primer for Nephrologists. Kidney Int Rep 2021; 6:1197-1199. [PMID: 33821223 PMCID: PMC8012272 DOI: 10.1016/j.ekir.2021.03.876] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Accepted: 03/05/2021] [Indexed: 12/27/2022] Open
Affiliation(s)
- Sam Kant
- Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Andreas Kronbichler
- Department of Internal Medicine IV, Nephrology and Hypertension, Medical University Innsbruck, Innsbruck, Austria
| | - Antonio Salas
- Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Annette Bruchfeld
- Department of Renal Medicine, Karolinska University Hospital and CLINTEC Karolinska Institutet, Stockholm, Sweden
| | - Duvuru Geetha
- Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Speeckaert R, Lambert J, Puig L, Speeckaert M, Lapeere H, De Schepper S, van Geel N. Comment on "An evidence-based guide to SARS-CoV-2 vaccination of patients on immunotherapies in dermatology". J Am Acad Dermatol 2021; 85:e89-e90. [PMID: 33744352 PMCID: PMC7965843 DOI: 10.1016/j.jaad.2021.03.038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 02/27/2021] [Accepted: 03/02/2021] [Indexed: 10/26/2022]
Affiliation(s)
| | - Jo Lambert
- Department of Dermatology, Ghent University Hospital, Ghent, Belgium
| | - Lluís Puig
- Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
| | | | - Hilde Lapeere
- Department of Dermatology, Ghent University Hospital, Ghent, Belgium
| | - Sofie De Schepper
- Department of Dermatology, Ghent University Hospital, Ghent, Belgium
| | - Nanja van Geel
- Department of Dermatology, Ghent University Hospital, Ghent, Belgium
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Doulberis M, Papaefthymiou A, Kotronis G, Gialamprinou D, Soteriades ES, Kyriakopoulos A, Chatzimichael E, Kafafyllidou K, Liatsos C, Chatzistefanou I, Anagnostis P, Semenin V, Ntona S, Gkolia I, Papazoglou DD, Tsinonis N, Papamichos S, Kirbas H, Zikos P, Niafas D, Kountouras J. Does COVID-19 Vaccination Warrant the Classical Principle " ofelein i mi vlaptin"? MEDICINA (KAUNAS, LITHUANIA) 2021; 57:253. [PMID: 33803295 PMCID: PMC7999356 DOI: 10.3390/medicina57030253] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 02/26/2021] [Accepted: 03/04/2021] [Indexed: 12/20/2022]
Abstract
The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic warrants an imperative necessity for effective and safe vaccination, to restrain Coronavirus disease 2019 (COVID-19) including transmissibility, morbidity, and mortality. In this regard, intensive medical and biological research leading to the development of an arsenal of vaccines, albeit incomplete preconditioned evaluation, due to emergency. The subsequent scientific gap raises some concerns in the medical community and the general public. More specifically, the accelerated vaccine development downgraded the value of necessary pre-clinical studies to elicit medium- and long-term beneficial or harmful consequences. Previous experience and pathophysiological background of coronaviruses' infections and vaccine technologies, combined with the global vaccines' application, underlined the obligation of a cautious and qualitative approach, to illuminate potential vaccination-related adverse events. Moreover, the high SARS-CoV-2 mutation potential and the already aggregated genetical alterations provoke a rational vagueness and uncertainty concerning vaccines' efficacy against dominant strains and the respective clinical immunity. This review critically summarizes existing evidence and queries regarding SARS-CoV-2 vaccines, to motivate scientists' and clinicians' interest for an optimal, individualized, and holistic management of this unprecedented pandemic.
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Affiliation(s)
- Michael Doulberis
- Second Medical Clinic, School of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, 54652 Thessaloniki, Greece; (M.D.); (A.P.); (S.P.)
| | - Apostolis Papaefthymiou
- Second Medical Clinic, School of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, 54652 Thessaloniki, Greece; (M.D.); (A.P.); (S.P.)
- Department of Gastroenterology, University Hospital of Larisa, Mezourlo, 41110 Larisa, Greece
| | - Georgios Kotronis
- Department of Internal Medicine, General Hospital Aghios Pavlos of Thessaloniki, 55134 Thessaloniki, Greece;
| | - Dimitra Gialamprinou
- Second Neonatal Department and NICU, Aristotle University of Thessaloniki, Papageorgiou General Hospital, 56403 Thessaloniki, Greece;
| | - Elpidoforos S. Soteriades
- Healthcare Management Program, School of Economics and Management, Open University of Cyprus, Nicosia 2252, Cyprus;
- Department of Environmental Health, Environmental and Occupational Medicine and Epidemiology (EOME), Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
| | - Anthony Kyriakopoulos
- Nasco AD Biotechnology Laboratory, Department of Research and Development, 18536 Piraeus, Greece;
| | - Eleftherios Chatzimichael
- Center for Integrative Psychiatry, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric University Hospital of Zurich, University of Zurich, 8032 Zurich, Switzerland;
| | - Kyriaki Kafafyllidou
- Department of Pediatrics, University Children’s Hospital of Zurich, 8032 Zurich, Switzerland;
| | - Christos Liatsos
- Department of Gastroenterology, 401 Army General Hospital of Athens, 11525 Athens, Greece;
| | - Ioannis Chatzistefanou
- Department of Maxillofacial Surgery, 424 General Military Hospital, Ring Road Efkarpia, 56429 Thessaloniki, Greece;
| | - Paul Anagnostis
- ORL and Psychiatry Private Practice, 8032 Zurich, Switzerland;
| | - Vitalii Semenin
- Neurology and Psychiatry Private Practice, 2502 Biel, Switzerland;
| | - Smaragda Ntona
- Alexandrovska University Hospital, Medical University Sofia, 1431 Sofia, Bulgaria;
| | - Ioanna Gkolia
- Psychiatric Hospital of Thessaloniki, Stavroupolis, 56429 Thessaloniki, Greece;
| | - Dimitrios David Papazoglou
- Department of General, Visceral and Thoracic Surgery, Bürgerspital Solothurn, 4500 Solothurn, Switzerland;
| | | | - Spyros Papamichos
- Second Medical Clinic, School of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, 54652 Thessaloniki, Greece; (M.D.); (A.P.); (S.P.)
| | - Hristos Kirbas
- Department of Nuclear Medicine, “Thegeneio” Cancer Hospital, 54007 Thessaloniki, Greece;
| | - Petros Zikos
- Department of Oral and Maxillofacial Surgery, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece;
| | | | - Jannis Kountouras
- Second Medical Clinic, School of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, 54652 Thessaloniki, Greece; (M.D.); (A.P.); (S.P.)
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Blunted vaccines responses after ocrelizumab highlight need for immunizations prior to treatment. Mult Scler Relat Disord 2021; 50:102851. [PMID: 33636615 PMCID: PMC7897403 DOI: 10.1016/j.msard.2021.102851] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 02/12/2021] [Accepted: 02/19/2021] [Indexed: 12/16/2022]
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Chaudhry F, Jageka C, Levy PD, Cerghet M, Lisak RP. Review of the COVID-19 Risk in Multiple Sclerosis. JOURNAL OF CELLULAR IMMUNOLOGY 2021; 3:68-77. [PMID: 33959727 PMCID: PMC8098748 DOI: 10.33696/immunology.3.080] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The ongoing pandemic of the novel coronavirus of 2019 (COVID-19) has resulted in over 1 million deaths, primarily affecting older patients with chronic ailments. Multiple sclerosis (MS) patients have been deemed particularly vulnerable given their high rates of disability and increased susceptibility to infections. There have also been concerns regarding disease-modifying therapy (DMT) during the pandemic as many DMTs may increase the risk of infection due to some of their immunosuppressive properties. Furthermore, due to MS-related chronic inflammatory damage within the central nervous system, there have been concerns for worsening neurological injury by COVID-19. This has resulted in an alarmingly high level of anxiety and stress among the MS community leading to a lack of compliance with medications and routine check-ups, and even failure to obtain treatment for relapse. However, there is currently substantial evidence that MS and most DMT usage is not associated with increased COVID-19 severity. MS patients who suffer worse outcomes were more likely to be older and suffer from significant disabilities and comorbid conditions, which would also be expected from those in the general population. Likewise, there is little if any evidence demonstrating an increased susceptibility of MS patients to COVID-19-related neurological complications. Therefore, we aim to summarize the most recent findings related to COVID-19 and MS demonstrating that MS and most DMTs do not appear as risk factors for severe COVID-19.
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Affiliation(s)
- Farhan Chaudhry
- Department of Emergency Medicine and Integrative Biosciences, Wayne State University School of Medicine, Detroit, MI, USA
- Department of Neurology, Henry Ford Health System, Detroit, MI, USA
| | - Cristina Jageka
- Department of Neurology, Henry Ford Health System, Detroit, MI, USA
| | - Phillip D. Levy
- Department of Emergency Medicine and Integrative Biosciences, Wayne State University School of Medicine, Detroit, MI, USA
| | - Mirela Cerghet
- Department of Neurology, Henry Ford Health System, Detroit, MI, USA
- Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA
| | - Robert P Lisak
- Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA
- Department of Neurology, Wayne State University School of Medicine and the Detroit Medical Center, Detroit, MI, USA
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Immunogenicity of The Influenza Vaccine in Multiple Sclerosis Patients: A Systematic Review and Meta-Analysis. Mult Scler Relat Disord 2020; 48:102698. [PMID: 33385826 DOI: 10.1016/j.msard.2020.102698] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 12/04/2020] [Accepted: 12/12/2020] [Indexed: 12/15/2022]
Abstract
OBJECTIVE Multiple sclerosis is a neurodegenerative disease thought to be of autoimmune origin. It can lead to development of neurological symptoms and increase the risk of infection from communicable diseases. Thus, vaccines are endorsed to mitigate this risk. However, it has not yet been confirmed whether the dysfunctional immune system of these patients combined with taking immunosuppressants can lead to a dampened immunity in response to the influenza vaccine. Infection with the influenza virus is a concern for multiple sclerosis patients. Previous research on multiple sclerosis patients who have received the influenza vaccine focuses on safety and relapse rates. Studies that focus on the immune response mounted against the vaccine in this patient cohort are scant. This study serves to provide a comprehensive picture of the immunogenicity of the influenza vaccine in MS patients. METHODS A systematic review of compiled research was conducted. Data obtained from the research was used in a meta-analysis using risk differences with a 95% confidence interval. RESULTS Across the various strains incorporated into the influenza vaccine analyzed in this paper, there was no statistical difference in immune response mounted against the influenza vaccine between healthy controls and multiple sclerosis patients. CONCLUSION The results of this study suggest that multiple sclerosis patients can mount an adequate immune response to the influenza vaccine when compared to healthy controls. Most of the immunotherapies these patients are on do not appear to affect this immune response. Therefore, the influenza vaccine should continue to be recommended to multiple sclerosis patients.
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Baker D, Roberts CAK, Pryce G, Kang AS, Marta M, Reyes S, Schmierer K, Giovannoni G, Amor S. COVID-19 vaccine-readiness for anti-CD20-depleting therapy in autoimmune diseases. Clin Exp Immunol 2020; 202:149-161. [PMID: 32671831 PMCID: PMC7405500 DOI: 10.1111/cei.13495] [Citation(s) in RCA: 148] [Impact Index Per Article: 29.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 07/06/2020] [Accepted: 07/08/2020] [Indexed: 12/17/2022] Open
Abstract
Although most autoimmune diseases are considered to be CD4 T cell- or antibody-mediated, many respond to CD20-depleting antibodies that have limited influence on CD4 and plasma cells. This includes rituximab, oblinutuzumab and ofatumumab that are used in cancer, rheumatoid arthritis and off-label in a large number of other autoimmunities and ocrelizumab in multiple sclerosis. Recently, the COVID-19 pandemic created concerns about immunosuppression in autoimmunity, leading to cessation or a delay in immunotherapy treatments. However, based on the known and emerging biology of autoimmunity and COVID-19, it was hypothesised that while B cell depletion should not necessarily expose people to severe SARS-CoV-2-related issues, it may inhibit protective immunity following infection and vaccination. As such, drug-induced B cell subset inhibition, that controls at least some autoimmunities, would not influence innate and CD8 T cell responses, which are central to SARS-CoV-2 elimination, nor the hypercoagulation and innate inflammation causing severe morbidity. This is supported clinically, as the majority of SARS-CoV-2-infected, CD20-depleted people with autoimmunity have recovered. However, protective neutralizing antibody and vaccination responses are predicted to be blunted until naive B cells repopulate, based on B cell repopulation kinetics and vaccination responses, from published rituximab and unpublished ocrelizumab (NCT00676715, NCT02545868) trial data, shown here. This suggests that it may be possible to undertake dose interruption to maintain inflammatory disease control, while allowing effective vaccination against SARS-CoV-29, if and when an effective vaccine is available.
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Affiliation(s)
- D. Baker
- Blizard Institute, Barts and the London School of Medicine and DentistryQueen Mary University of LondonLondonUK
| | - C. A. K. Roberts
- Blizard Institute, Barts and the London School of Medicine and DentistryQueen Mary University of LondonLondonUK
| | - G. Pryce
- Blizard Institute, Barts and the London School of Medicine and DentistryQueen Mary University of LondonLondonUK
| | - A. S. Kang
- Blizard Institute, Barts and the London School of Medicine and DentistryQueen Mary University of LondonLondonUK
- Centre for Oral Immunobiology and Regenerative MedicineInstitute of Dentistry, Barts and The London School of Medicine and DentistryQueen Mary University of LondonLondonUK
| | - M. Marta
- Blizard Institute, Barts and the London School of Medicine and DentistryQueen Mary University of LondonLondonUK
- Clinical Board: Medicine (Neuroscience)The Royal London HospitalBarts Health NHS TrustLondonUK
| | - S. Reyes
- Blizard Institute, Barts and the London School of Medicine and DentistryQueen Mary University of LondonLondonUK
- Clinical Board: Medicine (Neuroscience)The Royal London HospitalBarts Health NHS TrustLondonUK
| | - K. Schmierer
- Blizard Institute, Barts and the London School of Medicine and DentistryQueen Mary University of LondonLondonUK
- Clinical Board: Medicine (Neuroscience)The Royal London HospitalBarts Health NHS TrustLondonUK
| | - G. Giovannoni
- Blizard Institute, Barts and the London School of Medicine and DentistryQueen Mary University of LondonLondonUK
- Clinical Board: Medicine (Neuroscience)The Royal London HospitalBarts Health NHS TrustLondonUK
| | - S. Amor
- Blizard Institute, Barts and the London School of Medicine and DentistryQueen Mary University of LondonLondonUK
- Pathology DepartmentAmsterdam UMCVUmc siteAmsterdamThe Netherlands
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31
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Riva A, Barcella V, Benatti SV, Capobianco M, Capra R, Cinque P, Comi G, Fasolo MM, Franzetti F, Galli M, Gerevini S, Meroni L, Origoni M, Prosperini L, Puoti M, Scarpazza C, Tortorella C, Zaffaroni M, Moiola L. Vaccinations in patients with multiple sclerosis: A Delphi consensus statement. Mult Scler 2020; 27:347-359. [PMID: 32940128 DOI: 10.1177/1352458520952310] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
BACKGROUND Patients with multiple sclerosis (MS) are at increased risk of infection. Vaccination can mitigate these risks but only if safe and effective in MS patients, including those taking disease-modifying drugs. METHODS A modified Delphi consensus process (October 2017-June 2018) was used to develop clinically relevant recommendations for making decisions about vaccinations in patients with MS. A series of statements and recommendations regarding the efficacy, safety and timing of vaccine administration in patients with MS were generated in April 2018 by a panel of experts based on a review of the published literature performed in October 2017. RESULTS Recommendations include the need for an 'infectious diseases card' of each patient's infectious and immunisation history at diagnosis in order to exclude and eventually treat latent infections. We suggest the implementation of the locally recommended vaccinations, if possible at MS diagnosis, otherwise with vaccination timing tailored to the planned/current MS treatment, and yearly administration of the seasonal influenza vaccine regardless of the treatment received. CONCLUSION Patients with MS should be vaccinated with careful consideration of risks and benefits. However, there is an urgent need for more research into vaccinations in patients with MS to guide evidence-based decision making.
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Affiliation(s)
- Agostino Riva
- III Division of Infectious Diseases, ASST Fatebenefratelli-Sacco, L. Sacco Hospital, Milan, Italy
| | - Valeria Barcella
- Department of Neurology and Multiple Sclerosis Center, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Simone V Benatti
- Department of Infectious Diseases, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Marco Capobianco
- SCDO Neurology and Regional Reference Multiple Sclerosis Center, Azienda Ospedaliero-Universitaria San Luigi Gonzaga, Orbassano, Italy
| | - Ruggero Capra
- Multiple Sclerosis Center, Spedali Civili of Brescia, Montichiari, Italy
| | - Paola Cinque
- Division of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy/Institute of Experimental Neurology and Multiple Sclerosis Center IRCCS, San Raffaele Hospital, Milan, Italy
| | - Giancarlo Comi
- Institute of Experimental Neurology and Multiple Sclerosis Center IRCCS, San Raffaele Hospital, Milan, Italy
| | - Maria Michela Fasolo
- Division of Infectious Diseases, Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, University Hospital, Milan, Italy
| | - Fabio Franzetti
- Infectious Diseases Unit, Busto Arsizio Hospital, Varese, Italy
| | - Massimo Galli
- Department of Clinical Sciences, Luigi Sacco Hospital, University of Milan, Milan, Italy
| | - Simonetta Gerevini
- Division of Neuroradiology, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neuroradiology Department, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Luca Meroni
- III Division of Infectious Diseases, ASST Fatebenefratelli-Sacco, L. Sacco Hospital, Milan, Italy
| | - Massimo Origoni
- Department of Gynecology and Obstetrics, Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele, Milano, Italy
| | - Luca Prosperini
- Department of Neuroscience, San Camillo-Forlanini Hospital, Rome, Italy
| | - Massimo Puoti
- SC Infectious Diseases, ASST Niguarda Ca' Grande Hospital, Milan, Italy
| | - Cristina Scarpazza
- Multiple Sclerosis Center, Spedali Civili of Brescia, Montichiari, Italy/Department of General Psychology, University of Padova, Padova, Italy
| | - Carla Tortorella
- Department of Neuroscience, San Camillo-Forlanini Hospital, Rome, Italy
| | - Mauro Zaffaroni
- Multiple Sclerosis Center, Hospital of Gallarate, ASST della Valle Olona, Gallarate, Italy
| | - Lucia Moiola
- Multiple Sclerosis Center, IRCCS San Raffaele Hospital, Milan, Italy/Neurology Department, IRCCS San Raffaele Hospital, Milan, Italy
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Houot R, Levy R, Cartron G, Armand P. Could anti-CD20 therapy jeopardise the efficacy of a SARS-CoV-2 vaccine? Eur J Cancer 2020; 136:4-6. [PMID: 32619884 PMCID: PMC7315961 DOI: 10.1016/j.ejca.2020.06.017] [Citation(s) in RCA: 51] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2020] [Accepted: 06/16/2020] [Indexed: 12/28/2022]
Abstract
A vaccine against SARS-CoV-2 might represent the most promising approach to halt durably the current COVID-19 pandemic. We believe that anti-CD20 therapy may jeopardise the efficacy of such a vaccine. This is regrettable because patients receiving anti-CD20 therapy (i.e. those with haematologic malignancies or autoimmune disorders) are particularly at risk of severe COVID-19 and, as such, are the most in need of a vaccine. Here, we review the reasons why anti-CD20 therapy may abrogate or diminish the efficacy of a vaccine against SARS-CoV-2 and we draw physicians' attention towards this potential risk so that it can be considered when evaluating the risk/benefit ratio of anti-CD20 therapy during the current pandemic.
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Affiliation(s)
- Roch Houot
- Department of Hematology, CHU Rennes, University of Rennes, INSERM U1236, Rennes, France; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
| | - Ronald Levy
- Department of Medical Oncology, Stanford University School of Medicine, Stanford, CA, USA
| | - Guillaume Cartron
- Department of Hematology, CHU Montpellier University Hospitality, University of Montpellier, Institut de Génétique Moléculaire de Montpellier, CNRS UMR 5535, Montpellier, France
| | - Philippe Armand
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
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Reyes S, Ramsay M, Ladhani S, Amirthalingam G, Singh N, Cores C, Mathews J, Lambourne J, Marta M, Turner B, Gnanapavan S, Dobson R, Schmierer K, Giovannoni G. Protecting people with multiple sclerosis through vaccination. Pract Neurol 2020; 20:435-445. [DOI: 10.1136/practneurol-2020-002527] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/26/2020] [Indexed: 12/28/2022]
Abstract
Vaccination is one of the most effective and cost-efficient methods for protecting people with multiple sclerosis (MS) from infections. However, use of vaccines has often been problematic because of misguided concerns that they may exacerbate the disease and/or that some disease-modifying therapies may influence the immune response to immunisations and/or their safety. People with MS risk higher morbidity and mortality from vaccine-preventable infections. It is, therefore, important to address any patient’s reluctance to accept vaccination and to provide clear guidance for clinicians on which vaccinations to consider proactively. We have reviewed the current literature and provide recommendations regarding vaccines in adults with MS, including specific advice regarding vaccination safety in patients receiving—or going to receive—disease-modifying therapies, vaccination during pregnancy, pretravel counselling and patient education.
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Risiken und Chancen von Immuntherapien in Zeiten der Coronavirus-2019-Pandemie. DGNEUROLOGIE 2020. [PMCID: PMC7284681 DOI: 10.1007/s42451-020-00205-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Immuntherapien stellen die essenzielle Grundlage der Behandlung von neuroinflammatorischen Erkrankungen dar. In Zeiten der Coronavirus-2019 (COVID-19)-Pandemie ergibt sich im klinischen Alltag jedoch zunehmend die Frage, ob eine Immuntherapie bei neurologischen Patienten aufgrund des potenziellen Infektionsrisikos eingeleitet, intensiviert, pausiert oder gar beendet werden sollte. Unsicherheit besteht v. a. deshalb, weil verschiedene nationale und internationale Fachgesellschaften diesbezüglich unterschiedliche Empfehlungen veröffentlichten. In diesem Artikel soll ein Überblick über die Wirkmechanismen von Immuntherapien und den daraus abzuleitenden Infektionsrisiken in Bezug auf COVID-19 (durch den Coronavirus verursachte Erkrankung) gegeben werden. Potenzielle Chancen und vorteilhafte Effekte einzelner Substrate in der Akuttherapie von COVID-19 werden diskutiert.
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35
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Maghzi AH, Houtchens MK, Preziosa P, Ionete C, Beretich BD, Stankiewicz JM, Tauhid S, Cabot A, Berriosmorales I, Schwartz THW, Sloane JA, Freedman MS, Filippi M, Weiner HL, Bakshi R. COVID-19 in teriflunomide-treated patients with multiple sclerosis. J Neurol 2020; 267:2790-2796. [PMID: 32494856 PMCID: PMC7268971 DOI: 10.1007/s00415-020-09944-8] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 05/18/2020] [Accepted: 05/20/2020] [Indexed: 01/08/2023]
Abstract
The outbreak of a severe acute respiratory syndrome caused by a novel coronavirus (COVID-19), has raised health concerns for patients with multiple sclerosis (MS) who are commonly on long-term immunotherapies. Managing MS during the pandemic remains challenging with little published experience and no evidence-based guidelines. We present five teriflunomide-treated patients with MS who subsequently developed active COVID-19 infection. The patients continued teriflunomide therapy and had self-limiting infection, without relapse of their MS. These observations have implications for the management of MS in the setting of the COVID-19 pandemic.
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Affiliation(s)
- Amir Hadi Maghzi
- Department of Neurology, Ann Romney Center for Neurologic Diseases, Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Mailbox 9002L, Boston, MA, 02115, USA
| | - Maria K Houtchens
- Department of Neurology, Ann Romney Center for Neurologic Diseases, Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Mailbox 9002L, Boston, MA, 02115, USA
| | - Paolo Preziosa
- Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Carolina Ionete
- Department of Neurology, University of Massachusetts, Worcester, MA, USA
| | | | - James M Stankiewicz
- Department of Neurology, Ann Romney Center for Neurologic Diseases, Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Mailbox 9002L, Boston, MA, 02115, USA
| | - Shahamat Tauhid
- Department of Neurology, Ann Romney Center for Neurologic Diseases, Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Mailbox 9002L, Boston, MA, 02115, USA
| | - Ann Cabot
- Department of Neurology, Concord Hospital, Concord, NH, USA
| | | | | | - Jacob A Sloane
- Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Mark S Freedman
- University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Massimo Filippi
- Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.,Vita-Salute San Raffaele University, Milan, Italy
| | - Howard L Weiner
- Department of Neurology, Ann Romney Center for Neurologic Diseases, Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Mailbox 9002L, Boston, MA, 02115, USA
| | - Rohit Bakshi
- Department of Neurology, Ann Romney Center for Neurologic Diseases, Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Mailbox 9002L, Boston, MA, 02115, USA.
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Pawlitzki M, Zettl UK, Ruck T, Rolfes L, Hartung HP, Meuth SG. Merits and culprits of immunotherapies for neurological diseases in times of COVID-19. EBioMedicine 2020; 56:102822. [PMID: 32535547 PMCID: PMC7286830 DOI: 10.1016/j.ebiom.2020.102822] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 05/14/2020] [Accepted: 05/19/2020] [Indexed: 12/12/2022] Open
Abstract
Immunosuppression and immunomodulation are valuable therapeutic approaches for managing neuroimmunological diseases. In times of the Coronavirus disease 2019 (COVID-19) pandemic, clinicians must deal with the question of whether immunotherapy should currently be initiated or discontinued in neurological patients. Uncertainty exists especially because different national medical associations publish different recommendations on the extent to which immunotherapies must be continued, monitored, or possibly switched during the current pandemic. Based on the most recently available data both about the novel coronavirus and the approved immunotherapies for neurological diseases, we provide an updated overview that includes current treatment strategies and the associated COVID-19 risk, but also the potential of immunotherapies to treat COVID-19.
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Affiliation(s)
- Marc Pawlitzki
- Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany.
| | - Uwe K Zettl
- Department of Neurology, Neuroimmunological Section, University of Rostock, Rostock, Germany
| | - Tobias Ruck
- Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany
| | - Leoni Rolfes
- Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany
| | - Hans-Peter Hartung
- Department of Neurology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany
| | - Sven G Meuth
- Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany.
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Jakimovski D, Weinstock-Guttman B, Ramanathan M, Dwyer MG, Zivadinov R. Infections, Vaccines and Autoimmunity: A Multiple Sclerosis Perspective. Vaccines (Basel) 2020; 8:vaccines8010050. [PMID: 32012815 PMCID: PMC7157658 DOI: 10.3390/vaccines8010050] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Revised: 01/21/2020] [Accepted: 01/24/2020] [Indexed: 12/13/2022] Open
Abstract
Background: Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease that is associated with multiple environmental factors. Among suspected susceptibility events, studies have questioned the potential role of overt viral and bacterial infections, including the Epstein Bar virus (EBV) and human endogenous retroviruses (HERV). Furthermore, the fast development of immunomodulatory therapies further questions the efficacy of the standard immunization policies in MS patients. Topics reviewed: This narrative review will discuss the potential interplay between viral and bacterial infections and their treatment on MS susceptibility and disease progression. In addition, the review specifically discusses the interactions between MS pathophysiology and vaccination for hepatitis B, influenza, human papillomavirus, diphtheria, pertussis, and tetanus (DTP), and Bacillus Calmette-Guerin (BCG). Data regarding potential interaction between MS disease modifying treatment (DMT) and vaccine effectiveness is also reviewed. Moreover, HERV-targeted therapies such as GNbAC1 (temelimab), EBV-based vaccines for treatment of MS, and the current state regarding the development of T-cell and DNA vaccination are discussed. Lastly, a reviewing commentary on the recent 2019 American Academy of Neurology (AAN) practice recommendations regarding immunization and vaccine-preventable infections in the settings of MS is provided. Conclusion: There is currently no sufficient evidence to support associations between standard vaccination policies and increased risk of MS. MS patients treated with immunomodulatory therapies may have a lower benefit from viral and bacterial vaccination. Despite their historical underperformance, new efforts in creating MS-based vaccines are currently ongoing. MS vaccination programs follow the set back and slow recovery which is widely seen in other fields of medicine.
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Affiliation(s)
- Dejan Jakimovski
- Buffalo Neuroimaging Analysis Center, Department of Neurology, University at Buffalo, State University of New York, Buffalo, NY 14203, USA
- Correspondence:
| | - Bianca Weinstock-Guttman
- Jacobs MS Center, Department of Neurology, University at Buffalo, State University of New York, Buffalo, NY 14203, USA
| | - Murali Ramanathan
- School of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14214, USA
| | - Michael G. Dwyer
- Buffalo Neuroimaging Analysis Center, Department of Neurology, University at Buffalo, State University of New York, Buffalo, NY 14203, USA
| | - Robert Zivadinov
- Buffalo Neuroimaging Analysis Center, Department of Neurology, University at Buffalo, State University of New York, Buffalo, NY 14203, USA
- Center for Biomedical Imaging at Clinical Translational Science Institute, University at Buffalo, State University of New York, Buffalo, NY 14203, USA
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Signoriello E, Bonavita S, Sinisi L, Russo CV, Maniscalco GT, Casertano S, Saccà F, Lanzillo R, Morra VB, Lus G. Is antibody titer useful to verify the immunization after VZV Vaccine in MS patients treated with Fingolimod? A case series. Mult Scler Relat Disord 2020; 40:101963. [PMID: 31986424 DOI: 10.1016/j.msard.2020.101963] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2019] [Revised: 01/12/2020] [Accepted: 01/19/2020] [Indexed: 01/26/2023]
Abstract
BACKGROUND Fingolimod (FTY720, Gilenya) is a second line therapy to treat relapsing MS not responding to first-line treatments and/or with a high disease activity (according to Italian Regulatory authorities). Before starting Fingolimod, patients' immunity to varicella zoster virus (VZV) needs to be assessed and seronegative patients vaccinated. To test susceptibility and response, IgG antibodies are tested after immunization. Since Fingolimod determines a reduction of circulating B lymphocytes and immunoglobulins, we aimed at describing the trend of VZV antibodies in seronegative vaccinated patients with MS before and after treatment. METHODS A total of 23 patients vaccinated for VZV before starting Fingolimod treatment, were recruited in this observational retrospective study involving five MS Centers in Campania (Italy). Of these, 12 patients were excluded for missing data. Patients received two doses of Varivax® Vaccine. After vaccination patients were re-tested and were all positive for IgG-VZV. We re-tested IgG-VZV in the same laboratory after a mean time of 2.42 years from Fingolimod therapy start. RESULTS During Fingolimod therapy we observed a global reduction of antibody titer and a disappearance in 7/11 patients. Titer disappearance was more probable in patients with lower post-vaccination titer. Of the 7 patients with vanishing IgG-VZV, three suspended Fingolimod for adverse event. In two of them, we observed a reappearance of antibody titer after treatment cessation. In one patient chickenpox infection occurred one year later. DISCUSSION AND CONCLUSIONS Our observational study shows that Fingolimod could influence antibody titer probably through its effect on B lymphocytes, but the efficacy of the vaccination should be verified. In conclusion, it is necessary to pay attention to therapies acting on B lymphocytes as they could influence the antibody titer and efficacy of vaccination making the search for other markers of vaccine efficacy desirable such as cell-mediated immunity with proliferation and induction of memory T lymphocytes in response to viral glycoproteins.
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Affiliation(s)
- E Signoriello
- Multiple Sclerosis Center, Second Division of Neurology, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Italy.
| | - S Bonavita
- Multiple Sclerosis Center, Second Division of Neurology, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Italy
| | - L Sinisi
- Multiple Sclerosis Center, Division of Neurology, San Paolo Hospital, ASL Napoli 1 Centro
| | - C V Russo
- Department of Neurological Sciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Italy
| | - G T Maniscalco
- Multiple Sclerosis Center, Department of Neurology and Stroke Unit and o "AORN A.Cardarelli", Naples, Italy
| | - S Casertano
- Multiple Sclerosis Center, Second Division of Neurology, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Italy
| | - F Saccà
- Department of Neurological Sciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Italy
| | - R Lanzillo
- Department of Neurological Sciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Italy
| | - V Brescia Morra
- Department of Neurological Sciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Italy
| | - G Lus
- Multiple Sclerosis Center, Second Division of Neurology, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Italy
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Farez MF, Correale J, Armstrong MJ, Rae-Grant A, Gloss D, Donley D, Holler-Managan Y, Kachuck NJ, Jeffery D, Beilman M, Gronseth G, Michelson D, Lee E, Cox J, Getchius T, Sejvar J, Narayanaswami P. Practice guideline update summary: Vaccine-preventable infections and immunization in multiple sclerosis. Neurology 2019; 93:584-594. [DOI: 10.1212/wnl.0000000000008157] [Citation(s) in RCA: 80] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2019] [Accepted: 06/18/2019] [Indexed: 12/26/2022] Open
Abstract
ObjectiveTo update the 2002 American Academy of Neurology (AAN) guideline regarding immunization and multiple sclerosis (MS).MethodsThe panel performed a systematic review and classified articles using the AAN system. Recommendations were based on evidence, related evidence, principles of care, and inferences according to the AAN 2011 process manual, as amended.Major recommendations (Level B except where indicated)Clinicians should discuss the evidence regarding immunizations in MS with their patients and explore patients' opinions, preferences, and questions. Clinicians should recommend that patients with MS follow all local vaccine standards, unless there are specific contraindications and weigh local vaccine-preventable disease risks when counseling patients. Clinicians should recommend that patients with MS receive the influenza vaccination annually. Clinicians should counsel patients with MS about infection risks associated with specific immunosuppressive/immunomodulating (ISIM) medications and treatment-specific vaccination guidance according to prescribing information (PI) and vaccinate patients with MS as needed at least 4–6 weeks before initiating patients' ISIM therapy. Clinicians must screen for infections according to PI before initiating ISIM medications (Level A) and should treat patients testing positive for latent infections. In high-risk populations, clinicians must screen for latent infections before starting ISIM therapy even when not specifically mentioned in PI (Level A) and should consult specialists regarding treating patients who screen positive for latent infection. Clinicians should recommend against using live-attenuated vaccines in people with MS receiving ISIM therapies. Clinicians should delay vaccinating people with MS who are experiencing a relapse.
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Lovett-Racke AE, Gormley M, Liu Y, Yang Y, Graham C, Wray S, Racke MK, Shubin R, Twyman C, Alvarez E, Bass A, Eubanks JL, Fox E. B cell depletion with ublituximab reshapes the T cell profile in multiple sclerosis patients. J Neuroimmunol 2019; 332:187-197. [DOI: 10.1016/j.jneuroim.2019.04.017] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Revised: 04/29/2019] [Accepted: 04/29/2019] [Indexed: 01/28/2023]
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Whittam DH, Tallantyre EC, Jolles S, Huda S, Moots RJ, Kim HJ, Robertson NP, Cree BAC, Jacob A. Rituximab in neurological disease: principles, evidence and practice. Pract Neurol 2019; 19:5-20. [PMID: 30498056 DOI: 10.1136/practneurol-2018-001899] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Rituximab is a widely used B-cell-depleting monoclonal antibody. It is unlicensed for use in neurological disorders and there are no treatment guidelines. However, as a rapidly acting, targeted therapy with growing evidence of efficacy and tolerability in several neuroinflammatory disorders, it is an attractive alternative to conventional immunomodulatory medications. This practical review aims to explain the basic principles of B-cell depletion with therapeutic monoclonal antibodies. We present the evidence for using rituximab in neurological diseases, and describe the practical aspects of prescribing, including dosing, monitoring, safety, treatment failure and its use in special circumstances such as coexisting viral hepatitis, pregnancy and lactation. We provide an administration guide, checklist and patient information leaflet, which can be adapted for local use. Finally, we review the safety data of rituximab and ocrelizumab (a newer and recently licensed B-cell-depleting therapy for multiple sclerosis) and suggest monitoring and risk reduction strategies.
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Affiliation(s)
- Daniel H Whittam
- Department of Neurology, The Walton Centre NHS Foundation Trust, Liverpool, UK
| | - Emma C Tallantyre
- Helen Durham Centre for Neuroinflammation, University Hospital or Wales, Cardiff, UK
- Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK
| | - Stephen Jolles
- Immunodeficiency Centre for Wales, University Hospital of Wales, Cardiff, UK
- School of Medicine, Cardiff University, Cardiff, UK
| | - Saif Huda
- Department of Neurology, The Walton Centre NHS Foundation Trust, Liverpool, UK
| | - Robert J Moots
- Department of Musculoskeletal Diseases, Institute of Ageing and Chronic Diseases, University of Liverpool, Liverpool, UK
| | - Ho Jin Kim
- Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, South Korea
| | - Neil P Robertson
- Helen Durham Centre for Neuroinflammation, University Hospital or Wales, Cardiff, UK
- Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK
| | - Bruce A C Cree
- Weill Institute for Neurosciences, University of California, San Francisco, California, USA
| | - Anu Jacob
- Department of Neurology, The Walton Centre NHS Foundation Trust, Liverpool, UK
- School of Medicine, University of Liverpool, Liverpool, UK
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Cho A, Bradley B, Kauffman R, Priyamvada L, Kovalenkov Y, Feldman R, Wrammert J. Robust memory responses against influenza vaccination in pemphigus patients previously treated with rituximab. JCI Insight 2017; 2:93222. [PMID: 28614800 PMCID: PMC5470882 DOI: 10.1172/jci.insight.93222] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2017] [Accepted: 05/16/2017] [Indexed: 12/21/2022] Open
Abstract
Rituximab is a therapeutic anti-CD20 monoclonal antibody widely used to treat B cell lymphoma and autoimmune diseases, such as rheumatic arthritis, systemic lupus erythematosus, and autoimmune blistering skin diseases (AIBD). While rituximab fully depletes peripheral blood B cells, it remains unclear whether some preexisting B cell memory to pathogens or vaccines may survive depletion, especially in lymphoid tissues, and if these memory B cells can undergo homeostatic expansion during recovery from depletion. The limited data available on vaccine efficacy in this setting have been derived from rituximab-treated patients receiving concomitant chemotherapy or other potent immunosuppressants. Here, we present an in-depth analysis of seasonal influenza vaccine responses in AIBD patients previously treated with rituximab, who generally did not receive additional therapeutic interventions. We found that, despite a lack of influenza-specific memory B cells in the blood, patients mount robust recall responses to vaccination, comparable to healthy controls, both at a cellular and a serological level. Repertoire analyses of plasmablast responses suggest that they likely derive from a diverse pool of tissue-resident memory cells, refractory to depletion. Overall, these data have important implications for establishing an effective vaccine schedule for AIBD patients and the clinical care of rituximab-treated patients in general and contribute to our basic understanding of maintenance of normal and pathogenic human B cell memory.
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Affiliation(s)
- Alice Cho
- Department of Pediatrics, Division of Infectious Disease.,Emory Vaccine Center, and
| | - Bridget Bradley
- Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Robert Kauffman
- Department of Pediatrics, Division of Infectious Disease.,Emory Vaccine Center, and
| | - Lalita Priyamvada
- Department of Pediatrics, Division of Infectious Disease.,Emory Vaccine Center, and
| | - Yevgeniy Kovalenkov
- Department of Pediatrics, Division of Infectious Disease.,Emory Vaccine Center, and
| | - Ron Feldman
- Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Jens Wrammert
- Department of Pediatrics, Division of Infectious Disease.,Emory Vaccine Center, and
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Söderholm S, Fu Y, Gaelings L, Belanov S, Yetukuri L, Berlinkov M, Cheltsov AV, Anders S, Aittokallio T, Nyman TA, Matikainen S, Kainov DE. Multi-Omics Studies towards Novel Modulators of Influenza A Virus-Host Interaction. Viruses 2016; 8:v8100269. [PMID: 27690086 PMCID: PMC5086605 DOI: 10.3390/v8100269] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2016] [Revised: 09/13/2016] [Accepted: 09/22/2016] [Indexed: 12/20/2022] Open
Abstract
Human influenza A viruses (IAVs) cause global pandemics and epidemics. These viruses evolve rapidly, making current treatment options ineffective. To identify novel modulators of IAV–host interactions, we re-analyzed our recent transcriptomics, metabolomics, proteomics, phosphoproteomics, and genomics/virtual ligand screening data. We identified 713 potential modulators targeting 199 cellular and two viral proteins. Anti-influenza activity for 48 of them has been reported previously, whereas the antiviral efficacy of the 665 remains unknown. Studying anti-influenza efficacy and immuno/neuro-modulating properties of these compounds and their combinations as well as potential viral and host resistance to them may lead to the discovery of novel modulators of IAV–host interactions, which might be more effective than the currently available anti-influenza therapeutics.
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Affiliation(s)
- Sandra Söderholm
- Institute of Biotechnology, University of Helsinki, Helsinki 00014, Finland.
- Finnish Institute of Occupational Health, Helsinki 00250, Finland.
| | - Yu Fu
- Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00014, Finland.
| | - Lana Gaelings
- Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00014, Finland.
| | - Sergey Belanov
- Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00014, Finland.
| | - Laxman Yetukuri
- Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00014, Finland.
| | - Mikhail Berlinkov
- Institute of Mathematics and Computer Science, Ural Federal University, Yekaterinburg 620083, Russia.
| | - Anton V Cheltsov
- Q-Mol L.L.C. in Silico Pharmaceuticals, San Diego, CA 92037, USA.
| | - Simon Anders
- Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00014, Finland.
| | - Tero Aittokallio
- Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00014, Finland.
- Department of Mathematics and Statistics, University of Turku, Turku 20014, Finland.
| | | | - Sampsa Matikainen
- Finnish Institute of Occupational Health, Helsinki 00250, Finland.
- Department of Rheumatology, Helsinki University Hospital, University of Helsinki, Helsinki 00015, Finland.
| | - Denis E Kainov
- Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00014, Finland.
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Wiedermann U, Sitte HH, Burgmann H, Eser A, Falb P, Holzmann H, Kitchen M, Köller M, Kollaritsch H, Kundi M, Lassmann H, Mutz I, Pickl WF, Riedl E, Sibilia M, Thalhammer F, Tucek B, Zenz W, Zwiauer K. [Guidelines for vaccination of immunocompromised individuals]. Wien Klin Wochenschr 2016; 128 Suppl 4:337-76. [PMID: 27457874 DOI: 10.1007/s00508-016-1033-6] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2016] [Accepted: 06/04/2016] [Indexed: 12/14/2022]
Abstract
Immunosuppression of various origins is associated with an increased risk of infection; therefore the prevention of infectious diseases by vaccination is especially important in immunocompromised patients. However, the response to vaccinations is often reduced in these risk groups and the application of live vaccines is contraindicated during immunosuppression.In the following expert statement, recommendations for vaccination were created on the basis of current evidence and theoretical/immunological considerations. A first, general part elaborates on efficacy and safety of vaccinations during immunosuppression, modes of action of immunosuppressive medications and recommended time intervals between immunosuppressive treatments and vaccinations. A core piece of this part is a graduation of immunosuppression into three stages, i. e. no relevant immunosuppression, mild to moderate and severe immunosuppression and the assignment of various medications (including biologicals) to one of those stages; this is followed by an overview of possible and necessary vaccinations in each of those stages.The second part gives detailed vaccination guidelines for common diseases and therapies associated with immunosuppression. Primary immune deficiencies, chronic kidney disease, diabetes mellitus, solid and hematological tumors, hematopoetic stem cell transplantation, transplantation of solid organs, aspenia, rheumatological-, gastroenterologic-, dermatologic-, neurologic diseases, biologicals during pregnancy and HIV infection are dealt with.These vaccination guidelines, compiled for the first time in Austria, aim to be of practical help for physicians to facilitate and improve vaccination coverage in immunocompromised patients and their household members and contact persons.
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Affiliation(s)
- Ursula Wiedermann
- Institut für Spezifische Prophylaxe und Tropenmedizin, Medizinische Universität Wien, Kinderspitalgasse 15, 1090, Wien, Österreich.
| | - Harald H Sitte
- Institut für Pharmakologie, Medizinische Universität Wien, Wien, Österreich
| | - Heinz Burgmann
- Klinische Abteilung für Infektionen und Tropenmedizin, Medizinische Universität Wien, Wien, Österreich
| | - Alexander Eser
- Klinische Abteilung für Gastroenterologie und Hepatologie, Medizinische Universität Wien, Wien, Österreich
| | - Petra Falb
- Medizinmarktaufsicht, Agentur für Gesundheit und Ernährungssicherheit, Wien, Österreich
| | | | - Maria Kitchen
- Universitätsklinik für Dermatologie und Venerologie, Medizinische Universität Innsbruck, Innsbruck, Österreich
| | - Marcus Köller
- Sozialmedizinisches Zentrum Sophienspital, Wien, Österreich
| | - Herwig Kollaritsch
- Institut für Spezifische Prophylaxe und Tropenmedizin, Medizinische Universität Wien, Kinderspitalgasse 15, 1090, Wien, Österreich
| | - Michael Kundi
- Institut für Umwelthygiene, Medizinische Universität Wien, Wien, Österreich
| | - Hans Lassmann
- Abteilung für Neuroimmunologie, Medizinische Universität Wien, Wien, Österreich
| | | | - Winfried F Pickl
- Institut für Immunologie, Medizinische Universität Wien, Wien, Österreich
| | - Elisabeth Riedl
- Universitätsklinik für Dermatologie, Medizinische Universität Wien, Wien, Österreich
| | - Maria Sibilia
- Institut für Krebsforschung, Medizinische Universität Wien, Wien, Österreich
| | - Florian Thalhammer
- Klinische Abteilung für Infektionen und Tropenmedizin, Medizinische Universität Wien, Wien, Österreich
| | - Barbara Tucek
- Medizinmarktaufsicht, Agentur für Gesundheit und Ernährungssicherheit, Wien, Österreich
| | - Werner Zenz
- Klinische Abteilung für allgemeine Pädiatrie, Medizinische Universität Graz, Graz, Österreich
| | - Karl Zwiauer
- Klinische Abteilung für Kinder- und Jugendheilkunde, Universitätsklinikum St. Pölten, St. Pölten, Österreich
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Cheng DR, Barton R, Greenway A, Crawford NW. Rituximab and protection from vaccine preventable diseases: applying the evidence to pediatric patients. Expert Rev Vaccines 2016; 15:1567-1574. [PMID: 27216827 DOI: 10.1080/14760584.2016.1193438] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
INTRODUCTION This article analyses and highlights the challenge of immunization and preventing vaccine preventable diseases in pediatric patients on rituximab. Rituximab is a chimeric anti-CD 20 monoclonal antibody that is an immunosuppressant affecting both cellular and humoral immunity. Children and adolescents on rituximab are at increased risk of infection and vaccine preventable diseases, and require additional strategies to optimize and maximize their protection against such illnesses. Areas covered: This article provides a comprehensive MEDLINE and Pubmed review of existing literature regarding vaccine immunogenicity and safety in patients on rituximab, and assists in providing an evidence base to develop immunization guidelines. Of particular note, the use of live-attenuated vaccines and optimum timing of vaccines post rituximab is considered and discussed. Expert commentary: The increasing use of rituximab in a variety of novel areas within pediatrics must be accompanied by informed discussion around mitigating the risks. These include immunosuppression, and potential susceptibility to infection. Optimizing vaccine status by establishing adequate antibody titers prior to commencement remains the best preventative strategy.
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Affiliation(s)
- Daryl R Cheng
- a General Medicine , The Royal Children's Hospital , Melbourne , VIC , Australia.,b Department of Paediatrics , The University of Melbourne , Melbourne , VIC , Australia.,c SAEFVIC , Murdoch Children's Research Institute , Melbourne , VIC , Australia
| | - Rebecca Barton
- d Haematology Department , The Royal Children's Hospital , Melbourne , VIC , Australia
| | - Anthea Greenway
- d Haematology Department , The Royal Children's Hospital , Melbourne , VIC , Australia.,e Haematology Research Group , Murdoch Children's Research Institute , Melbourne , VIC , Australia
| | - Nigel W Crawford
- a General Medicine , The Royal Children's Hospital , Melbourne , VIC , Australia.,b Department of Paediatrics , The University of Melbourne , Melbourne , VIC , Australia.,c SAEFVIC , Murdoch Children's Research Institute , Melbourne , VIC , Australia
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Abstract
Neuromyelitis optica spectrum disorders (NMOSD) are important evolving entities, which have reached much attention in the recent years. NMOSD are characterized by inflammatory lesions in the optic nerves, spinal cord, and central parts of the brain, as well as an autoimmune process directed against aquaporin-4. As disability in NMOSD accumulates by inflammatory damage from attacks, both the treatment and prevention of attacks are decisive for the long-term outcome. NMOSD attacks are treated with high-dose intravenous corticosteroids and apheresis therapies, in particular therapeutic plasma exchange. In cases of incomplete remission, escalation of attack treatment is recommended. Preventive therapy is immunosuppressive and should by commenced as early as possible. Apart from classical immunosuppressants such as azathioprine and mycophenolate mofetil, repurposed biologicals are increasingly used. B-cell depletion with rituximab and other agents, inhibition of the interleukin-6 receptor with tocilizumab, and blockade of complement-mediated damage by eculizumab all are promising therapeutic strategies evaluated in randomized controlled trials. In this review, we will discuss present and future immunotherapies for NMOSD and also consider combination of treatments, plasma, cellular and other therapies. Current advances in immunopathological knowledge are translated into innovative concepts and begin a new era of NMOSD therapy.
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Affiliation(s)
- Ingo Kleiter
- Department of Neurology, St. Josef-Hospital, Ruhr-University, Bochum, Germany.
| | - Ralf Gold
- Department of Neurology, St. Josef-Hospital, Ruhr-University, Bochum, Germany
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McKinnon JE, Maksimowicz-McKinnon K. Autoimmune disease and vaccination: impact on infectious disease prevention and a look at future applications. Transl Res 2016; 167:46-60. [PMID: 26408802 DOI: 10.1016/j.trsl.2015.08.008] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2015] [Revised: 08/27/2015] [Accepted: 08/28/2015] [Indexed: 12/11/2022]
Abstract
Vaccines hold promise both for the prevention of infections and as potential immunologic therapy for patients with autoimmune disease (AD). These patients are at high risk for both common and opportunistic infections, but this risk can be significantly reduced and even obviated with the use of recommended available vaccines. Unfortunately, patients with ADs are not routinely offered or provided indicated vaccinations and have higher rates of complications from vaccine-preventable illnesses than patients without ADs. In addition, vaccine therapy is currently under study for the treatment of autoimmune disorders, with early studies demonstrating immunomodulatory effects that may counter undesired immune activation and alleviate disease activity.
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Affiliation(s)
- John E McKinnon
- Department of Medicine, Division of Infectious Diseases, Henry Ford Hospital System, Detroit, Mich.
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Loechelt BJ, Green M, Gottlieb PA, Blumberg E, Weinberg A, Quinlan S, Baden LR. Screening and Monitoring for Infectious Complications When Immunosuppressive Agents Are Studied in the Treatment of Autoimmune Disorders. J Pediatric Infect Dis Soc 2015; 4:198-204. [PMID: 26336066 PMCID: PMC4554203 DOI: 10.1093/jpids/piu055] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2013] [Accepted: 05/11/2014] [Indexed: 01/31/2023]
Abstract
Significant progress has been made in the development, investigation, and clinical application of immunosuppressive agents to treat a variety of autoimmune disorders. The expansion of clinical applications of these new agents requires the performance of large multicenter clinical trials. These large clinical trials are particularly important as one considers these agents for the treatment of type 1 diabetes, which although autoimmune in its pathogenesis, is not classically treated as an autoimmune disorder. Although these agents hold promise for amelioration or cure of this disease, they have the potential to facilitate infectious complications. There are limited data regarding the prospective assessment of infectious risks with these agents in trials of this nature. Pediatric subjects may be at greater risk due to the higher likelihood of primary infection. A subgroup of experts associated with TrialNet (a National Institutes of Health [NIH]-funded Type 1 diabetes mellitus research network) with expertise in infectious diseases, immunology, and diagnostics developed an approach for screening and monitoring of immunosuppression-associated infections for prospective use in clinical trials. The goals of these recommendations are to provide a structured approach to monitor for infections, to identify specific laboratory testing and surveillance methods, and to consider therapies for treatment of these potential complications. Prospective evaluations of these infectious risks allow for greater scientific rigor in the evaluation of risk, which must be balanced with the potential benefits of these therapies. Our experience supports an important role for investigators with expertise in infections in immunocompromised individuals in protocol development of immunosuppressive trials in type 1diabetes and potentially other autoimmune diseases.
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Affiliation(s)
- Brett J. Loechelt
- Children's National Medical Center, Washington, District of Columbia
- The George Washington University, District of Columbia
| | | | | | - Emily Blumberg
- Perelman School of Medicine of the University of Pennsylvania, Philadelphia
| | | | - Scott Quinlan
- The George Washington University, District of Columbia
| | - Lindsey R. Baden
- Brigham and Women's Hospital/Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts
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Kim SH, Hyun JW, Jeong IH, Joung A, Yeon JL, Dehmel T, Adams O, Kieseier BC, Kim HJ. Anti-JC virus antibodies in rituximab-treated patients with neuromyelitis optica spectrum disorder. J Neurol 2015; 262:696-700. [PMID: 25559683 DOI: 10.1007/s00415-014-7629-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2014] [Revised: 12/22/2014] [Accepted: 12/23/2014] [Indexed: 01/01/2023]
Abstract
Rituximab, a chimeric monoclonal anti-CD20 antibody, has been proposed to be effective for neuromyelitis optica spectrum disorder (NMOSD). A concern for developing progressive multifocal leukoencephalopathy (PML), which is caused by John Cunningham virus (JCV), has been suggested particularly in patients treated long term with rituximab. In this study, using a modified enzyme-linked immunosorbent assay with glutathione S-transferase-tagged VP1 as the antigen, we investigated the seroprevalence of anti-JCV antibodies among 78 Korean patients with NMOSD and the change in anti-JCV antibody serostatus following long-term rituximab treatment. The overall seroprevalence of anti-JCV antibodies was 69 % prior to rituximab administration. Over a mean of 4 years of repeated treatment with rituximab, no patient developed PML. Of 24 initially seronegative patients, none converted into seropositive, whereas six (11 %) of 54 initially seropositive patients converted into seronegative. Our results might support the safety of long-term rituximab treatment in patients with NMOSD with regard to the risk of developing PML.
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Affiliation(s)
- Su-Hyun Kim
- Department of Neurology, Research Institute and Hospital of National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, Korea,
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Affiliation(s)
- A H V Schapira
- Department of Clinical Neurosciences, UCL Institute of Neurology, London, UK.
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