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      Systematic Review of Safety and Efficacy of Second- and Third-Generation CD20-Targeting Biologics in Treating Immune-Mediated Disorders

      systematic-review

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          Abstract

          Background

          B cells can contribute to immune-mediated disorders. Targeting CD20 has proved to be efficacious in several B cell-mediated immunopathologies, as illustrated by the use of rituximab, the first anti-CD20 monoclonal antibody (mAb). Following rituximab, second- and third-generation anti-CD20 mAbs have been developed and tried in immune-mediated diseases, including obinutuzumab, ocrelizumab, ofatumumab, ublituximab, and veltuzumab. However, their safety and efficacy has not been systematically reviewed.

          Objective

          To evaluate safety and efficacy of obinutuzumab, ocrelizumab, ofatumumab, ublituximab, and veltuzumab for the treatment of immune-mediated disorders compared to placebo, conventional treatment or other biologics.

          Methods

          The PRISMA checklist guided the reporting of the data. We searched the PubMed database between 4 October 2016 and 22 July 2021 concentrating on immune-mediated disorders.

          Results

          The literature search identified 2220 articles. After screening titles and abstracts against the inclusion and exclusion criteria and assessing full texts, 27 articles were finally included in a narrative synthesis.

          Conclusions

          Obinutuzumab has shown promising results in a case series of patients with phospholipase A 2 receptor-associated membranous nephropathy and mixed results in systemic lupus erythematosus. Ocrelizumab has been approved for the use in patients with relapsing-remitting multiple sclerosis and primary progressive multiple sclerosis. Ocrelizumab was also tested in patients with rheumatoid arthritis, demonstrating promising results, and in systemic lupus erythematosus, revealing mixed results; however, in these conditions, its use was associated with increased risk of serious infections. Ofatumumab received approval for treating patients with relapsing-remitting multiple sclerosis. Moreover, ofatumumab showed promising results in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis, rheumatoid arthritis, and systemic lupus erythematosus, as well as mixed results in phospholipase A 2 receptor-associated membranous nephropathy. Ublituximab was assessed in relapsing-remitting multiple sclerosis and neuromyelitis optica spectrum disorder, with promising results, however, the included number of patients was too small to conclude. Veltuzumab was tested in patients with immune thrombocytopenia resulting in improved platelet counts.

          Systematic Review Registration

          https://www.crd.york.ac.uk/prospero/, identifier CRD4201913421.

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          Most cited references52

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          Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement

          David Moher, Alessandro Liberati, Jennifer Tetzlaff … (2012)
          David Moher and colleagues introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses
          Article 0 comments Cited 5077 times – based on 0 reviews     Review now
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            The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions

            S H Downs, C N Black (1998)
            Article 0 comments Cited 641 times – based on 0 reviews     Review now
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              Immune regulation by glucocorticoids

              Derek Cain, JOHN CIDLOWSKI (2017)
              In this Review, the authors discuss the effects of glucocorticoids on both innate and adaptive immunity. They explain the mechanistic basis of glucocorticoid-mediated immunosuppression and highlight the less well-appreciated roles of glucocorticoids in enhancing immune responses.
              Article 0 comments Cited 450 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Journal
                Journal ID (nlm-ta): Front Immunol
                Journal ID (iso-abbrev): Front Immunol
                Journal ID (publisher-id): Front. Immunol.
                Title: Frontiers in Immunology
                Publisher: Frontiers Media S.A.
                ISSN (Electronic): 1664-3224
                Publication date (Electronic): 02 February 2022
                Publication date Collection: 2021
                Volume: 12
                Electronic Location Identifier: 788830
                Affiliations
                [1] 1 Department of Immunology, University Hospital Zurich , Zurich, Switzerland
                [2] 2 Faculty of Medicine, University of Zurich , Zurich, Switzerland
                Author notes

                Edited by: Ioannis Parodis, Karolinska Institutet (KI), Sweden

                Reviewed by: Harry Alexopoulos, National and Kapodistrian University of Athens, Greece; Venkat Reddy, University College London, United Kingdom

                *Correspondence: Onur Boyman, onur.boyman@ 123456uzh.ch

                This article was submitted to Autoimmune and Autoinflammatory Disorders, a section of the journal Frontiers in Immunology

                Article
                DOI: 10.3389/fimmu.2021.788830
                PMC ID: 8847774
                PubMed ID: 35185862
                SO-VID: 969c2679-d703-4d8d-9818-a9da3f5edc90
                Copyright © Copyright © 2022 Kaegi, Wuest, Crowley and Boyman
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                Date received : 03 October 2021
                Date accepted : 17 December 2021
                Page count
                Figures: 1, Tables: 5, Equations: 0, References: 52, Pages: 16, Words: 10096
                Categories
                Subject: Immunology
                Subject: Systematic Review

                ScienceOpen disciplines: Immunology
                Keywords: obinutuzumab,ocrelizumab,ofatumumab,ublituximab,veltzumab,immune-mediated diseases,systemic lupus erythematosus,multiple sclerosis
                Data availability:
                ScienceOpen disciplines: Immunology
                Keywords: obinutuzumab, ocrelizumab, ofatumumab, ublituximab, veltzumab, immune-mediated diseases, systemic lupus erythematosus, multiple sclerosis

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