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B-cell depletion in SLE: clinical and trial experience with rituximab and ocrelizumab and implications for study design

Reddy, V; Jayne, D; Close, D; Isenberg, D; (2013) B-cell depletion in SLE: clinical and trial experience with rituximab and ocrelizumab and implications for study design. Arthritis Research & Therapy , 15 (Sup 1) S2. 10.1186/ar3910. Green open access

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Abstract

B cells are believed to be central to the disease process in systemic lupus erythematosus (SLE), making them a target for new therapeutic intervention. In recent years there have been many publications regarding the experience in SLE of B-cell depletion utilising rituximab, an anti-CD20 mAb that temporarily depletes B cells,reporting promising results in uncontrolled open studies and in routine clinical use. However, the two large randomised controlled trials in extra-renal lupus (EXPLORER study) and lupus nephritis (LUNAR study) failed to achieve their primary endpoints. Based on the clinical experience with rituximab this failure was somewhat unexpected and raised a number of questions and concerns, not only into the true level of benefit of B-cell depletion in a broad population but also how to test the true level of effectiveness of an investigational agent as we seek to improve the design of therapeutic trials in SLE. A better understanding of what went wrong in these trials is essential to elucidate the underlying reasons for the disparate observations noted in open studies and controlled trials. In this review, we focus on various factors that may affect the ability to accurately and confidently establish the level of treatment effect of the investigational agent, in this case rituximab, in the tw studies and explore hurdles faced in the randomised controlled trials investigating the efficacy of ocrelizumab, the humanised anti-CD20 mAb, in SLE. Further, based on the lessons learned from the clinical trials, we make suggestions that could be implemented in future clinical trial design to overcome the hurdles faced.

Type: Article
Title: B-cell depletion in SLE: clinical and trial experience with rituximab and ocrelizumab and implications for study design
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/ar3910
Publisher version: http://dx.doi.org/10.1186/ar3910
Language: English
Additional information: Copyright on any open access article in a journal published by BioMed Central is retained by the author(s). Authors grant BioMed Central a license to publish the article and identify itself as the original publisher. Authors also grant any third party the right to use the article freely as long as its integrity is maintained and its original authors, citation details and publisher are identified. The Creative Commons Attribution License 4.0 (http://creativecommons.org/licenses/by/4.0/) formalizes these and other terms and conditions of publishing articles. In accordance with our Open Data policy, the Creative Commons CC0 1.0 Public Domain Dedication (http://creativecommons.org/publicdomain/zero/1.0/) waiver applies to all published data in BioMed Central open access articles.
Keywords: Antibodies, Monoclonal, Humanized, Antibodies, Monoclonal, Murine-Derived, B-Lymphocytes, Dose-Response Relationship, Drug, Humans, Immunologic Factors, Lupus Erythematosus, Systemic, Randomized Controlled Trials as Topic, Treatment Outcome
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: https://discovery.ucl.ac.uk/id/eprint/1471530
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