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B-Cell-Targeted Therapy for Systemic Lupus Erythematosus

An Update

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Abstract

Systemic lupus erythematosus (SLE) is a classic autoimmune disease characterized by a myriad of immune system aberrations, most likely resulting from pathogenic autoantibody production, immune complex deposition, and subsequent end-organ damage. B cells play a key role in the pathogenesis; therefore, B-cell-targeted therapies, including B-cell depletion and blockage of B-cell survival factors such as B-lymphocyte stimulator (BLyS), are potential therapeutic targets for SLE. In uncontrolled clinical trials from approximately 20 studies, rituximab — a mouse-human chimeric anti-CD20 monoclonal antibody that effectively depletes B cells — has been demonstrated to reduce disease activity and decrease serum autoantibodies, with a clinical response of 86% in a case series of approximately 400 SLE patients with refractory disease, with or without concomitant use of cyclophosphamide. Epratuzumab, a humanized anti-CD22 monoclonal antibody that partially depletes B cells, has also been shown to reduce disease activity but not to decrease autoantibody levels in patients with moderately active SLE. Randomized controlled phase I/II trials in patients with active SLE have documented that belimumab, a humanized anti-BLyS monoclonal antibody, reduces B-cell numbers, inhibits disease activity and decreases anti-double-stranded DNA autoantibody in SLE patients. All these therapies are well tolerated, but accompanying infectious complications have been observed. Other B-cell-targeted therapies such as ‘humanized’ monoclonal antibodies to CD20 (e.g. ocrelizumab) and agents that interrupt B-cell/T-cell interactions also have potential, and the efficacy of these, along with rituximab, belimumab and epratuzumab, needs to be determined by randomized controlled trials

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Acknowledgments

No sources of funding were used to assist in the preparation of this review. Dr Jones has been involved in Roche clinical trials and has served as a member of the advisory boards and speakers’ bureaux for these trials. Drs Ding and Foote have no conflicts of interest relevant to the content of this review.

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  1. Menzies Research Institute, University of Tasmania, Private Bag 23, Hobart, Tasmania, TAS 7000, Australia

    Changhai Ding, Simon Foote & Graeme Jones

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  1. Changhai Ding
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Correspondence to Changhai Ding.

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Ding, C., Foote, S. & Jones, G. B-Cell-Targeted Therapy for Systemic Lupus Erythematosus. BioDrugs 22, 239–249 (2008). https://doi.org/10.2165/00063030-200822040-00003

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