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B Cell-Targeted Therapies for Systemic Lupus Erythematosus

An Update on Clinical Trial Data

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Abstract

In the past year there has been remarkable activity and some important success in the development of B cell-targeted therapies for the treatment of systemic lupus erythematosus (SLE). The most promising studies were BLISS-52 and BLISS-76, large phase III studies that demonstrated measurable efficacy for belimumab, a monoclonal antibody against B cell-activating factor (BAFF). The moderate-sized phase II/III trials EXPLORER and LUNAR that tested rituximab, an anti-CD20 monoclonal antibody, for treatment of non-renal and renal lupus, disappointed many investigators with anecdotal success in refractory patients. These rituximab trials were intended to detect a large clinical effect in patients with very active disease and this was not found. Nevertheless, arguments can be made for additional studies in targeted populations or with a change in design to detect smaller or longer-term effects. Epratuzumab, a monoclonal antibody against the B cell surface antigen CD22, and atacicept, a chimeric molecule formed by a receptor for BAFF and a proliferation-inducing ligand (APRIL) with immunoglobulin (Ig)-G, have both been promising in initial small trials and now larger clinical trials are underway. Thus, recent clinical trial data show that B cell-targeting therapies are beginning to fulfil their promise as treatments for SLE and there are good reasons to hope for further progress in the near future.

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Acknowledgements

Dr Looney is supported by the U19 Autoimmunity Center of Excellence AI56390 and the Lupus Clinical Trials Consortium. He has been an advisor for Genentech, IDEC/Biogen, Roche, Amgen, Novo Nordisk, Proteolix, Centocor, Pfizer and Bristol-Myers Squibb, and has received funding for investigator-initiated studies from Genentech (2000) and Proteolix (2009). Dr Looney was one of the authors of the 2009 American College of Rheumatology abstract presenting the LUNAR (LUpus Nephritis Assessment with Rituximab) trial results.

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    R. John Looney

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Looney, R.J. B Cell-Targeted Therapies for Systemic Lupus Erythematosus. Drugs 70, 529–540 (2010). https://doi.org/10.2165/11535420-000000000-00000

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