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J. disease. and [56]. Interestingly, anti-BR3 antibodies reduce the numbers of B cells more effectively than anti-BLyS mAb, BR3-Fc and TACI-Fc [57]. A-623 & BR3-Fc A-623, formerly AMG 623, is a polypeptide fusion protein (peptibody) that inhibits B-cell survival and maturation by neutralizing BLyS. A-623 is currently in Phase II clinical trials. BR3-Fc (briobacept) is a homodimeric fusion glycoprotein of the extracellular ligand-binding portion of BAFF-R and DGAT1-IN-1 the Fc portion of an IgG1 that blocks BLyS from binding to BAFF-R, thus inhibiting activation and promoting a poptosis of B cells. Both AMG 623 and BR3-Fc are in clinical trials and appear well tolerated. Their efficacy in SLE is unknown at present [58C59]. Atacicept Atacicept is a recombinant fusion protein made of the extracellular ligand-binding portion of TACI (see previous section) fused to the Fc portion of a human IgG. It is a soluble receptor that binds BLyS and APRIL, thus blocking the activation of TACI. Although a Phase II/III lupus nephritis trial that evaluated doseCeffectiveness in SLE patients gave disappointing results and the study was discontinued owing to the development of severe infections in some patients, a new Phase II/III trial of atacicept in generalized SLE is ongoing [60]. Conclusion Biologics have dramatically improved the clinical management of several autoimmune diseases. In SLE, where multiple immune imbalances associate with a significant complexity and a diversity of clinical disease manifestations, the use of mAbs to cytokines has shown rapid advancement and potential promise. Concerns with the use of biologics remain the risk of immediate and delayed toxicities and the development of drug resistance. Although no biological response modifiers are currently approved for SLE, it is likely that belimumab will be approved this year, and new open-label trials will soon be added to the list reviewed here. 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