Target Agent Mechanism of Action Key Clinical Trials (*denotes ongoing or upcoming trial) Primary Endpoint Met
B cells Rituximab Chimeric monoclonal anti-CD20 antibody Phase III (EXPLORER) [67]: SLE
Phase III (LUNAR) [68]: lupus nephritis
Phase III (RING) [69]*: lupus nephritis
No No
B cells Belimumab BLyS inhibitor Phase III (BLISS 52) [70]: SLE
Phase III (BLISS 76) [71]: SLE Phase III (BLISS-LN) [73]*: lupus nephritis
Phase III/IV (EMBRACE) [75]*: SLE in African Americans
Yes
Yes (only for 10 mg/kg Belimumab group)
B cells Atacicept BLyS and APRIL inhibitor Phase II/III (APRIL-LN) [79]: lupus nephritis Phase II/III [80] (APRIL SLE)*: SLE No (study prematurely terminated)
B cells Abetimus B cell tolerogenic DNA-oligomeric construct active against anti-dsDNA Phase II/III [82]: lupus nephritis
Phase III [83]: lupus nephritis
No No
B cells Ocrelizumab Humanized monoclonal anti-CD20 antibody Phase III (BEGIN) [84]: SLE Phase III (BELONG) [85]*: lupus nephritis No (study prematurely terminated)
B cells Epratuzumab Humanized monoclonal anti-CD22 antibody Phase II (EMBLEM) [87]: SLE
Phase III (EMBODY 1) [88]*: SLE
Yes
T cells Abatacept T-cell costimulation blockade Phase IIb [89]: SLE
Phase II/III [90]: lupus nephritis Phase II (ACCESS), Phase III [91,92]*: lupus nephritis
No
No (study prematurely terminated)
T cells Rapamycin Regulation of mitochondrial transmembrane potential and calcium flow Phase I [93]: SLE Phase II [94]*: SLE Preliminary efficacy observed
T cells N-acetylcysteine mTOR inhibitor in T lymphocytes Phase I/II [95]: SLE Preliminary efficacy observed (except for 1.2 g daily N-acetylcysteine group)
T cells R788 Spleen tyrosine kinase inhibitor None (only murine lupus data) [96,97]  
T cells BG9588 Humanized anti-CD40 ligand antibody Phase II [99]: SLE No (study prematurely terminated)
T cells Laquinimod Promotes TH2 over TH1 response Phase IIa [101]*: SLE
Phase IIa [102]*: lupus nephritis
 
T cells Paquinimod Promotes TH2 over TH1 response Phase Ib [103]: SLE N/A
Cytokines Sifalimumab IFN-alpha inhibitor Phase I [104]: SLE Phase II, Phase IIb [105,106]*: SLE Preliminary efficacy observed
Cytokines Rontalizumab IFN-alpha inhibitor Phase I [107]: SLE
Phase II (ROSE) [108]: SLE
N/A
No
Cytokines Tocilizumab Humanized monoclonal antibody against IL-6 receptor Phase I [114]: SLE Preliminary efficacy observed
Cytokines B-N10 Murine anti-IL-10 monoclonal antibody Phase I [115]: SLE Preliminary efficacy observed
Cytokines Infliximab Chimeric TNF-alpha inhibitor Phase I (two trials) [116,117]: SLE
Phase II/III (TRIAL) [121]: SLE
Preliminary efficacy observed
No (study prematurely terminated)
Cytokines Etanercept Soluble TNF-receptor fusion protein Phase II [122]: SLE No (study prematurely terminated)
Table 1: Summary of targeted agents investigated for the treatment of SLE.