TY - JOUR
T1 - Biologics in the treatment of systemic lupus erythematosus
AU - Lateef, Aisha
AU - Petri, Michelle
PY - 2010/9
Y1 - 2010/9
N2 - Purpose Of Review: The pathogenesis of systemic lupus erythematosus (SLE) involves aberrancy in multiple components of the immune system including B cells, T cells, cytokines and growth factors. Therapeutic agents targeting these mediators selectively have been tested for the treatment of SLE. This review summarizes the recent advances in the fast expanding field of these biological therapies. Recent Findings: The two large phase 2/3 randomized placebo-controlled trials of B-cell depletion, using anti-CD20 antibody, rituximab, in SLE, reported unexpected negative results. On the contrary, two large phase 3 trials of belimumab, the monoclonal antibody against B-lymphocyte stimulator (BLyS), showed significant clinical benefit. Response rates were 57.6 and 43.2% for 10 mg/kg belimumab, compared with 43.6 and 33.8% for placebo in BLISS-52 and BLISS-76, respectively. Studies of a co-stimulation blocker (abatacept), tumor necrosis factor inhibitor (infliximab), and interleukin-6 inhibitor (tocilizumab) were either negative (abatacept) or were associated with high rates of adverse events. Studies of T cell and interferon inhibition remain in the early development phase. Summary: Despite the enthusiasm in the field of biologic therapies, the majority of these new modalities have fallen short of expectations for various reasons. Only belimumab has recently met its primary outcome in two phase 3 trials.
AB - Purpose Of Review: The pathogenesis of systemic lupus erythematosus (SLE) involves aberrancy in multiple components of the immune system including B cells, T cells, cytokines and growth factors. Therapeutic agents targeting these mediators selectively have been tested for the treatment of SLE. This review summarizes the recent advances in the fast expanding field of these biological therapies. Recent Findings: The two large phase 2/3 randomized placebo-controlled trials of B-cell depletion, using anti-CD20 antibody, rituximab, in SLE, reported unexpected negative results. On the contrary, two large phase 3 trials of belimumab, the monoclonal antibody against B-lymphocyte stimulator (BLyS), showed significant clinical benefit. Response rates were 57.6 and 43.2% for 10 mg/kg belimumab, compared with 43.6 and 33.8% for placebo in BLISS-52 and BLISS-76, respectively. Studies of a co-stimulation blocker (abatacept), tumor necrosis factor inhibitor (infliximab), and interleukin-6 inhibitor (tocilizumab) were either negative (abatacept) or were associated with high rates of adverse events. Studies of T cell and interferon inhibition remain in the early development phase. Summary: Despite the enthusiasm in the field of biologic therapies, the majority of these new modalities have fallen short of expectations for various reasons. Only belimumab has recently met its primary outcome in two phase 3 trials.
KW - B-cell depletion
KW - belimumab
KW - rituximab
KW - systemic lupus erythematosus
UR - http://www.scopus.com/inward/record.url?scp=77955173179&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955173179&partnerID=8YFLogxK
U2 - 10.1097/BOR.0b013e32833b475e
DO - 10.1097/BOR.0b013e32833b475e
M3 - Review article
C2 - 20502332
AN - SCOPUS:77955173179
SN - 1040-8711
VL - 22
SP - 504
EP - 509
JO - Current opinion in rheumatology
JF - Current opinion in rheumatology
IS - 5
ER -