Aisha Lateef1, Michelle Petri. 1. Division of Rheumatology, Johns Hopkins University, School of Medicine, Johns Hopkins Lupus Center, Baltimore, Maryland, USA.
Abstract
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.
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.
Authors: Matthew D Rockstrom; Liangyu Chen; Ping Taishi; Joseph T Nguyen; Cody M Gibbons; Sigrid C Veasey; James M Krueger Journal: Sleep Med Rev Date: 2017-11-17 Impact factor: 11.609