Reduces autoreactive B cells, autoantibodies, IFN production, and class switching, along with amelioration of GN in animal models Dampens cognate interactions between T-B cells and reduction in autoimmune-driven inflammation
No statistically significant difference in new BILAG A or B flares in a RCT of 175 patients. If only BILAG A was assessed in post hoc analyses, more patients on placebo flared than those received Tx (54.4% versus 40.7%). More adverse events were noted in placebo than Tx group (19.8% versus 6.8%) In another RCT of 290 patients with class III or IV lupus nephritis, no significant difference was found between both Tx and placebo groups in complete renal response. Using the ALMS and LUNAR response criteria in post hoc analyses, more patients on the Tx group than those on placebo had complete renal response The ACCESS trial is currently underway
No change in L count and phenotypes in NZB/W F1 mice was noted. Drives production of IFN & Th2 cytokine and apoptosis upon T-cell stimulation with OVA in SCID mice. In humans, ICOS expression is elevated in CD4+ and CD8+ T cells
Delays the onset of proteinuria, inhibits IgG production, reduces GN, and prolongs survival in NZB/W F1 mice. Improves renal histology and disease progression in NZB/W F1 mice with established disease
Phase 1b trial (AMG557) for the treatment of stable lupus has just been completed. Data are being awaited
Agonistic to CD137, leading to reduction of GN, splenic CD4+ T cells, anti-dsDNA production, germinal center formation, and reduced mortality in MRL/lpr mice. In NZW/B F1 mice, similar effect as in MRL/lpr mice yet no reduction in splenic CD4+ count but elevation of splenic CD25+ Treg cells In nonlupus human samples, CD137 agonization induces vascular inflammation, plaque formation, and atherosclerosis
Reduces IL6, anti-dsDNA and IFN levels in CD134mAb-treated splenocytes of BXSB mice Reduces Th2 but increases IFN production in PBMCs of patients with SLE
Reduces anti-DNA autoantibody production and renal disease and significantly prolongs survival in NZB/W lupus-prone mice. No renal damage and even absence of immune depositions are noted in mice that responded to treatment
A 20-week phase II RCT of 85 patients with mild to moderate SLE receiving IDEC-131 or placebo did not reach both primary and secondary endpoints A phase II open-label trial of 28 patients with proliferative GN receiving BG9588 was terminated prematurely due to 2 cases of cardiac events although significant reduction of proteinuria, haematuria and serum anti-dsDNA titre, and elevation of serum C3 were achieved with BG9588
Abbreviations: ref: references; CTLA-4: cytotoxic T-lymphocyte-associated protein 4; IFN: interferongamma; GN: glomerulonephritis; BILAG: British Isles Lupus Assessment Group index; RCT: randomized controlled trial; Tx: treatment; mAb: monoclonal antibody; ALMS: Aspreva Lupus Management Study; LUNAR: Lupus Nephritis Assessment with Rituximab; ICOS: inducible costimulator; L: lymphocyte; OVA: ovalbumin; SCID: severe combined immunodeficiency; CD: cluster of differentiation; B7RP1: B7-related protein 1; NZW/B: New Zealand white/black; Treg cells: regulatory T cells; and PBMC: peripheral blood mononuclear cells.
