Abstract
Background Studies performed in Lyn-/- mice indicate that IgE autoantibodies induce a lupus nephritis-like disease. In SLE, these autoantibodies are associated with increased disease activity. We propose that omalizumab, a monoclonal antibody that binds IgE,?will reduce SLE activity by reducing circulating IgE autoantibodies, subsequently blocking basophil activation and immune dysregulation. The primary aim of this study was to determine the safety and tolerability of omalizumab in mild to moderate SLE.
Methods SLE participants (n=16) with SLEDAI >4 were randomised to receive omalizumab or placebo (2:1) added to their baseline SLE therapy for 16 weeks, followed by a 16 week open label and 4 week washout period. The regimen was a loading dose of omalizumab 600 mg dose followed by 300 mg every 4 weeks. Type I Interferon (IFN) gene signature was determined using a previously validated four gene interferon score (IFI27, IFI44, IFI44L, RSAD2) using quantitative PCR.
Demographics Variables n=16
Age (Years)
Mean 43.4
STD 13.2
Range 22–69
Disease Duration (years)
Mean 16
STD 13.3
Range 4–50
Race/Ethnicity, N (%)
African American 3 (18.8%)
Asian 2 (12.5%)
Caucasian 4 (25.0%)
Hispanic 7 (43.8%)
Sex, N (%)
Female 16
Male 0
Safety: There were a total of 52 adverse events, with the majority (49) being classified as mild. Three events met the criteria for SAE (primary varicella, pulmonary embolism, and bronchitis). No local or systemic allergic reactions were observed.
Clinical: There was a trend during the first 16 weeks of therapy toward reduction in the SLEDAI 2K score (p=0.077).
Biological: There was a trend in the reduction in the type I IFN signature in subjects treated in the first 16 weeks (p=0.11), especially in those subjects with high baseline IFN scores (p=0.052).
Conclusion The use of omalizumab in subjects with SLE appears to be well tolerated. There was a trend showing efficacy of omalizumab. The type I IFN signature also trended down, particularly in subjects with high signatures at baseline. The data analysis of other clinical parameters and mechanistic studies is still ongoing.
