OBJECTIVE: To evaluate the safety and tolerability of multiple intravenous (IV) 
doses of sifalimumab in adults with moderate-to-severe systemic lupus 
erythematosus (SLE).
METHODS: In this multicenter, double-blind, placebo-controlled, sequential 
dose-escalation study, patients were randomized 3:1 to receive IV sifalimumab 
(0.3, 1.0, 3.0, or 10.0 mg/kg) or placebo every 2 weeks to week 26, then 
followed up for 24 weeks. Safety assessment included recording of 
treatment-emergent adverse events (AEs) and serious AEs. Pharmacokinetics, 
immunogenicity, and pharmacodynamics were evaluated, and disease activity was 
assessed.
RESULTS: Of 161 patients, 121 received sifalimumab (26 received 0.3 mg/kg; 25, 
1.0 mg/kg; 27, 3.0 mg/kg; and 43, 10 mg/kg) and 40 received placebo. Patients 
were predominantly female (95.7%). At baseline, patients had moderate-to-severe 
disease activity (mean SLE Disease Activity Index score 11.0), and most (75.2%) 
had a high type I interferon (IFN) gene signature. In the sifalimumab group 
versus the placebo group, the incidence of ≥1 treatment-emergent AE was 92.6% 
versus 95.0%, ≥1 serious AE was 22.3% versus 27.5%, and ≥1 infection was 67.8% 
versus 62.5%; discontinuations due to AEs occurred in 9.1% versus 7.5%, and 
death occurred in 3.3% (n=4) versus 2.5% (n=1). Serum sifalimumab concentrations 
increased in a linear and dose-proportional manner. Inhibition of the type I IFN 
gene signature was sustained during treatment in patients with a high baseline 
signature. No statistically significant differences in clinical activity (SLEDAI 
and British Isles Lupus Assessment Group score) between sifalimumab and placebo 
were observed. However, when adjusted for excess burst steroids, SLEDAI change 
from baseline showed a positive trend over time. A trend toward normal 
complement C3 or C4 level at week 26 was seen in the sifalimumab groups compared 
with baseline.
CONCLUSION: The observed safety/tolerability and clinical activity profile of 
sifalimumab support its continued clinical development for SLE.