OBJECTIVE: To assess the efficacy and safety of anifrolumab, a type I interferon 
(IFN) receptor antagonist, in a phase IIb, randomized, double-blind, 
placebo-controlled study of adults with moderate-to-severe systemic lupus 
erythematosus (SLE).
METHODS: Patients (n = 305) were randomized to receive intravenous anifrolumab 
(300 mg or 1,000 mg) or placebo, in addition to standard therapy, every 4 weeks 
for 48 weeks. Randomization was stratified by SLE Disease Activity Index 2000 
score (<10 or ≥10), oral corticosteroid dosage (<10 or ≥10 mg/day), and type I 
IFN gene signature test status (high or low) based on a 4-gene expression assay. 
The primary end point was the percentage of patients achieving an SLE Responder 
Index (SRI[4]) response at week 24 with sustained reduction of oral 
corticosteroids (<10 mg/day and less than or equal to the dose at week 1 from 
week 12 through 24). Other end points (including SRI[4], British Isles Lupus 
Assessment Group [BILAG]-based Composite Lupus Assessment [BICLA], modified 
SRI[6], and major clinical response) were assessed at week 52. The primary end 
point was analyzed in the modified intent-to-treat (ITT) population and type I 
IFN-high subpopulation. The study result was considered positive if the primary 
end point was met in either of the 2 study populations. The Type I error rate 
was controlled at 0.10 (2-sided), within each of the 2 study populations for the 
primary end point analysis.
RESULTS: The primary end point was met by more patients treated with anifrolumab 
(34.3% of 99 for 300 mg and 28.8% of 104 for 1,000 mg) than placebo (17.6% of 
102) (P = 0.014 for 300 mg and P = 0.063 for 1,000 mg, versus placebo), with 
greater effect size in patients with a high IFN signature at baseline (13.2% in 
placebo-treated patients versus 36.0% [P = 0.004] and 28.2% [P = 0.029]) in 
patients treated with anifrolumab 300 mg and 1,000 mg, respectively. At week 52, 
patients treated with anifrolumab achieved greater responses in SRI(4) (40.2% 
versus 62.6% [P < 0.001] and 53.8% [P = 0.043] with placebo, anifrolumab 300 mg, 
and anifrolumab 1,000 mg, respectively), BICLA (25.7% versus 53.5% [P < 0.001] 
and 41.2% [P = 0.018], respectively), modified SRI(6) (28.4% versus 49.5% 
[P = 0.002] and 44.7% [P = 0.015], respectively), major clinical response (BILAG 
2004 C or better in all organ domains from week 24 through week 52) (6.9% versus 
19.2% [P = 0.012] and 17.3% [P = 0.025], respectively), and several other global 
and organ-specific end points. Herpes zoster was more frequent in the 
anifrolumab-treated patients (2.0% with placebo treatment versus 5.1% and 9.5% 
with anifrolumab 300 mg and 1,000 mg, respectively), as were cases reported as 
influenza (2.0% versus 6.1% and 7.6%, respectively), in the anifrolumab 
treatment groups. Incidence of serious adverse events was similar between groups 
(18.8% versus 16.2% and 17.1%, respectively).
CONCLUSION: Anifrolumab substantially reduced disease activity compared with 
placebo across multiple clinical end points in the patients with 
moderate-to-severe SLE.