OBJECTIVES: To compare the pharmacokinetics (PK), safety and tolerability of 
subcutaneous (SC) and intravenous anifrolumab, an anti-type I interferon 
receptor monoclonal antibody in development for SLE, in healthy volunteers.
METHODS: In this Phase I randomised, placebo-controlled study, 30 adults were 
assigned to three treatment cohorts (anifrolumab 300 mg SC (n=6), anifrolumab 
300 mg intravenous (n=6), anifrolumab 600 mg SC (n=6)) and placebo (n=4/cohort). 
Serial blood samples were collected up to Day 84 to measure anifrolumab 
concentrations and antidrug antibodies (ADAs). PK parameters were estimated by 
noncompartmental analysis.
RESULTS: Maximum serum concentrations in SC cohorts occurred after 4-7 days. 
Anifrolumab serum concentrations were below the limit of detection in all 
individuals by Day 84. Exposure to SC anifrolumab increased dose proportionally 
from 300 mg to 600 mg based on area under the serum concentration-time curve. 
Anifrolumab 300 mg SC exposure reached 87% of the intravenous exposure. 
Anifrolumab 300 mg SC and placebo administration elicited minimal injection-site 
reactions. Transient injection-site induration occurred in five of six 
individuals after anifrolumab 600 mg SC and two of four individuals after 
placebo. Transient, mild to moderate injection-site induration and pruritus 
occurred simultaneously in two of six individuals after anifrolumab 600 mg SC. 
Adverse events were reported by 50% (n=9) of anifrolumab-treated individuals and 
33% (n=4) of placebo-treated individuals. ADAs were detected in only one 
individual in the anifrolumab 300-mg intravenous group at the Day 84 assessment.
CONCLUSION: Anifrolumab 300-mg SC exposure was 87% of intravenous 
administration, with single SC anifrolumab administrations well tolerated in 
healthy volunteers.