title: Anifrolumab, an Anti-Interferon-α Receptor Monoclonal Antibody, in Moderate-to-Severe Systemic Lupus Erythematosus.
abstract: 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).
  
  
  
  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.
  
  
  
  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).
  
  
  
  Anifrolumab substantially reduced disease activity compared with placebo across multiple clinical end points in the patients with moderate-to-severe SLE.
authors.affiliation: Hofstra Northwell School of Medicine, Northwell Health, New York, New York.
authors.forename: Richard
authors.initials: R
authors.lastname: Furie
authors.affiliation: King's College London and St. Thomas' Hospital, London, UK.
authors.forename: Munther
authors.initials: M
authors.lastname: Khamashta
authors.affiliation: Oklahoma Medical Research Foundation, Oklahoma City.
authors.forename: Joan T
authors.initials: JT
authors.lastname: Merrill
authors.affiliation: Philadelphia VA Medical Center and University of Pennsylvania, Philadelphia.
authors.forename: Victoria P
authors.initials: VP
authors.lastname: Werth
authors.affiliation: University of California at San Diego School of Medicine, La Jolla, California.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kalunian
authors.affiliation: MedImmune, Gaithersburg, Maryland.
authors.forename: Philip
authors.initials: P
authors.lastname: Brohawn
authors.affiliation: MedImmune, Gaithersburg, Maryland.
authors.forename: Gabor G
authors.initials: GG
authors.lastname: Illei
authors.affiliation: MedImmune, Gaithersburg, Maryland.
authors.forename: Jorn
authors.initials: J
authors.lastname: Drappa
authors.affiliation: MedImmune, Gaithersburg, Maryland.
authors.forename: Liangwei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Regenxbio, Rockville, Maryland.
authors.forename: Stephen
authors.initials: S
authors.lastname: Yoo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D053633:Receptor, Interferon alpha-beta / Q000276:immunology; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053633:Receptor, Interferon alpha-beta; C582345:anifrolumab