title: Sifalimumab, an anti-interferon-α monoclonal antibody, in moderate to severe systemic lupus erythematosus: a randomised, double-blind, placebo-controlled study.
abstract: OBJECTIVE
  The efficacy and safety of sifalimumab were assessed in a phase IIb, randomised, double-blind, placebo-controlled study (NCT01283139) of adults with moderate to severe active systemic lupus erythematosus (SLE).
  
  
  METHODS
  431 patients were randomised and received monthly intravenous sifalimumab (200 mg, 600 mg or 1200 mg) or placebo in addition to standard-of-care medications. Patients were stratified by disease activity, interferon gene-signature test (high vs low based on the expression of four genes) and geographical region. The primary efficacy end point was the percentage of patients achieving an SLE responder index response at week 52.
  
  
  RESULTS
  Compared with placebo, a greater percentage of patients who received sifalimumab (all dosages) met the primary end point (placebo: 45.4%; 200 mg: 58.3%; 600 mg: 56.5%; 1200 mg 59.8%). Other improvements were seen in Cutaneous Lupus Erythematosus Disease Area and Severity Index score (200 mg and 1200 mg monthly), Physician's Global Assessment (600 mg and 1200 mg monthly), British Isles Lupus Assessment Group-based Composite Lupus Assessment (1200 mg monthly), 4-point reductions in the SLE Disease Activity Index-2000 score and reductions in counts of swollen joints and tender joints. Serious adverse events occurred in 17.6% of patients on placebo and 18.3% of patients on sifalimumab. Herpes zoster infections were more frequent with sifalimumab treatment.
  
  
  CONCLUSIONS
  Sifalimumab is a promising treatment for adults with SLE. Improvement was consistent across various clinical end points, including global and organ-specific measures of disease activity.
  
  
  BACKGROUND
  NCT01283139; Results.
authors.affiliation: Graham Hughes Lupus Research Laboratory, Division of Women's Health, King's College London, The Rayne Institute, St Thomas' Hospital, London, UK.
authors.forename: Munther
authors.initials: M
authors.lastname: Khamashta
authors.affiliation: Clinical Pharmacology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
authors.forename: Joan T
authors.initials: JT
authors.lastname: Merrill
authors.affiliation: Lupus Research Institute, Philadelphia VA Medical Center, Philadelphia, Pennsylvania, USA University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Victoria P
authors.initials: VP
authors.lastname: Werth
authors.affiliation: Division of Rheumatology, Northwell Health, Great Neck, New York, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Furie
authors.affiliation: Department of Rheumatology, UCSD School of Medicine, La Jolla, California, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kalunian
authors.affiliation: Clinical Development, Respiratory, Inflammation and Autoimmunity, MedImmune, Gaithersburg, Maryland, USA.
authors.forename: Gabor G
authors.initials: GG
authors.lastname: Illei
authors.affiliation: Clinical Development, Respiratory, Inflammation and Autoimmunity, MedImmune, Gaithersburg, Maryland, USA.
authors.forename: Jorn
authors.initials: J
authors.lastname: Drappa
authors.affiliation: Department of Biostatistics, MedImmune, Gaithersburg, Maryland, USA.
authors.forename: Liangwei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Clinical Development, Respiratory, Inflammation and Autoimmunity, MedImmune, Gaithersburg, Maryland, USA.
authors.forename: Warren
authors.initials: W
authors.lastname: Greth
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000941:Antigens / Q000097:blood; D003598:Cytoskeletal Proteins / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008565:Membrane Proteins / Q000097:blood; D008875:Middle Aged; D044925:Oxidoreductases Acting on CH-CH Group Donors; D011506:Proteins / Q000032:analysis; D012720:Severity of Illness Index; D016896:Treatment Outcome; D000090123:Viperin Protein
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000941:Antigens; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D044925:Oxidoreductases Acting on CH-CH Group Donors; D011506:Proteins; C406887:IFI27 protein, human; C065888:IFI44 protein, human; C444427:RSAD2 protein, human; D000090123:Viperin Protein; C568334:sifalimumab
keywords: Autoimmune Diseases; Systemic Lupus Erythematosus; Treatment