title: Efficacy and safety of subcutaneous tabalumab, a monoclonal antibody to B-cell activating factor, in patients with systemic lupus erythematosus: results from ILLUMINATE-2, a 52-week, phase III, multicentre, randomised, double-blind, placebo-controlled study.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of tabalumab, a human IgG4 monoclonal antibody that neutralises membrane and soluble B-cell activating factor (BAFF).
  
  
  METHODS
  This randomised, placebo-controlled study enrolled 1124 patients with moderate-to-severe systemic lupus erythematosus (SLE) (Safety of Estrogens in Lupus Erythematosus National Assessment- SLE Disease Activity Index ≥6 at baseline). Patients received standard of care plus subcutaneous study drug, starting with a loading dose (240 mg) at week 0 and followed by 120 mg every 2 weeks (120 Q2W), 120 mg every 4 weeks (120 Q4W) or placebo. Primary endpoint was proportion achieving SLE Responder Index 5 (SRI-5) improvement at week 52.
  
  
  RESULTS
  Clinical characteristics were balanced across groups. The primary endpoint was met with 120 Q2W (38.4% vs 27.7%, placebo; p=0.002), but not with the less frequent 120 Q4W regimen (34.8%, p=0.051). Although key secondary endpoints (time to severe flare, corticosteroid sparing and fatigue) were not met, patients treated with tabalumab had greater SRI-5 response rates in a serologically active subset and improvements in more stringent SRI cut-offs, SELENA-SLEDAI, Physician's Global Assessment, anti-double-stranded DNA antibodies, complement, total B cells and immunoglobulins. The incidences of deaths, serious adverse events (AEs), and treatment-emergent AEs were similar in the 120 Q2W, 120 Q4W and placebo groups, but depression and suicidal ideation, albeit rare events, were more commonly reported with tabalumab.
  
  
  CONCLUSIONS
  SRI-5 was met with 120 Q2W and although key secondary endpoints were not met, numerous other secondary endpoints significantly improved in addition to pharmacodynamic evidence of BAFF pathway blockade. The safety profile for tabalumab was similar to placebo, except for depression and suicidality, which were uncommon.
  
  
  BACKGROUND
  NCT01205438.
authors: Oklahoma Medical Research Foundation, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
authors: J T
authors: JT
authors: Merrill
authors: Department of Medicine, Karolinska Institute, Stockholm, Sweden.
authors: R F
authors: RF
authors: van Vollenhoven
authors: New York University School of Medicine, New York, New York, USA.
authors: J P
authors: JP
authors: Buyon
authors: Division of Rheumatology and Allergy-Clinical Immunology, Hofstra North Shore-LIJ School of Medicine, Great Neck, New York, USA.
authors: R A
authors: RA
authors: Furie
authors: Rheumatology, University of Southern California Keck School of Medicine, Los Angeles, California, USA.
authors: W
authors: W
authors: Stohl
authors: Eli Lilly and Company, Indianapolis, Indiana, USA.
authors: M
authors: M
authors: Morgan-Cox
authors: Eli Lilly and Company, Indianapolis, Indiana, USA.
authors: C
authors: C
authors: Dickson
authors: Eli Lilly and Company, Indianapolis, Indiana, USA.
authors: P W
authors: PW
authors: Anderson
authors: Eli Lilly and Company, Indianapolis, Indiana, USA.
authors: C
authors: C
authors: Lee
authors: Eli Lilly and Company, Indianapolis, Indiana, USA.
authors: P-Y
authors: PY
authors: Berclaz
authors: Medicine/Rheumatology and Clin Immunology, Charité Universitätsmedizin, Berlin, Germany.
authors: T
authors: T
authors: Dörner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000097:blood; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D001323:Autoantibodies / Q000097:blood; D053264:B-Cell Activating Factor / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D001402:B-Lymphocytes / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D044383:Black People; D003176:Complement C3 / Q000378:metabolism; D003181:Complement C4 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000208:ethnology; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001323:Autoantibodies; D053264:B-Cell Activating Factor; D015415:Biomarkers; D003176:Complement C3; D003181:Complement C4; C575974:tabalumab
keywords: Autoimmune Diseases; B cells; Disease Activity; Systemic Lupus Erythematosus