title: Pharmacokinetics and safety of single doses of tabalumab in subjects with rheumatoid arthritis or systemic lupus erythematosus.
abstract: OBJECTIVE
  Two phase 1 studies evaluated the pharmacokinetics (PK), safety and biological activity of tabalumab, a human monoclonal antibody against B-cell activating factor (BAFF), administered intravenously (i.v.) or subcutaneously (s.c.) in subjects with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE).
  
  
  METHODS
  In study A, subjects with RA (n = 23) or SLE (n = 6) received a single i.v. dose of tabalumab (RA 0.01, 0.04, 0.125, 0.5, 2.0, and 8.0 mg kg(-1) and SLE 0.125 or 2.0 mg kg(-1) ) or placebo. In study B, subjects with RA received a single tabalumab dose i.v. (10 mg) (n = 12) or s.c. (20 mg) (n = 12). Serum tabalumab and CD20+ B cells were evaluated and safety was assessed throughout both studies.
  
  
  RESULTS
  Tabalumab PK were non-linear across the 0.01 to 8.0 mg kg(-1) dose range. Clearance (CL) decreased from 2.9 to 0.1 l day(-1) and terminal half-life (t1/2 ) increased from about 1.6 to 25 days. Subjects with RA or SLE had similar PK. After s.c. dosing, tabalumab time to maximal concentration (tmax ) was 5.5 days. Absolute bioavailability (F) was approximately 62%. Following tabalumab dosing, CD20+ B cells transiently increased from baseline followed by a progressive decrease below baseline.
  
  
  CONCLUSIONS
  A single tabalumab dose administered i.v. or s.c. was well tolerated and had non-linear CL over the dose range investigated in subjects with RA and SLE. The non-linearity likely reflects target-mediated CL due to binding to BAFF. Tabalumab showed biological activity based on changes in peripheral CD20+ lymphocyte numbers in both subjects with RA and SLE.
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Witcher
authors.affiliation: Metroplex Clinical Research Center, Dallas, Texas.
authors.forename: Roy
authors.initials: R
authors.lastname: Fleischmann
authors.affiliation: Pinnacle Research Group, Anniston, Alabama, USA.
authors.forename: Vishala L
authors.initials: VL
authors.lastname: Chindalore
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Hansen
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: Leijun
authors.initials: L
authors.lastname: Hu
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: David
authors.initials: D
authors.lastname: Radtke
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: James
authors.initials: J
authors.lastname: Voelker
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: Elisa
authors.initials: E
authors.lastname: Gomez
authors.affiliation: Eli Lilly and Company, Windlesham, UK.
authors.forename: Juliet
authors.initials: J
authors.lastname: McColm
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized; D018951:Antigens, CD20 / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D053264:B-Cell Activating Factor / Q000037:antagonists & inhibitors*; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018951:Antigens, CD20; D053264:B-Cell Activating Factor; C505719:TNFSF13B protein, human; C575974:tabalumab
keywords: B-cell activating factor; pharmacokinetics; rheumatoid arthritis; systemic lupus erythematosus; tabalumab