title: The impact of tabalumab on the kidney in systemic lupus erythematosus: results from two phase 3 randomized, clinical trials.
abstract: BACKGROUND
  Tabalumab is a monoclonal antibody that neutralizes membrane and soluble B-cell activating factor. Two 52-week, randomized, double-blind, placebo controlled phase 3 trials evaluated the safety and efficacy of tabalumab in systemic lupus erythematosus.
  
  
  METHODS
  Patients with moderate to severe active systemic lupus erythematosus (without severe active lupus nephritis) were randomly assigned 1:1:1 to receive tabalumab (120 mg subcutaneously every 2 or 4 weeks) or placebo for 52 weeks. Serum creatinine concentration, estimated glomerular filtration rate, urine protein/creatinine ratio, renal flares and renal adverse events were determined monthly. Data were analyzed for the intent-to-treat population and for intent-to-treat patients with baseline urine protein/creatinine ratio >20 mg/mmol (intent-to-treat plus urine protein/creatinine ratio).
  
  
  RESULTS
  The trials enrolled 2262 patients. At baseline, demographics, systemic lupus erythematosus disease activity, serum creatinine concentration, estimated glomerular filtration rate and urine protein/creatinine ratio were similar among the treatment arms (with the exception of disease duration). In the intent-to-treat and intent-to-treat plus urine protein/creatinine ratio populations, there were no differences between the arms in the baseline-to-endpoint change in serum creatinine concentration, glomerular filtration rate, urine protein/creatinine ratio, or renal flare rates. Tabalumab resulted in a significant B-cell reduction and decreased immunoglobulin G levels at both doses.
  
  
  CONCLUSIONS
  Compared to placebo, tabalumab did not significantly affect the serum creatinine concentration, glomerular filtration rate, urine protein/creatinine ratio, or renal flare rates over 1 year in intent-to-treat or intent-to-treat plus urine protein/creatinine ratio patients. There were no significant renal safety signals.ClinicalTrials.gov identifiers: NCT01205438 and NCT01196091 Lupus (2016) 25, 1597-1601.
authors.affiliation: Department of Internal Medicine at their respective institutions, Ohio State University, Columbus, USA rovin.1@osu.edu.
authors.forename: B H
authors.initials: BH
authors.lastname: Rovin
authors.affiliation: Department of Internal Medicine at their respective institutions, University of North Carolina, Chapel Hill, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Dooley
authors.affiliation: Department of Internal Medicine at their respective institutions, Columbia University, New York, USA.
authors.forename: J
authors.initials: J
authors.lastname: Radhakrishnan
authors.affiliation: Department of Internal Medicine at their respective institutions, SUNY Downstate, Brooklyn, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Ginzler
authors.affiliation: Eli Lilly & Company, Indianapolis, USA.
authors.forename: T D
authors.initials: TD
authors.lastname: Forrester
authors.affiliation: Eli Lilly & Company, Indianapolis, USA.
authors.forename: P W
authors.initials: PW
authors.lastname: Anderson
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D053264:B-Cell Activating Factor / Q000037:antagonists & inhibitors; D001402:B-Lymphocytes / Q000187:drug effects*; D003404:Creatinine / Q000097:blood; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007668:Kidney / Q000187:drug effects*; D007677:Kidney Function Tests; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014481:United States
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053264:B-Cell Activating Factor; D007074:Immunoglobulin G; D003404:Creatinine; C575974:tabalumab
keywords: B-cell activating factor; Tabalumab; kidney