title: A randomized, double-blind, placebo-controlled study of tumor necrosis factor-alpha blockade in severe persistent asthma.
abstract: BACKGROUND
  The treatment effect of golimumab, a human monoclonal antibody against tumor necrosis factor (TNF)-alpha, in severe persistent asthma is unknown.
  
  
  OBJECTIVE
  To assess the safety and efficacy of golimumab in a large population of patients with uncontrolled, severe persistent asthma.
  
  
  METHODS
  From 2004 to 2006, 309 patients with severe and uncontrolled asthma, despite high-dose inhaled corticosteroids and long-acting beta(2) agonists, were randomized 1:1:1:1 to monthly subcutaneous injections of placebo or golimumab (50, 100, or 200 mg) through Week 52. Coprimary endpoints were the change from baseline through Week 24 in prebronchodilator percent-predicted FEV(1) and the number of severe asthma exacerbations through Week 24.
  
  
  RESULTS
  No significant differences were observed for the change in percent-predicted FEV1 (least squares mean: placebo, 2.44 [95% confidence interval (CI) -0.574 to 5.461]; combined 100-mg and 200-mg, 2.91 [0.696-5.116]) or severe exacerbations (mean +/- SD: placebo, 0.5 +/- 1.07 vs. combined 100-mg and 200-mg 0.5 +/- 0.97) through week 24. Through Week 24, 2.6% of patients treated with placebo vs. 19.5% of those treated with golimumab discontinued the study agent, and 1.3% and 7.8% discontinued study participation, respectively. An unfavorable risk-benefit profile led to early discontinuation of study-agent administration after the Week-24 database lock. Through Week 76, 20.5% of patients treated with placebo and 30.3% of patients treated with golimumab experienced serious adverse events, with serious infections occurring more frequently in golimumab-treated patients. One death and all eight malignancies occurred in the active groups.
  
  
  CONCLUSIONS
  Overall, treatment with golimumab did not demonstrate a favorable risk-benefit profile in this study population of patients with severe persistent asthma. Clinical trial registered with www.clinicaltrials.gov (NCT00207740).
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA. wenzelse@upmc.edu
authors.forename: Sally E
authors.initials: SE
authors.lastname: Wenzel
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Barnes
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Bleecker
authors.forename: Jean
authors.initials: J
authors.lastname: Bousquet
authors.forename: William
authors.initials: W
authors.lastname: Busse
authors.forename: Sven-Erik
authors.initials: SE
authors.lastname: Dahlén
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Holgate
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Meyers
authors.forename: Klaus F
authors.initials: KF
authors.lastname: Rabe
authors.forename: Adam
authors.initials: A
authors.lastname: Antczak
authors.forename: James
authors.initials: J
authors.lastname: Baker
authors.forename: Ildiko
authors.initials: I
authors.lastname: Horvath
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Mark
authors.forename: David
authors.initials: D
authors.lastname: Bernstein
authors.forename: Edward
authors.initials: E
authors.lastname: Kerwin
authors.forename: Rozsa
authors.initials: R
authors.lastname: Schlenker-Herceg
authors.forename: Kim Hung
authors.initials: KH
authors.lastname: Lo
authors.forename: Rosemary
authors.initials: R
authors.lastname: Watt
authors.forename: Elliot S
authors.initials: ES
authors.lastname: Barnathan
authors.forename: Pascal
authors.initials: P
authors.lastname: Chanez
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007239:Infections / Q000209:etiology; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; C529000:golimumab