A randomized, double-blind, placebo-controlled study of tumor necrosis factor-α blockade in severe persistent asthma

Sally E. Wenzel, Peter J. Barnes, Eugene R. Bleecker, Jean Bousquet, William Busse, Sven Erik Dahlén, Stephen T. Holgate, Deborah A. Meyers, Klaus F. Rabe, Adam Antczak, James Baker, Ildiko Horvath, Zsuzsanna Mark, David Bernstein, Edward Kerwin, Rozsa Schlenker-Herceg, Kim Hung Lo, Rosemary Watt, Elliot S. Barnathan, Pascal Chanez

Research output: Contribution to journalArticlepeer-review

425 Scopus citations

Abstract

Rationale: The treatment effect of golimumab, a human monoclonal antibody against tumor necrosis factor (TNF)-α, in severe persistent asthma is unknown. Objectives: 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 β 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. Measurements and Main Results: No significant differences were observed for the change in percent-predicted FEV 1 (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.

Original languageEnglish (US)
Pages (from-to)549-558
Number of pages10
JournalAmerican journal of respiratory and critical care medicine
Volume179
Issue number7
DOIs
StatePublished - Apr 1 2009
Externally publishedYes

Keywords

  • Asthma
  • Golimumab
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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