A Randomized, Double-blind, Placebo-controlled Study of Tumor Necrosis Factor-[alpha] Blockade in Severe Persistent Asthma.
Wenzel, Sally E. 1,*; Barnes, Peter J. 2; Bleecker, Eugene R. 3; Bousquet, Jean 4; Busse, William 5; Dahlen, Sven-Erik 6; Holgate, Stephen T. 7; Meyers, Deborah A. 3; Rabe, Klaus F. 8; Antczak, Adam 9,++; Baker, James 10; Horvath, Ildiko 11; Mark, Zsuzsanna 12; Bernstein, David 13,[spacing circumflex]; Kerwin, Edward 14; Schlenker-Herceg, Rozsa 15; Lo, Kim Hung 15; Watt, Rosemary 15; Barnathan, Elliot S. 15; Chanez, Pascal 16,[//]; on behalf of the T03 Asthma Investigators +
[Miscellaneous]
American Journal of Respiratory & Critical Care Medicine.
179(7):549-558, April 1, 2009.
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Rationale: The treatment effect of golimumab, a human monoclonal antibody against tumor necrosis factor (TNF)-[alpha], 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 [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 FEV1 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 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).
(C) 2009 American Thoracic Society