TY - JOUR
T1 - A randomized, double-blind, placebo-controlled study of tumor necrosis factor-α blockade in severe persistent asthma
AU - Wenzel, Sally E.
AU - Barnes, Peter J.
AU - Bleecker, Eugene R.
AU - Bousquet, Jean
AU - Busse, William
AU - Dahlén, Sven Erik
AU - Holgate, Stephen T.
AU - Meyers, Deborah A.
AU - Rabe, Klaus F.
AU - Antczak, Adam
AU - Baker, James
AU - Horvath, Ildiko
AU - Mark, Zsuzsanna
AU - Bernstein, David
AU - Kerwin, Edward
AU - Schlenker-Herceg, Rozsa
AU - Lo, Kim Hung
AU - Watt, Rosemary
AU - Barnathan, Elliot S.
AU - Chanez, Pascal
PY - 2009/4/1
Y1 - 2009/4/1
N2 - 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.
AB - 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.
KW - Asthma
KW - Golimumab
KW - Tumor necrosis factor-α
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U2 - 10.1164/rccm.200809-1512OC
DO - 10.1164/rccm.200809-1512OC
M3 - Article
C2 - 19136369
AN - SCOPUS:62549084077
VL - 179
SP - 549
EP - 558
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
SN - 1073-449X
IS - 7
ER -