Wenzel, S. E., Barnes, P. J., Bleecker, E. R., Bousquet, J., Busse, W., Dahlen, S.-E., Holgate, S. T., Meyers, D. A., Rabe, K. F., Antczak, A., Baker, J., Horvath, I., Mark, Z., Bernstein, D., Kerwin, E., Schlenker-Herceg, R., Lo, K. H., Watt, R., Barnathan, E. S. and Chanez, P.
A randomized, double-blind, placebo-controlled study of tumor necrosis factor- blockade in severe persistent asthma.
American Journal of Respiratory and Critical Care Medicine, 179, (7), . (doi:10.1164/rccm.200809-1512OC).
Rationale: The treatment effect of golimumab, a human monoclonal antibody against tumor necrosis factor (TNF)-?, 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 ?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.
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