A Randomized, Double-blind, Placebo-controlled Study of Tumor Necrosis Factor-α Blockade in Severe Persistent Asthma

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Rationale</jats:title> <jats:p>The treatment effect of golimumab, a human monoclonal antibody against tumor necrosis factor (TNF)-α, in severe persistent asthma is unknown.</jats:p> </jats:sec> <jats:sec> <jats:title>Objectives</jats:title> <jats:p>To assess the safety and efficacy of golimumab in a large population of patients with uncontrolled, severe persistent asthma.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>From 2004 to 2006, 309 patients with severe and uncontrolled asthma, despite high-dose inhaled corticosteroids and long-acting β2 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.</jats:p> </jats:sec> <jats:sec> <jats:title>Measurements and Main Results</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Overall, treatment with golimumab did not demonstrate a favorable risk–benefit profile in this study population of patients with severe persistent asthma.</jats:p> <jats:p>Clinical trial registered with www.clinicaltrials.gov (NCT00207740).</jats:p> </jats:sec>