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

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

1073-449X
549-558
Wenzel, S. E.
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Barnes, P. J.
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Bleecker, E. R.
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Bousquet, J.
fda25127-be6f-45cd-a455-883cc90d8e0e
Busse, W.
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Dahlen, S.-E.
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Holgate, S. T.
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Meyers, D. A.
b059dd6c-e702-46b9-b1ad-285dd6aa3a46
Rabe, K. F.
d2b8c358-1126-49b7-bb38-f36eb9ff5b3d
Antczak, A.
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Baker, J.
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Horvath, I.
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Mark, Z.
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Bernstein, D.
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Kerwin, E.
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Schlenker-Herceg, R.
ba0749e1-70d0-4084-bbbc-ddfeb3912986
Lo, K. H.
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Watt, R.
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Barnathan, E. S.
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Chanez, P.
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Wenzel, S. E.
92502fb1-8928-41e1-99c3-bf608c94a7e2
Barnes, P. J.
0cd31428-a5db-4725-a1d5-0a89ddfd8b86
Bleecker, E. R.
4aea50a8-9b77-4fa5-821a-df1ad5e5e4c7
Bousquet, J.
fda25127-be6f-45cd-a455-883cc90d8e0e
Busse, W.
d510b1a1-1793-47e3-a314-bd7f82e42c79
Dahlen, S.-E.
4452f0d3-ccb0-4020-99e7-2523a14dc55f
Holgate, S. T.
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Meyers, D. A.
b059dd6c-e702-46b9-b1ad-285dd6aa3a46
Rabe, K. F.
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Antczak, A.
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Baker, J.
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Horvath, I.
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Mark, Z.
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Bernstein, D.
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Kerwin, E.
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Schlenker-Herceg, R.
ba0749e1-70d0-4084-bbbc-ddfeb3912986
Lo, K. H.
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Watt, R.
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Barnathan, E. S.
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Chanez, P.
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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. (2009) 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), 549-558. (doi:10.1164/rccm.200809-1512OC).

Record type: Article

Abstract

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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Published date: January 2009
Organisations: Clinical & Experimental Sciences

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Local EPrints ID: 341520
URI: http://eprints.soton.ac.uk/id/eprint/341520
ISSN: 1073-449X
PURE UUID: 2bea416e-a41e-43b2-bfbf-d342e11718c8

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Date deposited: 26 Jul 2012 14:32
Last modified: 14 Mar 2024 11:40

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Contributors

Author: S. E. Wenzel
Author: P. J. Barnes
Author: E. R. Bleecker
Author: J. Bousquet
Author: W. Busse
Author: S.-E. Dahlen
Author: S. T. Holgate
Author: D. A. Meyers
Author: K. F. Rabe
Author: A. Antczak
Author: J. Baker
Author: I. Horvath
Author: Z. Mark
Author: D. Bernstein
Author: E. Kerwin
Author: R. Schlenker-Herceg
Author: K. H. Lo
Author: R. Watt
Author: E. S. Barnathan
Author: P. Chanez

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