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Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial

Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial
Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial
Background: Some patients with severe asthma have recurrent asthma exacerbations associated with eosinophilic airway inflammation. Early studies suggest that inhibition of eosinophilic airway inflammation with mepolizumab-a monoclonal antibody against interleukin 5-is associated with a reduced risk of exacerbations. We aimed to establish efficacy, safety, and patient characteristics associated with the response to mepolizumab.

Methods: We undertook a multicentre, double-blind, placebo-controlled trial at 81 centres in 13 countries between Nov 9, 2009, and Dec 5, 2011. Eligible patients were aged 12-74 years, had a history of recurrent severe asthma exacerbations, and had signs of eosinophilic inflammation. They were randomly assigned (in a 1:1:1:1 ratio) to receive one of three doses of intravenous mepolizumab (75 mg, 250 mg, or 750 mg) or matched placebo (100 mL 0·9% NaCl) with a central telephone-based system and computer-generated randomly permuted block schedule stratified by whether treatment with oral corticosteroids was required. Patients received 13 infusions at 4-week intervals. The primary outcome was the rate of clinically significant asthma exacerbations, which were defined as validated episodes of acute asthma requiring treatment with oral corticosteroids, admission, or a visit to an emergency department. Patients, clinicians, and data analysts were masked to treatment assignment. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01000506.

Findings: 621 patients were randomised: 159 were assigned to placebo, 154 to 75 mg mepolizumab, 152 to 250 mg mepolizumab, and 156 to 750 mg mepolizumab. 776 exacerbations were deemed to be clinically significant. The rate of clinically significant exacerbations was 2·40 per patient per year in the placebo group, 1·24 in the 75 mg mepolizumab group (48% reduction, 95% CI 31-61%; p<0·0001), 1·46 in the 250 mg mepolizumab group (39% reduction, 19-54%; p=0·0005), and 1·15 in the 750 mg mepolizumab group (52% reduction, 36-64%; p<0·0001). Three patients died during the study, but the deaths were not deemed to be related to treatment.

Interpretation: Mepolizumab is an effective and well tolerated treatment that reduces the risk of asthma exacerbations in patients with severe eosinophilic asthma.
0140-6736
651-659
Pavord, Ian D.
ee414b70-d199-4271-be4f-408da5bcad8f
Korn, Stephanie
0530b974-2c62-40ae-8e2d-001e40989b9d
Howarth, Peter
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Bleecker, Eugene R.
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Buhl, Roland
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Keene, Oliver N.
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Ortega, Hector
ca1def40-59bd-462a-8b7d-e22d11a82351
Chanez, Pascal
695ba8e7-e6b7-49db-a88f-e5f5a366b869
Pavord, Ian D.
ee414b70-d199-4271-be4f-408da5bcad8f
Korn, Stephanie
0530b974-2c62-40ae-8e2d-001e40989b9d
Howarth, Peter
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Bleecker, Eugene R.
33edc1f3-57c5-44f6-93b7-311eea7e18ec
Buhl, Roland
05200fd4-c811-4bdc-8474-8ac835a0292b
Keene, Oliver N.
99c6db41-acbd-4cf8-91b4-27f6d786c04f
Ortega, Hector
ca1def40-59bd-462a-8b7d-e22d11a82351
Chanez, Pascal
695ba8e7-e6b7-49db-a88f-e5f5a366b869

Pavord, Ian D., Korn, Stephanie, Howarth, Peter, Bleecker, Eugene R., Buhl, Roland, Keene, Oliver N., Ortega, Hector and Chanez, Pascal (2012) Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. The Lancet, 380 (9842), 651-659. (doi:10.1016/S0140-6736(12)60988-X). (PMID:22901886)

Record type: Article

Abstract

Background: Some patients with severe asthma have recurrent asthma exacerbations associated with eosinophilic airway inflammation. Early studies suggest that inhibition of eosinophilic airway inflammation with mepolizumab-a monoclonal antibody against interleukin 5-is associated with a reduced risk of exacerbations. We aimed to establish efficacy, safety, and patient characteristics associated with the response to mepolizumab.

Methods: We undertook a multicentre, double-blind, placebo-controlled trial at 81 centres in 13 countries between Nov 9, 2009, and Dec 5, 2011. Eligible patients were aged 12-74 years, had a history of recurrent severe asthma exacerbations, and had signs of eosinophilic inflammation. They were randomly assigned (in a 1:1:1:1 ratio) to receive one of three doses of intravenous mepolizumab (75 mg, 250 mg, or 750 mg) or matched placebo (100 mL 0·9% NaCl) with a central telephone-based system and computer-generated randomly permuted block schedule stratified by whether treatment with oral corticosteroids was required. Patients received 13 infusions at 4-week intervals. The primary outcome was the rate of clinically significant asthma exacerbations, which were defined as validated episodes of acute asthma requiring treatment with oral corticosteroids, admission, or a visit to an emergency department. Patients, clinicians, and data analysts were masked to treatment assignment. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01000506.

Findings: 621 patients were randomised: 159 were assigned to placebo, 154 to 75 mg mepolizumab, 152 to 250 mg mepolizumab, and 156 to 750 mg mepolizumab. 776 exacerbations were deemed to be clinically significant. The rate of clinically significant exacerbations was 2·40 per patient per year in the placebo group, 1·24 in the 75 mg mepolizumab group (48% reduction, 95% CI 31-61%; p<0·0001), 1·46 in the 250 mg mepolizumab group (39% reduction, 19-54%; p=0·0005), and 1·15 in the 750 mg mepolizumab group (52% reduction, 36-64%; p<0·0001). Three patients died during the study, but the deaths were not deemed to be related to treatment.

Interpretation: Mepolizumab is an effective and well tolerated treatment that reduces the risk of asthma exacerbations in patients with severe eosinophilic asthma.

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Published date: 18 August 2012
Organisations: Clinical & Experimental Sciences

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Local EPrints ID: 341333
URI: http://eprints.soton.ac.uk/id/eprint/341333
ISSN: 0140-6736
PURE UUID: 1f9c17b1-a792-4603-81bf-9097c394ca01

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Date deposited: 23 Jul 2012 10:53
Last modified: 15 Aug 2024 17:07

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Contributors

Author: Ian D. Pavord
Author: Stephanie Korn
Author: Peter Howarth
Author: Eugene R. Bleecker
Author: Roland Buhl
Author: Oliver N. Keene
Author: Hector Ortega
Author: Pascal Chanez

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