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Randomised controlled trials in severe asthma: Selection by phenotype or stereotype

Randomised controlled trials in severe asthma: Selection by phenotype or stereotype
Randomised controlled trials in severe asthma: Selection by phenotype or stereotype

Previous publications have highlighted the disparity between research trial populations and those in clinical practice, but it has not been established how this relates to randomised controlled trials (RCTs) of phenotype-targeted biological therapies in severe asthma. Detailed characterisation data for 342 severe asthma patients within the Wessex Severe Asthma Cohort (WSAC) was compared against comprehensive trial eligibility criteria for published phase IIB and phase III RCTs evaluating biological therapies in severe asthma since 2000. 37 RCTs evaluating 20 biological therapies were identified. Only a median of 9.8% (range 3.5-17.5%) of severe asthma patients were found to be eligible for enrolment in the phase III trials. Stipulations for airflow obstruction, bronchodilator reversibility and smoking history excluded significant numbers of patients. A median of 78.9% (range 73.2-86.6%) of patients with severe eosinophilic asthma would have been excluded from participation in the phase III licensing trials of interleukin (IL)-5/IL-5R targeted therapies. Despite including only well characterised and optimally treated severe asthmatics under specialist care within the WSAC study, the vast majority were excluded from trial participation by criteria designed to re-confirm diagnostic labels rather than by biomarker criteria that predict the characteristic addressed by the treatment.

0903-1936
Brown, Thomas
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Jones, Thomas
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Gove, Kerry
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Barber, Clair
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Elliott, Scott
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Chauhan, Anoop
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Howarth, Peter
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Aitkin, L.
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Babu, S.
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Dennison, P.
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Djukanovic, R.
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Grainge, C.
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Hewitt, L.
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Jayasekera, N.
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Kurukulaaratchy, R.
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Kerley, S.
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Lau, L.
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Laws, D.
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Owen, J.
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Ray, E.
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Reynish, D.
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Rupani, H.
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Scullion-Win, O.
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Wessex Severe Asthma Cohort (WSAC)
Brown, Thomas
ee38a284-8d96-40c9-8a4b-8f79e8e97d06
Jones, Thomas
2ed43a38-d65d-4786-9208-a1e1298ce413
Gove, Kerry
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Barber, Clair
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Elliott, Scott
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Chauhan, Anoop
1b479cfe-69ee-4a0e-95d1-b05060d39374
Howarth, Peter
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Aitkin, L.
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Babu, S.
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Dennison, P.
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Djukanovic, R.
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Grainge, C.
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Hewitt, L.
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Jayasekera, N.
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Kurukulaaratchy, R.
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Kerley, S.
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Lau, L.
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Laws, D.
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Owen, J.
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Ray, E.
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Reynish, D.
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Rupani, H.
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Scullion-Win, O.
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Brown, Thomas, Jones, Thomas, Gove, Kerry, Barber, Clair, Elliott, Scott, Chauhan, Anoop, Howarth, Peter, Aitkin, L., Babu, S., Dennison, P., Djukanovic, R., Grainge, C., Hewitt, L., Jayasekera, N., Kurukulaaratchy, R., Kerley, S., Lau, L., Laws, D., Owen, J., Ray, E., Reynish, D., Rupani, H. and Scullion-Win, O. , Wessex Severe Asthma Cohort (WSAC) (2018) Randomised controlled trials in severe asthma: Selection by phenotype or stereotype. European Respiratory Journal, 52 (6), [1801444]. (doi:10.1183/13993003.01444-2018).

Record type: Article

Abstract

Previous publications have highlighted the disparity between research trial populations and those in clinical practice, but it has not been established how this relates to randomised controlled trials (RCTs) of phenotype-targeted biological therapies in severe asthma. Detailed characterisation data for 342 severe asthma patients within the Wessex Severe Asthma Cohort (WSAC) was compared against comprehensive trial eligibility criteria for published phase IIB and phase III RCTs evaluating biological therapies in severe asthma since 2000. 37 RCTs evaluating 20 biological therapies were identified. Only a median of 9.8% (range 3.5-17.5%) of severe asthma patients were found to be eligible for enrolment in the phase III trials. Stipulations for airflow obstruction, bronchodilator reversibility and smoking history excluded significant numbers of patients. A median of 78.9% (range 73.2-86.6%) of patients with severe eosinophilic asthma would have been excluded from participation in the phase III licensing trials of interleukin (IL)-5/IL-5R targeted therapies. Despite including only well characterised and optimally treated severe asthmatics under specialist care within the WSAC study, the vast majority were excluded from trial participation by criteria designed to re-confirm diagnostic labels rather than by biomarker criteria that predict the characteristic addressed by the treatment.

Full text not available from this repository.

More information

Accepted/In Press date: 5 October 2018
e-pub ahead of print date: 13 December 2018
Published date: December 2018

Identifiers

Local EPrints ID: 429235
URI: http://eprints.soton.ac.uk/id/eprint/429235
ISSN: 0903-1936
PURE UUID: 453147df-7243-49e3-9d6b-b004045f6af9
ORCID for Clair Barber: ORCID iD orcid.org/0000-0001-5335-5129
ORCID for R. Djukanovic: ORCID iD orcid.org/0000-0001-6039-5612

Catalogue record

Date deposited: 22 Mar 2019 17:30
Last modified: 17 Dec 2019 02:03

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Contributors

Author: Thomas Brown
Author: Thomas Jones
Author: Kerry Gove
Author: Clair Barber ORCID iD
Author: Scott Elliott
Author: Anoop Chauhan
Author: Peter Howarth
Author: L. Aitkin
Author: S. Babu
Author: P. Dennison
Author: R. Djukanovic ORCID iD
Author: C. Grainge
Author: L. Hewitt
Author: N. Jayasekera
Author: R. Kurukulaaratchy
Author: S. Kerley
Author: L. Lau
Author: D. Laws
Author: J. Owen
Author: E. Ray
Author: D. Reynish
Author: H. Rupani
Author: O. Scullion-Win

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