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.
Abstract
RCTs of biological therapies in severe asthma are poorly generalisable with most patients excluded by outmoded disease concepts despite possessing the targetable trait addressed by the treatment http://ow.ly/iog930md0J3
Footnotes
Author contributions: T. Brown, T. Jones, A. Chauhan and P. Howarth contributed to the literatures search, study design, data collection, data analysis, data interpretation and writing of this manuscript. K. Gove, C. Barbar and S. Elliott contributed to the data collection, data analysis and the writing of this manuscript. All other members of the Wessex Severe Asthma Cohort (WSAC) team contributed to the data collection.
Members of the Wessex Severe Asthma Cohort (WSAC) team: L. Aitkin, S. Babu, P. Dennison, R. Djukanovic, C. Grainge, L. Hewitt, N. Jayasekera, R. Kurukulaaratchy, S. Kerley, L. Lau, D. Laws, J. Owen, E. Ray, D. Reynish, H. Rupani and O. Scullion-Win.
Conflict of interest: T. Brown reports personal fees from Teva, Chiesi Farmaceutici, Novartis and Napp, and non-financial support from AstraZeneca, outside the submitted work. T. Jones reports non-financial support from Teva, personal fees and non-financial support from Chiesi Farmaceutici, outside the submitted work. K. Gove has nothing to disclose. C. Barber has nothing to disclose. S. Elliott has nothing to disclose.
Conflict of interest: A. Chauhan reports personal fees and non-financial support from Teva, non-financial support from Boehringer Ingelheim, and personal fees from AstraZeneca, outside the submitted work.
Conflict of interest: P. Howarth reports grants from the Medical Research Council, during the conduct of the study; and is a part-time employee of GlaxoSmithKline.
This article has supplementary material available from erj.ersjournals.com
Support statement: This work was funded by Research Councils UK: Medical Research Council (MRC; G0800649). Funding information for this article has been deposited with the Crossref Funder Registry.
- Received July 30, 2018.
- Accepted October 5, 2018.
- Copyright ©ERS 2018
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