Dissociation between clinical trial inclusion and exclusion criteria for trials in severe asthma and the reality of the patient population

Brown, Tom, Rupani, Hitasha, Barber, Clair, Elliott, Scott P, Gove, Kerry, Lau, Laurie, Hewitt, Lorraine, Ray, Emma, Marouzet, Lisa, Kerley, Sumita, Kurukulaaratchy, Ramesh, Grainge, Christopher, Djukanovic, Ratko, Chauhan, Anoop and Howarth, Peter (2014) Dissociation between clinical trial inclusion and exclusion criteria for trials in severe asthma and the reality of the patient population. European Respiratory Journal, 44 (Suppl 58), [P3326].

Abstract

Rationale: Clinical trials of new biologics in adults with severe asthma require standardised entry criteria. These commonly include a history of disease exacerbation, current poor control, impaired lung function and evidence of bronchodilator reversibility. Cigarette smoking history and oral steroid therapy are often exclusion criteria. With therapies targeting Th2 inflammation there are also requirements for evidence of eosinophilic disease. To determine the proportion of patients eligible for such studies these criteria were evaluated in the Wessex Severe Asthma cohort (WSAC).

Methods: Four hundred and thirty four patients with asthma managed at steps 4 (65.9%) and 5 (34.1%) of the guidelines with a history of at least one severe exacerbation in the last year underwent detailed characterization.

Results: At this time point 87.8% had an asthma control questionnaire (ACQ)6 of ≥1.5, 55.1% had a pre-bronchodilator FEV1 between 40-80% predicted, 40.8% had ≥12% reversibility with nebulized salbutamol (2.5mg) and 24.2% were either ex-smokers with ≥10 pack year history (18.4%) or current smokers (5.8%). Only 10.6% fulfilled all these inclusion and exclusion criteria and the addition of a further eosinophilic filter (peripheral blood eosinophils ≥0.3 x 109/L or FeNO ≥ 50ppb or sputum eosinophils ≥2%) reduced this figure to 6.5% of the starting population.

Conclusion: Standard asthma inclusion and exclusion criteria used in trials of new therapies in severe asthma exclude the vast majority of patients with this spectrum of disease and do not address the unmet need.

Funding: WSAC was funded by the Medical Research Council UK.

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Contributors

Author: Clair Barber

Author: Ramesh Kurukulaaratchy

Author: Ratko Djukanovic

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