Outcome measures and predictors of response to biological treatments for severe asthma

Abstract

Severe asthma affects 5-10% of the total asthma population but imposes a disproportionate burden on both healthcare systems and individual patients. The emergence of novel therapies, particularly biologics, promises an era of personalised medicine for improved management of severe asthma. However, achieving this requires optimal outcome measures and predictors of treatment response. Therefore, this thesis aimed to: i) identify ‘priority’ outcome measures, ii) develop a paediatric quality of life (QoL) measure, and iii) identify predictors of biologic response, for use in severe asthma research and practice. Chapter 2 reports a systematic review of outcome measures considered to be a ‘priority’ for severe asthma. Following a multi-step process, 24 ‘priority’ measures were selected by key stakeholders, including patients. An assessment of the methodological quality of studies reporting on these measures revealed that existing paediatric QoL tools were not developed with input from Children and Young People (CYP) with severe asthma, and thus fail to capture the deficits experienced by this group. Chapter 3 reports the development of a QoL tool for paediatric severe asthma. Qualitative interviews with CYP with severe asthma, parents, and healthcare professionals (n=46) revealed that the adult Severe Asthma Questionnaire (SAQ) is mostly relevant for the paediatric population subject to removal of adult-related examples and rewording to enhance comprehensibility. The findings informed the development of the prototype PSAQ. Preliminary field testing of the PSAQ amongst CYP and parents (n=40) found that 9 of 15 items were deemed as most important for inclusion in the questionnaire. The survey is ongoing, following which the prototype PSAQ will be finalised. Chapter 4 reports a systematic review and meta-analysis of response predictors for anti-IL-5, anti-IL-4Ra, and anti-IL-13 therapies. From a total of 4704 records, 29 studies were included in the analysis. There was consistent evidence for the ability of high blood eosinophil counts and FeNO levels to predict response to anti-IL-4Ra therapy, but inconclusive evidence for other variables investigated such as lung function parameters, clinical and sociodemographic characteristics. This thesis makes several contributions to the field of severe asthma. The systematic review of ‘priority’ outcome measures informed the development of a core outcome measurement set for severe asthma. The PSAQ, once validated, will be an invaluable tool for assessing treatment response in clinical trials and practice. Lastly, the systematic review of biologic response predictors provides evidence to inform clinical decision making about optimal biologic selection. Taken together, this work is a step towards achieving personalised medicine for severe asthma.

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Identifiers

ORCID for Anna Rattu: orcid.org/0000-0002-7497-9552

ORCID for Graham Roberts: orcid.org/0000-0003-2252-1248

ORCID for Ratko Djukanovic: orcid.org/0000-0001-6039-5612

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