Abstract
Severe obstructive lung disease, which encompasses patients with asthma, chronic obstructive pulmonary disease (COPD) or features of both, remains a considerable global health problem and burden on healthcare resources. However, the clinical definitions of severe asthma and COPD do not reflect the heterogeneity within these diagnoses or the potential for overlap between them, which may lead to inappropriate treatment decisions. Furthermore, most studies exclude patients with diagnoses of both asthma and COPD. Clinical definitions can influence clinical trial design and are both influenced by, and influence, regulatory indications and treatment recommendations. Therefore, to ensure its relevance in the era of targeted biologic therapies, the definition of severe obstructive lung disease must be updated so that it includes all patients who could benefit from novel treatments and for whom associated costs are justified. Here, we review evolving clinical definitions of severe obstructive lung disease and evaluate how these have influenced trial design by summarising eligibility criteria and primary outcomes of phase III randomised controlled trials of biologic therapies. Based on our findings, we discuss the advantages of a phenotype- and endotype-based approach to select appropriate populations for future trials that may influence regulatory approvals and clinical practice, allowing targeted biologic therapies to benefit a greater proportion and range of patients. This calls for co-ordinated efforts between investigators, pharmaceutical developers and regulators to ensure biologic therapies reach their full potential in the management of severe obstructive lung disease.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Dr. Martin reports grants from NHLBI, grants from MedImmune, grants from Chiesi Farmaceutici SpA, personal fees from AstraZeneca, personal fees from PMD Healthcare, personal fees from Regeneron, personal fees from Boehringer Ingelheim, outside the submitted work.
Conflict of interest: Dr. Bel reports non-financial support from AstraZeneca during the conduct of the study; grants and personal fees from AstraZeneca, GSK, Novartis, and Teva , and personal fees from Boehringer Ingelheim, Sanofi/Regeneron, and Vectura, outside the submitted work.
Conflict of interest: Dr. Pavord reports personal fees from AstraZeneca, personal fees from GSK, personal fees from Boehringer Ingelheim, grants and personal fees from Chiesi, personal fees from Sanofi/Regeneron, personal fees from Circassia, personal fees from Merck, personal fees from Novartis, personal fees from Mundipharma, personal fees from Teva, personal fees from Knopp, grants and personal fees from Afferent, personal fees from Roche/Genentech, outside the submitted work.
Conflict of interest: Dr. Price reports grants and personal fees from Aerocrine, grants from AKL Research and Development Ltd, personal fees from Almirall, personal fees from Amgen, grants and personal fees from AstraZeneca, grants and personal fees from Boehringer Ingelheim, grants from British Lung Foundation, grants and personal fees from Chiesi, personal fees from Cipla, personal fees from GlaxoSmithKline, personal fees from Kyorin, personal fees from Merck, grants and personal fees from Mylan, grants and personal fees from Mundipharma, grants and personal fees from Napp, grants and personal fees from Novartis, grants and personal fees from Pfizer, grants and personal fees from Regeneron Pharmaceuticals, grants from Respiratory Effectiveness Group, grants and personal fees from Sanofi Genzyme, personal fees from Skyepharma, grants and personal fees from Teva, grants and personal fees from Theravance, grants from UK National Health Service, grants and personal fees from Zentiva (Sanofi Generics), non-financial support from Efficacy and Mechanism Evaluation programme, non-financial support from Health Technology Assessment, outside the submitted work; and stock/stock options from AKL Research and Development Ltd which produces phytopharmaceuticals; and owns 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 74% of Observational and Pragmatic Research Institute Pte Ltd (Singapore).
Conflict of interest: Dr. Reddel reports grants, personal fees and non-financial support from AstraZeneca, grants, personal fees and non-financial support from GlaxoSmithKline, personal fees from Boehringer Ingelheim, personal fees from Merck, personal fees from Novartis, personal fees from Teva, from Mundipharma, outside the submitted work.
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