Designing Clinical Trials for Anti-Inflammatory Therapies in Cystic Fibrosis
The inflammatory response in the CF airway begins early in the disease process and becomes persistent through life in most patients. Inflammation, which is predominantly neutrophilic, worsens airway obstruction and plays a critical role in the development of structural lung damage. While cystic fibr...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-09-01
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| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2020.576293/full |
| _version_ | 1831717150693261312 |
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| author | Lucy Perrem Lucy Perrem Lucy Perrem Felix Ratjen Felix Ratjen Felix Ratjen |
| author_facet | Lucy Perrem Lucy Perrem Lucy Perrem Felix Ratjen Felix Ratjen Felix Ratjen |
| author_sort | Lucy Perrem |
| collection | DOAJ |
| description | The inflammatory response in the CF airway begins early in the disease process and becomes persistent through life in most patients. Inflammation, which is predominantly neutrophilic, worsens airway obstruction and plays a critical role in the development of structural lung damage. While cystic fibrosis transmembrane regulator modulators will likely have a dramatic impact on the trajectory of CF lung disease over the coming years, addressing other important aspects of lung disease such as inflammation will nevertheless remain a priority. Considering the central role of neutrophils and their products in the inflammatory response, potential therapies should ultimately affect neutrophils and their products. The ideal anti-inflammatory therapy would exert a dual effect on the pro-inflammatory and pro-resolution arms of the inflammatory cascade, both of which contribute to dysregulated inflammation in CF. This review outlines the key factors to be considered in the design of clinical trials evaluating anti-inflammatory therapies in CF. Important lessons have been learned from previous clinical trials in this area and choosing the right efficacy endpoints is key to the success of any anti-inflammatory drug development program. Identifying and validating non-invasive biomarkers, novel imaging techniques and sensitive lung function tests capable of monitoring disease activity and therapeutic response are important areas of research and will be useful for the design of future anti-inflammatory drug trials. |
| first_indexed | 2024-12-21T00:53:06Z |
| format | Article |
| id | doaj.art-00d7c607950f4e1d9bc30e1e433e83e5 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-21T00:53:06Z |
| publishDate | 2020-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-00d7c607950f4e1d9bc30e1e433e83e52022-12-21T19:21:22ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-09-011110.3389/fphar.2020.576293576293Designing Clinical Trials for Anti-Inflammatory Therapies in Cystic FibrosisLucy Perrem0Lucy Perrem1Lucy Perrem2Felix Ratjen3Felix Ratjen4Felix Ratjen5Division of Respiratory Medicine, The Hospital for Sick Children, Toronto, ON, CanadaDepartment of Paediatrics, University of Toronto, Toronto, ON, CanadaTranslational Medicine Program, SickKids Research Institute, Toronto, ON, CanadaDivision of Respiratory Medicine, The Hospital for Sick Children, Toronto, ON, CanadaDepartment of Paediatrics, University of Toronto, Toronto, ON, CanadaTranslational Medicine Program, SickKids Research Institute, Toronto, ON, CanadaThe inflammatory response in the CF airway begins early in the disease process and becomes persistent through life in most patients. Inflammation, which is predominantly neutrophilic, worsens airway obstruction and plays a critical role in the development of structural lung damage. While cystic fibrosis transmembrane regulator modulators will likely have a dramatic impact on the trajectory of CF lung disease over the coming years, addressing other important aspects of lung disease such as inflammation will nevertheless remain a priority. Considering the central role of neutrophils and their products in the inflammatory response, potential therapies should ultimately affect neutrophils and their products. The ideal anti-inflammatory therapy would exert a dual effect on the pro-inflammatory and pro-resolution arms of the inflammatory cascade, both of which contribute to dysregulated inflammation in CF. This review outlines the key factors to be considered in the design of clinical trials evaluating anti-inflammatory therapies in CF. Important lessons have been learned from previous clinical trials in this area and choosing the right efficacy endpoints is key to the success of any anti-inflammatory drug development program. Identifying and validating non-invasive biomarkers, novel imaging techniques and sensitive lung function tests capable of monitoring disease activity and therapeutic response are important areas of research and will be useful for the design of future anti-inflammatory drug trials.https://www.frontiersin.org/article/10.3389/fphar.2020.576293/fullanti-inflammatoriescystic fibrosisclinical trialslungairway inflammation |
| spellingShingle | Lucy Perrem Lucy Perrem Lucy Perrem Felix Ratjen Felix Ratjen Felix Ratjen Designing Clinical Trials for Anti-Inflammatory Therapies in Cystic Fibrosis Frontiers in Pharmacology anti-inflammatories cystic fibrosis clinical trials lung airway inflammation |
| title | Designing Clinical Trials for Anti-Inflammatory Therapies in Cystic Fibrosis |
| title_full | Designing Clinical Trials for Anti-Inflammatory Therapies in Cystic Fibrosis |
| title_fullStr | Designing Clinical Trials for Anti-Inflammatory Therapies in Cystic Fibrosis |
| title_full_unstemmed | Designing Clinical Trials for Anti-Inflammatory Therapies in Cystic Fibrosis |
| title_short | Designing Clinical Trials for Anti-Inflammatory Therapies in Cystic Fibrosis |
| title_sort | designing clinical trials for anti inflammatory therapies in cystic fibrosis |
| topic | anti-inflammatories cystic fibrosis clinical trials lung airway inflammation |
| url | https://www.frontiersin.org/article/10.3389/fphar.2020.576293/full |
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