Phase 2 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis

Chalmers, James D.; Haworth, Charles; Metersky, Mark L.; Loebinger, Michael R.; Blasi, Francesco; Sibila, Oriol; O’Donnell, Anne E.; Sullivan, Eugene J.; Mange, Kevin C.; Fernández, Carlos; Zou, Jun; Daley, Charles L.; Investigators, Willow

doi:10.1056/nejmoa2021713

Cited by 210 publications

(199 citation statements)

References 21 publications

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“…Professor Chalmers concluded his talk by briefly mentioning the promising data from the Willow study, which demonstrated that reduction of neutrophil serine protease activity with brensocatib in patients with bronchiectasis is associated with reduction in exacerbation risk and prolonged time to first exacerbation [45]. Thus, the future of bronchiectasis management may not be antibiotics.…”

Section: The Future Of Bronchiectasis Managementmentioning

confidence: 99%

ERS International Congress 2020: highlights from the Respiratory Infections assembly

et al. 2021

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In the COVID-19 pandemic year 2020, the 30th edition of the ERS Congress took place for the first time in a fully virtual format. Despite the challenging nature of the task to create and deliver an online event of this size and scope, the ERS Congress 2020 turned to be a great success, welcoming over 33 000 delegates to the specially designed online platform and offering more than 450 scientific and educational sessions. Somewhat predictable, this year's Congress dedicated a full day on COVID-19 topic, highlighting that infection with SARS-CoV-2 is a respiratory disease. In this article the Early Career Members of the Assembly 10 (Respiratory Infections and Tuberculosis) review some of the most interesting sessions including presentations and posters on respiratory infections and tuberculosis that were deemed as important.

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Section: The Future Of Bronchiectasis Managementmentioning

confidence: 99%

ERS International Congress 2020: highlights from the Respiratory Infections assembly

et al. 2021

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“…Also neutrophil serine proteases, which are elevated in asthma [152] could be a promising target, based on a recent trial in patients with bronchiectasis [153]. Indeed, bronchiectasis patientswith abnormally dilated airwayshave high levels of neutrophil serine proteases and frequent exacerbations that are thought to be related with neutrophilic inflammation.…”

Section: Other Potential Approaches Impacting On Neutrophilic Inflammation or Function And Future Perspectivesmentioning

confidence: 99%

“…Treatment of bronchiectasis patients with brensocatiban oral inhibitor of dipeptidyl peptidase 1 (DDP-1) that is responsible for neutrophil serine protease activationwas associated with improvements in clinical outcomes in a 24-week trial (prolonged time to first exacerbation, lower frequency of exacerbations). No safety issues related to the treatment were described [153]. Metalloproteinase-9 (MMP-9) has been implicated in airway remodeling in severe asthma patients [154,155].…”

Section: Other Potential Approaches Impacting On Neutrophilic Inflammation or Function And Future Perspectivesmentioning

confidence: 99%

Targeting neutrophils in asthma: A therapeutic opportunity?

Volder

Vereecke

Joos

et al. 2020

Biochemical Pharmacology

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“…There are no licensed medications available and current management guidelines have emphasised the importance of randomised controlled trials to direct care [1,2]. Evidence from recent clinical trials supports the use of some medications including macrolides, inhaled antibiotics and novel anti-inflammatory therapies [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Psychometrics of health-related quality of life questionnaires in bronchiectasis: a systematic review and meta-analysis

et al. 2021

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IntroductionUnderstanding the psychometric properties of health related quality of life (HRQoL) questionnaires can help inform selection in clinical trials.ObjectiveTo assess the psychometric properties of HRQoL questionnaires in bronchiectasis.MethodsA literature search was conducted. HRQoL questionnaires were assessed for psychometric properties (reliability, validity, minimal clinically important difference (MCID), floor/ceiling effects). Meta-analyses assessed the associations of HRQoL with clinical measures and responsiveness of HRQoL in clinical trials.Results166 studies and 12 HRQoL questionnaires were included. The BHQ, LCQ, CAT and SF-36 had good internal consistency in all domains reported (Cronbach's α≥0.7) across all studies and the QoL-B, SGRQ, CRDQ and SOLQ had good internal consistency in all domains in the majority of (but not all) studies. The BHQ, SGRQ, LCQ and CAT had good test-retest reliability in all domains reported ((intraclass correlation coefficient) ICC ≥0.7) across all studies and the QoL-B, CRDQ and SOLQ had good test-retest reliability in all domains in the majority of (but not all) studies. HRQoL questionnaires were able to discriminate between demographics, important markers of clinical status, disease severity, exacerbations and bacteriology. For HRQoL responsiveness, there was a difference between the treatment and placebo effect.ConclusionSGRQ was the most widely used HRQoL questionnaire in bronchiectasis studies and it had good psychometric properties, however good psychometric data are growing on bronchiectasis specific HRQoL questionnaires, QoL-B and BHQ. Future studies should focus on the medium-long term test-retest reliability, responsiveness and MCID in these HRQoL questionnaires which show potential in bronchiectasis.

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Phase 2 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis

Cited by 210 publications

References 21 publications

ERS International Congress 2020: highlights from the Respiratory Infections assembly

ERS International Congress 2020: highlights from the Respiratory Infections assembly

Targeting neutrophils in asthma: A therapeutic opportunity?

Psychometrics of health-related quality of life questionnaires in bronchiectasis: a systematic review and meta-analysis

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