MedicalResearch.com Interview with:
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Dr. Chapman[/caption]
Kenneth R. Chapman, MD MSc FRCPC FACP
FCCP, FERS
Director, Asthma & Airway Centre, University Health Network,
Professor of Medicine, University of Toronto,
GSK-CIHR Research Chair in Respiratory Health Care Delivery,
Toronto, Ontario
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Guidelines regard inhaled bronchodilators as foundational pharmacotherapy in COPD while inhaled corticosteroids are to be used sparingly. Inhaled corticosteroids are used to reduce exacerbation tendency but come with the added risk of pneumonia, osteoporosis and other corticosteroid related adverse effects. Although only a minority of COPD patients are exacerbation prone, many patients with COPD are treated unnecessarily with inhaled corticosteroids alongside long-acting anticholinergic and beta2 agonist bronchodilators - so-called "triple therapy". In patients who have minimal exacerbation histories, inhaled corticosteroid withdrawal is suggested to reduce side-effects.
Although studies have suggested this is a reasonable strategy, study limitations have been noted. The best known inhaled corticosteroid withdrawal study, the WISDOM trial, recruited only 39% of patients using triple therapy regularly before inhaled corticosteroid withdrawal; the remainder were placed on triple therapy solely for the purposes of the withdrawal study.
In the SUNSET trial, long term triple therapy patients with no more than one exacerbation in the preceding year were randomized to continue triple therapy or to de-escalate to a second generation dual bronchodilator therapy - indacaterol/glycopyrronium 110/50 once daily. This one step de-escalation better mirrored clinical practice than the gradual tapering approach of the WISDOM trial. There was no increase in exacerbations after de-escalation and although average FEV1 decreased by 26 ml in the group that de-escalated, the decrease is so small as to be immeasureable in individuals. In a post-hoc analysis, a subset of patients with persistently elevated blood eosinophil counts (greater than 300 cells per uL) were the ones most likely to have exacerbations in follow-up or to have changes in FEV1.
Dr. Ryerson[/caption]
Christopher J. Ryerson, M.D.
Assistant Professor
Centre for Heart Lung Innovation
University of British Columbia
Vancouver, Canada
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: A new Idiopathic pulmonary fibrosis (IPF) mortality analysis presented at the American Thoracic Society’s 2018 annual conference suggests that treatment with nintedanib may be associated with reduced risk of death in patients with the rare lung disease idiopathic pulmonary fibrosis (IPF).
Pooled data from the two Phase II INPULSIS trials and the Phase II TOMORROW study compared the number of deaths observed versus the number predicted based on GAP stage over one year. GAP stage is used to predict IPF prognosis and is based on gender, age and lung function (as measured by forced vital capacity [FVC] decline predicted and DLco % predicted). Higher stages of GAP are associated with an increased risk of death.
Across the population in the analysis (n=1,228), there were fewer deaths observed in each treatment group than predicted based on GAP stage at baseline (nintedanib: 42 vs. 89.9; placebo: 41 vs. 64.2). In the treated group, the number of observed deaths was 46.7% of the number predicted based on GAP stage, while in the placebo group the number of observed deaths was 63.9% of the number predicted. Based on these observations, the analysis suggests that nintedanib may be associated with a 26.8% relative reduction in the risk of death compared with placebo over one year.
