Nintedanib (OFEV®) May Offer Survival Advantage for IPF Patients

MedicalResearch.com Interview with:

Christopher J. Ryerson, M.D. Assistant Professor Centre for Heart Lung Innovation University of British Columbia Vancouver, Canada

Dr. Ryerson

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.  Continue reading

Antifibrotic Drug Stabilized Lung Function For Patients with Idiopathic Pulmonary Fibrosis

MedicalResearch.com Interview with:

Pierre Laurin, CEO Prometic

Pierre Laurin

Pierre Laurin, CEO
Prometic Life Sciences

MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by idiopathic pulmonary fibrosis?

Response: Idiopathic pulmonary fibrosis (IPF) is a chronic, devastating, and ultimately fatal disease characterized by a progressive decline in lung function. It is a specific type of interstitial lung disease in which the small air sacs of the lung, the “alveoli,” gradually become replaced by fibrotic (scar) tissue and is the cause of worsening dyspnea (shortness of breath). The 5-year mortality rate for patients with IPF is estimated to range from 50% to 70%.

Small molecule candidate PBI-4050’s anti-fibrotic activity has been observed in various fibrosis models in different organs: lung, kidney, heart, liver, and pancreas. PBI-4050 has been shown to improve forced vital capacity (FVC) in an open-label Phase 2 study in IPF.

The main objective of this exploratory study was to determine whether treatment with PBI-4050 alters the level of key biomarkers in patients with IPF. Subjects with a confirmed diagnosis of IPF received daily oral doses of 800 mg PBI-4050 with or without nintedanib or pirfenidone for 12 weeks. The biomarkers chosen for measurement can be divided into two main groups: cytokines and matrix metalloproteinases associated with fibrosis and inflammation.

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SUNSET Trial Supports Bronchodilators as Foundation of COPD Therapy

MedicalResearch.com Interview with:

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

Dr. Chapman

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.  Continue reading

Reducing Opioids Near End of Hospital Stay May Limit Outpatient Use

MedicalResearch.com Interview with:

Jason Kennedy, MS Research project manager Department of Critical Care Medicine University of Pittsburgh

Jason Kennedy

Jason Kennedy, MS
Research project manager
Department of Critical Care Medicine
University of Pittsburgh

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: Most previous studies of opioid use in health care have focused on the outpatient setting. But opioids are often introduced during hospitalization. That’s something clinicians can control, so we looked at inpatient prescription of these drugs to identify targets that may reduce opioid use once patients are out of the hospital.

We analyzed the medical records of 357,413 non-obstetrical adults hospitalized between 2010 and 2014 at 12 University of Pittsburgh Medical Center (UPMC) hospitals in southwestern Pennsylvania. The region is one of the areas of the country where opioid addiction is a major public health problem. We focused on the 192,240 patients who had not received an opioid in the year prior to their hospitalization – otherwise known as “opioid naïve” patients.

Nearly half (48 percent) of these patients received an opioid while hospitalized.  After discharge, those patients receiving hospital opioids were more than twice as likely to report outpatient opioid use within 90-days (8.4 percent vs. 4.1 percent). Patients who receive an opioid for most of their hospital stay and patients who are still taking an opioid within 12 hours of being discharged from the hospital appear more likely to fill a prescription for opioids within 90 days of leaving the hospital.  Continue reading