Evidence-Based Inhaler Therapy for COPD in 2018

See the winner of the 2018 Best of ATS Video Lecture Series: Penn PET Project: Evidence-Based Inhaler Therapy for #COPD

Triple versus Dual Inhaler Therapy in Patients with COPD - IMPACT Trial can change COPD Guidelines in 2019

The Informing the Pathway of COPD Treatment (IMPACT) trial, now reported in the The New England Journal of Medicine, aims to fill this gap with a report on the effectiveness of LAMA–LABA–inhaled glucocorticoid treatment, contained in a single inhaler, in COPD.

Background

The benefits of triple therapy for chronic obstructive pulmonary disease (COPD) with an inhaled glucocorticoid, a long-acting muscarinic antagonist (LAMA), and a long-acting β₂-agonist (LABA), as compared with dual therapy (either inhaled glucocorticoid–LABA or LAMA–LABA), are uncertain.

Methods

In this randomized trial involving 10,355 patients with COPD, we compared 52 weeks of a once-daily combination of fluticasone furoate (an inhaled glucocorticoid) at a dose of 100 μg, umeclidinium (a LAMA) at a dose of 62.5 μg, and vilanterol (a LABA) at a dose of 25 μg (triple therapy) with fluticasone furoate–vilanterol (at doses of 100 μg and 25 μg, respectively) and umeclidinium–vilanterol (at doses of 62.5 μg and 25 μg, respectively). Each regimen was administered in a single Ellipta inhaler. The primary outcome was the annual rate of moderate or severe COPD exacerbations during treatment.

Results

The rate of moderate or severe exacerbations in the triple-therapy group was 0.91 per year, as compared with 1.07 per year in the fluticasone furoate–vilanterol group (rate ratio with triple therapy, 0.85; 95% confidence interval [CI], 0.80 to 0.90; 15% difference; P<0.001) and 1.21 per year in the umeclidinium–vilanterol group (rate ratio with triple therapy, 0.75; 95% CI, 0.70 to 0.81; 25% difference; P<0.001). The annual rate of severe exacerbations resulting in hospitalization in the triple-therapy group was 0.13, as compared with 0.19 in the umeclidinium–vilanterol group (rate ratio, 0.66; 95% CI, 0.56 to 0.78; 34% difference; P<0.001). There was a higher incidence of pneumonia in the inhaled-glucocorticoid groups than in the umeclidinium–vilanterol group, and the risk of clinician-diagnosed pneumonia was significantly higher with triple therapy than with umeclidinium–vilanterol, as assessed in a time-to-first-event analysis (hazard ratio, 1.53; 95% CI, 1.22 to 1.92; P<0.001).

Conclusions

Triple therapy with fluticasone furoate, umeclidinium, and vilanterol resulted in a lower rate of moderate or severe COPD exacerbations than fluticasone furoate–vilanterol or umeclidinium–vilanterol in this population. Triple therapy also resulted in a lower rate of hospitalization due to COPD than umeclidinium–vilanterol.

full text:

http://www.nejm.org/doi/full/10.1056/NEJMoa1713901

Higher cigarette prices would help millions avoid poor health and extreme poverty

According to a study published in the these days in BMJ, a significant increase in prices of cigarette would aid millions of people at the global level to avoid poor health and extreme poverty.
Objective To examine the impact of a 50% increase in market prices of cigarettes on health, poverty, and financial protection.

Design Compartmental model study.

Setting 13 middle income countries, totalling two billion men.

Participants 500 million male smokers.

Main outcome measures Life years gained, averted treatment costs, number of men avoiding catastrophic healthcare expenditures and poverty, and additional tax revenue by income group.

Results A 50% increase in cigarette prices would lead to about 450 million years of life gained across the 13 countries from smoking cessation, with half of these in China. Across all countries, men in the bottom income group (poorest 20% of the population) would gain 6.7 times more life years than men in the top income group (richest 20% of the population; 155 v 23 million). The average life years gained from cessation for each smoker in the bottom income group was 5.1 times that of the top group (1.46 v 0.23 years). Of the $157bn (£113bn; €127bn) in averted treatment costs, the bottom income group would avert 4.6 times more costs than the top income group ($46bn v $10bn). About 15.5 million men would avoid catastrophic health expenditures in a subset of seven countries without universal health coverage. As result, 8.8 million men, half of them in the bottom income group, would avoid falling below the World Bank definition of extreme poverty. These 8.8 million men constitute 2.4% of people living in extreme poverty in these countries. In contrast, the top income group would pay twice as much as the bottom income group of the $122bn additional tax collected. Overall, the bottom income group would get 31% of the life years saved and 29% each of the averted disease costs and averted catastrophic health expenditures, while paying only 10% of the additional taxes.

Conclusions Higher prices of cigarettes provide more health and financial gains to the poorest 20% than to the richest 20% of the population. Higher excise taxes support the targets of the sustainable development goals on non-communicable diseases and poverty, and provides financial protection against illness.

What is already known on this topic

• Higher excise taxes on tobacco are essential to reach the sustainable development goals to reduce mortality from non-communicable diseases by one third by 2030
• Low income groups are more responsive to price increases than high income groups
• There are few published studies of the distributional impact of higher tobacco taxes on health and financial outcomes

What this study adds

• Despite differences in socioeconomic class and health finance arrangements a 50% increase in tobacco prices strongly favours those in the bottom income group for life years saved, out-of-pocket expenses from tobacco attributable treatment costs averted, and avoidance of catastrophic health expenditures or poverty
• Higher tobacco excise taxes are a powerful but generally underused tool by most governments to reduce expenditures on treatment of diseases that are a major cause of income poverty
• In 13 middle income countries studied, around 450 million life years would be saved from higher excise taxes, contributing substantially to the target of the sustainable development goals of a one third reduction in mortality from non-communicable diseases at ages 30-69 by 2030

Full text

Emerging biological therapies for treating eosinophilic COPD

In Pulmonary Pharmacology & Therapeutics was published meta-analysis by great Italian team on hot topic Emerging biological therapies for treating chronic obstructive pulmonary disease: A pairwise and network meta-analysis.

Inflammation in COPD is often corticosteroid resistant and, thus, alternative anti-inflammatory approaches are needed. Since it is still not clear whether blocking specific pro-inflammatory factors may provide clinical benefit in COPD, we have performed a meta-analysis to quantify the impact of monoclonal antibodies (mABs) targeting the cytokine/chemokine-mediated inflammation in COPD.

A pairwise and network meta-analyses were performed by extracting data from randomized clinical trials on COPD concerning the impact of mABs vs. placebo on the risk of exacerbation, forced expiratory volume in 1 s (FEV₁), and St. George's Respiratory Questionnaire (SGRQ).

Data on the interleukin (IL)-1β antagonist canakinumab, IL-1R1 antagonist MEDI8986, IL-5 antagonist mepolizumab, IL-5R antagonist benralizumab, IL-8 antagonist ABX-IL8, and TNF-α antagonist infliximab were found. Overall, mAB therapy had a moderate impact on the risk exacerbation, but not on FEV₁ and SGRQ. The pairwise meta-analysis performed in eosinophilic patients, and the network approach, indicated that mepolizumab elicited a beneficial effect against the risk of exacerbation, whereas benralizumab was more effective in improving both FEV₁ and SGRQ.

This study demonstrates that targeting the pathway activated by IL-5 may have a beneficial impact in eosinophilic COPD patients.

Full text:

https://www.sciencedirect.com/science/article/pii/S1094553918300579