From the Journals

Triple-therapy cuts COPD exacerbations

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More data on COPD triple therapy but questions remain

The data from the IMPACT study fills a gap in the evidence supporting a step-up from dual to triple inhaled therapy for COPD, which so far has been recommended only for patients with severe loss of lung function and those with frequent exacerbations despite maximum bronchodilator treatment. The study has the strengths of comparing the step-up to triple therapy with the GOLD guideline–recommended dual therapies and using the same dosages in the triple therapy as in the dual therapy

However, it is important to note that nearly 40% of patients enrolled in the trial were already being treated with triple therapy, 70% were receiving a glucocorticoid, and patients with a history of asthma were not excluded. This means patients assigned to the dual therapy without glucocorticoids would have had an abrupt cessation of their glucocorticoid therapy, which may explain a rapid surge in exacerbations in the first month and the lower rate of exacerbations in the dual-therapy group that did include glucocorticoids. The choice of patients for the study could potentially have artificially inflated the observed effectiveness of triple therapy over dual bronchodilator treatment.

As such, we suggest clinicians stick with the GOLD 2017 recommendations that escalation to triple therapy only occur after maximization of bronchodilator treatment.

Dr. Samy Suissa (PhD) is with the Center for Clinical Epidemiology at Lady Davis Institute–Jewish General Hospital, and the departments of epidemiology and biostatistics and medicine at McGill University, Montreal. Dr. Jeffrey M. Drazen is editor-in-chief of the New England Journal of Medicine. These comments are taken from an editorial (N Engl J Med. 2018 Apr 18. doi: 10.1056/NEJMe1716802 ). Dr. Suissa declared personal fees and grants from the pharmaceutical industry outside the submitted work.


 

FROM NEW ENGLAND JOURNAL OF MEDICINE


All-cause mortality was significantly lower in patients who received the inhaled glucocorticoid, although the authors said this finding was “fragile” and needed further investigation.

The rate of discontinuation or withdrawal from the trial was 6% for the triple therapy group, 8% for the fluticasone furoate–vilanterol group, and 9% for the vilanterol-umeclidinium group. The rates of serious adverse events in each group were 22%, 21%, and 23%, respectively.

At trial entry, 38% of patients were already receiving triple therapy and 29% were taking an inhaled glucocorticoid. The authors noted that any patients taking an inhaled glucocorticoid who were randomized to the vilanterol-umeclidinium group would have had to abruptly stop taking their inhaled glucocorticoids.

“It is unknown whether the abrupt discontinuation of inhaled glucocorticoids would have contributed to our finding of a lower rate of exacerbations in the inhaled glucocorticoid groups than in the LAMA-LABA group,” they wrote.

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