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


“Therefore any patients who would require an inhaled glucocorticoid may have had an increase in exacerbations and a decrease in lung function during the run-in period and would have been forced to leave the trial,” they wrote.

Patients with higher eosinophil levels seemed to do even better with triple therapy. In those with eosinophil levels of 150 cells per microliter or above, the annual rate of moderate to severe exacerbations was 0.95 with triple therapy, 1.08 with fluticasone furoate–vilanterol, and 1.39 with vilanterol-umeclidinium.

Triple therapy also was associated with a significantly longer time to first event and greater improvements in quality of life, compared with the dual therapies.

Overall, the adverse event profile of triple therapy was similar to that of dual therapy. Contrasting that finding were differences in the incidences of physician-diagnosed pneumonia between the treatment groups. Physician-diagnosed pneumonia was 53% higher among patients who received fluticasone furoate – either in dual or triple therapy combinations. Eight percent of patients in the triple therapy group experienced pneumonia, compared with 7% of patients in the fluticasone furoate–vilanterol group and 5% in the vilanterol-umeclidinium group.

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