Damian McNamara

November 08, 2016

Patients with chronic obstructive pulmonary disease (COPD) experienced significantly fewer acute exacerbations when a long-acting muscarinic antagonist (LAMA) was added to a long-acting beta agonist (LABA) than when an inhaled corticosteroid (ICS) was added, an analysis of data from the FLAME and LANTERN studies reveals.

"We were not surprised by the results," said Francesco Patalano, MD, Senior Global Program Head–Inhaled Respiratory Portfolio, Novartis.

The fixed-dose combination of indacaterol and glycopyrronium (Ultibro Breezhaler, Novartis) was better than the fixed-dose combination of salmeterol and fluticasone (Seretide Diskus, GlaxoSmithKline) for "reducing the overall risk of COPD exacerbations, and it was supported by analyses in all relevant subgroups," according to Dr Patalano and his colleagues.

"This may come as a surprise to some clinicians, who have looked to LABA/ICS to reduce exacerbations. Our results show clear benefit from the LABA/LAMA, without the sort of risks you would see with an inhaled corticosteroid-containing regimen," they report.

Dr Patalano and his colleagues assessed the reduction in moderate or severe COPD exacerbations in 3362 patients from the FLAME study who experienced one or more exacerbations in the previous year (N Engl J Med. 2016;374:2222-2234) and in 744 patients from the LANTERN study who experienced zero or one exacerbation in the previous year (Int J Chron Obstruct Pulmon Dis. 2015;10:1015-1026). Both studies compared the two fixed-dose combinations.

Differences in annualized rates and time to first moderate or severe COPD exacerbation favored LABA plus LAMA over LABA plus ICS in the combined analysis presented at CHEST 2016 in Los Angeles.

Table. Table: Reduction in Moderate or Severe COPD Exacerbations With LABA/LAMA Compared With LABA/ICS

Studies Decrease in Risk, % P Value
Annualized rate    
   FLAME study 17 <.001
   LANTERN study 31 .048
Time to first exacerbation    
   FLAME study 22 <.001
   LANTERN study 35 .028


The reductions associated with LABA plus LAMA occurred regardless of whether patients had a history of exacerbations in the previous year.

This is a "good study," said John Studdard, MD, a pulmonary and critical care physician in private practice in Jackson, Mississippi, who is president designate of the American College of Chest Physicians.

"For me as a clinician, it really comes down to the uniqueness of the patient that you are seeing," he explained.

For most patients with pure COPD and no inflammatory component, "I clearly think step 1 is going to be a long-acting beta agonist and a long-acting anti-muscarinic, as this study has borne out," Dr Studdard told Medscape Medical News. "But it's not necessarily an either/or proposition."

In certain patients, a long-acting beta agonist and an inhaled corticosteroid "is a very valuable combination, like those in the COPD–asthma overlap group," he said.

"This disease has huge clinical and economic impact. With COPD, there are about 120,000 deaths each year in the United States," Dr Studdard reported. "It's the third-leading cause of death and there are huge costs related to the care of COPD, both inpatient and outpatient."

The next generation of COPD agents will probably have all three components — a long-acting beta agonist, an inhaled corticosteroid, and a long-acting anti-muscarinic — combined into one product, he added.

Future studies will be needed to determine whether such triple-combination products prove to be superior to two-drug combinations, such as LABA/LAMA, in reducing risk for COPD exacerbations.

Novartis funded the FLAME and LANTERN studies. Dr Patalano and his colleagues are employees of Novartis. Dr Studdard has disclosed no relevant financial relationships.

CHEST 2016: American College of Chest Physicians Annual Meeting. Presented October 25, 2016.


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