Nebulized LABA found safe for long-term use in COPD

No long term safety signals were seen in randomized trial that tested the formoterol fumurate inhalation solution against placebo in patients with moderate to severe chronic obstructive pulmonary disease.

Safety was confirmed despite patients being permitted to remain on other background treatment for COPD, including inhaled corticosteroids and anticholinergics, in this study presented at the CHEST annual meeting. An additional benefit of the therapy was that it significantly improved lung function from baseline, according to some spirometry measures.

“The results are certainly reassuring from the safety perspective and confirmed previously published shorter-term efficacy and safety studies with this medication.”

The Food and Drug Administration approved formoterol fumarate, a long acting beta2-agonist (LABA), as a nebulized maintenance treatment for bronchoconstriction in COPD. Because of a concern about long-term LABA safety in asthma patients, The FDA mandated this one-year phase 4 study to evaluate long-term safety of formoterol in patients with moderate to severe COPD.

This multicenter, double-blind, noninferiority study randomly assigned 1,071 patients with moderate to severe COPD (mean forced expiratory volume in 1 second [FEV  1], 44 .4 percent of predicted value, at least one exacerbation in the past 12 months) to receive either nebulized formoterol 20 mcg/ 2 mL twice daily or matching placebo for up to 12 months. Subject were permitted to remain stable COPD therapy including inhaled corticosteroids and anticholinergics but excluding long-acting beta-agonists.

Formeterol was non-inferior to placebo for the primary safety endpoint, defined as a first occurrence of respiratory-related death, COPD-related emergency department visit, or COPD-related hospitalization, with an estimate hazard ratio of 0.965.

Formoterol significantly improved through FEV1, compared with placebo at three and six months of treatment, with (least squares) mean estimated difference of 42 mL (P = .007) and 41 mL (P= .025), respectively, but not at 9 or 12 months. Forced vital capacity was significantly improved with formoterol over placebo at all study visits (3, 6, 9, and 12 months), but improvements from baseline in inspiratory capacity did not significantly differ from placebo.

Mean age of study patients was 62.6 years, and 48.5 percent were female. At baseline, about half of patients were still smokers, half were inhaled corticosteroids, and about one-third were on concomitant long-acting muscarinic antagonists, mainly tiotropium. The vast majority of patients had moderate or severe COPD, with less than one percent having severe disease at baseline.

In response to a question on dosing, “One thing we have to keep in mind is that formoterol is a full agonist, so there are dose-dependent adverse effects. So, even though you get better lung function as you go up the dose, there’s no free lunch and always the potential for adverse effects.”