DENVER – In patients with stable COPD, a fixed-dose combination of aclidinium/formoterol provided significantly greater improvements in bronchodilation compared with a fixed-dose combination of salmeterol/fluticasone, with equivalent benefits in symptom control and reduction in exacerbation risk, a randomized, controlled trial showed.
“This study will be important to building further evidence for the clinical use of inhaled long-acting muscarinic antagonist (LAMA) and long-acting beta agonist (LABA) fixed-dose combinations as a valuable tool in the treatment armamentarium for COPD,” Dr. Claus Vogelmeier said in an interview in advance of an international conference of the American Thoracic Society, where the work was presented during a poster session.
Dr. Claus Vogelmeier
“While there have been other positive studies showing benefits in LAMA/LABA fixed-dose combinations over the specific ICS/LABA fixed-dose combination of salmeterol/fluticasone, this is the first head-to-head study that compares the efficacy and safety of aclidinium/formoterol with salmeterol/fluticasone in COPD patients,” he said.
For the phase III study, Dr. Vogelmeier, professor of medicine and head of the pulmonary division at Marburg University Hospital, Germany, and his associates randomized 933 symptomatic COPD patients 1:1 to 24 weeks of treatment with aclidinium/formoterol 400/12 mcg twice daily via Genuair/Pressair (AstraZeneca) or salmeterol/fluticasone 50/500 mcg twice daily via Accuhaler (GlaxoSmithKline).
The primary efficacy endpoint was peak forced expiratory volume in 1 second (FEV1) at week 24. Other efficacy endpoints included peak FEV1 at each visit, Transition Dyspnea Index (TDI) focal score and COPD Assessment Test (CAT) score at week 24, and the proportion of patients who experienced at least one exacerbation defined by health care resource utilization (HCRU) or identified using the Exacerbations of Chronic Pulmonary Disease Tool (EXACT). Adverse events and serious adverse events were monitored throughout the study.
Of the 933 patients, 788 (85%) completed the study. Their mean age was 63 years and 65% were male. Dr. Vogelmeier reported that peak FEV1 was significantly greater with aclidinium/formoterol versus salmeterol/fluticasone after the first dose on day 1, an improvement that was maintained at week 24 (treatment differences of 83 mL and 93 mL, respectively; both P less than .0001).
Improvements in TDI focal score at week 24 were similar in both groups (a mean of 1.88 for both), and there were no significant differences between groups in CAT total score at week 24 (15.81 vs. 16.11). The proportion of patients who experienced one exacerbation or more was comparable between groups when assessed via HCRU (odds ratio .95) or EXACT (OR .94).
The incidence of adverse events was similar among the aclidinium/formoterol and the salmeterol/fluticasone groups (50% vs. 57%, respectively), as were serious adverse events, (7.5% vs. 7.1%), and adverse events leading to study discontinuation (5.4% vs. 7.3%). Adverse events related to inhaled corticosteroid use, including pneumonia and osteoporosis/osteopenia, were more common in patients receiving salmeterol/fluticasone than in patients receiving aclidinium/formoterol (10.7% vs. 4.3%).
“For clinicians like me, it is helpful to have choices available to address our patients’ needs,” Dr. Vogelmeier said. “Knowing that aclidinium/formoterol has shown greater bronchodilation compared to salmeterol/fluticasone will give us confidence in prescribing. These data offer physicians a new perspective and option for treating symptomatic patients at a time when the role of LAMA/LABA fixed-dose combinations is being increasingly recognized in the management of symptomatic COPD.”
He acknowledged certain limitations of the study, including the fact that it was limited to COPD patients who may have experienced up to one exacerbation in the year before the study. The study did not include frequent exacerbators.
The study was funded by Almirall, Barcelona, Spain, and Forest Laboratories, a subsidiary of Actavis. Dr. Vogelmeier disclosed ties with Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Grifols, Janssen, Mundipharma, Novartis, and Takeda.
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