Effect of Fluticasone Propionate/Salmeterol (250/50) on COPD Exacerbations and Impact on Patient Outcomes

Abstract

Prevention and treatment of COPD exacerbations are recognized as key goals in disease management. This randomized, double-blind, parallel-group, multicenter study evaluated the effect of fluticasone propionate/salmeterol 250 mcg/50 mcg (FSC 250/50) and salmeterol 50 mcg (SAL) twice-daily on moderate/severe exacerbations. Subjects received treatment with FSC 250/50 during a one month run-in, followed by randomization to FSC 250/50 or SAL for 52 weeks. Moderate/severe exacerbations were defined as worsening symptoms of COPD requiring antibiotics, oral corticosteroids and/or hospitalization. In 797 subjects with COPD (mean FEV(1) = 0.98L, 34% predicted normal), treatment with FSC 250/50 significantly reduced the annual rate of moderate/severe exacerbations by 30.4% compared with SAL (1.10 and 1.59 per subject per year, respectively, p < 0.001), the annual rate of exacerbations requiring oral corticosteroids by 34% (p < 0.001) and the annual rate of moderate/severe exacerbations requiring hospitalization by 36% (p = 0.043). Clinical improvements observed during run-in treatment with FSC 250/50 were better maintained over 52 weeks with FSC 250/50 compared to SAL. Statistically significant reductions in albuterol use, dyspnea scores, and nighttime awakenings and numerical benefits on quality of life were seen with FSC 250/50 compared with SAL. The incidence of adverse events was similar across groups. Pneumonia was reported more frequently with FSC 250/50 compared with SAL (7% vs. 2%). FSC 250/50 is more effective than SAL at reducing the rate of moderate/severe exacerbations. These data confirm the beneficial effect of FSC on the management of COPD exacerbations and support the use of FSC in patients with COPD.

Steroid-induced Deficiency of Mucosal-associated Invariant T Cells in the Chronic Obstructive Pulmonary Disease Lung. Implications for Nontypeable Haemophilus influenzae Infection

“…Although MAIT cells may not be required for defense against monomicrobial infections with S. pneumoniae, a deficiency of MAIT cells in nonstreptococcal bacterial sepsis has been described in the intensive care setting, and is associated with increased acquisition of nosocomial infections (47). Thus, our findings may begin to provide an explanation for the increased risk of pneumonia associated with ICS use in COPD (13)(14)(15)(16)(17)(18). In addition, although NTHi is a commensal of the upper respiratory tract, it is not present as a persistent, distinct microbial community in the lower respiratory tract in health.…”

“…However, effects of ICS are modest and likely restricted to certain subgroups of this heterogeneous condition (3) whereas evidence is accumulating from well-designed clinical trials that ICS increase the incidence of community-acquired pneumonia (13)(14)(15)(16)(17)(18). The mechanisms underlying this effect remain unknown, and have been highlighted as a research priority (3).…”

Tratamento farmacológico da DPOC

“…(17) In patients with moderate or severe COPD, as determined by the GOLD classification, the use of salmeterol in combination with fluticasone was shown to be superior to the use of SABAs in combination with SAMAs, (18) as well as to the use of salmeterol in isolation. (19)(20)(21) In patients with severe or very severe COPD, as determined by the GOLD classification, there were no differences between the salmeterol-fluticasone and formoterolbudesonide combinations in terms of symptom The process of selection allowed us to include 84 original articles in the present review. Many of those articles addressed more than one class of medication and various outcomes, which generated 420 analyses.…”

“…Donohue et al (16) found no significant differences between patients treated with formoterol and those treated with salmeterol regarding the number of exacerbations occurring in one year. In the analyses evaluated, the use of LABAs and ICs in combination was shown to be superior to that of LABAs or ICs in isolation for the following outcome measures (19)(20)(21)43,47) : number of exacerbations; severe exacerbations requiring hospitalization; and use of systemic corticosteroids.…”

“…(32) In contrast, an observational study compared those same medications and found no differences regarding cardiac ischemic events, arrhythmias, or pneumonia. (68) The use of fluticasone was compared with that of salmeterol in isolation, (19,20,43,79) as well as with that of LAMAs in isolation, (69) and was shown to increase the risk of developing pneumonia.…”