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Long-term safety of mometasone furoate/formoterol combination for treatment of patients with persistent asthma.

Maspero JF, Nolte H, Chérrez-Ojeda I, P04139 Study Gro - J Asthma (2010)

Bottom Line: Additional safety evaluations included plasma cortisol 24-hour area under the curve (AUC(0-24 h)) and ocular changes.Only three patients discontinued the study because of treatment-related ocular AEs (two for lens disorders in the MF/F 400/10 μg group; one for reduced visual acuity in the FP/S 250/50 μg group) and no asthma-related deaths occurred.Furthermore, MF/F showed numerical improvement in lung function and clinical benefits by reducing asthma symptoms and rescue medication use.

View Article: PubMed Central - PubMed

Affiliation: Fundacion CIDEA, Allergy/Respiratory Research, Buenos Aires, Argentina. maspero@ciudad.com.ar

ABSTRACT

Objective: The combination of inhaled corticosteroid (ICS) and long-acting β₂-agonist is recommended for treatment of patients with persistent asthma inadequately controlled on ICS monotherapy. This study was conducted to evaluate the long-term safety of mometasone furoate/formoterol (MF/F) administered through metered-dose inhaler (MDI) in patients with persistent asthma previously on medium- to high-dose ICS.

Methods: This was a 52-week, randomized, multicenter, parallel-group, open-label, evaluator-blinded study. At baseline, 404 patients (aged ≥12 years) were stratified according to their previous ICS dose (medium or high), then randomized 2:1 to receive twice-daily treatment of MF/F (200/10 or 400/10 μg) or fluticasone propionate/salmeterol (FP/S; 250/50 or 500/50 μg). The primary endpoint was the number and percentage of patients reporting any adverse event (AE). Additional safety evaluations included plasma cortisol 24-hour area under the curve (AUC(0-24 h)) and ocular changes. Pulmonary function, asthma symptoms, and use of rescue medication were monitored.

Results: The incidence of ≥1 treatment-emergent AE was similar across treatment groups (MF/F 200/10 μg, 77.3% [n= 109]; FP/S 250/50 μg, 82.4% [n= 56]; MF/F 400/10 μg, 79.2% [n= 103]; FP/S 500/50 μg, 76.9% [n= 50]). Rates of treatment-related AEs were also similar across treatment groups (MF/F 200/10 μg, 28.4%; FP/S 250/50 μg, 23.5%; MF/F 400/10 μg, 23.1%; FP/S 500/50 μg, 20.0%). Headache (3.7%) and dysphonia (2.7%) were the most common treatment-related AEs overall. The nature and frequency of AEs and the decreases in plasma cortisol AUC(0-24 h) observed with MF/F treatment were similar to those observed with FP/S treatment. Ocular events were rare (2-6% overall incidence among treatment groups); in particular, no posterior subcapsular cataracts were reported. Only three patients discontinued the study because of treatment-related ocular AEs (two for lens disorders in the MF/F 400/10 μg group; one for reduced visual acuity in the FP/S 250/50 μg group) and no asthma-related deaths occurred. Furthermore, MF/F showed numerical improvement in lung function and clinical benefits by reducing asthma symptoms and rescue medication use.

Conclusions: One-year treatment with the new combination therapies - twice-daily MF/F-MDI 200/10 and 400/10 μg - is safe and well tolerated in patients with persistent asthma.

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Related in: MedlinePlus

Mean plasma cortisol 24-hour AUC at baseline, week 26, and week 52. Patients who had both 0- and 24-hour measurements were included in the analysis. AUC, area under the curve; FP/S, fluticasone propionate/salmeterol; MF/F, mometasone furoate/formoterol.*p < .043 versus baseline within treatment groups.
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fig2: Mean plasma cortisol 24-hour AUC at baseline, week 26, and week 52. Patients who had both 0- and 24-hour measurements were included in the analysis. AUC, area under the curve; FP/S, fluticasone propionate/salmeterol; MF/F, mometasone furoate/formoterol.*p < .043 versus baseline within treatment groups.

Mentions: The safety of long-term use of MF/F was further evaluated by measuring changes in plasma cortisol AUC0–24 h in 57 patients (Figure 2). Mean baseline plasma cortisol AUC0–24h levels were higher in the MF/F 200/10 μg and FP/S 500/50 μg groups (210.5 and 238.3 μg • h/dL, respectively) than in the MF/F 400/10 μg and FP/S 250/50 μg groups (188.8 and 189.2 μg • h/dL), which was likely because of high values found in three individuals (two in the MF/F and one in the FP/S groups). Compared with the baseline values, there were sustained statistically significant reductions in plasma cortisol AUC0–24h in all treatment groups (p < .043) at weeks 26 and 52, with the exception of a nonsignificant reduction for FP/S 250/50 μg at week 52 (p = .076). At week 26, the extents of decreases were 37.5% for MF/F 200/10 μg, 28.8% for FP/S 250/50 μg, 33.3% for MF/F 400/10 μg, and 22.3% for FP/S 500/50 μg. At week 52, the corresponding decreases were 2.2%, 16.7%, 29.6%, and 32.2%.


Long-term safety of mometasone furoate/formoterol combination for treatment of patients with persistent asthma.

Maspero JF, Nolte H, Chérrez-Ojeda I, P04139 Study Gro - J Asthma (2010)

Mean plasma cortisol 24-hour AUC at baseline, week 26, and week 52. Patients who had both 0- and 24-hour measurements were included in the analysis. AUC, area under the curve; FP/S, fluticasone propionate/salmeterol; MF/F, mometasone furoate/formoterol.*p < .043 versus baseline within treatment groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2993043&req=5

fig2: Mean plasma cortisol 24-hour AUC at baseline, week 26, and week 52. Patients who had both 0- and 24-hour measurements were included in the analysis. AUC, area under the curve; FP/S, fluticasone propionate/salmeterol; MF/F, mometasone furoate/formoterol.*p < .043 versus baseline within treatment groups.
Mentions: The safety of long-term use of MF/F was further evaluated by measuring changes in plasma cortisol AUC0–24 h in 57 patients (Figure 2). Mean baseline plasma cortisol AUC0–24h levels were higher in the MF/F 200/10 μg and FP/S 500/50 μg groups (210.5 and 238.3 μg • h/dL, respectively) than in the MF/F 400/10 μg and FP/S 250/50 μg groups (188.8 and 189.2 μg • h/dL), which was likely because of high values found in three individuals (two in the MF/F and one in the FP/S groups). Compared with the baseline values, there were sustained statistically significant reductions in plasma cortisol AUC0–24h in all treatment groups (p < .043) at weeks 26 and 52, with the exception of a nonsignificant reduction for FP/S 250/50 μg at week 52 (p = .076). At week 26, the extents of decreases were 37.5% for MF/F 200/10 μg, 28.8% for FP/S 250/50 μg, 33.3% for MF/F 400/10 μg, and 22.3% for FP/S 500/50 μg. At week 52, the corresponding decreases were 2.2%, 16.7%, 29.6%, and 32.2%.

Bottom Line: Additional safety evaluations included plasma cortisol 24-hour area under the curve (AUC(0-24 h)) and ocular changes.Only three patients discontinued the study because of treatment-related ocular AEs (two for lens disorders in the MF/F 400/10 μg group; one for reduced visual acuity in the FP/S 250/50 μg group) and no asthma-related deaths occurred.Furthermore, MF/F showed numerical improvement in lung function and clinical benefits by reducing asthma symptoms and rescue medication use.

View Article: PubMed Central - PubMed

Affiliation: Fundacion CIDEA, Allergy/Respiratory Research, Buenos Aires, Argentina. maspero@ciudad.com.ar

ABSTRACT

Objective: The combination of inhaled corticosteroid (ICS) and long-acting β₂-agonist is recommended for treatment of patients with persistent asthma inadequately controlled on ICS monotherapy. This study was conducted to evaluate the long-term safety of mometasone furoate/formoterol (MF/F) administered through metered-dose inhaler (MDI) in patients with persistent asthma previously on medium- to high-dose ICS.

Methods: This was a 52-week, randomized, multicenter, parallel-group, open-label, evaluator-blinded study. At baseline, 404 patients (aged ≥12 years) were stratified according to their previous ICS dose (medium or high), then randomized 2:1 to receive twice-daily treatment of MF/F (200/10 or 400/10 μg) or fluticasone propionate/salmeterol (FP/S; 250/50 or 500/50 μg). The primary endpoint was the number and percentage of patients reporting any adverse event (AE). Additional safety evaluations included plasma cortisol 24-hour area under the curve (AUC(0-24 h)) and ocular changes. Pulmonary function, asthma symptoms, and use of rescue medication were monitored.

Results: The incidence of ≥1 treatment-emergent AE was similar across treatment groups (MF/F 200/10 μg, 77.3% [n= 109]; FP/S 250/50 μg, 82.4% [n= 56]; MF/F 400/10 μg, 79.2% [n= 103]; FP/S 500/50 μg, 76.9% [n= 50]). Rates of treatment-related AEs were also similar across treatment groups (MF/F 200/10 μg, 28.4%; FP/S 250/50 μg, 23.5%; MF/F 400/10 μg, 23.1%; FP/S 500/50 μg, 20.0%). Headache (3.7%) and dysphonia (2.7%) were the most common treatment-related AEs overall. The nature and frequency of AEs and the decreases in plasma cortisol AUC(0-24 h) observed with MF/F treatment were similar to those observed with FP/S treatment. Ocular events were rare (2-6% overall incidence among treatment groups); in particular, no posterior subcapsular cataracts were reported. Only three patients discontinued the study because of treatment-related ocular AEs (two for lens disorders in the MF/F 400/10 μg group; one for reduced visual acuity in the FP/S 250/50 μg group) and no asthma-related deaths occurred. Furthermore, MF/F showed numerical improvement in lung function and clinical benefits by reducing asthma symptoms and rescue medication use.

Conclusions: One-year treatment with the new combination therapies - twice-daily MF/F-MDI 200/10 and 400/10 μg - is safe and well tolerated in patients with persistent asthma.

Show MeSH
Related in: MedlinePlus