Long-term safety of mometasone furoate/formoterol combination for treatment of patients with persistent asthma.
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.
Maspero
Jorge F
JF
Fundacion CIDEA, Allergy/Respiratory Research, Buenos Aires, Argentina. maspero@ciudad.com.ar
Nolte
Hendrik
H
Chérrez-Ojeda
Iván
I
D000280:Administration, Inhalation; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002386:Cataract; D004983:Ethanolamines / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D000068759:Formoterol Fumarate; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007429:Intraocular Pressure; D008297:Male; D036501:Metered Dose Inhalers; D000068656:Mometasone Furoate; D011244:Pregnadienediols / Q000008:administration & dosage* / Q000009:adverse effects; D016037:Single-Blind Method; D013147:Spirometry
D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D004983:Ethanolamines; D011244:Pregnadienediols; D000068656:Mometasone Furoate; D000068759:Formoterol Fumarate; D006854:Hydrocortisone