Patient-reported outcomes in adults with moderate to severe asthma after use of budesonide and formoterol administered via 1 pressurized metered-dose inhaler.

BACKGROUND: Patient-reported outcomes (PROs) are important for evaluating asthma therapy. OBJECTIVE: To evaluate PROs in adults with moderate to severe persistent asthma receiving budesonide and formoterol administered via 1 pressurized metered-dose inhaler (pMDI). METHODS: This 12-week, double-blind, double-dummy, placebo-controlled, multicenter study randomized 596 patients 12 years or older to budesonide/formoterol pMDI 160/4.5 microg x 2 inhalations (320/9 microg); budesonide pMDI 160 microg x 2 inhalations (320 microg) + formoterol dry powder inhaler (DPI) 4.5 microg x 2 inhalations (9 microg); budesonide pMDI 160 microg x 2 inhalations (320 microg); formoterol DPI 4.5 microg x 2 inhalations (9 microg); or placebo, each twice daily, after 2 weeks of budesonide pMDI 80 microg x 2 inhalations (160 microg) twice daily. PROs were assessed in 553 patients 18 years or older using the standardized Asthma Quality of Life Questionnaire (AQLQ[S]), Medical Outcomes Survey (MOS) Sleep Scale, Patient Satisfaction With Asthma Medication (PSAM) questionnaire, diary data, and global assessments. RESULTS: Patients receiving budesonide/formoterol reported significantly greater improvements from baseline on the AQLQ(S) and asthma control variables (based on symptoms and rescue medication use; all P < .001) vs placebo. Clinically important improvements (increase of > or = 0.5 points) from baseline to end of treatment in AQLQ(S) overall scores were achieved by 43.6% of patients receiving budesonide/formoterol vs 22.6% of patients receiving placebo (P = .001). The MOS Sleep Scale scores generally showed no differences among treatment groups. Patients receiving budesonide/formoterol had significantly greater PSAM questionnaire scores and better outcomes on physician-patient global assessments at end of treatment vs placebo (all P < or = .001). CONCLUSION: Significantly greater improvements in health-related quality of life and asthma control and greater treatment satisfaction were observed with budesonide/formoterol pMDI vs placebo.

Long-term safety and efficacy of intranasal ciclesonide in adult and adolescent patients with perennial allergic rhinitis.

BACKGROUND: Ciclesonide is a corticosteroid in development for allergic rhinitis that has been shown to be safe and effective in seasonal allergic rhinitis and perennial allergic rhinitis (PAR) trials of up to 6 weeks in duration. However, the long-term safety and efficacy of ciclesonide are unknown. OBJECTIVE: To demonstrate the long-term safety of intranasal ciclesonide, 200 microg once daily, in patients with PAR. METHODS: Patients (> or = 12 years old) with a 2-year or longer history of PAR were randomized in a double-blind fashion to receive ciclesonide, 200 microg, or placebo once daily in the morning for up to 52 weeks. Spontaneous and elicited adverse events were monitored throughout the study. Ear, nose, and throat examinations were performed to evaluate local tolerability. Additionally, 24-hour urinary free cortisol level, morning plasma cortisol level, intraocular pressure, and lens opacification were monitored to evaluate the systemic safety of intranasal ciclesonide. Ciclesonide efficacy was determined by measuring 24-hour reflective total nasal symptom scores. RESULTS: No clinically relevant differences were observed between the ciclesonide and placebo groups in adverse events, ear, nose, and throat examinations, or 24-hour urinary free or morning plasma cortisol levels. Similarly, no clinically relevant differences were found between treatment groups in intraocular pressure, visual acuity, or lens opacification. With regard to efficacy, ciclesonide achieved a significantly greater reduction in 24-hour reflective total nasal symptom score compared with placebo over more than 52 weeks (P < .001). CONCLUSION: In this study, intranasal ciclesonide, 200 microg once daily, was safe and effective for the long-term treatment of PAR, with no evidence of tachyphylaxis.

Effects of treatment with mometasone furoate dry powder inhaler in children with persistent asthma.

BACKGROUND: Mometasone furoate dry powder inhaler (DPI) has been shown to effectively treat asthma in children. OBJECTIVE: To evaluate the efficacy and safety of 2 dosing regimens of mometasone furoate DPI in the treatment of mild-to-moderate persistent asthma in children previously using inhaled corticosteroids (ICSs). METHODS: A 12-week, multicenter, double-blind, parallel-group, placebo-controlled study evaluated 2 dosing regimens of mometasone furoate DPI (100 microg every evening and 100 microg twice daily) in 296 children 4 to 11 years old with asthma previously using ICSs. The primary efficacy variable was the change in percentage of predicted forced expiratory volume in 1 second (FEV1) from baseline to end point. Secondary efficacy variables included absolute FEV1, forced expiratory flow between 25% and 75% forced vital capacity, morning and evening peak expiratory flow, asthma symptom scores, albuterol use, nocturnal awakenings, response to therapy, and health-related quality of life. RESULTS: Mean changes from baseline at end point in predicted FEV1 were 4.73 and 5.52 percentage points for mometasone furoate DPI, 100 microg every evening and 100 microg twice daily, respectively, the difference of which was not significant, and -1.77 percentage points for placebo (P < or = .002). Significant improvements in secondary efficacy variables were also observed for both mometasone furoate DPI treatments over placebo. Both mometasone furoate DPI doses were well tolerated, and no significant differences were noted among the 3 treatment groups in adverse event reporting. CONCLUSIONS: Both mometasone furoate DPI doses were well tolerated and significantly improved lung function, maintained effective asthma control, and improved quality of life in children with asthma.

Fluticasone propionate HFA-134a pressurized metered-dose inhaler in adolescents and adults with moderate to severe asthma.

In this randomized, double-blind, placebo-controlled trial, 397 patients with moderate to severe asthma, previously treated with bronchodilators alone, received fluticasone propionate 88, 220, or 440 microg twice daily, or placebo via metered dose inhaler (MDI) for 12 weeks. Mean change from baseline to endpoint in pre-dose percent predicted forced expiratory volume in one second (FEV1) was greater (p < 0.001) in each fluticasone propionate group (9.0%, 88 microg bid; 9.8%, 220 microg bid; 11.2%, 440 microg bid) versus placebo (3.4%). Morning and evening peak expiratory flow (PEF), asthma symptoms, and supplemental albuterol use also improved in all fluticasone propionate groups versus placebo. The incidence of adverse events and 24-hour urine cortisol excretion rates were similar between active treatments and placebo.

Efficacy and safety of desloratadine/pseudoephedrine tablet, 2.5/120 mg two times a day, versus individual components in the treatment of patients with seasonal allergic rhinitis.

Although antihistamines are highly effective in alleviating many symptoms associated with seasonal allergic rhinitis (SAR), relief from nasal congestion is variable. The efficacy of desloratadine, an effective antihistamine, in combination with pseudoephedrine, a potent nasal decongestant, was evaluated to determine whether combination therapy was more effective than individual component therapy in reducing nasal congestion, as well as other SAR symptoms. This multicenter, randomized, double-blind, three-arm study included 650 patients with SAR. For 2 weeks, patients were administered a combination tablet of desloratadine plus pseudoephedrine (desloratadine/pseudoephedrine, 2.5/120 mg) twice per day (b.i.d.), desloratadine (5 mg) once per day, or pseudoephedrine (120 mg) b.i.d. Patients assessed the severity of their SAR symptoms twice daily on symptom diary cards. The primary variable-change from baseline in the reflective A.M./P.M. total symptom score, excluding nasal congestion-was significantly superior (-6.7) compared with desloratadine (-5.4) or pseudoephedrine (-5.3) alone (p < or = 0.001 versus either group). Secondary efficacy variables including total symptom scores (plus congestion), total nasal symptom scores, and total nonnasal symptom scores were significantly reduced after desloratadine/pseudoephedrine therapy compared with the individual components. The most frequently reported adverse events were insomnia, headache, and dry mouth. Desloratadine/pseudoephedrine, 2.5/120 mg b.i.d., therapy was more effective in reducing total symptom scores of SAR, including nasal congestion, than were the individual components. These results support the use of this combination therapy over desloratadine or pseudoephedrine alone.

A comparison of the effects of oral montelukast and inhaled salmeterol on response to rescue bronchodilation after challenge.

OBJECTIVES: To compare the effects of addition of montelukast or salmeterol to inhaled corticosteroids (ICS) on the response to rescue beta2-agonist use after exercise-induced bronchoconstriction. METHODS: A double-blind, placebo-controlled study was performed at 16 centers in the United States. Patients with asthma (n = 122, ages 15-58) whose symptoms were uncontrolled on Low-dose inhaled fluticasone and who had a history of exercise-induced worsening of asthma were randomized to receive either montelukast (10 mg once daily), salmeterol (50microg twice daily), or placebo for 4 weeks. Standardized spirometry after exercise challenge and beta2-agonist rescue was performed at baseline, week 1 and 4. RESULTS: Maximum achievable forced expiratory volume in 1 s (FEV1) percent predicted after rescue beta2-agonist improved in the montelukast (+1.5%) and placebo (+1.2%) groups at 4 weeks, but diminished in the salmeterol (-3.9%) group (P < 0.001). Although pre-exercise FEV1 was greatest with salmeterol (P = 0.10), patients taking montelukast had significantly greater protection from an exercise-induced decrease in FEV1 than those taking salmeterol (P < 0.001). Both the magnitude and rate of rescue bronchodilation were greater with montelukast compared with salmeterol (P < 0.001). Five minutes after rescue beta2-agonist, 92% of patients taking montelukast and 68% of those taking placebo had recovered to pre-exercise levels, whereas only 50% of those taking salmeterol had recovered to pre-exercise levels. CONCLUSION: In patients whose asthma symptoms remain uncontrolled using ICS, addition of montelukast permits a greater and more rapid rescue bronchodilation with a short-acting beta2-agonist than addition of salmeterol and provides consistent and clinically meaningful protection against exercise-induced bronchoconstriction.

Montelukast for treating fall allergic rhinitis: effect of pollen exposure in 3 studies.

BACKGROUND: Montelukast, a potent leukotriene receptor antagonist, is an effective therapy for symptoms of seasonal allergic rhinitis, a disease governed by patients' individual sensitivity and exposure to relevant allergens. OBJECTIVE: To evaluate the relationship of montelukast treatment effect vs pollen exposure in studies conducted during 3 consecutive fall allergy seasons. METHOD: A combined analysis of these multicenter, randomized, double-blind, parallel-group studies was performed; 1 of the 3 studies is presented for the first time in this article. After a placebo run-in period, 1,862 symptomatic patients were randomly assigned to receive either a 10-mg montelukast tablet (n = 929) or placebo (n = 933) once daily for 2 weeks. Pollen exposure was summarized by mean daily weed pollen count. The interaction between treatment effect and pollen exposure was evaluated on the primary efficacy endpoint and daytime nasal symptom score, as rated by patients; also evaluated was the influence of the timing of the 2-week treatment period relative to the peak of the weed pollen season. RESULTS: Montelukast significantly improved daytime nasal symptoms score and individual scores of congestion, rhinorrhea, itching, and sneezing compared with placebo. There was a significant interaction (P < .043) between treatment effect and weed pollen exposure; a larger treatment effect was noted in patients exposed to higher pollen counts. An interaction between treatment effect and timing of treatment in relation to peak pollen season was suggested. CONCLUSIONS: Montelukast significantly improved daytime nasal symptoms score in patients with seasonal allergic rhinitis, and the effect was greater in patients exposed to higher pollen levels.

Omalizumab, an anti-IgE antibody, in the treatment of adults and adolescents with perennial allergic rhinitis.

BACKGROUND: Treatment with omalizumab, an anti-IgE antibody, improves symptoms and quality of life in patients with seasonal allergic rhinitis but has not previously been investigated in patients with perennial symptoms. OBJECTIVE: To investigate the efficacy, safety, and tolerability of omalizumab in the treatment of perennial allergic rhinitis (PAR). METHODS: Two hundred eighty-nine patients (aged 12 to 70 years) with moderate-to-severe symptomatic PAR were randomized to 16 weeks' double-blind subcutaneous treatment with either placebo (n = 145) or omalizumab (at least 0.016 mg/kg/IgE [IU/mL] per 4 weeks; n = 144). The primary efficacy variable was the mean daily nasal severity score, as determined from patient daily diary cards. Secondary efficacy variables included use of rescue antihistamine, rhinoconjunctivitis-specific quality of life (RQoL), and patients' evaluation of treatment efficacy. Safety and tolerability were evaluated from adverse event reports and laboratory safety parameters. RESULTS: Throughout 16 weeks of treatment, the mean daily nasal severity score was significantly lower in omalizumab-treated patients than with placebo (P < 0.001). The improvement in symptoms when taking omalizumab was paralleled by a reduction in use of rescue antihistamine (P < or = 0.005 overall) and improved RQoL relative to placebo. Patients' evaluation of treatment efficacy significantly favored omalizumab over placebo (P = 0.001). Omalizumab therapy was well tolerated. There were no safety concerns. CONCLUSIONS: Omalizumab was safe and well tolerated in the treatment of patients with PAR, providing effective control of symptoms and improved RQoL while simultaneously minimizing reliance on rescue antihistamines.

Effects of montelukast and beclomethasone on airway function and asthma control.

BACKGROUND: Maintaining asthma control is a major objective of therapy. Traditionally, the effectiveness of asthma therapy has been judged primarily by its effect on airway function rather than on multiaspect asthma control. OBJECTIVE: An inhaled corticosteroid and a leukotriene receptor antagonist were compared to determine whether they provided equivalent effects, as judged by days of asthma control. METHODS: In a randomized, multicenter, double-blind, placebo-controlled, parallel-group study, asthmatic patients (n = 782) with FEV(1) percent predicted values of between 50% and 85% and a weekly average beta-agonist use of more than 2 puffs per day were randomized to receive montelukast (10 mg daily), beclomethasone (200 microg twice daily), or placebo treatment for 6 weeks in a double-dummy fashion. We examined the distribution of the primary end point: percentage of days of asthma control. Secondary end points included FEV(1), albuterol use, occurrence of an asthma attack, asthma flare-up, rescue corticosteroid use, sustained asthma control, and adverse experiences. RESULTS: The percentage of days of asthma control was almost identical between the montelukast and beclomethasone groups (98% overlap in the distribution). Montelukast was at least equal to beclomethasone, and both were greater than placebo on the basis of frequency of asthma attacks, asthma flare-ups, and rescue corticosteroid use. Beclomethasone had a greater effect than montelukast and both treatments were better than placebo at improving FEV(1). CONCLUSIONS: Montelukast was as effective as beclomethasone, as judged by indices of clinical control other than FEV(1). When evaluating the outcome of montelukast therapy, FEV(1) might underestimate clinical effectiveness.

Efficacy and safety of doxofylline compared to theophylline in chronic reversible asthma -- a double-blind randomized placebo-controlled multicentre clinical trial.

BACKGROUND: Experimental studies have shown that doxofylline is endowed with a remarkable bronchodilator activity with less extra-respiratory effects than theophylline. This trial was designed to compare the efficacy and safety of doxofylline, theophylline, and placebo in patients with chronic reversible bronchial asthma. MATERIAL/METHODS: Three hundred forty-six patients were randomly assigned to a 12-week oral treatment with either doxofylline 400 mg t.i.d. (high dose), doxofylline 200 mg t.i.d. (low dose), theophylline 250 mg t.i.d. (active control) or placebo. Pulmonary function tests (PFTs) were performed biweekly. Patients kept records of peak flow meter (PFM) measurements, asthma attack rate and beta-2-agonist use (albuterol). RESULTS: Changes in FEV1 2 hours after the administration of treatments versus baseline exhibited statistically significant differences between doxofylline 400 mg t.i.d. and placebo and between theophylline and placebo. Similar differences were monitored on the other variables (FVC, PFER, FEF(25-75%). Asthma attack rate and use of albuterol decreased remarkably with doxofylline 400 mg t.i.d. and theophylline. There were few statistically significant differences between doxofylline 200 mg t.i.d. and placebo. Significantly more patients had to interrupt treatment because of adverse events under theophylline than under doxofylline 400 mg t.i.d. (p=0.001). With doxofylline 400 mg t.i.d., the number of patients treated to spare one drop-out due to theophylline was 5. CONCLUSIONS: This study provides evidence that doxofylline 400 mg t.i.d. is an effective treatment for relieving airway obstruction and displays a better safety profile with respect to theophylline 250 mg t.i.d. with a favorable risk-to-benefit ratio.

Fluticasone Propionate Reduces Oral Prednisone Use While it Improves Asthma Control.

This study examined the effect of fluticasone propionate aerosol on oral prednisone requirements in patients with severe asthma. Ninety-six patients dependent on oral prednisone were treated with placebo or fluticasone propionate aerosol (750 or 1000 &mgr;g twice daily) for 16 weeks. The dosage of oral prednisone was adjusted weekly according to predetermined criteria. Fluticasone propionate 750 and 1000 &mgr;g twice daily resulted in 69% and 88% of patients (low and high doses, respectively) not using any prednisone compared to 3% of placebo-treated patients by the end of the study. In the fluticasone propionate groups, forced expiratory volume in 1 s (FEV(1)) and peak expiratory flow rates and the number of nighttime awakenings improved at the last evaluable visit. In addition, the number of nighttime awakenings and symptomatic albuterol use declined relative to placebo values (p < 0.05). Fluticasone propionate aerosol was well tolerated. Fluticasone propionate aerosol (750 or 1000 &mgr;g twice daily) effectively and safely allowed most asthmatics who were dependent on oral corticosteriods to reduce or eliminate oral prednisone use while improving pulmonary function.