Safety and efficacy of desloratadine 5 mg in asthma patients with seasonal allergic rhinitis and nasal congestion.

BACKGROUND: Antihistamines relieve most seasonal allergic rhinitis (SAR) symptoms, with the exception of nasal congestion, which is often the most troublesome symptom for patients. A nonsedating antihistamine that significantly decreases nasal congestion and improves symptoms of seasonal allergic asthma would be a significant advance in therapy. OBJECTIVES: To evaluate the safety and efficacy of desloratadine 5 mg in patients experiencing moderate SAR, nasal congestion, and symptoms of seasonal allergic asthma. METHODS: This 4-week, multicenter, parallel-group, double-blind study evaluated desloratadine treatment (5 mg once daily) versus placebo in 331 subjects with SAR and mild seasonal allergic asthma. Subjects evaluated SAR and asthma symptoms twice daily, recording 12-hour reflective and instantaneous severity evaluation scores. The primary efficacy parameter was the difference from baseline in AM/PM reflective total symptom scores. Changes in individual SAR and asthma symptoms were also analyzed. RESULTS: Compared with placebo, desloratadine significantly reduced mean AM/PM reflective total symptom scores for SAR, beginning with the first dose (P < 0.001) and continuing throughout days 1 to 15 (-4.90 vs -2.98; P < 0.001) and days 1 to 29 (-5.47 vs -3.73; P < 0.001). Desloratadine significantly decreased AM/PM reflective total asthma symptom scores for days 1 to 15 (P = 0.023) and AM/PM reflective nasal congestion scores over days 1 to 15 and days 1 to 29 (P = 0.006 and P = 0.014, respectively). Desloratadine was safe and well tolerated; adverse events were similar to placebo overall. CONCLUSIONS: Desloratadine provided significant relief from the signs and symptoms of SAR, including nasal congestion. In this patient population, symptoms of seasonal allergic asthma also improved.     

Desloratadine relieves nasal congestion and improves quality-of-life in persistent allergic rhinitis

Background:  Symptoms of allergic rhinitis (AR), particularly nasal congestion, can impair quality-of-life (QoL). However, only a modest correlation exists between these symptoms and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores, suggesting that both be evaluated for a complete assessment of health.
Methods:  Subjects with a ≥2-year history of moderate-to-severe AR to dust mite or cat dander were randomized to desloratadine 5 mg/day ( n  =   293) or placebo/day ( n  =   291) for 28 days. Primary endpoint was change from baseline in a.m./p.m. nasal congestion score. Secondary outcomes included change from baseline in total nasal symptom score, individual symptom scores and RQLQ scores (completed on days 1, 7, and 28).
Results:  The Allergic Rhinitis and its Impact on Asthma criteria for persistent allergic rhinitis (PER) were fulfilled by 99% of subjects in the placebo arm. Between-treatment difference in a.m./p.m. nasal congestion score, observed from day 8 onward, significantly favored desloratadine ( P  =   0.0003). Desloratadine significantly improved a.m./p.m. nasal congestion and RQLQ scores after 1 week and at treatment end ( P  <   0.05). Improvements in 5 of 7 RQLQ domain scores exceeded the minimal important difference. On days 7 and 28, desloratadine was also significantly superior to placebo in mean change from baseline in a.m./p.m. total nasal symptom score and rhinorrhea score (both P  ≤   0.01). Symptomatic benefit was primarily driven by improvement in nasal congestion and rhinorrhea.
Conclusions:  Desloratadine 5 mg/day significantly improved symptoms associated with PER, including nasal congestion, and provided significant improvement in QoL after 1 week of treatment.     

Effect of desloratadine therapy on symptom scores and measures of nasal patency in seasonal allergic rhinitis: results of a single-center, placebo-controlled trial.

BACKGROUND: Desloratadine reduces symptoms and maintains nasal airflow in patients with seasonal allergic rhinitis (SAR) during experimental allergen exposure. OBJECTIVE: To compare the effects of desloratadine and placebo on symptom scores, quality of life (QOL), and nasal airway patency in patients with SAR during the allergy season. METHODS: Adults with symptomatic SAR were randomized in a double-blind manner to receive desloratadine, 5 mg, or placebo for 14 days. Patient-rated SAR symptoms were recorded twice daily (morning and evening). On days 1 and 15, SAR symptoms were scored jointly (investigator and patient), nasal airflow was measured using 4-phase rhinomanometry, and QOL and the overall condition of SAR were rated. Overall treatment response was scored on day 15. Adverse events were recorded. RESULTS: At day 15, total symptom (P = .03) and total nasal symptom (P = .02) scores and patient morning-rated individual nasal symptom scores (except nasal stuffiness) (P < or = .04) decreased significantly from baseline with desloratadine vs placebo. Flow in the descending expiratory nasal airflow phase was significantly greater (P = .046) and the percentage increase in total inspiratory nasal airway resistance was less (P = .03) in the desloratadine group vs the placebo group. The overall condition of SAR was less severe (P = .045), the therapeutic response was greater (P = .004), and the nasal symptom domain of the QOL score was significantly better (P = .03) in the desloratadine group. Adverse event rates were similar in both groups. CONCLUSION: Desloratadine treatment for 14 days improved nasal airflow and resistance as well as symptom and QOL scores in patients with symptomatic SAR during the allergy season.     

Efficacy of diphenhydramine vs desloratadine and placebo in patients with moderate-to-severe seasonal allergic rhinitis.

BACKGROUND: Previous studies have shown that diphenhydramine and desloratadine effectively relieve symptoms of seasonal allergic rhinitis (SAR). OBJECTIVE: To compare the relative efficacy of 50 mg of diphenhydramine hydrochloride, 5 mg of desloratadine, and placebo in relieving symptoms in patients with moderate-to-severe SAR. METHODS: In this 1-week, multicenter, parallel-group, randomized, double-blind, double-dummy, placebo-controlled study, 610 patients with moderate-to-severe SAR received 50 mg of diphenhydramine hydrochloride 3 times daily, 5 mg of desloratadine once daily, or placebo. Daily 24-hour reflective total nasal symptom scores (TNSSs) (primary end point), total symptom scores, and individual symptom scores were evaluated. A global evaluation of response to treatment was conducted at 2 posttreatment visits. RESULTS: The mean reduction from baseline in 24-hour reflective TNSSs relative to the placebo response was 77.6% for the diphenhydramine group (P < .001) and 21.0% for the desloratadine group (P = .12). A TNSS between-treatment difference of -1.81 (46.7%; P < .001) was observed when comparing diphenhydramine with desloratadine. A similar between-treatment difference was observed for the 24-hour reflective total symptom score comparing diphenhydramine to desloratadine (-3.35; 45.5%; P < .001). Diphenhydramine provided clinically and statistically significant reductions vs placebo and desloratadine in all individual symptoms, including nasal congestion. Desloratadine had a tendency toward improvement compared with placebo for most individual symptom scores. However, a statistically significant result was reached only for sneezing (-0.27; 33.9%; P = .04). CONCLUSIONS: Diphenhydramine, 50 mg, given for 1 week provided statistically significant and clinically superior improvements in symptoms compared with 5 mg of desloratadine in patients with moderate-to-severe SAR. Somnolence occurred more frequently with diphenhydramine (22.1%) compared with desloratadine (4.5%) and placebo (3.4%).     

Comparison of the effects of desloratadine 5-mg daily and placebo on nasal airflow and seasonal allergic rhinitis symptoms induced by grass pollen exposure

BACKGROUND: Nasal congestion is a chronic symptom of seasonal allergic rhinitis (SAR) that is often difficult to treat with antihistamines. Desloratadine, a new, potent, H1-receptor antagonist has been shown to decrease nasal congestion in clinical trials and to maintain nasal airflow in response to grass pollen exposure. We compared the effects of desloratadine 5 mg and placebo on nasal airflow, nasal secretion weights and SAR symptoms, including nasal congestion, in patients exposed to grass pollen in an environmental exposure unit. METHODS: Forty-six grass pollen allergic SAR patients received desloratadine or placebo for 7 days, followed by a 10-day washout, and then crossed over to the other treatment for 7 days. A 6-h allergen exposure was performed at the end of each treatment period. RESULTS: Desloratadine was significantly superior to placebo in maintaining nasal airflow (P 相似文献   

Two first-line therapies in the treatment of mild asthma: use of peak flow variability as a predictor of effectiveness.

BACKGROUND: New drug evaluations in patients with mild asthma are sometimes complicated by enrollment of patients whose disease is too mild to show improvement with therapy. A peak expiratory flow (PEF) variability criterion may help to more clearly define a mild asthmatic population. OBJECTIVE: To evaluate the effectiveness of zafirlukast (20 mg twice daily) and cromolyn sodium (1600 microg four times daily) compared with placebo as first-line therapy for mild asthma using a retrospective analysis, which stratified patients by PEF variability (<10% or > or =10%). STUDY DESIGN: Symptomatic patients (daytime asthma symptoms score > or =8) were randomized to 13 weeks of treatment in a double-blind, double-dummy, placebo-controlled, parallel-group, multicenter trial. PATIENTS AND METHODS: Patients (n = 287) were nonsmokers (age > or =12 years) with reversible airway disease, a forced expiratory volume in one second (FEV1) of > or = 55% of predicted, and previous treatment with beta2-agonist or theophylline only. Assessments included changes from baseline to endpoint in daytime and nocturnal asthma symptoms, beta2-agonist use, PEF, and FEV1. Response to treatment was assessed by predetermined diary card and FEV1 criteria. Safety was determined from adverse events and laboratory test results. RESULTS: No significant treatment effects were seen across efficacy measures for patients with PEF variability < 10%. For patients with PEF variability > or = 10%, both active treatments significantly (P < .05) decreased the daytime asthma symptoms score, nighttime awakenings, and beta2-agonist use, and increased morning PEF and FEV1 compared with placebo. Response to diary card criteria was 70% and 75% for zafirlukast and cromolyn, respectively; response to FEV1 criteria was 47% for both treatments. All treatments were tolerated well by patients. CONCLUSIONS: Zafirlukast and cromolyn are effective first-line therapies for mild asthma, with both therapies producing greater benefits in patients whose PEF variability was > or = 10%. In prospective trials to evaluate therapies in patients with mild asthma, it may be worthwhile to include PEF variability with a 10% cutoff either as an inclusion criteria or as a tool for subset analysis.     

Response to montelukast among subgroups of children aged 2 to 14 years with asthma

BACKGROUND: Determining who responds to asthma therapies, particularly leukotriene modifiers, continues to be explored. OBJECTIVE: We sought to identify patient characteristics predictive of response to montelukast. METHODS: We used data from 2 clinical trials in which children with asthma received either montelukast or placebo. Symptoms, beta-agonist use, and unanticipated health resource use caused by asthma were recorded in validated daily diaries for children 2 to 5 (n = 689) and 6 to 14 (n = 336) years old. We defined primary end points of days without asthma in 2- to 5-year-old patients (24 hours without symptoms, beta-agonist use, or asthma attack) and change in percent predicted FEV(1) in 6- to 14-year-old children. Asthma attack was defined by the use of rescue oral corticosteroids or by an unscheduled visit to a medical provider. Patients were grouped according to baseline characteristics, such as family history of asthma, personal history of allergy, frequency of asthma symptoms, eosinophilia, and concomitant use of inhaled corticosteroids or cromolyn. We examined the stratum-specific effects of montelukast on the percentage of days without asthma, change in percent predicted FEV(1), asthma attack, and a variety of secondary symptom and FEV(1) end points. RESULTS: We did not identify characteristics that predicted response to montelukast in either preschool or 6- to 14-year-old children. These findings were consistent across all symptom and FEV(1) outcomes. There was also no differential response to montelukast in either age group when asthma attack was the outcome. CONCLUSION: The patient characteristics studied do not appear to provide an indication of who will benefit most from treatment with montelukast.     

Impact and modulation of nasal obstruction

Nasal obstruction, the leading symptom of allergic rhinitis, results from the combined activity of early- and late-phase allergic reactions. Desloratadine inhibits both early- and late-phase inflammatory mediators in vitro . Thus, double-blind, placebo-controlled, randomized, crossover trials were conducted to assess the efficacy of desloratadine against nasal obstruction, measured objectively and subjectively, during controlled exposure of patients with seasonal allergic rhinitis to allergen. Positive results were obtained in three single-dose studies; desloratadine 5 mg resulted in a greater improvement from baseline than did placebo in the total symptom score and the nasal obstruction symptom score ( P  ≤ 0.02). Desloratadine was more effective than placebo in a multiple-dose study; desloratadine 5 mg was given once daily for 7 days, and a 6-h allergen challenge was administered at the end of treatment compared with placebo. Desloratadine treatment was associated with less deterioration from baseline in the mean nasal airflow ( P  < 0.05) and in the mean severity score for the symptom of nasal obstruction ( P  < 0.03). Desloratadine significantly reduces the severity of nasal obstruction in patients with seasonal allergic rhinitis.     

Effect of combined montelukast and desloratadine on the early asthmatic response to inhaled allergen

BACKGROUND: The early asthmatic response (EAR) to inhaled allergen results from IgE-mediated release of multiple mast-cell mediators, including leukotrienes and histamine, both of which cause bronchoconstriction. Combination therapy directed at blocking the effects of both mediators might protect against the EAR better than either therapy alone. OBJECTIVE: We sought to evaluate the effect of desloratadine and montelukast, administered alone and in combination, on the EAR to inhaled allergen. METHODS: Ten adults with mild-to-moderate atopic asthma participated in a randomized, 4-way crossover study design comparing placebo, 5 mg of desloratadine, 10 mg of montelukast, and the combination administered at 26 hours and 2 hours before each allergen challenge conducted at least 7 days apart. The primary end point was the concentration of allergen that resulted in a 20% decrease in FEV1 (PC20). RESULTS: The geometric mean allergen PC20 (mean log +/- SEM) for combination therapy, montelukast, desloratadine, and placebo was 697 U/mL (2.8433 +/- 0.3253), 338 U/mL (2.5295 +/- 0.2979), 123 U/mL (2.0883 +/- 0.2102), and 104 U/mL (2.0166 +/- 0.2553), respectively (n = 9; P < .00001, ANOVA). Montelukast increased the allergen PC20 4.8-fold, and combination therapy increased the allergen PC20 8.9-fold. The effect of the combination was greater than that with montelukast alone (P < .02). Desloratadine treatment was no different than placebo. CONCLUSIONS: The early response to inhaled allergen was unchanged after desloratadine therapy and partially inhibited with montelukast therapy. The combination of desloratadine and montelukast provided superior efficacy to either blocker administered alone. Investigations into the possible mechanisms of the enhanced inhibition are necessary.     

Effect of desloratadine versus placebo on nasal airflow and subjective measures of nasal obstruction in subjects with grass pollen-induced allergic rhinitis in an allergen-exposure unit

BACKGROUND: Unlike many antihistamines, desloratadine can reduce nasal congestion in patients with seasonal allergic rhinitis (SAR). OBJECTIVE: We compared the effects of 5 mg of desloratadine and placebo on nasal airflow and SAR symptoms, including nasal congestion, in response to grass pollen in an allergen-exposure unit. METHODS: In a randomized, double-blind, placebo-controlled, crossover trial, 47 subjects with histories of SAR received desloratadine or placebo every morning for 7 days and, after a 10-day washout period, were crossed over to the other treatment arm for 7 days. Subjects underwent a 6-hour allergen exposure on day 7 of each treatment period. Nasal airflow and nasal secretion weights were measured before and every 30 minutes during allergen exposure; SAR symptoms (including nasal congestion) were scored before exposure and every 15 minutes thereafter. RESULTS: Nasal obstruction, as measured by nasal airflow, was less severe with desloratadine than with placebo (P <.02). Individual and combined SAR symptom severity scores, including nasal congestion and sneezing, were significantly lower with desloratadine than with placebo (all P < or =.003). Within 30 minutes of allergen exposure, less severely decreased nasal airflow (P <.02), less nasal secretions (P <.001), and less severe symptoms, including nasal congestion (P <.002), rhinorrhea, and sneezing, occurred with desloratadine compared with placebo, and this continued throughout (0-6 hours) allergen exposure. Desloratadine was well tolerated, with an adverse event profile similar to that of placebo. CONCLUSION: In subjects with allergen-induced SAR symptoms, desloratadine significantly reduced the severity of nasal obstruction and accompanying complaints of nasal congestion and other SAR symptoms compared with the effects of placebo.     

Desloratadine improves quality of life and symptom severity in patients with allergic rhinitis

BACKGROUND: Desloratadine is associated with decreased signs and symptoms and improved nasal airflow in multiple clinical trials in patients with allergic rhinitis (AR). The effect of desloratadine on quality of life (QOL) in AR has not been widely reported to date. We compared the effects of desloratadine and placebo on QOL in seasonal AR using validated, disease-specific measures. METHODS: This was a multicenter, double-blind, randomized, parallel-group study of desloratadine 5 mg or placebo daily for 2 weeks in patients with symptomatic seasonal AR. QOL was assessed at baseline and at day 14 using the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). AR signs/symptoms and the global response to therapy were measured at baseline and at day 14; signs/symptoms were also rated AM/PM in patient diaries. Adverse events (AE) were recorded. RESULTS: Overall 234 patients received desloratadine and 249 received placebo. At day 14 desloratadine was associated with a significantly larger improvement from baseline in the mean total RQLQ score vs placebo (P = 0.0003). Desloratadine also led to significant improvements from baseline in all RQLQ sub-domains (P < or = 0.043). At day 14 significant decreases from baseline were noted in the desloratadine group for total nasal (P = 0.0003), total non-nasal (P = 0.001) and total symptoms scores (P = 0.0001). Morning AR symptoms were significantly decreased in the desloratadine group after 1 day of treatment. Desloratadine was well tolerated, with an AE rate similar to placebo. CONCLUSION: Significant reductions in signs and symptoms of AR with desloratadine treatment were accompanied by improved disease-specific QOL measures.     

Desloratadine therapy for symptoms associated with perennial allergic rhinitis.

BACKGROUND: Perennial allergic rhinitis (PAR) has a substantial negative social and economic impact. Recent studies emphasize the potential seriousness of PAR and the need for improved treatment of this condition. OBJECTIVE: To confirm the efficacy and safety of the H1-antihistamine desloratadine in reducing the symptoms of PAR in a randomized, double-blind, placebo-controlled trial. METHODS: Patients with PAR (N = 1,179) from 67 US/international centers received desloratadine, 5 mg once daily, or identical placebo tablets. The primary efficacy measure was the change from baseline to week 4 in average morning and evening reflective total symptom scores (TSSs). Secondary end points included changes from baseline in total nasal and nonnasal symptom scores and peak nasal inspiratory flow (PNIF) rates. RESULTS: Desloratadine was significantly more effective than placebo in reducing morning and evening reflective TSSs for each week and during weeks 1 through 4 (P = .001). Mean changes in TSSs during the 4-week study were -3.9 (26.6% reduction) and -3.2 (22.3% reduction) for the desloratadine and placebo groups, respectively (P = .001, desloratadine vs placebo). With desloratadine therapy, significant improvements were also seen in secondary efficacy end points compared with placebo use (total nasal and nonnasal symptom scores: P < or = .04). Improvements in mean morning PNIF were significantly greater in the desloratadine-treated group than in the placebo group (P = .03). CONCLUSIONS: These results confirm and extend previous findings that desloratadine is safe and is associated with a statistically significant reduction in nasal and nonnasal symptoms in patients with PAR. Objective nasal airflow, evaluated by PNIF, was statistically significantly improved after desloratadine treatment.     

Advances in allergy management

Our understanding of the pathophysiology of allergy has moved to the molecular level, while study of epidemiology and genetics has revealed risks of developing allergies based on environmental and genetic profiles, and pharmacoeconomic data have enabled accurate measurement of the immense burden of allergic disease. These advances in allergy research have affected its management, particularly the search for new antiallergy therapies. New therapies should intervene in the systemic allergy inflammatory cascade and provide clinical efficacy that extends to multiple allergic disease states. In addition, these new therapies should present no additional safety issues, offer improvements over existing therapies, and have an impact on disease-impaired quality of life. In vitro studies show that desloratadine, a new, once-daily, nonsedating, selective histamine H₁-receptor antagonist, blocks the systemic allergy cascade at multiple points. Desloratadine 5 mg once daily relieves the symptoms of chronic idiopathic urticaria and of both seasonal (SAR) and perennial allergic rhinitis. In patients with concomitant asthma and SAR, asthma symptoms are relieved and β₂-agonist medication use is decreased by desloratadine. Unlike many other second-generation histamine H₁-receptor antagonists, desloratadine provides the added benefit of efficacy against nasal obstruction in SAR. Desloratadine improves quality of life by decreasing the impact of allergic symptoms on sleep and on daily activities.     

Comparative efficacy and anti-inflammatory profile of once-daily therapy with leukotriene antagonist or low-dose inhaled corticosteroid in patients with mild persistent asthma.

BACKGROUND: Current guidelines advocate the use of preventative anti-inflammatory therapy for mild persistent asthma. OBJECTIVE: We compared the efficacy and anti-inflammatory profiles of a leukotriene receptor antagonist and a low dose of inhaled corticosteroid in patients with mild persistent asthma. METHODS: Twenty-one adult patients with mild asthma received 4 weeks of either once-daily inhaled hydrofluoroalkane triamcinolone acetonide (450 microg/day ex-actuator dose) or oral montelukast (10 mg/day) in a randomized, placebo-controlled, single-blinded crossover study. Measurements were made before and after 2 and 4 weeks of each treatment. RESULTS: At the endpoint (after 4 weeks), triamcinolone and montelukast had improved the primary outcome (provocative dose of methacholine required to produce a 20% fall in FEV(1)) in comparison with placebo (P <.05), there being no difference between the treatments (1.09-fold; 95% CI 0.73 to 1.63). Triamcinolone was better than placebo or montelukast for effects on all other surrogate inflammatory markers (P <.05), including exhaled nitric oxide, blood eosinophils, serum eosinophil cationic protein, plasma intracellular circulating adhesion molecule 1, and plasma E-selectin. Both treatments improved (P <.05) morning and evening peak flow, nighttime beta2-agonist use, and symptoms in comparison with placebo, though triamcinolone was better than montelukast (P <.05) with regard to peak flow. Triamcinolone produced suppression (P <.05) of overnight urinary cortisol/creatinine and serum osteocalcin. CONCLUSION: Once-daily inhaled corticosteroid and leukotriene antagonist improved the primary outcome variable of bronchial hyperresponsiveness to a similar degree.     

Efficacy of montelukast during the allergy season in patients with chronic asthma and seasonal aeroallergen sensitivity.

BACKGROUND: Montelukast has proven efficacy in the treatment of chronic asthma and seasonal allergic rhinitis, but it has not been evaluated in the subpopulation of asthmatic patients with seasonal asthma symptoms. OBJECTIVE: To determine the effectiveness of montelukast treatment in improving the control of asthma symptoms during the allergy season in patients with active asthma and seasonal aeroallergen sensitivity. METHODS: Adults with a history of chronic asthma who are also symptomatic during the allergy season and with skin test sensitivity to seasonal aeroallergens were enrolled in a randomized, parallel-group, multicenter study with a 1-week, single-blind, placebo run-in period followed by 3 weeks of double-blind treatment during the spring of 2004. After the run-in period, eligible patients were randomly assigned to receive either oral montelukast (10 mg) or placebo. Daytime and nighttime asthma symptom scores, beta-agonist use, and morning and evening peak expiratory flow rates were recorded daily using an electronic diary. The primary end point was mean change from baseline to week 3 in the daytime asthma symptom score. RESULTS: Of 455 randomized patients, 433 completed the study. Compared with placebo, treatment with montelukast resulted in a significant improvement from baseline in the daytime asthma symptom score (-0.54 vs -0.34; P = .002) and in beta-agonist use, nighttime symptoms, and peak expiratory flow rates. Few patients in the montelukast and placebo groups discontinued study participation because of asthma (1.3% and 3.0%, respectively). CONCLUSION: In patients with chronic asthma and seasonal aeroallergen sensitivity, montelukast treatment provided significant asthma control during the allergy season compared with placebo.     

A comparison of topical budesonide and oral montelukast in seasonal allergic rhinitis and asthma

BACKGROUND: Allergic rhinitis and asthma commonly coexist and are both mediated by similar inflammatory mechanisms. Leukotriene antagonists may therefore be an alternative to corticosteroid therapy. OBJECTIVE: To compare oral montelukast with inhaled plus intranasal budesonide in patients with seasonal allergic rhinitis and asthma. PATIENTS AND METHODS: A single-blind double-dummy placebo-controlled crossover study was performed comparing once daily 10 mg oral montelukast with 400 microg inhaled plus 200 microg intranasal budesonide in 12 patients with allergic rhinitis and asthma: mean (S.E.) age 34.0 years (2.7), forced expiratory volume in 1 s (FEV1) 91.2 (3.8)% predicted. Each treatment was for 2 weeks with a 1-week placebo run-in and washout. Measurements were made after each active treatment and placebo for: adenosine monophosphate bronchial challenge, exhaled and nasal nitric oxide. Patients also recorded their domiciliary peak expiratory flow, nasal peak inspiratory flow, asthma and seasonal allergic rhinitis symptoms. RESULTS: There were no significant differences between the placebos for any measurement. For adenosine monophosphate PC20, geometric mean fold differences (95% confidence interval (CI) for difference) were 6.4 (2.2-18.6) for placebo vs. budesonide, 2.9 (1.0-8.4) for placebo vs. montelukast, and 2.1 (1.1-4.5) for budesonide vs. montelukast. For exhaled nitric oxide (p.p.b.) there was significant (P < 0.05) suppression with both montelukast (10.9) and budesonide (10.1) compared with placebo (18.8). For nasal nitric oxide and nasal peak flow there were only significant differences with budesonide compared with placebo. Both treatments reduced total seasonal allergic rhinitis symptoms but only budesonide had a significant effect on nasal symptoms. CONCLUSION: Once-daily inhaled plus intranasal budesonide and once daily montelukast showed comparable efficacy on lower airway, but only the budesonide had significant efficacy on upper airway inflammatory markers. Both treatments significantly reduced allergic rhinitis symptoms.     

Immunological and clinical changes in allergic asthmatics following treatment with omalizumab

IgE plays a key role in allergic asthma. We investigated whether omalizumab treatment of patients with moderate to severe allergic asthma leads to changes in inflammatory mediators and clinical symptoms. This sub-study was conducted on 35 patients with a positive skin prick test (SPT) requiring daily administration of beclomethasone dipropionate (500-1,000 microg), who participated in a multicentre, randomised, double-blind, placebo-controlled study. Omalizumab or placebo was administered at 0.016 mg/kg/IgE every 4 weeks. Patients recorded peak expiratory flow, asthma symptom score and beta(2)-agonist use in daily diaries and spirometry was performed at each visit. beta(2)-Agonist use and SPT wheal reaction decreased significantly (p < 0.05). Circulating levels of IL-5, IL-6, IL-8, IL-10, IL-13 and s-ICAM were measured before and after 16 weeks of treatment. IL-13 and s-ICAM were measured before and after 16 weeks of treatment. IL-13 decreased significantly (p < 0.01). IL-5 and IL-8 decreased in the omalizumab group compared to baseline. The other circulating mediators did not demonstrate any changes. Histamine release was significantly reduced (p < 0.01). Airway resistance (p < 0.05) and the provocative concentration inducing a 20% decrease in FEV(1) (p < 0.05) were measured before, after 16 weeks, and 3 months after completion of treatment. Both parameters decreased significantly (p < 0.05). Peripheral eosinophil count decreased significantly compared to placebo (p < 0.01). These findings suggest that omalizumab has potential as a novel treatment for allergic asthma.     

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.     

Determining economic feasibility of fluticasone propionate-salmeterol vs montelukast in the treatment of persistent asthma using a net benefit approach and cost-effectiveness acceptability curves.

BACKGROUND: The choice of treatment can have a major impact on the total costs associated with asthma care. OBJECTIVE: To determine the relative cost-effectiveness of twice-daily treatment with inhaled fluticasone propionate-salmeterol via Diskus, 100/50 microg, with that of once-daily treatment with oral montelukast as initial maintenance therapy in patients with persistent asthma uncontrolled with a short-acting beta2-agonist alone. METHODS: Data from a randomized, double-blind, double-dummy, 12-week clinical trial were analyzed. Efficacy end points included (1) symptom-free days (SFDs) during the 12-week period and (2) a 12% or greater increase in forced expiratory volume in 1 second (FEV1) from baseline. The economic analysis was performed from a payer's perspective, and hence only direct costs were included in the analysis. The incremental cost-effectiveness ratio (ICER), which is the mean difference in average costs divided by the mean difference in average effectiveness, was calculated for both effectiveness outcomes (SFDs and FEV1). RESULTS: For the SFDs end point, the ICER for fluticasone propionate-salmeterol vs montelukast was $2.87 (95% confidence interval, -$1.08 to $6.65), indicating that it costs, on average, an extra $2.87 per day for an additional SFD with fluticasone propionate-salmeterol than with montelukast. With regard to FEV1, the ICER was $1.79 (95% confidence interval, -$0.72 to $3.86), indicating that it costs, on average, an extra $1.79 per day to achieve a lung function improvement of 12% or greater from baseline with fluticasone propionate-salmeterol than with montelukast. At a widely acceptable ceiling ratio of $9.95 per day, the probability of fluticasone propionate-salmeterol being more cost-effective than montelukast was 99.8% for SFDs and was almost 100% for an FEV1 improvement of 12% of greater. CONCLUSIONS: Treating 2 main components of asthma, inflammation and smooth muscle dysfunction, using fluticasone propionate-salmeterol is more cost-effective than using a single mediator antagonist alone, such as montelukast, as initial maintenance therapy for persistent asthma in patients treated with a short-acting beta2-agonist only.     

Comparison of the efficacy and safety of bilastine 20 mg vs desloratadine 5 mg in seasonal allergic rhinitis patients

Background: Bilastine is a novel, nonsedating H₁‐antihistamine developed for symptomatic treatment of Allergic Rhinitis and Chronic Idiopathic Urticaria. The objective of this study was to compare the efficacy and safety of bilastine 20 mg vs placebo and desloratadine 5 mg in subjects with seasonal allergic rhinitis (SAR). Methods: This randomized, double blind, placebo‐controlled, parallel‐group multicentre study evaluated the effect of 2 weeks’ treatment with bilastine 20 mg, desloratadine 5 mg or matched placebo once daily, in 12–70 years old symptomatic SAR patients. All subjects assessed the severity of nasal (obstruction, rhinorrhoea, itching, and sneezing) and nonnasal (ocular itching, tearing, ocular redness, itching of ears and/or palate) symptoms on a predetermined scale to provide a total symptom score (TSS), composed of nasal and nonnasal symptom scores (NSS and NNSS, respectively). The primary efficacy measure was the area under the curve (AUC) for the TSS over the entire treatment period. Results: Bilastine 20 mg significantly reduced the AUC of TSS to a greater degree from baseline compared to placebo (98.4 with bilastine vs 118.4 with placebo; P < 0.001), but not compared to desloratadine 5 mg (100.5). Bilastine 20 mg was not different from desloratadine 5 mg but significantly more effective than placebo in improving the NSS, NNSS, and rhinitis‐associated discomfort scores (P < 0.05), and rhinoconjunctivitis quality of life questionnaire total (P < 0.005) and four out of seven individual domain (P < 0.05) scores. The incidence of treatment emergent adverse events was similar for bilastine (20.6%), desloratadine (19.8%), and placebo (18.8%). Conclusion: Bilastine 20 mg once daily was efficacious, safe and not different from desloratadine 5 mg once daily in the treatment of SAR symptoms.