Step-Up Therapy in Black Children and Adults with Poorly Controlled Asthma.

BACKGROUND: Morbidity from asthma is disproportionately higher among black patients than among white patients, and black patients constitute the minority of participants in trials informing treatment. Data indicate that patients with inadequately controlled asthma benefit more from addition of a long-acting beta-agonist (LABA) than from increased glucocorticoids; however, these data may not be informative for treatment in black patients. METHODS: We conducted two prospective, randomized, double-blind trials: one involving children and the other involving adolescents and adults. In both trials, the patients had at least one grandparent who identified as black and had asthma that was inadequately controlled with low-dose inhaled glucocorticoids. We compared combinations of therapy, which included the addition of a LABA (salmeterol) to an inhaled glucocorticoid (fluticasone propionate), a step-up to double to quintuple the dose of fluticasone, or both. The treatments were compared with the use of a composite measure that evaluated asthma exacerbations, asthma-control days, and lung function; data were stratified according to genotypic African ancestry. RESULTS: When quintupling the dose of fluticasone (to 250 µg twice a day) was compared with adding salmeterol (50 µg twice a day) and doubling the fluticasone (to 100 µg twice a day), a superior response occurred in 46% of the children with quintupling the fluticasone and in 46% of the children with doubling the fluticasone and adding salmeterol (P = 0.99). In contrast, more adolescents and adults had a superior response to added salmeterol than to an increase in fluticasone (salmeterol-low-dose fluticasone vs. medium-dose fluticasone, 49% vs. 28% [P = 0.003]; salmeterol-medium-dose fluticasone vs. high-dose fluticasone, 49% vs. 31% [P = 0.02]). Neither the degree of African ancestry nor baseline biomarkers predicted a superior response to specific treatments. The increased dose of inhaled glucocorticoids was associated with a decrease in the ratio of urinary cortisol to creatinine in children younger than 8 years of age. CONCLUSIONS: In contrast to black adolescents and adults, almost half the black children with poorly controlled asthma had a superior response to an increase in the dose of an inhaled glucocorticoid and almost half had a superior response to the addition of a LABA. (Funded by the National Heart, Lung, and Blood Institute; BARD ClinicalTrials.gov number, NCT01967173.).

Randomized, placebo-controlled study of cetirizine and loratadine in children with seasonal allergic rhinitis.

BACKGROUND: Pharmacologic treatment is a mainstay of allergy therapy and many caregivers use over-the-counter antihistamines for the treatment of seasonal allergic rhinitis (SAR) symptoms in children. OBJECTIVE: To assess the efficacy and safety of cetirizine 10 mg syrup versus loratadine 10 mg syrup versus placebo syrup in a randomized double-blind study of children, ages 6-11 years, with SAR. METHODS: This randomized, double-blind, parallel-group, placebo-controlled study was conducted at 71 U.S. centers during the spring tree and grass pollen season. After a 1-week placebo run-in period, qualified subjects were randomized to once-daily cetirizine 10 mg (n = 231), loratadine 10 mg (n = 221), and placebo (n = 231) for 2 weeks. The primary efficacy end point was change from baseline in the subject's mean reflective total symptom severity complex (TSSC) score over 14 days. RESULTS: Children treated with cetirizine experienced significantly greater TSSC score reductions versus children treated with placebo over 14 days (least square mean change, -2.1 versus -1.6; p = 0.006). The differences in TSSC score improvement over 14 days between the cetirizine versus loratadine groups (-2.1 versus -1.8; p = 0.124) and between the loratadine versus placebo groups (-1.8 versus -1.6; p = 0.230) were not statistically significant. Predominant adverse events in the cetirizine, loratadine, and placebo groups were headache (3.5, 3.6, and 3.1%, respectively) and pharyngitis (3.5, 2.7, and 3.5%, respectively). Somnolence was reported in three subjects (1.3%) treated with cetirizine and in none of the other subjects. CONCLUSION: Cetirizine 10 mg was statistically significantly more efficacious than placebo in the treatment of SAR symptoms in children ages 6-11 years. Symptom improvement was not significantly different between the loratadine 10 mg and placebo groups.

Once-daily indacaterol 75 µg in moderate- to-severe COPD: results of a Phase IV study assessing time until patients' perceived onset of effect.

BACKGROUND: Indacaterol 75 µg once daily is a long-acting ß2 agonist approved for maintenance bronchodilator treatment in patients with chronic obstructive pulmonary disease (COPD). The purpose of this study was to evaluate patients' perception of onset of effect with a single dose. METHODS: In this double-blind, crossover, Phase IV study, 40 patients were randomized to receive a single dose of indacaterol 75 µg or placebo via a dry powder inhaler device. The primary variable was time until patient's perception of onset of effect, using a simple self-administered (nonvalidated) questionnaire that patients answered at nine protocol-specified time points. Exploratory variables included change in forced expiratory volume in 1 second (FEV1) and change in percent predicted FEV1 from predose to postdose (determined 60-75 minutes postdose). RESULTS: The least-squares mean time to patient's perception of onset of effect was 25.4 minutes and 23.9 minutes for indacaterol and placebo, respectively. There was no significant effect for treatment, period, or sequence on the time to patient's perception. In addition, no statistically significant differences between treatments were observed for patient's global satisfaction with onset of effect and global expectation of treatment adherence. For the exploratory variable change in FEV1 from predose to postdose, indacaterol showed superiority over placebo with a clinically relevant least-squares mean treatment difference of 0.12 L (P<0.0001). There was little or no association between patient's perception of time to onset of effect and change in FEV1, or change in percent predicted FEV1. Both treatments were well tolerated. CONCLUSION: A single dose of indacaterol 75 µg did not separate from placebo in terms of patient perception of onset, although there was an improvement in FEV1 for indacaterol compared with placebo. Development and use of a validated questionnaire may be needed to address the inconsistency in evaluating this patient-related outcome.

Effect of cetirizine on symptom severity and quality of life in perennial allergic rhinitis.

The effect of cetirizine on quality of life (QOL) in subjects with perennial allergic rhinitis (PAR) has been previously evaluated using generic instruments. While generic QOL tools are used across various conditions, disease-specific instruments evaluate the impact of treatment on areas that are affected by that particular condition. This study evaluated the effect of cetirizine on symptom severity and health-related QOL, using a disease-specific instrument, in adults with PAR. This randomized, double-blind, placebo-controlled study was conducted at 15 U.S. centers outside the pollen allergy season. After a 1-week placebo run-in period, qualified subjects aged 18-65 years with PAR were randomized to once-daily cetirizine 10 mg (n = 158) or placebo (n = 163) for 4 weeks. Change from baseline in total symptom severity complex (TSSC) and overall Rhinitis Quality of Life Questionnaire (RQLQ) scores were primary efficacy end points. Cetirizine produced significantly greater improvements in mean TSSC for each treatment week (p < 0.05) and for the entire 4-week treatment period (p = 0.005) compared with placebo. After 4 weeks, cetirizine-treated subjects reported significantly greater overall improvement in RQLQ scores compared with placebo-treated subjects (p = 0.004). After 1 week, cetirizine produced significant improvements in the nasal symptoms, practical problems, and activities RQLQ domain scores compared with placebo (p < 0.05). After 4 weeks, cetirizine-treated subjects reported significant reductions in these RQLQ domain scores and in emotion domain scores compared with placebo-treated subjects (p < 0.05). Cetirizine 10 mg daily produced significant improvements in symptom severity and allergic rhinitis-related QOL compared with placebo in adults with PAR.

Efficacy and safety of once-daily fluticasone furoate/vilanterol (100/25 mcg) versus twice-daily fluticasone propionate/salmeterol (250/50 mcg) in COPD patients.

BACKGROUND: Fluticasone furoate/vilanterol (FF/VI) is an inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA), recently approved as once-daily maintenance therapy for COPD. We compared the lung function effects of FF/VI with those of twice-daily fluticasone propionate/salmeterol (FP/SAL). METHODS: Three 12 week studies comparing FF/VI and FP/SAL were conducted. Patients aged ≥40 years with moderate-to-very severe COPD were randomized to receive double-blind, double-dummy FF/VI 100/25 mcg once-daily, or FP/SAL 250/50 mcg twice-daily for 12 weeks following a 2 week placebo run-in period. The primary endpoint of each study was change from baseline trough in 0-24 h weighted mean FEV(1) (wmFEV(1)) on Day 84. Safety was also assessed. RESULTS: In Study 1 (HZC113109) (intent-to-treat n: FF/VI = 260; FP/SAL = 259), the increase from baseline in 0-24 h wmFEV(1) was significantly greater with FF/VI than FP/SAL (Δ80 mL, P < 0.001). In Study 2 (HZC112352) (intent-to-treat n: FF/VI = 259; FP/SAL = 252) and Study 3 (RLV116974) (intent-to-treat n: FF/VI = 412; FP/SAL = 416), the increase from baseline in 0-24 h wmFEV(1) was not significantly greater with FF/VI than FP/SAL (Δ29 mL, P = 0.267; Δ25 mL, P = 0.137). The treatment difference was statistically but not clinically significant in a pooled analysis (Δ41 mL, P < 0.001). Pooled adverse events (FF/VI 27%; FP/SAL 28%) and serious adverse events (FF/VI 2%; FP/SAL 3%) were similar between treatments. CONCLUSIONS: Our data suggest that once-daily FF/VI 100/25 mcg provides FEV(1) improvement in COPD that is at least comparable with that conferred by twice-daily FP/SAL 250/50 mcg, although interpretation is limited by differences in individual study outcomes. The safety profiles of FF/VI 100/25 mcg and FP/SAL 250/50 mcg are similar. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov: NCT01323634; NCT01323621; NCT01706328. GlaxoSmithKline study codes: HZC113109; HZC112352; RLV116974.

Fluticasone/Formoterol combination therapy compared with monotherapy in adolescent and adult patients with mild to moderate asthma.

OBJECTIVES: This study investigated the efficacy and tolerability of a new asthma therapy combining fluticasone propionate and formoterol fumarate (fluticasone/formoterol)*, administered twice daily (BID) via a single aerosol inhaler, compared with fluticasone propionate (fluticasone) or formoterol fumarate (formoterol) administered alone, in patients with mild to moderate asthma. METHODS: Patients aged ≥12 years were evenly randomized to 12 weeks of treatment with fluticasone/formoterol (100/10 µg BID), fluticasone (100 µg BID), or formoterol (10 µg BID), in this multicenter, double-blind, parallel-group, study. The 2 coprimary end points were: (1) change in forced expiratory volume in 1 second (FEV(1)) from morning predose at baseline to predose at week 12 for the comparison of the combination product with formoterol alone; and (2) change in FEV(1) from morning predose at baseline to 2 hours postdose at week 12 for the comparison of the combination product with fluticasone alone. The secondary objective was to demonstrate the efficacy of fluticasone/formoterol using other pulmonary function tests and clinical end points. Tolerability was assessed based on adverse events, clinical laboratory tests and vital sign evaluations. RESULTS: Statistically significant differences were demonstrated for the 2 coprimary end points. Fluticasone/formoterol combination therapy showed significantly greater improvements from baseline to end of study in the change in predose FEV(1) compared with formoterol (least squares [LS] mean treatment difference, 0.118 L [95% CI, 0.034-0.201; P = 0.006]) and the change in predose compared with 2 hours postdose FEV(1) versus fluticasone (LS mean treatment difference, 0.122 L [95% CI, 0.040-0.204; P = 0.004]). Statistical analyses of the secondary efficacy endpoints revealed that evaluations of lung function, asthma exacerbations, asthma symptoms, rescue medication use and asthma control were supportive overall of the superior efficacy of fluticasone/formoterol combination therapy compared with its individual components; were supportive overall of the efficacy of fluticasone/formoterol combination therapy compared with its individual components. Since the secondary endpoints were analyzed using the sequential gatekeeper approach, only the mean change from baseline to final week in morning peak expiratory flow rate between the combination-therapy and formoterol groups returned statistically significant results (least squares mean difference, 20.05 [95% CI, 7.631-32.472; P = 0.002]). The fluticasone/formoterol combination therapy had a good tolerability profile over the 12-week treatment period. CONCLUSIONS: Fluticasone/formoterol had a good tolerability profile and showed statistically superior efficacy for the two co-primary endpoints compared to fluticasone or formoterol, in adolescents and adults with mild to moderate asthma. ClinicalTrials.gov identifier: NCT00394199.

Safety and efficacy of once-daily treatment with beclomethasone dipropionate nasal aerosol in subjects with perennial allergic rhinitis.

Intranasal corticosteroids are recommended as first-line therapy for the treatment of the symptoms of persistent allergic rhinitis (AR). Since the phase-out of chlorofluorocarbon nasal aerosols, intranasal corticosteroids have been available only as aqueous nasal sprays. This study was designed to assess the efficacy, safety, and quality-of-life benefits of beclomethasone dipropionate (BDP) hydrofluoroalkane nasal aerosol in subjects with perennial AR (PAR). After a 7- to 21-day placebo run-in period, eligible subjects aged ≥12 years with PAR were randomized to 6 weeks of once-daily treatment with BDP nasal aerosol at 320 µg or placebo. Reflective and instantaneous total nasal symptom scores (rTNSS and iTNSS, respectively), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score, and physician-assessed total nasal symptom score were evaluated. The primary end point was change from baseline in average morning (A.M.) and evening (P.M.) subject-reported rTNSS over the 6-week treatment period. Safety and tolerability were also assessed. Treatment with BDP nasal aerosol showed significantly greater improvement in average A.M. and P.M. rTNSS compared with placebo (mean treatment difference, -0.84; 95% confidence interval, -1.2, -0.5; p < 0.001). Greater improvements in rTNSS were reported as early as day 1 and were maintained throughout the 6-week treatment period with the exception of day 2. Greater improvements were seen for all four individual nasal symptoms (nasal congestion, nasal itching, rhinorrhea, and sneezing) with BDP nasal aerosol compared with placebo. Similarly, significant improvements were seen in average A.M. and P.M. iTNSS (p < 0.001) and RQLQ score (p = 0.001) with BDP nasal aerosol compared with placebo. In addition, BDP nasal aerosol treatment was well tolerated, and its safety profile was comparable to that of placebo. This clinical study indicated that treatment with BDP nasal aerosol provides statistically significant and clinically meaningful nasal symptom relief accompanied by improved quality of life in subjects with PAR. Additionally, treatment with BDP nasal aerosol was well tolerated with a safety profile comparable to that of placebo. This study was part of the clinical trial NCT01134705 registered in www.ClinicalTrials.gov.

Two-week comparison study of olopatadine hydrochloride nasal spray 0.6% versus azelastine hydrochloride nasal spray 0.1% in patients with vasomotor rhinitis.

Olopatadine hydrochloride nasal spray 0.6% (OLO) and azelastine nasal spray 137 micrograms (AZE) are effective in treating allergic rhinitis and AZE is indicated for nonallergic vasomotor rhinitis (VMR). This study evaluates the relative safety and efficacy of OLO and AZE in patients with VMR. This randomized, double-blind, parallel-group, multicenter study compared OLO (an investigational use) with AZE over 14 days in patients (n = 129) ≥12 years of age with chronic VMR. Efficacy included the severity of nasal symptom scores. Safety included adverse events (AEs) and nasal examinations. Patient perceptions of treatment satisfaction and changes in allergy condition were determined using the Treatment Satisfaction Questionnaire for Medication and Patient Global Assessment scores. In the OLO and AZE groups, reflective scores for individual nasal symptoms (nasal congestion, rhinorrhea, postnasal drip, and sneezing) and total nasal VMR symptom scores decreased significantly from baseline to day 14 (p < 0.05). No significant between-group differences were observed (p > 0.05). No serious AEs were reported in either group. Overall, 22 and 20 AEs were reported in the OLO and AZE groups, respectively. The most common AE was taste disturbance, reported by three (5.3%) and six (10.3%) patients in the OLO and AZE groups, respectively. Patients in both groups reported similar treatment satisfaction scores and a majority of patients in both groups perceived an overall improvement in their rhinitis condition. OLO has a similar efficacy and safety profile to AZE for the management of VMR in patients ≥12 years of age.

Evaluation of olopatadine hydrochloride nasal spray, 0.6%, used in combination with an intranasal corticosteroid in seasonal allergic rhinitis.

The combination of intranasal antihistamines and intranasal corticosteroids results in superior relief of seasonal allergic rhinitis (SAR) symptoms compared with monotherapy. This study was designed to evaluate the safety and efficacy of olopatadine hydrochloride nasal spray, 0.6% (OLO), administered in combination with fluticasone nasal spray, 50 micrograms (FNS), relative to azelastine nasal spray, 0.1% (AZE), administered in combination with FNS in the treatment of SAR. This was a multicenter, double-blind, randomized, parallel-group comparison of OLO + FNS versus AZE + FNS administered for 14 days to patients > or =12 years of age with histories of SAR. Efficacy assessments recorded by patients in a daily diary included nasal symptom scores. Safety was evaluated based on adverse events (AEs). Pretreatment values for reflective total nasal symptoms scores (rTNSS) were similar for both treatment groups. The mean (SD) 2-week average rTNSS was 4.28 (2.63) for OLO + FNS and 4.15 (2.63) for AZE + FNS; these scores were not statistically different between treatment groups. No significant differences (p > 0.05) between OLO + FNS and AZE + FNS were observed for the average 2-week percent changes from baseline in rTNSS or in the individual nasal symptoms (nasal congestion, rhinorrhea, itchy nose, and sneezing). Compared with baseline, both groups had statistically significant improvement in rTNSS (p < 0.05). No serious AEs were reported in either group during the study period. Overall, 19 AEs were reported in the OLO + FNS group and 29 AEs were reported in the AZE + FNS group. OLO, when administered adjunctively with FNS, is effective, safe, and well-tolerated in patients with SAR.

Evaluation of olopatadine hydrochloride nasal spray, 0.6%, used in combination with an intranasal corticosteroid in seasonal allergic rhinitis.

The combination of intranasal antihistamines and intranasal corticosteroids results in superior relief of seasonal allergic rhinitis (SAR) symptoms compared with monotherapy. This study was designed to evaluate the safety and efficacy of olopatadine hydrochloride nasal spray, 0.6% (OLO), administered in combination with fluticasone nasal spray, 50 micrograms (FNS), relative to azelastine nasal spray, 0.1% (AZE), administered in combination with FNS in the treatment of SAR. This was a multicenter, double-blind, randomized, parallel-group comparison of OLO + FNS versus AZE + FNS administered for 14 days to patients ≥12 years of age with histories of SAR. Efficacy assessments recorded by patients in a daily diary included nasal symptom scores. Safety was evaluated based on adverse events (AEs). Pretreatment values for reflective total nasal symptoms scores (rTNSS) were similar for both treatment groups. The mean (SD) 2-week average rTNSS was 4.28 (2.63) for OLO + FNS and 4.15 (2.63) for AZE + FNS; these scores were not statistically different between treatment groups. No significant differences (p > 0.05) between OLO + FNS and AZE + FNS were observed for the average 2-week percent changes from baseline in rTNSS or in the individual nasal symptoms (nasal congestion, rhinorrhea, itchy nose, and sneezing). Compared with baseline, both groups had statistically significant improvement in rTNSS (p < 0.05). No serious AEs were reported in either group during the study period. Overall, 19 AEs were reported in the OLO + FNS group and 29 AEs were reported in the AZE + FNS group. OLO, when administered adjunctively with FNS, is effective, safe, and well-tolerated in patients with SAR.

Fluticasone propionate hydrofluoroalkane inhalation aerosol in patients receiving inhaled corticosteroids.

BACKGROUND: Inhaled corticosteroids (ICSs) delivered by metered-dose inhalers that contain chlorofluorocarbon propellants are being discontinued because of the harmful effects of chlorofluorocarbon on the ozone layer. Therefore, some metered-dose inhaler products are being reformulated with "ozone-friendly" hydrofluoroalkane propellants. OBJECTIVE: To evaluate treatment with fluticasone propionate hydrofluoroalkane inhalation aerosol, 88, 220, and 440 microg twice daily, vs placebo in patients with asthma receiving an ICS. METHODS: Randomized, double-blind, parallel-group, 12-week study. RESULTS: Mean morning predose percent predicted forced expiratory volume in 1 second increased by 2.2%, 3.2%, and 4.6% in the fluticasone propionate, 88-, 220-, and 440-microg twice-daily, groups, respectively, compared with an 8.3% decrease for placebo (P < .001 vs placebo for all groups). Secondary pulmonary function end points and asthma symptoms showed similar improvements compared with placebo. Discontinuation from the study due to lack of efficacy was 50% in the placebo group and 11%, 10%, and 6% in the fluticasone propionate, 88-, 220-, and 440-microg twice-daily, groups, respectively. At week 12, the probability of remaining in the study was 0.89, 0.90, and 0.94 for the fluticasone propionate, 88-, 220-, and 440-microg twice-daily, groups, respectively, vs 0.45 for the placebo group (P < .001 for all). Changes in 24-hour urinary cortisol excretion rates were similar among treatment groups. CONCLUSIONS: Fluticasone propionate hydrofluoroalkane, previously shown to be a clinically suitable alternative to fluticasone propionate chlorofluorocarbon, was effective and well tolerated. The ability to switch from fluticasone propionate chlorofluorocarbon and other chlorofluorocarbon-containing ICSs to fluticasone propionate hydrofluoroalkane without sacrificing asthma control or tolerability will facilitate a smooth transition to this nonchlorofluorocarbon-containing medicinal.

Effect of ciclesonide and fluticasone on hypothalamic-pituitary-adrenal axis function in adults with mild-to-moderate persistent asthma.

BACKGROUND: Despite their proven efficacy in the treatment and prevention of asthma exacerbations, current inhaled corticosteroids carry safety concerns, especially adrenal suppression. Ciclesonide (hydrofluoroalkane propellant) is a novel inhaled corticosteroid with few, if any, clinical adverse events. OBJECTIVE: To evaluate the potential effects of ciclesonide therapy on the dynamic cortisol response to sequential low- and high-dose cosyntropin stimulation in adults with mild-to-moderate persistent asthma. METHODS: This was a double-blind, randomized, placebo-controlled, 12-week study in adults with mild-to-moderate asthma. One hundred sixty-four patients were randomized and treated; 148 patients completed the study. Fluticasone propionate (chlorofluorocarbon propellant) was used as an active comparator. The doses administered were 320 microg of ciclesonide once daily, 320 microg of ciclesonide twice daily, and 440 microg of fluticasone propionate twice daily, all doses ex-actuator. RESULTS: For both ciclesonide groups, changes in mean low- and high-dose peak serum cortisol levels and in 24-hour urinary free cortisol levels corrected for creatinine were small vs baseline and comparable with placebo. For the fluticasone propionate group, significant reductions vs placebo in serum cortisol levels in response to high-dose cosyntropin stimulation and in 24-hour urinary free cortisol levels were observed. Oral candidiasis rates were 2.5% for 320-microg/d ciclesonide, 2.4% for 640-microg/d ciclesonide, and 22.0% for 880-microg/d fluticasone propionate. CONCLUSIONS: These findings confirm the safety of ciclesonide therapy, demonstrating that at doses up to 640 microg/d, the drug does not affect sensitive markers of adrenal function.

Montelukast effectively treats the nighttime impact of seasonal allergic rhinitis.

BACKGROUND: Nighttime problems constitute a significant burden on the quality of life of patients with seasonal allergic rhinitis (SAR). The aim of this study was to evaluate the effectiveness of montelukast on nighttime AR symptoms. METHODS: In seven multicenter, double-blind, parallel-group trials, nighttime problems were assessed as the nighttime symptoms score (NSS), an average of three individual symptom scores: difficulty going to sleep, nighttime awakening, and nasal congestion on awakening (each rated 0 = none to 3 = severe). Patients (aged 15-82 years) were randomized to receive montelukast, 10 mg (n = 1751), placebo (n = 1557), or the positive control loratadine, 10 mg (n = 1616). RESULTS: In a combined analysis, changes from baseline (mean +/- SE) in NSS were -0.28 +/- 0.01, -0.16 +/- 0.01, and -0.24 +/- 0.01 for the montelukast, placebo, and loratadine groups, respectively. Difference versus placebo in least-squares mean change from baseline were -0.11 (95% confidence interval, -0.14, -0.08; p < or = 0.001) for montelukast and -0.09 (-0.12, -0.06; p < or = 0.001) for loratadine. Strong baseline correlations (R > 0.70; p < 0.001) of NSS and two of its individual symptoms with the sleep domain of the validated Rhinoconjunctivitis Quality of Life Questionnaire support the validity and importance of measuring nighttime morbidity in SAR. Furthermore, a clinically important benefit of montelukast on the nighttime impact of SAR was shown using an analysis anchored on the Patient's Global Evaluation. CONCLUSION: These data underscore the importance of nighttime problems in patients with SAR and the need to treat nighttime symptoms. In these studies, montelukast significantly improved the NSS, a clinically relevant and valid measure in patients with SAR.

Efficacy of azelastine nasal spray in seasonal allergic rhinitis patients who remain symptomatic after treatment with fexofenadine.

BACKGROUND: Currently available oral second-generation antihistamines do not provide adequate symptom relief for many allergy patients. OBJECTIVE: To determine the ability of azelastine nasal spray to improve rhinitis symptoms in patients with seasonal allergic rhinitis who remained symptomatic after treatment with fexofenadine. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled, 2-week study in patients with moderate-to-severe seasonal allergic rhinitis. The study began with a 1-week, open-label lead-in period, during which patients received fexofenadine, 60 mg twice daily. Patients who improved less than 25% to 33% with fexofenadine were randomized to treatment with (1) azelastine nasal spray, 2 sprays per nostril twice daily; (2) azelastine nasal spray, 2 sprays per nostril twice daily, plus fexofenadine, 60 mg twice daily; or (3) placebo (saline) nasal spray and placebo capsules twice daily. The primary efficacy variable was the change from baseline to day 14 in the total nasal symptom score (TNSS), consisting of runny nose, sneezing, itchy nose, and nasal congestion symptom scores. RESULTS: A total of 334 patients who remained symptomatic after treatment with fexofenadine were included in the efficacy analysis. After 2 weeks of treatment, azelastine nasal spray (P = .007) and azelastine nasal spray plus fexofenadine (P = .003) significantly improved the TNSS compared with placebo. Azelastine nasal spray monotherapy was as effective as the combination of azelastine nasal spray plus fexofenadine as measured by the TNSS and individual symptoms of the TNSS. CONCLUSIONS: Azelastine nasal spray is effective monotherapy for patients who remain symptomatic after treatment with fexofenadine and should be considered in the initial management of patients with seasonal allergic rhinitis.

Randomized controlled trial evaluating the clinical benefit of montelukast for treating spring seasonal allergic rhinitis.

BACKGROUND: Symptoms of allergic rhinitis are mediated in part by cysteinyl leukotrienes. OBJECTIVE: To evaluate the clinical benefit of montelukast, a cysteinyl leukotriene receptor antagonist, administered once daily for treating seasonal allergic rhinitis. METHODS: This multicenter, randomized, double-blind, placebo- and active-controlled study enrolled 1,214 healthy, nonsmoking outpatients aged 15 to 85 years with spring allergic rhinitis, positive skin test to a spring allergen, and predefined daytime nasal symptoms. After a 3- to 5-day placebo run-in period, patients were randomly assigned to treatment with montelukast 10 mg (n = 522), loratadine 10 mg (n = 171), or placebo (n = 521) once daily at bedtime for 2 weeks. During the run-in and treatment periods, symptoms were evaluated in a daily diary using a 0 (best) to 3 (worst) scale. RESULTS: Baseline characteristics of randomized patients were clinically similar in the three treatment groups. Montelukast was significantly more effective than placebo (P = 0.003) in improving the daytime nasal symptoms score (difference in least square means, -0.09; 95% confidence interval, -0.16, -0.03) averaged over 2 weeks of therapy. The treatment effect of montelukast was significantly greater (P < 0.05), relative to placebo, for all secondary endpoints, including nighttime symptoms and daytime eye symptoms, patient and physician global evaluations of allergic rhinitis, and rhinoconjunctivitis quality of life. Loratadine, which served as a positive control, was significantly more effective than placebo for most endpoints, validating the study results. Both montelukast and loratadine were well tolerated. CONCLUSION: Therapy with montelukast significantly improves assessments of symptom severity as well as quality-of-life parameters for patients with seasonal allergic rhinitis.