Abstracts from the North American Rhinology & Allergy Conference, February 3, 2011, Puerto Rico.

INTRODUCTION: To establish the efficacy of bepotastine besilate ophthalmic solution (bepotastine) 1.5%, a dual acting histamine H1 receptor antagonist approved for treatment of ocular itching associated with allergic conjunctivitis, compared to placebo in relieving ocular itching and redness for subjects with active allergic rhinoconjunctivitis. METHODS: A randomized, double-masked, placebo-controlled, confirmatory natural exposure study of bepotastine 1.5% and placebo was conducted during allergy season at 12 clinical sites throughout the U.S. Following a 7-day screening period, eligible subjects ≥12 years old were assigned in a 1:1 ratio to dosing OU b.i.d. either bepotastine 1.5% (n = 123) or placebo (n = 122). Subjects recorded instantaneous grades for their ocular symptoms prior to their next dose for 14 consecutive days. Clinically significant reduction in ocular sign or symptom grades between treatment groups required p ≤ 0.05 as determined by ANCOVA analysis. RESULTS: Significant clinical effectiveness with bepotastine 1.5% was demonstrated over the 2-week treatment period in comparison to placebo in the intent-to-treat population for reducing mean instantaneous grades for both ocular itching (p = 0.007) and redness (p = 0.001). Investigator rating of efficacy over the 2-week treatment period across response categories was also superior for bepotastine 1.5% compared to placebo (p = 0.024). Only one subject discontinued participation in the study due to an adverse event. CONCLUSIONS: These data support bepotastine 1.5% as an effective treatment for allergen-induced signs and symptoms in a clinical study designed to closely resemble the conditions under which patients with allergic rhinoconjunctivitis would require treatment.

Treatment with intranasal fluticasone propionate significantly improves ocular symptoms in patients with seasonal allergic rhinitis.

BACKGROUND: If monotherapy with an intranasal corticosteroid can alleviate both nasal and ocular symptoms of allergic rhinitis, treatment may be simplified and costs may be reduced. OBJECTIVE: The purpose of this study was to evaluate the efficacy of once-daily fluticasone propionate (FP) aqueous nasal spray 200 microg compared with vehicle placebo and oral loratadine (LOR) 10 mg in reducing ocular symptoms associated with seasonal allergic rhinitis. METHODS: A total of 471 patients received vehicle placebo, LOR, or FP in this multi-centre, double-blind, double-dummy, randomized study. Patients were > or =12 years old with a history of seasonal allergic rhinitis and a positive skin test for a relevant allergen. During the baseline and treatment periods, patients rated the severity of eye itching, tearing, and redness via visual analogue scales that ranged from 0 (no symptoms) to 100 (most severe symptoms). The three ocular ratings were added to derive the total ocular symptom score (TOSS). Patients with a TOSS > or =120 on at least 4 of the 7 days before the randomization visit were enrolled. The primary outcome was the difference between FP and vehicle placebo in the mean change from baseline in the reflective TOSS overall (averaged over the 28-day treatment period). A difference between FP and vehicle placebo of 25.5 was considered clinically significant. RESULTS: The overall mean change from baseline in the TOSS was significantly greater in the FP group compared with vehicle placebo (clinically significant difference of 28.8; P<0.001) and compared with LOR (difference of 16.2; P=0.028). Overall mean (SEM) changes were -59.9 (5.4) for the placebo group, -72.5 (5.4) for the LOR group, and -88.7 (5.3) for the FP group. The FP treatment group also showed significantly greater overall mean changes in ocular itching, tearing, and redness compared with vehicle placebo (P<0.001) and compared with LOR (P< or =0.045). CONCLUSION: Patients treated with intranasal FP had clinically and statistically significant decreases in ocular symptom scores compared with vehicle placebo. Data also suggest that FP reduced ocular symptoms more than or comparable with oral LOR. Patients experiencing ocular symptoms associated with allergic rhinitis may benefit from monotherapy with intranasal FP.

Montelukast for treating seasonal allergic rhinitis: a randomized, double-blind, placebo-controlled trial performed in the spring.

BACKGROUND: Cysteinyl leukotrienes are important proinflammatory mediators believed to have a role in allergic rhinitis. OBJECTIVE: This multicentre, randomized, double-blind, placebo- and active-controlled trial evaluated the effectiveness and tolerability of montelukast, a cysteinyl leukotriene receptor antagonist, for treating patients with seasonal allergic rhinitis. METHODS: After a 3- to 5-day, single-blind placebo run-in period, 1302 male and female patients (aged 15-81 years) with active allergic rhinitis symptoms were randomly assigned to receive montelukast 10 mg (n = 348), loratadine 10 mg (n = 602), or placebo (n = 352) administered once daily at bedtime for 2 weeks during the spring allergy season. RESULTS: Mean patient characteristics and symptom scores at baseline were similar for the three treatment groups. The primary end-point, daytime nasal symptoms score (mean of nasal congestion, rhinorrhea, nasal pruritus, and sneezing scores; 0-3 scale), improved from baseline during treatment by (least squares mean, 95% confidence interval) - 0.37 (- 0.43, - 0.31), - 0.47 (- 0.52, - 0.43), and - 0.24 (- 0.29, - 0.18) in the montelukast, loratadine, and placebo groups, respectively (P < or = 0.001 comparing each active treatment with placebo). Mean changes from baseline in all other diary-based scores, including night-time and eye symptom scores, were significantly greater for each active treatment than for placebo. The rhinoconjunctivitis quality of life overall score improved significantly with montelukast and with loratadine as compared with placebo. Montelukast and loratadine showed a safety profile comparable to that of placebo. CONCLUSION: Montelukast is well tolerated and provides improvements in daytime and night-time symptoms, as well as quality of life parameters, for patients with seasonal allergic rhinitis.

A dose-ranging study of mometasone furoate aqueous nasal spray in children with seasonal allergic rhinitis.

BACKGROUND: The efficacy and safety of mometasone furoate aqueous nasal spray (MFNS; Nasonex) 200 microg once daily for the treatment and prophylaxis of seasonal allergic rhinitis (SAR) and treatment of perennial rhinitis have been demonstrated in adults. However, the dose response of MFNS in pediatric patients has not yet been characterized. OBJECTIVE: This study was conducted to determine the dose-response relationship of 3 different doses of MFNS in a pediatric population. METHODS: This was a multicenter, double-blind, active- and placebo-controlled study of 679 children 6 to 11 years of age with histories of SAR and documented positive skin test responses. Patients were randomized to one of the following treatment groups for 4 weeks: MFNS 25 microgram once daily, MFNS 100 microgram once daily, MFNS 200 microgram once daily, beclomethasone dipropionate 84 microgram twice daily (168 microgram/day), or placebo. Physician evaluations were performed at days 4, 8, 15, and 29, and patient evaluations were analyzed for days 1 to 15 and 16 to 29. RESULTS: The mean reduction from baseline in physician-evaluated total nasal symptom scores at day 8 (the primary efficacy variable) was significantly greater in the MFNS and beclomethasone dipropionate groups than in the placebo group (P

Efficacy and safety of levocabastine nasal spray for seasonal allergic rhinitis.

This multicenter, double-blind, placebo-controlled trial evaluated the efficacy and safety of levocabastine nasal spray, a potent and selective H1-receptor antagonist, in the control of histamine-mediated symptoms of seasonal allergic rhinitis. Adults with > or = 2 year history of allergic rhinitis due to Mountain Cedar were randomized to treatment with levocabastine nasal spray (0.2 mg twice daily) or placebo for 28 days during the 1994-1995 Mountain Cedar allergy season. Patients assessed the severity of their rhinitis symptoms on a four-point scale twice daily. At the end of the trial, patients also performed a global evaluation of treatment efficacy on a five-point scale. Overall for the 4-week treatment period, levocabastine nasal spray significantly reduced major nasal (runny nose and sneezing) and primary rhinitis (runny nose, sneezing, and itchy/gritty eyes) symptoms compared with placebo on both repeated measures (p = 0.023; p = 0.01) and ANOVA (p = 0.003; p < 0.001) analyses. Global evaluations of treatment efficacy at the end of the trial significantly favored levocabastine over placebo (p = 0.002). Overall, the incidence of adverse events was similar for both treatment groups. In general, most adverse events were mild in intensity, with sinusitis (17% each group), headache (17% placebo, 14% levocabastine), and rhinitis (8% placebo, 2% levocabastine) most commonly reported. Levocabastine nasal spray 0.2 mg twice daily was significantly more effective than placebo in the relief of histamine-mediated symptoms in patients with seasonal allergic rhinitis and was well tolerated over the 28-day treatment period.

A comparison of the efficacy of fluticasone propionate aqueous nasal spray and loratadine, alone and in combination, for the treatment of seasonal allergic rhinitis.

BACKGROUND: Intranasal corticosteroids and oral antihistamines are both effective in the treatment of seasonal allergic rhinitis, although the therapeutic value of administering the two types of agents concurrently has rarely been evaluated. This study was designed to compared the efficacy, safety, and impact on quality of life of fluticasone propionate aqueous nasal spray (FP ANS), loratadine, FP ANS plus loratadine, and placebo (an aqueous nasal spray plus tablet) in the treatment of seasonal allergic rhinitis during the mountain cedar allergy season in south central Texas. METHODS: Six hundred patients with seasonal allergic rhinitis were treated for 2 weeks with either FP ANS 200 microgram once daily, loratadine 10 mg once daily, the FP ANS and loratadine regimens combined, or placebo in a multicenter, randomized, double-blind, double-dummy, parallel-group study. RESULTS: Clinician- and patient-rated total and individual nasal symptom scores after 7 and 14 days of therapy and overall evaluations were significantly lower (P < .001) in the FP ANS and FP ANS plus loratadine groups compared with the loratadine only and placebo groups. Loratadine was not statistically different from placebo in clinician and patient symptom score ratings nor in overall clinician and patient evaluations. FP ANS plus loratadine and FP ANS monotherapy were comparable in efficacy in almost all evaluations; for some patient-rated symptoms the combination was found superior. Mean score changes in the Rhinoconjunctivitis Quality of Life Questionnaire from baseline to day 14 showed significantly greater improvement (P < .001) in quality of life in the FP ANS group than in the group of patients receiving loratadine only or placebo and no significant benefit was demonstrated in the FP ANS plus loratadine group over the FP ANS monotherapy group. No serious or unusual drug-related adverse events were reported. Combining loratadine with FP ANS did not alter the adverse events profile or frequency.

Brompheniramine maleate: a double-blind, placebo-controlled comparison with terfenadine for symptoms of allergic rhinitis.

This was a double-blind, randomized, placebo-controlled, multicenter, parallel study comparing the effectiveness, at recommended doses, of an extended-release formulation of brompheniramine maleate and terfenadine in the treatment of allergic rhinitis. Subjects with symptoms of seasonal and/or perennial allergic rhinitis received brompheniramine 12 mg (n = 106), 8 mg (n = 105), terfenadine 60 mg (n = 106), or placebo (n = 53) twice daily for 14 days. On treatment days 3, 7, and 14, symptom severity ratings (i.e., rhinorrhea, sneezing, nasal congestion, itchy nose, eyes or throat, excessive tearing, postnasal drip) were completed by the physician; subjects and physicians each completed a global efficacy evaluation. Brompheniramine 12 mg and 8 mg and terfenadine were more effective than placebo (p < or = 0.05) on the physicians' global: brompheniramine 12 mg was more effective than terfenadine (p < or = 0.05) on days 7 and 14 and brompheniramine 8 mg on day 3. On the subjects' global evaluation, brompheniramine 12 mg and 8 mg and terfenadine were more effective than placebo (p < or = 0.05); brompheniramine 12 mg was more effective than terfenadine (p < or = 0.05) on days 7 and 14 and brompheniramine 8 mg on day 3. In general, brompheniramine 8 mg was comparable to terfenadine. On days 3 and 7, the total symptom and total nasal symptom severity scores for subjects receiving brompheniramine 12 mg were significantly more improved than for placebo (p < 0.05); terfenadine was not different from placebo; brompheniramine 12 mg was significantly better than terfenadine on day 7 (p < 0.05) for reducing total symptom severity and on days 3, 7, and 14 for reducing total nasal symptom severity. Adverse experiences were reported by 155 (41.9%) of the 370 subjects enrolled in the study. The overall rate of adverse experiences in the brompheniramine 12 mg treatment group (57.5%) was significantly greater (p < 0.05) than for brompheniramine 8 mg (38.1%), terfenadine (31.1%), and placebo (39.6%). In conclusion, an extended-release formulation of brompheniramine 12 mg or 8 mg bid alleviates allergic rhinitis symptoms and brompheniramine 12 mg provides significantly better relief of these symptoms than terfenadine 60 mg bid.

Preseasonal, once daily triamcinolone acetonide nasal aerosol for seasonal allergic rhinitis.

BACKGROUND: Seasonal allergic rhinitis is a common and distressing illness for which treatment is often inadequate. There is a clinical need for safe and effective therapeutic options, including preseasonal treatment, to manage many of these patients. OBJECTIVE: The goal of this study was to evaluate the clinical effects of preseasonal administration of triamcinolone acetonide nasal aerosol in the management of this illness. METHODS: This multicenter, double-blind, placebo-controlled, randomized, parallel group study involved otherwise healthy subjects with a 2-year consecutive history of ragweed-induced seasonal allergic rhinitis. Patients were asymptomatic when randomized to receive 220 micrograms triamcinolone acetonide or placebo nasal aerosol (n = 56 each) once daily for 6 weeks, beginning at least 1 week before significant ragweed pollen was airborne. RESULTS: Triamcinolone acetonide was significantly (P < .001) more effective than placebo in preventing nasal symptoms as determined by mean placebo-adjusted nasal index scores. Patients in the triamcinolone acetonide group had significantly (P < or = .0004) lower scores in the severity of individual nasal symptoms and the overall mean nasal index score. Severity of ocular symptoms was reduced more in the triamcinolone acetonide than in the placebo group (not significant). Physicians' and patients' global evaluations of efficacy favored triamcinolone acetonide, with statistically significant between-group differences in moderate or complete prevention of rhinitis symptoms. The incidence of adverse effects was similar in the two groups, with the most common being headache and increased rhinitis. CONCLUSIONS: This study demonstrates that preseasonal administration of triamcinolone acetonide nasal aerosol is safe and effective for managing seasonal allergic rhinitis.

The efficacy of fluticasone propionate aqueous nasal spray for allergic rhinitis and its relationship to topical effects.

Fluticasone propionate aqueous nasal spray is an intranasal corticosteroid for the treatment of patients with allergic rhinitis. This double-masked, double-dummy, parallel-group study was conducted to confirm that the efficacy of fluticasone propionate nasal spray is attributable to topical rather than systemic effects. A total of 304 patients with documented seasonal allergic rhinitis were randomly assigned to receive fluticasone propionate nasal spray 200 micrograms once daily (n = 77), oral fluticasone propionate 5 mg once daily (n = 73), oral fluticasone propionate 10 mg once daily (n = 77), or placebo (n = 77) for 14 days. Plasma fluticasone propionate concentrations were determined at baseline and after 14 days of treatment (day 15). Nasal symptoms were recorded daily by patients and assessed weekly by clinicians. On day 15, more patients in the oral fluticasone propionate 5-mg or 10-mg groups, compared with patients in the fluticasone propionate nasal spray group or the placebo group, had detectable plasma fluticasone propionate concentrations, and mean concentrations were higher in the oral fluticasone propionate groups. Both clinician- and patient-rated total and individual nasal symptom scores for obstruction, rhinorrhea, sneezing, and itching were significantly lower in the fluticasone propionate nasal spray group compared with either of the oral fluticasone propionate groups or the placebo group. With few exceptions, oral fluticasone propionate (5 mg or 10 mg) was not significantly different from placebo on any measures of efficacy. These findings indicate that the efficacy of fluticasone propionate nasal spray (200 micrograms once daily) in the treatment of allergic rhinitis results from direct topical effects rather than from indirect effects after systemic absorption.

Double-strength beclomethasone dipropionate (84 micrograms/spray) aqueous nasal spray in the treatment of seasonal allergic rhinitis.

BACKGROUND: The use of intranasally administered corticosteroid sprays is an established treatment option for seasonal allergic rhinitis. METHODS: In this double-blind, placebo-controlled, multicenter study, 438 patients with moderate to severe symptoms of seasonal allergic rhinitis were treated for 4 weeks with double-strength beclomethasone dipropionate (BDP) aqueous nasal spray (84 micrograms/spray: BDP-ds), once daily; regular-strength BDP (42 micrograms/spray: BDP-rs), twice daily; high-strength BDP (336 micrograms/spray: BDP-hs), once daily; or placebo. BDP-hs was included as a safety comparison group. All treatments were given as two sprays per nostril. RESULTS: Physician-rated nasal symptom scores were significantly improved in all three active treatment groups compared with those of the placebo group within the initial 3 days of treatment. Improvement was maintained throughout the 4-week treatment period. BDP-ds and BDP-rs were equivalent at all time points. The BDP-ds, BDP-rs, and BDP-hs groups had greater numbers of patients with a good or excellent therapeutic response at end point than the placebo group. All treatments were well-tolerated, and no unexpected adverse events were reported. No effects on laboratory evaluations or vital signs were evident for any treatment group. CONCLUSIONS: The results of this study show that BDP-ds given once a day and BDP-rs given twice a day in the same total daily dose are comparably safe and effective in the treatment of patients with seasonal allergic rhinitis.

A clinical trial of ipratropium bromide nasal spray in patients with perennial nonallergic rhinitis.

Intranasal ipratropium bromide has been shown to significantly reduce rhinorrhea. Use of a freon-propelled intranasal preparation has resulted in side effects associated with the drying properties of the propellant. The purpose of the present trial was to study the safety and efficacy of a new isotonic aqueous ipratropium bromide nasal spray pump, specifically in patients with perennial nonallergic rhinitis. Two hundred thirty-three patients participated in an 8-week double-blind parallel comparison of ipratropium bromide nasal spray with its vehicle, a saline solution. Treatment with the ipratropium spray resulted in a 30% reduction in rhinorrhea; this reduction was significantly greater than that seen with the saline vehicle. There was a modest reduction in postnasal drip, sneezing, and congestion with both treatments, which may be attributable to the salutary effects of the saline solution. Patients also perceived a significant reduction in the degree to which rhinorrhea interfered with their daily activities and moods. Treatment was well tolerated, with no drug-related systemic adverse events and no evidence of nasal rebound on discontinuation of treatment. Minor, infrequent episodes of nasal dryness and epistaxis were the only significant adverse events reported; these did not limit treatment.

Use of ipratropium bromide nasal spray in chronic treatment of nonallergic perennial rhinitis, alone and in combination with other perennial rhinitis medications.

To study the long-term safety and effectiveness of ipratropium bromide nasal spray 0.03% in the treatment of nonallergic perennial rhinitis, we administered this medication for 1 year in an open-label trial involving 285 patients. Our intention was to maintain the highest protocol dose possible to gain a clearer picture of the long-term side effect profile of the compound. Ipratropium bromide was well tolerated with no serious side effects in this patient population. It provided a significant improvement in rhinorrhea throughout the year-long trial; only 17 of 285 patients (6%) were considered treatment failures. There was an improvement in patient quality of life, as well as a substantial reduction in the need for other medications (antihistamines, decongestants, and nasal steroids) used to treat perennial rhinitis symptoms.

Intranasal fluticasone propionate is more effective than terfenadine tablets for seasonal allergic rhinitis.

BACKGROUND: We compared the efficacy and tolerability of the intranasal corticosteroid fluticasone propionate with that of the antihistamine terfenadine in patients with seasonal allergic rhinitis. METHODS: Two hundred thirty-two adults and adolescents with seasonal allergic rhinitis received intranasal fluticasone propionate (200 micrograms once daily), terfenadine tablets (60 mg twice daily), or placebo for 2 weeks in a double-blind, randomized, parallel-group study. Main outcome measures were clinician- and patient-rated individual and total nasal symptom scores (based on ratings of nasal obstruction, sneezing, nasal itching, and rhinorrhea); clinician-rated overall response to therapy; changes in nasal inflammatory cell counts; adverse events; and morning plasma cortisol concentrations. RESULTS: Both clinician- and patient-rated total and individual nasal symptom scores were significantly lower in the fluticasone group than in either the terfenadine group or the placebo group at nearly every measured time point throughout the treatment period. After 2 weeks of therapy, clinician-rated total nasal symptom scores decreased by 49% in the fluticasone group compared with 27% in the terfenadine group and 19% in the placebo group. In general, therapy with terfenadine was not statistically distinguishable from that with placebo based on patient-rated total or individual nasal symptom scores. According to clinician ratings, 64% of fluticasone-treated patients compared with 49% and 44% of patients treated with terfenadine and placebo, respectively, experienced significant or moderate improvement. A greater percentage of fluticasone-treated patients compared with either terfenadine- or placebo-treated patients experienced reductions in intranasal eosinophil and basophil counts after 2 weeks of therapy. No unusual or serious drug-related adverse events were reported. Morning plasma cortisol concentrations after 2 weeks of therapy did not differ among groups. CONCLUSION: Fluticasone aqueous nasal spray, a well-tolerated corticosteroid preparation that can be administered once daily, is more effective than terfenadine tablets or placebo in controlling symptoms of seasonal allergic rhinitis.