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Background: Nasal congestion is the most troublesome symptom of allergic rhinitis (AR). First-generation and older second-generation antihistamines, while effective against nasal itching, sneezing, and rhinorrhea, have limited efficacy in relieving nasal congestion., Objective: This review included nasal challenge studies and clinical trials that reported the effects on nasal congestion of the newer second-generation antihistamines desloratadine, fexofenadine, and levocetirizine., Methods: MEDLINE and EMBASE were searched for nasal challenge studies and clinical trials published in English between January 1, 1991, and January 31, 2009, using the following terms, alone or in combination: antihistamines, second-generation antihistamines, allergic rhinitis, intermittent allergic rhinitis, perennial allergic rhinitis, persistent allergic rhinitis, seasonal allergic rhinitis, nasal challenge, nasal blockage, and nasal congestion. Studies that were not active or placebo controlled, that did not evaluate change in nasal congestion scores, or that focused on treatments other than desloratadine, fexofenadine, and levocetirizine for nasal congestion associated with AR were excluded., Results: Twenty-six clinical trials met the criteria for inclusion in the review. In 11 placebo-controlled trials that included objective assessment of nasal congestion, desloratadine, fexofenadine, and levocetirizine were associated with reductions in the severity of nasal congestion through maintenance of nasal airflow. The mean AUC for nasal airflow over 6 hours was significantly greater with desloratadine compared with placebo in 3 studies (P < 0.05); placebo-controlled trials of fexofenadine and levocetirizine had similar results. In 25 placebo- and active-controlled trials that reported subject-rated symptom scores, the 3 newer antihistamines were efficacious in the treatment of nasal congestion associated with AR. In 10 trials that reported objective and/or subjective measures, desloratadine was associated with significant improvements in nasal congestion compared with placebo (P < or = 0.05), beginning as early as the first 2 hours after allergen challenge. Fexofenadine was associated with significantly lower nasal congestion scores compared with placebo in 4 studies (P <- 0.05); nasal congestion scores were significantly reduced with levocetirizine in 3 placebo-controlled trials (P < or = 0.005)., Conclusions: In the studies reviewed, desloratadine, fexofenadine, and levocetirizine were effective in relieving the nasal congestion associated with AR compared with placebo. This effect began as early as day 2 and was consistent and progressive throughout treatment. Desloratadine, fexofenadine, and levocetirizine are appropriate options for the treatment of nasal congestion in patients with AR.

Background: The onset of action of antihistamine-decongestant combinations is an important factor in the treatment of subjects with seasonal allergic rhinitis (SAR)., Objective: This was a pooled analysis of 2 published studies with identical designs investigating the onset of action of the combination of fexofenadine hydrochloride 60 mg/pseudoephedrine hydrochloride 120 mg (FEX60/PSE120) in subjects with moderate to severe SAR., Methods: Subjects aged 12 years received single doses of FEX60/PSE120 or placebo in 2 randomized, double-blind, placebo-controlled, parallel-group, allergen exposure unit studies and recorded their SAR symptoms on diary cards before dosing, at 15-minute intervals for 2 hours after dosing, and at 30-minute intervals for the next 4 hours. The primary efficacy end point was onset of action, assessed in terms of absolute change in the major symptom complex (MSC) score, which was the sum of scores for the individual symptoms of stuffy nose, itchy nose, runny nose, watery eyes, itchy eyes, itchy ears/throat, and sneezing. Secondary end points included the absolute and percent change in the total symptom complex (TSC) score (the sum of the MSC score plus the scores for nose blowing, sniffles, postnasal drip, and cough) and individual symptom scores. Treatment-emergent adverse events (TEAEs) were recorded. Analyses were performed on the modified intention-to-treat (mITT) population, which included all subjects who were randomized to treatment and took the single dose of study medication according to the protocol., Results: A total of 1693 subjects were screened in the 2 studies, and 786 were randomized (298 in study 1, 488 in study 2). Two subjects withdrew from study 2; therefore, the mITT population consisted of 784 subjects. Subjects' mean age was 33.4 years, and 64.4% were female. The onset of action of FEX60/PSE120 was 45 minutes; the least squares mean (SD) treatment difference in the change from baseline in absolute MSC score was 0.8 (0.31) (95% CI, 0.2-1.4; P = 0.008). All subsequent changes from baseline in MSC scores were statistically significant for FEX60/PSE120 compared with placebo (P < 0.001). The absolute and percent change in TSC score and the percent change in MSC score were significantly decreased at all time points from 45 minutes after dosing for FEX60/PSE120 compared with placebo (all, P < 0.05). Individual symptoms (mean of hours 1 to 5) also were significantly improved with FEX60/PSE120 compared with placebo (all, P < 0.05). TEAEs were reported by 2.3% (9/391) and 4.3% (17/393) of subjects receiving FEX60/PSE120 and placebo, respectively. The most commonly occurring TEAS in the FEX60/PSE120 and placebo groups was somnolence (n = 4 and n = 6, respectively)., Conclusion: In this pooled analysis of 2 allergen exposure unit studies, FEX60/PSE120 had an onset of action of 45 minutes and a sustained effect throughout the 6-hour study period in subjects with moderate to severe SAR.

Background: It is presumed that exposure to allergens in the environment occurs through both the eyes and the nose. Allergic rhinoconjunctivitis is typically treated with a nasal spray or systemic antihistamine, neither of which may provide adequate relief of the ocular component of the disease., Objective: This study was designed to gain a better understanding of the physiologic interaction between the conjunctival and nasal mucosa and thus help establish a profile for the most effective ocular treatment in patients whose allergies have both an ocular and a nasal component., Methods: This was a single-center, randomized, double-masked clinical study using the conjunctival allergen challenge (CAC) and nasal allergen challenge (NAC) models. It compared the clinical signs and symptoms induced by CAC and NAC, the effects of drugs administered by 3 different routes, and the movement of fluorescein after instillation into the eye and nose (Jones test), and assessed levels of of inflammatory mediators in tears and nasal secretions. At visit l, subjects previously identified as CAC responders underwent NAC to determine the dose of allergen necessary to elicit a sufficient positive reaction. At visit 2, which took place 1 week later, subjects with a positive reaction at visit 1 were randomized to group A (CAC) or group B (NAC), and underwent challenge to confirm the allergen dose necessary to produce a positive reaction. Subjects who qualified were randomized to receive 1 of 3 treatments: olopatadine 0.1% ophthalmic solution, placebo nasal spray, and placebo tablets; mometasone furoate monohydrate 50-microg nasal spray, placebo topical solution, and placebo tablets; or fexofenadine hydrochloride 180-mg tablets, placebo topical solution, and placebo nasal spray. All study medications were administered according to their approved labeling: drops were administered twice daily in the eyes, and the nasal sprays and tablets were administered once daily. At visit 3, which took place 1 week after visit 2, subjects received study medication and 15 minutes later underwent CAC or NAC as before. The primary efficacy variables were ocular itching, ocular redness, and overall nasal symptoms (sneezing, rhino rrhea/postnasal drip, nasal pruritus, palatal pruritus, and nasal congestion) rated on standard scales. Peak nasal inspiratory flow (PNIF) was measured at each visit, and the Jones test was performed at visits 1 and 3. At baseline and after challenge at visits 2 and 3, tear and nasal lavage samples were collected from a subset of randomly selected subjects for analysis of eosinophil cationic protein and tryptase., Results: Seventy-three subjects (42 women, 31 men; mean age, 45.26 years [range, 21-73 years]) were screened, and all were randomized to treatment. Two subjects did not complete the study. CAC induced clinically significant (>1 unit difference) ocular and nasal signs and symptoms, whereas NAC induced clinically significant nasal signs and symptoms only. In group A, there was a greater reduction in ocular itching with olopatadine compared with mometasone and fexofenadine at 3 minutes (P = 0.003 and P = 0.008, respectively) and 5 minutes (P = 0.007 and P = 0.013) after challenge. Although the difference was not statistically significant, overall relief of conjunctival redness (average of 3 vessel beds) was greatest in the olopatadine group, followed by fexofenadine. In group B, prevention of total nasal symptoms was significantly greater with mometasone compared with fexofenadine at 20 minutes (P = 0.006) and 30 minutes (P = 0.014) after challenge. There were no statistically significant differences between treatment groups in nasal symptom scores at any time point after CAC. There were also no significant differences in PNIF between treatment groups. Fluorescein was present in nasal secretions within 5 minutes of being instilled into the eye; no fluorescein was detected in the eye after instillation into the nose., Conclusions: In this study, exposure of the nasal mucosa to allergen resulted in allergic rhinitis, and exposure of the ocular the ocular surface to allergen resulted in conjunctivitis with a secondary effect in the nose. These results suggest movement of allergens, their mediators, and antiallergy drugs from the ocular surfaces into the nasal cavity, with no meaningful movement from the nasal cavity to the ocular surface. In this controlled model, both the systemic agent and the nasal spray failed to control ocular symptoms. The topical ophthalmic solution provided the most effective management of allergic ocular signs and symptoms, and the nasal spray was most effective for nasal symptoms. Combined use of a nasal spray and topical ophthalmic solution may provide maximal relief in patients whose allergies have both ocular and nasal components.

Background: One approach to treating allergic rhinoconjunctivitis is the concomitant use of an intranasal spray such as fluticasone propionate to alleviate nasal symptoms and a topical or systemic agent to relieve ocular symptoms. It has not yet been determined whether a topical or systemic agent is more effective for the latter purpose., Objective: This study compared the efficacy of combined use of fluticasone and olopatadine with combined use of fluticasone and fexofenadine in the treatment of the signs and symptoms of allergic rhinoconjunctivitis., Methods: This 2-site, randomized, double-masked, placebo-controlled, parallel-group study employed the conjunctival allergen challenge (CAC) model, a standardized method of inducing ocular and nasal signs and symptoms of allergic rhinoconjunctivitis. At visit 1, subjects underwent CAC to determine the dose of allergen required to elicit a positive reaction. The allergen dose was confirmed at visit 2, and, according to a randomization schedule, subjects were dispensed fluticasone, olopatadine, and placebo pill; fluticasone, fexofenadine, and tear substitute; or placebo nasal spray, placebo pill, and tear substitute. CAC took place at visit 3, after patients had used the assigned medications for 2 weeks. Study medication was instilled 2 hours before CAC, after which allergic signs and symptoms were graded on standardized scales. The primary efficacy variables were ocular itching, ocular redness, and overall nasal symptoms., Results: Eighty subjects completed the study: 30 received fluticasone and olopatadine, 30 fluticasone and fexofenadine, and 20 placebo. Women constituted 63.8% of the study population and men 36.3%; 91.3% were white, 3.8% black, 2.5% Hispanic, 1.3% Asian, and 1.3% other. Concomitant use of fluticasone and olopatadine produced significantly greater improvements in ocular itching at 3 and 7 minutes after CAC compared with fluticasone and fexofenadine (P < 0.05). There were no significant differences in redness scores between groups; however, concomitant use of fluticasone and olopatadine produced significantly greater improvements in redness at 2 time points in each of the 3 vessel beds (ciliary, conjunctival, and episcleral) compared with placebo, and fluticasone and fexofenadine produced significantly greater improvement in redness at 1 time point in I vessel bed compared with placebo (both comparisons, P < 0.05). The 2 treatments had similar effects on total nasal symptom efficacy scores., Conclusions: In this study, concomitant use of the topical agents fluticasone and olopatadine was more effective than concomitant use of fluticasone plus fexofenadine for overall treatment of the signs and symptoms of induced allergic rhinoconjunctivitis.

Background: Nonsedating antihistamines are well-established treatment for seasonal allergic rhinitis (SAR), but patients do not always respond to the first antihistamine prescribed., Objective: This double-blind, double-dummy, randomized, 2-phase, multicenter study was designed primarily to compare the therapeutic responses to loratadine and fexofenadine in patients who failed initial therapy with the other drug., Methods: Male and female patients aged 12 to 60 years received loratadine 10 mg once daily (n = 331) or fexofenadine 60 mg twice daily (n = 328) for 14 days (phase 1); nonresponders (ie, those who had <25% reduction in the sum of 5 SAR symptoms rated by the investigator on a 4-point scale) subsequently received the alternate medication for 14 days (phase 2). The investigator's rating of relief (complete, marked, moderate, or slight relief of symptoms or treatment failure) at the end of phase 2 was the primary efficacy measure; changes in total symptom severity (TSS) assessed by the investigator (4-point scale) and the patient (11-point visual analog scale) were secondary measures., Results: Mean decreases in TSS were significantly greater with loratadine than with fexofenadine for the 659 patients who completed phase 1 (-12.7 vs -10.2, respectively; P = 0.019; patient assessment) and for the 389 patients who responded to initial therapy (-6.6 vs -6.1, respectively; P = 0.037; investigator assessment). Of the 389 patients who responded to initial therapy, 61.0% had received loratadine and 57.0% had received fexofenadine. More nonresponders to initial therapy had moderate, marked, or complete relief of symptoms after switching to loratadine than after switching to fexofenadine (62.4% vs 51.2%, respectively; P = 0.005) and treatment failure in 10.6% vs 21.7%, respectively (P = 0.011)., Conclusion: Overall, ioratadine provided significantly better therapeutic response than fexofenadine in patients who failed to respond to initial therapy with the other drug.

In a multicenter, parallel-group, double-masked, randomized study, two questionnaires were administered to a clinical study population to identify which specific symptoms of seasonal allergic rhinitis patients perceived as most important to relieve (personal preferences) and to learn whether any relationship existed between patient preferences and the severity of their symptoms during treatment with antihistamines. The group was composed of 256 males and 313 females. Their mean age was 32.4 years, and mean duration of seasonal allergic rhinitis was 14.5 years, with mean age of onset of 17.7 years. After receiving placebo for 1 week, patients were randomly allocated to receive an antihistamine (fexofenadine or loratadine) for 2 weeks. Patient preferences for relief of individual allergy symptoms (rhinitis; sneezing; itchy, watery, red eyes; itchy nose, palate, or throat) and related conditions (fatigue, physical limitations) were scored using 2 different questionnaires before treatment (0-to-10 category rating scale for assessing the 4 symptoms of allergic rhinitis) and after receiving placebo for 1 week (Feeling Thermometer). Symptom severity was reported in patient diaries after 1 and 2 weeks of antihistamine treatment and was measured by patient self-assessment. All symptoms were considered by the patients to be important to relieve, the most important being itchy, watery, red eyes and rhinorrhea. The severity of allergy symptoms was consistently related to the importance of symptoms identified before treatment. Therefore, including patient preferences in medical evaluations might be a useful tool in evaluating the success of their treatment.

This paper compares cost-efficacy ratios for intranasal fluticasone propionate and terfenadine tablets within a sample of patients with seasonal allergic rhinitis symptoms due to mountain cedar allergy. Efficacy was assessed using secondary data analysis of patient ratings of symptoms and their overall assessment of response to treatment within a previously conducted clinical trial. Costs include direct costs of the drugs used for therapy. Patients with documented mountain cedar allergy who were 12 years of age or older (N = 232) had been randomized to either receive intranasal fluticasone propionate, terfenadine, or placebo. The cost-efficacy ratios for intranasal fluticasone propionate 200 micrograms once daily were more favorable than the ratios for terfenadine 60 mg twice daily. This relationship remained throughout the sensitivity analysis. Because intranasal fluticasone propionate is only available in a fixed package size, the number of efficacy-adjusted days of terfenadine therapy that could be purchased to reach break-even costs for a 30-day supply of fluticasone was calculated. Cost efficacy-adjusted days ranged from 11 to 18 days. If cost-efficacy adjustments are not conducted, the upper end of the range increases from 18 to 22 days, since 22 days of terfenadine could be purchased for the price of a 30-day supply of intranasal fluticasone propionate. Depending on which of the efficacy measures the reader believes, if patients use terfenadine for longer than 11 to 22 days, fluticasone propionate is the more cost-efficacious choice. Because most allergies are seasonal and allergy seasons typically last longer than 11 to 22 days, it is likely that fluticasone propionate will frequently be the more cost-efficacious choice in the patient population represented in this study.

The efficacy and safety of loratadine and terfenadine in the treatment of 3- to 6-year-old children with seasonal allergic rhinitis were compared in a third-party-blind, randomized, parallel-group study. A total of 96 children were included in the efficacy analysis: 49 children received 5 or 10 mg of loratadine once daily, and 47 received 15 mg of terfenadine twice daily, for 14 days. The mean total score for both nasal and non-nasal symptoms was decreased significantly from baseline at days 3, 7, and 14 in both treatment groups. At endpoint, these scores had improved 73% in each group. There were no statistically significant differences between the two groups in the total symptom scores at any point during the study. Both treatments were effective in relieving individual nasal and nonnasal symptoms. Therapeutic response to treatment was good or excellent in 82% of loratadine-treated children and in 60% of terfenadine-treated children. Few adverse events were reported during the study; all were mild or moderate and were not significantly different between the two treatment groups. There were no reports of sedation or dry mouth in either group. Once-daily treatment with 5 or 10 mg of loratadine was as effective as twice-daily treatment with 15 mg of terfenadine in improving the symptoms of seasonal allergic rhinitis in children 3 to 6 years old. Both treatments were well tolerated.