George Georges

Fexofenadine hydrochloride, 180 mg, exhibits equivalent efficacy to cetirizine, 10 mg, with less drowsiness in patients with moderate-to-severe seasonal allergic rhinitis

BACKGROUND Previous studies have shown that fexofenadine and cetirizine effectively relieve symptoms of seasonal allergic rhinitis (SAR). OBJECTIVE To compare the effects of fexofenadine hydrochloride, 180 mg, and cetirizine, 10 mg, on symptoms, drowsiness, and motivation in patients with moderate-to-severe SAR. METHODS In this 2-week multicenter, double-blind, randomized study, 495 subjects with moderate-to-severe SAR received once-daily fexofenadine hydrochloride, 180 mg, or cetirizine, 10 mg, without regard to food intake. Daily 12-hour reflective (AM, PM) and instantaneous (AM) individual symptoms and total symptom score (TSS) were evaluated. Drowsiness and motivation were recorded daily using visual analog scale at 7 AM, 10 AM, and 3 PM. RESULTS Between-treatment differences in reduction from baseline in AM instantaneous and 24-hour reflective TSS were -0.18 [95% confidence interval (CI), -0.55 to 0.20) and -0.22 (95% CI, -0.59 to 0.15), respectively. Since CIs for reduction in TSS between treatments fell within a 0.7 margin (defined a priori), treatments were considered statistically equivalent. Patients receiving fexofenadine experienced significantly less overall drowsiness vs baseline than those receiving cetirizine [-2.33 (95% CI, -3.80 to 0.86) vs 0.37 (95% CI, -1.10 to 1.84), P = .0110]. There was a trend toward greater improvements in overall motivation with fexofenadine compared with cetirizine [-2.36 (95% CI, -3.83 to 0.90) vs -0.30 (95% CI, -1.76 to 1.17), P = .0504]. CONCLUSIONS Once-daily fexofenadine hydrochloride, 180 mg, given for 2 weeks caused statistically and clinically equivalent improvement in symptoms and significantly less drowsiness va baseline, compared with cetirizine, 10 mg, in patients with moderate-to-severe SAR.

Comparative efficacy, safety, and effect on quality of life of triamcinolone acetonide and fluticasone propionate aqueous nasal sprays in patients with fall seasonal allergic rhinitis

BACKGROUND The topical potency of fluticasone propionate (FP) is known to be four times greater than that of triamcinolone acetonide (TAA). However, the significance of this difference has not been proven in the clinical treatment of seasonal allergic rhinitis (SAR). OBJECTIVE To compare the efficacy, safety, and effect on health-related quality of life (HRQL) of FP and TAA aqueous nasal sprays in patients with SAR. METHODS Single-blind, parallel-group, active-controlled design. Patients were randomized to 3-week treatment with TAA 220 microg (n = 172) or FP 200 microg (n = 180) as two sprays/nostril once daily AM. Twelve-hour reflective symptom evaluations (nasal discharge, stuffiness, itching; sneezing; ocular itching/tearing/redness) were performed AM/PM, beginning at pretreatment baseline period. Incidences of specific treatment-related side effects were collected in daily questionnaires. HRQL was evaluated at baseline and end-of-treatment with a validated disease-specific, quality-of-life instrument. RESULTS TAA and FP produced similar improvement in daily total nasal symptom scores overall (49.4% and 52.7%, respectively; P = 0.332) and at every weekly time point (P > 0.05). There were no significant differences between TAA and FP in any individual symptom score at any time point except week 2 (FP provided greater reduction in sneezing, P = 0.046). No significant difference was found between groups in overall occurrence of specific treatment-related side effects. Overall Rhinoconjunctivitis Quality of Life Questionnaire scores were similar for TAA and FP at end-of-treatment. CONCLUSIONS Despite differing molecular potencies, FP and TAA demonstrated comparable efficacy in the treatment of SAR, and produced similar occurrences of specific treatment-related side effects and similar improvements in overall patient HRQL.

Efficacy and safety of levocetirizine in improving symptoms and health-related quality of life in US adults with seasonal allergic rhinitis: a randomized, placebo-controlled study.

BACKGROUND Levocetirizine, a second-generation antihistamine for symptomatic treatment of allergic rhinitis and chronic idiopathic urticaria, has not been previously studied in US patients. OBJECTIVE To assess the efficacy and safety of levocetirizine in improving symptoms and health-related quality of life in US adults with seasonal allergic rhinitis (SAR). METHODS This multicenter, double-blind trial randomized adults with SAR, sensitized to at least 1 grass allergen, to receive levocetirizine, 5 mg, or placebo once daily in the evening for 2 weeks. The primary end point was the 24-hour reflective Total 5-Symptom Score (T5SS; sum of rhinorrhea, sneezing, nasal congestion, and nasal and ocular pruritus) during the entire treatment period. Secondary assessments included the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), Work Productivity and Activity Impairment-Allergy Specific (WPAI-AS) questionnaire, and Epworth Sleepiness Scale (ESS), each assessed at week 1, week 2, and the end of treatment. RESULTS The intent-to-treat population comprised 287 patients taking levocetirizine and 290 taking placebo, with no significant between-group differences at baseline. Levocetirizine resulted in significantly greater improvement from baseline vs placebo in the T5SS (P < .001), overall RQLQ score (P < .001), general and work-related WPAI-AS subscores (P < .05), and ESS score (P < .001). Overall incidence of treatment-emergent adverse events was 14.4% for levocetirizine and 18.4% for placebo. The incidence of somnolence and fatigue was 0.7% and 1.8% with levocetirizine and 1.0% and 0% with placebo, respectively. CONCLUSIONS Levocetirizine was well tolerated and was significantly more effective than placebo in improving the naso-ocular symptoms and health-related quality of life in US patients with SAR.

Triamcinolone acetonide aqueous nasal spray and fluticasone propionate are equally effective for relief of nasal symptoms in patients with seasonal allergic rhinitis.

OBJECTIVE We compared 220 microg daily intranasal aqueous triamcinolone acetonide (TAA AQ) with 200 microg daily fluticasone propionate (FP) for relief of seasonal allergic rhinitis symptoms. Study design and setting Randomized, parallel-group, investigator-blind study included patients with symptomatic seasonal allergic rhinitis. After a baseline period, TAA AQ or FP was taken for about 21 days. Nasal symptom (discharge, stuffiness, itching, sneezing) severity was recorded twice daily; total nasal symptom score was calculated. Health-related quality of life was assessed by Rhinoconjunctivitis Quality of Life Questionnaire. RESULTS Reductions in individual symptoms and total nasal symptom score were statistically significant versus baseline and were equivalent between treatments: -3.15 +/- 0.19 with TAA AQ (n = 148) and approximately 3.17 +/- 0.18 with FP (n = 147) (95% confidence interval for the difference, -0.7391 to 0.3693). Clinically and statistically significant improvements in Rhinoconjunctivitis Quality of Life Questionnaire scores were comparable. CONCLUSION TAA AQ and FP were equally efficacious in relieving seasonal allergic rhinitis symptoms and improving health-related quality of life. SIGNIFICANCE Differences in molecular potency of intranasal steroids do not confer differences in efficacy.

Relative potency of fexofenadine HCl 180 mg, loratadine 10 mg, and placebo using a skin test model of wheal-and-flare suppression

BACKGROUND H1-receptor antagonists differ in their ability to produce peripheral H1-blockade. Suppression of histamine-induced flares and wheals is a useful objective test for measuring these differences. OBJECTIVE To evaluate the relative potency of fexofenadine HCI 180 mg, loratadine 10 mg, and placebo (PBO) in suppressing histamine-induced flares and wheals and compare the onset, duration, and maximum suppression of histamine achieved with each agent. METHODS Thirty healthy volunteers were enrolled in this randomized, double-blind, single-dose, crossover study. Flares and wheals induced by skin-prick testing with histamine 1.8 mg/mL were measured before treatment, every 20 minutes during the first hour after dosing, and thereafter hourly between 2 and 12 hours and between 23 and 25 hours postdose. RESULTS Fexofenadine was significantly more effective than loratadine in suppressing the histamine-induced flare response at hours 2 through 7 and 10 through 12 and produced greater flare suppression than did PBO at hours 2 through 25. Onset of flare suppression occurred 2 hours after dosing with fexofenadine and 4 hours after dosing with loratadine. Likewise, fexofenadine was superior to loratadine in suppressing the wheal response from hours 1 through 12 and was more effective than PBO at hours 1 through 12, 24, and 25. Throughout the 25-hour measurement interval, the magnitude of difference in both wheal and flare suppression consistently favored fexofenadine over loratadine. CONCLUSIONS In a skin test model of wheal-and-flare suppression, fexofenadine showed rapid distribution into the skin compartment with faster onset of action and greater potency vs loratadine.

Efficacy and safety of triamcinolone acetonide aqueous nasal spray in children aged 2 to 5 years with perennial allergic rhinitis: a randomized, double-blind, placebo-controlled study with an open-label extension

BACKGROUND Intranasal corticosteroids (INSs) are the most effective treatment for allergic rhinitis (AR). However, available INS safety and efficacy data in children younger than 6 years are limited. OBJECTIVE To report the first well-controlled study assessing the safety and efficacy of an INS in children aged 2 to 5 years with perennial AR. METHODS In a 4-week, multicenter, double-blind, parallel-group study, patients were randomized to receive triamcinolone acetonide aqueous nasal spray (TAA AQ), 110 microg once daily, or placebo. A subset of children continued into a 6-month, open-label phase. Efficacy end points included total nasal symptom scores. Safety measures included reports of adverse events, morning serum cortisol levels before and after cosyntropin infusion, and growth as measured using office stadiometry. RESULTS A total of 474 patients were randomized to receive TAA AQ (n = 236) or placebo (n = 238); 436 entered the open-label extension phase. Adjusted mean (SE) changes from baseline during the double-blind period in instantaneous and reflective total nasal symptom scores were -2.28 (0.16) and -2.31 (0.15), respectively, in the TAA AQ group (P = .09) vs -1.92 (0.16) and -1.87 (0.15) in the placebo group (P = .03). Adverse event rates were comparable between treatment groups. There was no significant change from baseline in serum cortisol levels after cosyntropin infusion at study end. The distribution of children by stature-for-age percentile remained stable during the study. CONCLUSIONS Use of TAA AQ, 110 microg once daily, for up to 6 months offers a favorable efficacy to safety ratio in children aged 2 to 5 years with perennial AR.

Study of levocetirizine in seasonal allergic rhinitis

Abstract Objective: To evaluate the efficacy of levocetirizine 5 mg once daily in reducing seasonal allergic rhinitis (SAR) symptoms in US adults. Research design and methods: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study enrolled adults aged 18 to 65 years with SAR symptoms in the spring in the US. After a single-blind placebo run-in period, subjects received levocetirizine 5 mg or placebo once daily over 14 days. ClinicalTrials.gov registry no.: Trial registration: ClinicalTrials.gov identifier: NCT00621959. Main outcome measures: Primary efficacy variable was the Total 5-Symptom Score (T5SS). Secondary variables included Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), Work Productivity and Activity Impairment–Allergy Specific (WPAI-AS) questionnaire, and Epworth Sleepiness Scale (ESS). Safety assessments were based on adverse events (AEs). Results: The intent-to-treat population comprised 596 subjects (levocetirizine, n = 301; placebo, n = 295). Comparison of mean T5SS over the total treatment period showed a nonsignificant between-group difference (levocetirizine, 8.90 ± 0.19; placebo, 9.04 ± 0.19; adjusted mean difference, −0.14; p = 0.546). Levocetirizine showed numerical (mean RQLQ, WPAI-AS, ESS) and statistically superior differences (two domains within WPAI-AS) compared with placebo upon analysis of secondary efficacy variables. The incidence of treatment-emergent AEs was similar (levocetirizine, 23.9%; placebo, 24.4%). As the lack of efficacy was inconsistent with all previous levocetirizine studies, post hoc analyses were performed to assess the influence of pollen counts, geography, and other factors; however, no conclusive explanation could be identified. Conclusions: In this study, levocetirizine 5 mg QD was well tolerated but failed to show significant efficacy compared with placebo in a US adult population with SAR. This finding is inconsistent with all previous studies with levocetirizine and in contrast to a concurrently run, similarly designed US study. It reflects the importance of conducting duplicate studies as there is always a small but real risk of false negative results in clinical studies, irrespective of the methodologic quality.

Efficacy of fexofenadine in the prophylactic control of cat allergen-induced allergic rhinitis

BACKGROUND To date, it is unknown whether fexofenadine mitigates the worsening of symptoms induced by the cat allergen Felis domesticus allergen 1. OBJECTIVE To determine the effects of a single dose of fexofenadine hydrochloride, 180 mg, in preventing and controlling cat allergen-induced allergic rhinitis symptoms using the cat room challenge model. METHODS This single-center, randomized, double-blind, placebo-controlled, 2-way crossover study consisted of a screening visit, 1 or 2 qualifying visits, and 2 treatment periods separated by a mean +/- SD washout period of 14 +/- 3 days. Patients were randomized to treatment sequence 1 (placebo followed by fexofenadine) or sequence 2 (fexofenadine followed by placebo). Baseline end points were obtained before study drug administration, and allergen challenges were initiated 1 1/2 hours after dosing. The primary end point was the change from predose baseline in the total symptom score (sum of rhinorrhea, itchy nose/palate/ throat, sneezing, and itchy/watery/red eyes) after 30 minutes of allergen exposure compared with placebo. RESULTS Of 211 patients screened, 66 were randomized and 63 completed the study. Mean change in the total symptom score from predose baseline was significantly less with fexofenadine compared with placebo 30 minutes after initiation of the cat allergen challenge (2 hours after dosing) (P = .03). The overall incidence of treatment-emergent adverse events was low and comparable for both groups. CONCLUSION Prophylactic treatment with a single dose of fexofenadine hydrochloride, 180 mg, significantly mitigated the worsening of allergic rhinitis symptoms induced by exposure to cat allergen compared with placebo use.

Development of questionnaires to measure patient preferences for intranasal corticosteroids in patients with allergic rhinitis

OBJECTIVE: To develop a questionnaire to evaluate preferences for attributes of intranasal corticosteroids (INSs) in clinical trials with allergic rhinitis (AR) patients. STUDY DESIGN AND SETTING: Established questionnaire development practices were used, including performance of a literature review and use of patient and physician focus groups, cognitive debriefing interviews, and pilot testing before validation. RESULTS: Findings from patient and physician focus groups suggest that sensory attributes are relevant to AR patients when choosing INSs. Physician focus groups identified the need for 2 distinct preference instruments, a clinical trial patient preference questionnaire (CTPPQ) and a clinical practice preference questionnaire (CPPPQ). A pilot study suggests that the CTPPQ is capable of discriminating between 2 INSs in the clinical trial setting. CONCLUSIONS: Initial findings suggest that items in the CTPPQ and CPPPQ are easy to understand and relevant to patients. Further validation studies with larger sample sizes are needed to assess the psychometric properties of both questionnaires. EBM rating: B-20.

Treating the ocular symptoms of seasonal allergic rhinitis with triamcinolone acetonide aqueous nasal spray.

TREATING THE OCULAR SYMPTOMS OF SEASONAL ALLERGIC RHINITIS WITH TRIAMCINOLONE ACETONIDE AQUEOUS NASAL SPRAY Allergic rhinitis (AR) is one of the most prevalent chronic diseases worldwide, with an estimated 20% of the global population thought to be affected. Ocular symptoms (eg, itching, tearing, and redness) are commonly bothersome components of AR and when present together with nasal symptoms are more properly termed allergic rhinoconjunctivitis. Although intranasal corticosteroids (INSs) are the most effective treatment option for controlling the inflammatory responses associated with AR, oral antihistamines have been the most commonly used rescue medication when not being used for prevention for allergic rhinoconjunctivitis. Recent evidence has suggested that INSs may have the potential to reduce ocular symptoms. The mechanism for this effect is unclear; several theories suggest modulation of a naso-ocular neurogenic reflex or nasolacrimal reflux. Triamcinolone acetonide aqueous nasal spray is currently approved for the treatment of the nasal symptoms of perennial AR and seasonal AR (SAR) in adults and children 6 years or older. A number of studies evaluating the effect of triamcinolone acetonide aqueous nasal spray on nasal symptoms have secondarily evaluated improvements of ocular symptoms.1–4 These studies were randomized, singleor double-blind, multicenter, parallel-group clinical trials comparing triamcinolone acetonide aqueous nasal spray, 220 g once daily, with either placebo or active INS comparators in patients 12 years or older with SAR. Results of the effect of triamcinolone acetonide aqueous nasal spray on ocular symptoms associated with SAR are summarized in Table 1. Compared with placebo, triamcinolone acetonide aqueous nasal spray showed significant improvements in mean total eye symptom score (ocular itching, tearing, or redness; scale of 0–3) during a 3-week treatment period. In the active comparator trials, all treatments improved the total eye symptom score from baseline, with no significant differences observed between triamcinolone acetonide aqueous nasal spray, 220 g once daily, and comparable doses of beclomethasone dipropionate and fluticasone propionate. In addition, triamcinolone acetonide aqueous nasal spray has shown a Disclosures: Dr Bielory has worked as a consultant for Schering-Plough, GlaxoSmithKline, UCB-Pharma, Sepracor, Jerini, and Ocusense; and has received research support from Schering-Plough, sanofi-aventis, Genentech, Viropharm [Lev Pharmaceuticals], Dyax, and Sepracor. Dr Georges is a full-time employee of sanofi-aventis. Dr Gross has worked as a consultant for Cornerstone Biopharma and Sepracot; has received grant/research support from Alcon, Amgen, Amphastar, Apieron, AstraZeneca, Capnia, J&J, sanofi-aventis, SkyePharma, GlaxoSmithKline, Norvartis, and Schering; served on the speakers’ bureau for AstraZeneca, GlaxoSmithKline, sanofiaventis, Genentech, Merck, and UCB; and is currently the executive vice president of the Joint Council of Allergy, Asthma, and Immunology and a consultant for the Texas Medical Board. Funding Sources: Editorial assistance was funded by sanofi-aventis US Inc.