Efficacy of Desloratadine and Levocetirizine in Patients with Cedar Pollen-Induced Allergic Rhinitis: A Randomized, Double-Blind Study.

BACKGROUND: No comparative study of antihistamines that differ in structural system has been conducted in allergic rhinitis. OBJECTIVE: This was a randomized, double-blind, crossover comparative study to verify the efficacy of antihistamines that differ in structural system. METHODS: A total of 50 patients with moderate or more severe Japanese cedar pollen-induced allergic rhinitis were randomized to receive either placebo, desloratadine 5 mg (a tricyclic), or levocetirizine 5 mg (a piperazine). One dose of the study drug was orally administered at 9 pm on the day before a pollen exposure test, which was performed for 3 h (9 a.m. to 12 p.m.) to assess symptoms in an environmental challenge chamber (ECC). Nasal and ocular symptoms were compared at an airborne pollen level of 8,000 grains/m3. The primary endpoint was mean total nasal symptom score (TNSS) from 120 to 180 min in the ECC. Subjects with a difference of ≥1 in TNSS between 2 drugs were extracted to the relevant drug-responsive group. RESULTS: The difference in TNSS from placebo was -2.42 (p < 0.0001) with levocetirizine and -1.66 (p < 0.01) with desloratadine, showing that both drugs were significantly more effective than placebo in controlling symptoms, but with no statistically significant difference between the 2 drugs. There were 12 subjects in the desloratadine-responsive group and 24 subjects in the levocetirizine-responsive group, with no contributor to response was detected. CONCLUSION: Levocetirizine tended to control nasal symptoms more effectively than desloratadine. However, the response to each antihistamine varied among individuals and the predictors to the response are unknown. CLINICAL TRIAL REGISTRATION NUMBER: UMIN ID: UMIN000029653.

Efficacy and safety of using a warming needle for persistent allergic rhinitis: study protocol for a randomized controlled trial.

BACKGROUND: Many previous studies have shown the potential therapeutic effect of acupuncture for allergic rhinitis. Most of these studies, however, were limited by the short duration of observations and lack of sham acupuncture as the control group. Our preliminary experiments showed that the use of a warm needling achieved a much more persistent effect in the treatment of allergic rhinitis (AR) compared with simple acupuncture therapy. Hence, we have designed a multicenter, randomized controlled trial (RCT) in which the first-line medication loratadine will be used as the control group, and the effect of warm needling therapy will be evaluated through long-term observation. METHODS/DESIGN: The trial is designed as a multicenter, parallel-group, randomized, single-blinded (outcome assessors), non-inferiority trial. A total of 98 patients with persistent AR will be randomly assigned into two groups. Patients in the treatment group will be treated with warm needling at GV14 and acupuncture at EX-HN3, ST2, LI20, EX-HN8, GV23, LU7, LU5 and LI4 three times a week, for a total of 4 weeks. Patients in the control group will be treated with oral loratadine 10 mg/day for 4 weeks. The primary outcome will be the change in the Total Nasal Symptom Score (TNSS) from baseline to that at 6 months after treatment during the follow-up period. The secondary outcomes will include the Total Non-nasal Symptom Score and the Rhinoconjunctivitis Quality of Life Questionnaire, changes in the TNSS from baseline to that at 2 and 4 weeks during treatment, and 3 months after treatment during the follow-up period. Outcomes will be measured at 2 and 4 weeks, and 3 and 6 months after treatment. Any side effects of treatment will be observed and recorded. DISCUSSION: We expect that the study results will provide evidence to determine the effects of warm needling compared with loratadine. Our final goal of the study is to evaluate the difference in the short-term and long-term effects between the two therapeutic methods, especially the long-term effect of warm needling. TRIAL REGISTRATION: ClinicalTrials.gov NCT02339714 . Registered on 14 January 2015.

Novel Inducers of Fetal Globin Identified through High Throughput Screening (HTS) Are Active In Vivo in Anemic Baboons and Transgenic Mice.

High-level fetal (γ) globin expression ameliorates clinical severity of the beta (ß) hemoglobinopathies, and safe, orally-bioavailable γ-globin inducing agents would benefit many patients. We adapted a LCR-γ-globin promoter-GFP reporter assay to a high-throughput robotic system to evaluate five diverse chemical libraries for this activity. Multiple structurally- and functionally-diverse compounds were identified which activate the γ-globin gene promoter at nanomolar concentrations, including some therapeutics approved for other conditions. Three candidates with established safety profiles were further evaluated in erythroid progenitors, anemic baboons and transgenic mice, with significant induction of γ-globin expression observed in vivo. A lead candidate, Benserazide, emerged which demonstrated > 20-fold induction of γ-globin mRNA expression in anemic baboons and increased F-cell proportions by 3.5-fold in transgenic mice. Benserazide has been used chronically to inhibit amino acid decarboxylase to enhance plasma levels of L-dopa. These studies confirm the utility of high-throughput screening and identify previously unrecognized fetal globin inducing candidates which can be developed expediently for treatment of hemoglobinopathies.

Onset of action of loratadine/montelukast in seasonal allergic rhinitis patients exposed to grass pollen.

Given the impact of allergic rhinitis (AR) on quality of life, it is important that AR medications have rapid onset of symptom relief. The objective of this study was to determine the onset of action of loratadine (CAS 79794-75-5)/montelukast (CAS 151767-02-1) 10 mg/10 mg (L/M) versus placebo in seasonal AR (SAR) subjects. In this single-center, double-blind, crossover study, subjects with SAR and confirmed sensitivity to grass pollen received single doses of L/M or placebo following exposure to grass pollen in the Vienna Challenge Chamber. Subjects recorded symptoms at 15-min intervals during the first 2 h post dose and at 30-min intervals during the next 2 h. After a 14-day washout, the subjects crossed over to the other treatment. The primary endpoint was onset of action of L/M, defined as the first time point at which the mean change from baseline in total symptom score became and remained significantly different with L/M versus placebo. Secondary endpoints included nasal congestion score and rhinomanometry findings. Onset of action with L/M for total symptom score was 1 h, 45 min (P < 0.01 vs placebo). Significant improvements in subject-assessed nasal congestion scores (P < 0.01) and rhinomanometry (P = 0.036) were noted with L/M as compared with placebo. Overall, L/M was well tolerated. In conclusion, L/M demonstrated rapid onset for broad symptom relief, including nasal congestion, in subjects with SAR.

Desloratadine for the treatment of cypress pollen-induced allergic rhinitis.

BACKGROUND: Few studies have been conducted to assess treatment options for patients with sensitivities to cypress pollens, important triggers of allergic rhinitis (AR) in the Mediterranean region. OBJECTIVE: To evaluate the effect of desloratadine, a second-generation antihistamine, on AR symptoms caused by cypress pollens native to France. METHODS: Adults (N=233) with symptomatic cypress pollen allergies were randomized to receive desloratadine, 5 mg, or placebo daily for 15 days during 2 consecutive cypress pollen seasons. The primary end point was the percentage change from baseline in morning total nasal symptom scores on day 14; secondary assessments included total symptom score, peak nasal inspiratory flow, the Rhinoconjunctivitis Quality of Life Questionnaire, and global response to therapy. RESULTS: On day 14, the desloratadine group had a significantly greater percentage decrease in total nasal symptom score vs the placebo group (-40% vs. -30%; P < .04). Similarly, on day 14, there was a 47% and 37% respective decrease in total symptom score (P = .01). Mean peak nasal inspiratory flow scores showed numeric, albeit not statistically significant, improvements from baseline through day 14 with desloratadine. A significantly greater improvement in Rhinoconjunctivitis Quality of Life Questionnaire scores occurred with desloratadine vs placebo on day 14 (-1.4 vs. -0.9; P = .004). The mean global response to therapy was better with desloratadine vs placebo (3.4 vs. 3.9; P = .004). The adverse event rate was similar in both groups. CONCLUSION: Desloratadine is efficacious and safe for the treatment of AR induced by cypress pollens; it also improved disease-related quality of life.

Efficacy and safety of fixed-dose loratadine/montelukast in seasonal allergic rhinitis: effects on nasal congestion.

A need exists for safe, effective therapy for the relief of the symptoms of allergic rhinitis (AR) that also consistently relieves nasal congestion, the most common and bothersome symptom. This study was performed to assess efficacy and safety of a once-daily tablet containing 10 mg of loratadine, an antihistamine, and 10 mg of montelukast, a leukotriene antagonist (SCH 445761) versus placebo and pseudoephedrine (PSE; 240 mg once-daily formulation; active comparator). In a multicenter, parallel-group, double-blind, double-dummy, randomized study, 1095 subjects with documented history of seasonal AR and positive skin-prick test to a prevailing aeroallergen were treated for 15 days with fixed-dose combination loratadine/montelukast (L/M), PSE, or placebo. After randomization, subjects rated severity of nasal congestion and measured peak nasal inspiratory flow (PNIF) rate in the morning and evening. The change in quality of life from baseline was also assessed. L/M and PSE were significantly more effective than placebo in alleviating nighttime and daytime nasal congestion and improving PNIF rate, an objective measure of nasal obstruction. There were no significant differences between L/M and PSE for any efficacy analysis including improvement in the quality of life. Subjects treated with L/M experienced a similar incidence of total adverse events versus placebo and a lower incidence of total adverse events (including dizziness, insomnia, jitteriness, nausea, and dry mouth) versus PSE. Nasal decongestant activity of L/M was significantly higher than that of placebo and similar to that of PSE in symptomatic AR subjects. L/M showed a safety profile similar to placebo and was better tolerated than PSE. Thus, L/M offers a safe and efficacious alternative to PSE for the treatment of nasal congestion associated with AR.

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

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

A comparison of once daily fexofenadine versus the combination of montelukast plus loratadine on domiciliary nasal peak flow and symptoms in seasonal allergic rhinitis.

BACKGROUND: The combination of montelukast (ML) and loratadine (LT) has previously been shown to be superior to either drug alone in managing seasonal allergic rhinitis (SAR), whilst fexofenadine (FEX) has been shown to be better than LT as monotherapy. OBJECTIVES: We wished to compare ML + LT vs. FEX alone for effects on daily measurements (am/pm) of peak inspiratory flow (PIF) and symptoms. METHODS: Thirty-seven patients with SAR (skin prick positive to grass pollen) were randomised into a single-blind, double-dummy placebo (PL)-controlled cross-over study during the grass pollen season, comparing 2 weeks of once daily treatment with (a) 120mg FEX or (b) 10mg ML + 10mg LT. There was a 7-10 day placebo run-in and washout prior to each randomised treatment. The average of am/pm PIF (the primary outcome variable) was analysed. Patients recorded their symptom scores (from 0 to 3) twice daily, for nasal blockage, discharge, itching and sneezing with; total eye symptoms, ocular cromoglycate use, and daily activity. The total nasal symptom score was calculated as a composite (out of 24). RESULTS: There were no significant differences between baselines after the run-in and washout placebos for any variables. There were significant (P < 0.05, Bonferroni) improvements in all symptoms and PIF compared to pooled placebo with both treatments for all end-points, but no differences between the two treatment regimes (as means and within-treatment 95% confidence intervals): PIF: PL 102 (98-107), FEX 111 (107-116), ML+LT 113 (109-118); total nasal symptoms: PL 7.4 (6.7-2.0), FEX 5.0 (4.3-5.7), ML + LT 4.0 (3.3-4.7). CONCLUSIONS: Once daily FEX as monotherapy was equally effective as the combination of once daily ML + LT in improving nasal peak flow and controlling symptoms in SAR. Further studies are indicated to assess whether ML confers additional benefits to FEX in SAR.

Cetirizine, loratadine, or placebo in subjects with seasonal allergic rhinitis: effects after controlled ragweed pollen challenge in an environmental exposure unit.

BACKGROUND: Allergic rhinitis affects nearly one in 10 Americans. Cetirizine is a newer once-daily selective H1-antagonist. In traditional clinical trials, cetirizine has been shown to be safe and effective for the treatment of seasonal and perennial allergic rhinitis and chronic idiopathic urticaria. OBJECTIVE: To better characterize the efficacy and onset of action of cetirizine in a more controlled but clinically relevant setting, this agent was compared with loratadine and placebo in patients with symptomatic seasonal allergic rhinitis undergoing controlled pollen challenge in an environmental exposure unit (EEU). METHODS: This was a double-blind, randomized, parallel-group study. After screening, patients were exposed to ragweed pollen (primed) in the EEU (up to six exposures), and those with qualifying symptom scores were randomized to controlled pollen exposure (two periods of 5.5 to 6.5 hours over 2 days) and once-daily treatment with 10 mg cetirizine (n = 67), 10 mg loratadine (n = 67), or placebo (n = 68). The mean ragweed pollen level was 3480 +/- 350 grains/m3 (standard deviation). The primary efficacy variables were the total symptom complex (TSC) and the major symptom complex (MSC) scores. Symptoms were evaluated every half hour in the EEU throughout the study. RESULTS: Cetirizine produced a 36.7% mean reduction in TSC scores overall versus 15.4% with loratadine and 12.0% with placebo (p < or = 0.01). Cetirizine also produced a 37.4% mean reduction in MSC scores overall versus 14.7% with loratadine and 6.7% with placebo (p < or = 0.01). Onset of action as assessed by reductions in TSC and MSC scores versus placebo was evident within 1 hour with cetirizine (p < or = 0.02) and 3 hours with loratadine (p < or = 0.03). The incidence of treatment-related side effects was similar among groups, with headache reported most commonly in each group. CONCLUSION: Cetirizine is well tolerated and effective in reducing symptoms of seasonal allergic rhinitis in patients undergoing controlled pollen challenge.

Comparative outdoor study of the efficacy, onset and duration of action, and safety of cetirizine, loratadine, and placebo for seasonal allergic rhinitis.

BACKGROUND: Cetirizine, a new once-daily highly specific H1-antagonist, has been shown in conventional studies to be efficacious in the treatment of seasonal and perennial allergic rhinitis and chronic idiopathic urticaria. OBJECTIVE: The efficacy, duration and onset of action, and safety of cetirizine, 10 mg once daily, was compared with that of loratadine, 10 mg once daily, and placebo in a field study of patients with seasonal allergic rhinitis. METHODS: This was a randomized, double-blind, parallel, double-dummy study conducted over 2 days in spring allergy season at outdoor parks in San Diego and Iowa City. Study medication was administered at 10:00 AM on both days. After screening, eligible patients completed rhinitis symptom diaries in the park hourly from 7:30 to 9:30 AM (baseline); at 10:30 AM and hourly from 11:00 AM to 4:00 PM (period I); at 6:00, 8:00, and 10:00 PM at home (period II); and the next day in the park hourly from 8:00 to 10:00 AM (period III), and from 11:00 AM to 4:00 PM (period IV). Major and total symptom complex scores, global efficacy and overall satisfaction, and adverse events were assessed. RESULTS: Of the 279 patients (140 men and 139 women; mean age, 29 years) randomized to treatment, 278 were included in the efficacy analysis. Cetirizine produced significantly greater mean reductions than loratadine or placebo in major symptom complex severity scores at all periods (p < or = 0.05), except period I for placebo. Cetirizine also produced mean reductions in total symptom complex severity scores that were superior to loratadine at every evaluation period (p < 0.05) and were statistically different from placebo at period II (p < 0.01). A rapid onset of action was observed with cetirizine, as was a better response pattern in the patient global assessment of efficacy compared with loratadine. Study medications were well tolerated; no patient stopped treatment because of side effects. The incidence of somnolence with cetirizine was 13% versus 2% with placebo (p < 0.05); headache occurred more frequently with loratadine (23%) than with cetirizine (11%, p = 0.03). CONCLUSIONS: Cetirizine relieved rhinitis symptoms more effectively and quickly than loratadine and placebo in this field study of seasonal allergic rhinitis. Both active agents were generally well tolerated.

Comparison of intranasal triamcinolone acetonide with oral loratadine for the treatment of patients with seasonal allergic rhinitis.

This multicenter, double-blind, randomized, controlled, parallel-group study compared the safety and efficacy of intranasal triamcinolone acetonide with oral loratadine in relieving symptoms of ragweed-induced seasonal allergic rhinitis. Patients from community-based allergy practices with a history of at least two seasons of seasonal allergic rhinitis verified by a positive skin test received either once-daily treatment with intranasal triacinolone acetonide 220 micrograms plus 1 placebo capsule or oral loratadine 10 mg plus placebo nasal spray. Other medications for rhinitis were prohibited. Changes in rhinitis symptoms were assessed by using patient evaluations, physician global evaluations, and withdrawal rates. Efficacy was evaluated in 274 of 298 patients randomized to treatment (134 to triamcinolone acetonide and 140 to loratadine). Mean total nasal symptom scores for weeks 1, 2, 3, and 4 and the overall score showed greater improvement (P = 0.001) with triamcinolone acetonide than with loratadine. Improvement in all rhinitis symptoms was significantly greater with triamcinolone acetonide than with loratadine; there was a trend for greater improvement in ocular symptoms with triamcinolone acetonide. Physicians' global evaluations indicated triamcinolone acetonide provided moderate-to-complete relief in 78% of patients compared with 58% of loratadine-treated patients (P < or = 0.0001). Both treatments were well tolerated; headache was the most commonly reported adverse event in both groups. Intranasal triamcinolone acetonide was significantly more effective than oral loratadine in relieving the symptoms of seasonal allergic rhinitis.

[Test for efficacy of cetirizine and loratadine as a treatment for seasonal allergic rhinitis in a 6 week cross-over comparative study]. / Badania porównawcze skutecznosci loratadyny i cetirizyny w leczeniu alergicznego sezonowego niezytu nosa w próbie skrzyzowanej prowadzonej przez 6 tygodni.

Cetirizine and loratadine-two new antihistaminic drugs were evaluated in 56 patients with seasonal rhinitis in cross-over open study. I our study, no difference between loratadine and cetirizine has been seen. Both evaluated drugs significantly inhibited the symptoms of allergic rhinitis and conjunctivitis. Adverse reaction and inhibition of histamine and codeine skin tests were similar.