Safety and tolerability of a short ragweed sublingual immunotherapy tablet.

BACKGROUND: MK-3641 is a short ragweed sublingual tablet under investigation for immunotherapy of ragweed pollen-induced allergic rhinitis. OBJECTIVE: To characterize the safety and tolerability of a ragweed sublingual tablet (Merck/ALK-Abelló) in ragweed-allergic adults with or without conjunctivitis. METHODS: Data from 4 randomized, double-blinded, placebo-controlled trials of MK-3641 (2 28-day and 2 52-week trials) were evaluated. Pooled analyses examined short-term safety over 28 days from all 4 trials and long-term safety from the 52-week trials. RESULTS: Across all studies, 757, 198, 454, and 1,058 subjects were randomized to placebo or 1.5, 6, or 12 Amb a 1-U of MK-3641, respectively. Treatment-related adverse events were more frequent in the 6- and 12-Amb a 1-U MK-3641 groups than in the placebo group and were primarily local application-site reactions occurring in the first few days of treatment. There was no treatment-associated loss of asthma control or worsening of asthma associated with treatment. No swellings led to airway obstruction or respiratory compromise. No treatment-related anaphylactic shock, life-threatening, or serious treatment-related adverse events were reported for any MK-3641 dose. Of the 1,707 MK-3641-treated subjects, 1 systemic (anaphylactic) reaction was reported (0.06%). The 52-week long-term assessment was generally similar to the safety profile based on the 28-day assessment. CONCLUSION: MK-3641 doses up to and including 12 Amb a 1-U were well tolerated, with no unexpected safety findings. Sublingual immunotherapy risks such as worsening asthma or airway swellings that could cause airway obstruction were not observed. Systemic reactions and use of epinephrine were uncommon. In these studies, after the first dose was administered in a health care setting, self-administration was well tolerated. TRIAL REGISTRATION: clinicaltrials.gov Identifiers: NCT01469182, NCT00783198, NCT00770315, and NCT00978029.

Beclomethasone dipropionate nasal aerosol with an integrated dose counter: functionality and performance.

Consistent medication delivery is critical for disease control including symptom management of allergic rhinitis (AR). Available aqueous intranasal corticosteroid devices lack an accurate dose (actuation) counter, which may lead patients to prematurely discard a unit or use a unit beyond its labeled number of actuations, therefore impacting patient adherence. Beclomethasone dipropionate (BDP) nasal aerosol, a nonaqueous hydrofluoroalkane formulation in a device with a novel integrated dose counter and an established efficacy/safety profile, was approved to treat AR-associated nasal symptoms in adolescent and adult patients. This study was designed to evaluate performance of the BDP nasal aerosol device with an integrated dose counter in perennial AR (PAR) patients. In a 6-week, double-blind, placebo-controlled study in PAR patients (≥12 years), patients were randomized to receive once-daily BDP nasal aerosol at 320 micrograms or placebo. In addition to assessing the primary efficacy end point, patients evaluated the performance of the device and reliability, accuracy, and functionality of the dose counter. Concordance between daily patient-reported actuations and dose counter readings was assessed by classifying discrepancies into four categories: "fire not count," "count not fire," "count unknown fire," and "count up unknown fire." Analysis was performed for the total device completer population (n = 374), which included all randomized patients completing ≥80% of actuations during the last 4 weeks of treatment. Low discrepancy rates were shown for all discrepancy categories. Of 41,891 patient-reported actuations, only 159 discrepancies (diary versus counter) were noted, resulting in an overall discrepancy rate of 0.38 per 100 actuations. The medically important discrepancy rate of "fire not count" was low (0.09 per 100 actuations). Overall, 79.1% of patients reported zero discrepancies, 9.4% reported one discrepancy, and 6.4% reported two discrepancies. These results showed the functionality and reliability of the BDP nasal aerosol device with an integrated dose counter in a clinical setting. (ClinicalTrials.gov identifier: NCT01134705.).

Mometasone furoate nasal spray reduces the ocular symptoms of seasonal allergic rhinitis.

BACKGROUND: Mometasone furoate nasal spray (MFNS), a potent intranasal corticosteroid with proved efficacy in relieving nasal allergic rhinitis symptoms, has demonstrated effectiveness in improving ocular symptoms associated with seasonal allergic rhinitis (SAR) in retrospective analyses. OBJECTIVE: We sought to evaluate prospectively the efficacy of MFNS in reducing total ocular symptom scores (TOSSs) and individual ocular symptoms in subjects with SAR. METHODS: Subjects 12 years or older (n = 429) with moderate-to-severe baseline symptoms were randomized to MFNS, 200 microg once daily, or placebo in this 15-day, double-blind, parallel-group study. Subjects evaluated morning instantaneous TOSSs and daily reflective TOSSs, total nasal symptom scores (TNSSs; both instantaneous TNSSs and reflective TNSSs, respectively), and individual ocular and nasal symptoms. Mean changes from baseline averaged over days 2 to 15 (instantaneous) and days 1 to 15 (reflective) were calculated. Quality of life was assessed by using the Rhinoconjunctivitis Quality of Life Questionnaire. RESULTS: MFNS treatment yielded significant reductions from baseline versus placebo in instantaneous TOSSs (-0.34, P = .026, coprimary end point), instantaneous TNSSs (-0.88, P < .001, coprimary end point), reflective TOSSs (-0.44, P = .005), and reflective TNSSs (-1.06, P < .001). Significant decreases in all individual reflective ocular symptoms and instantaneous eye itching/burning and eye watering/tearing were observed for MFNS versus placebo (P < .05). Numeric improvements in instantaneous eye redness were seen but did not reach statistical significance. Improvements in Rhinoconjunctivitis Quality of Life Questionnaire total scores and individual symptom domains were achieved with MFNS treatment versus placebo (P < .001). MFNS was well tolerated. CONCLUSION: This prospective study demonstrates that MFNS significantly reduces ocular symptoms in subjects with SAR.

Possible Protective Effect of Omalizumab on Lung Function Decline in Patients Experiencing Asthma Exacerbations.

BACKGROUND: Frequent exacerbations are associated with greater FEV1 decline in patients with asthma. The effect of omalizumab versus placebo on lung function in patients experiencing asthma exacerbations has not been previously examined. OBJECTIVE: To evaluate the relationship between postbaseline (treatment phase) exacerbation status and lung function decline in children, adolescents, and adults treated with omalizumab versus placebo using data from 3 pediatric and adolescent/adult studies. METHODS: Changes in percent predicted FEV1 (ppFEV1) and FEV1 by treatment (omalizumab/placebo) and postbaseline exacerbation status (exacerbators/nonexacerbators) were assessed in patients aged 6 to 11 years (IA05, n = 576) and 12 to 75 years (EXTRA/INNOVATE pooled, n = 1202). Pediatric patients were examined at treatment weeks 12, 24, 28, 40, and 52, and adolescent/adult data at weeks 4, 12, 20, and 28. RESULTS: Omalizumab-treated patients experienced larger increases in ppFEV1 and FEV1 compared with placebo-treated patients in the pediatric and pooled adolescent/adult populations. The response was observed in pediatric exacerbators, with significantly larger increases in ppFEV1 and FEV1 at week 12 (mean difference [95% CI], 4.11% [0.93%-7.30%], P = .011 for ppFEV1; 80 [10-140] mL, P = .017 for FEV1) and week 28 (mean difference [95% CI], 3.65% [0.11%-7.19%], P = .043 for ppFEV1; 100 [30-170] mL, P = .007 for FEV1). In the adolescent/adult population, both exacerbators and nonexacerbators derived similar benefit with omalizumab compared with placebo. CONCLUSIONS: Findings from this post hoc analysis suggest that omalizumab may confer some protection against lung function decline among patients who experienced exacerbations during treatment.

Keys to successful management of patients with allergic rhinitis: focus on patient confidence, compliance, and satisfaction.

OBJECTIVE: The American Academy of Otolaryngic Allergy (AAOA) convened an expert, multidisciplinary Working Group on Allergic Rhinitis to discuss patients' self-treatment behaviors and how health care providers approach and treat the condition. PROCEDURES AND DATA SOURCES: Co-moderators, who were chosen by the AAOA Board of Directors, were responsible for initial agenda development and selection of presenters and participants, based on their expertise in diagnosis and treatment of allergic rhinitis. Each presenter performed a literature search from which a presentation was developed, portions of which were utilized in developing this review article. SUMMARY OF FINDINGS: Allergic rhinitis is a common chronic condition that has a significant negative impact on general health, co-morbid illnesses, productivity, and quality of life. Treatment of allergic rhinitis includes avoidance of allergens, immunotherapy, and/or pharmacotherapy (ie, antihistamines, decongestants, corticosteroids, mast cell stabilizers, anti-leukotriene agents, anticholinergics). Despite abundant treatment options, 60% of all allergic rhinitis patients in an Asthma and Allergy Foundation of America survey responded that they are "very interested" in finding a new medication and 25% are "constantly" trying different medications to find one that "works." Those who were dissatisfied also said their health care provider does not understand their allergy treatment needs and does not take their allergy symptoms seriously. Dissatisfaction leads to decreased compliance and an increased reliance on multiple agents and over-the-counter products. Furthermore, a lack of effective communication between health care provider and patient leads to poor disease control, noncompliance, and unhappiness in a significant portion of patients. CONCLUSIONS: Health care providers must gain a greater understanding of patient expectations to increase medication compliance and patient satisfaction and confidence.

Clinical efficacy of olopatadine vs epinastine ophthalmic solution in the conjunctival allergen challenge model.

BACKGROUND: Olopatadine hydrochloride 0.1% ophthalmic solution (Patanol) and epinastine hydrochloride 0.05% ophthalmic solution (Elestat) are two topical antiallergic agents. Olopatadine is indicated for the treatment of the signs and symptoms of allergic conjunctivitis that include itching, redness, tearing, lid swelling, and chemosis. Epinastine is indicated for the prevention of itching associated with allergic conjunctivitis. OBJECTIVE: This study compared the clinical efficacy of olopatadine and epinastine in the prevention of itching and conjunctival redness in the conjunctival allergen challenge (CAC) model. RESEARCH DESIGN AND METHODS: This was a prospective, randomized, double-masked, contralaterally-controlled, single center allergen challenge study. Ninety-six subjects with a history of allergic conjunctivitis were screened, and the 66 who responded to conjunctival allergen challenge at visits 1 and 2 were randomized into 1 of 3 treatment groups at visit 3 to receive one drop of study medication in each eye: (1) olopatadine in one eye and epinastine in the fellow eye, (2) olopatadine in one eye and placebo in the fellow eye, and (3) epinastine in one eye and placebo in the fellow eye. Five minutes after study drop instillation, subjects were bilaterally challenged with the allergen concentration that had elicited a positive conjunctival allergic response at Visits 1 and 2. Subjective itching assessments were given at 3 min, 5 min, and 7 min post challenge. Objective redness and chemosis assessments were made at 10 min, 15 min, and 20 min post challenge. Paired sample two-tailed t-tests were performed on the mean scores at each time point to assess statistical significance in the differences between treatments. MAIN OUTCOME MEASURES; RESULTS: Fifty-three subjects were randomized into the olopatadine/epinastine treatment group, the primary analysis group. Olopatadine treated eyes exhibited significantly lower mean itching and conjunctival redness scores than the contralateral epinastine treated eyes, -0.19 (p = 0.003) and -0.52 (p < 0.001), respectively. Olopatadine treated eyes also exhibited significantly less chemosis -0.24 (p < 0.001), ciliary redness -0.55 (p < 0.001), and episcleral redness -0.58 (p < 0.001) than epinastine treated eyes. CONCLUSION: Olopatadine is significantly more effective than epinastine in controlling itching, redness and chemosis associated with allergic conjunctivitis in the CAC model.

Comparison of olopatadine 0.6% nasal spray versus fluticasone propionate 50 microg in the treatment of seasonal allergic rhinitis.

The efficacy of nasal antihistamines (NAHs) for allergic rhinitis (AR) is comparable with or better than second-generation oral antihistamines, with faster onset of action and greater effect on congestion. Limited data suggest that NAHs may be equivalent to intranasal corticosteroids at reducing the full range of nasal seasonal AR (SAR) symptoms, including congestion. The efficacy of olopatadine 0.6% nasal spray (2 sprays/nostril b.i.d.) for symptoms of SAR was compared with fluticasone 50 microg nasal spray (2 sprays/nostril q.d.) in a double-blind, randomized, parallel-group, 2-week noninferiority trial. A total of 130 symptomatic patients were randomized to treatment and they recorded nasal and ocular allergy symptom scores b.i.d. (morning and evening) in a diary. Both treatments reduced reflective and instantaneous assessments of nasal and ocular symptoms from baseline throughout the 2-week study period (p < 0.05). The reflective total nasal symptom score (the primary efficacy variable) decreased by an average of -45.4% for patients treated with olopatadine 0.6% and by -47.4% for those treated with fluticasone; statistical significance favoring olopatadine was demonstrated at day 1. No significant between-treatment differences were determined for the average 2-week percent changes from baseline for congestion, runny nose, sneezing, itchy nose, and ocular symptoms, although olopatadine had a faster onset of action for reducing all symptoms. Both treatments were safe and well tolerated. Olopatadine and fluticasone nasal sprays both reduced nasal and ocular SAR symptoms with no significant between-treatment differences except for a faster and greater onset of action with olopatadine.

State of world allergy report 2008: allergy and chronic respiratory diseases.

It is widely recognized that the incidence of allergies and allergic diseases is on the rise globally. As an international umbrella organization for regional and national allergy and clinical immunology societies, the World Allergy Organization is at the forefront of a combined united effort across nations and organizations to address this global concern by promoting the science of allergy and clinical immunology, and advancing exchange of information.The World Allergy Organization's State of World Allergy Reports will provide a biennial review of allergic diseases worldwide, consider their medical and socioeconomic contexts, and propose effective approaches to addressing these problems.In this first State of World Allergy Report 2008, experts from different regions of the world have attempted to define the extent of the global allergy problem, examine recent trends, and provide a framework for the collaboration among world medicine, science, and government agencies that is needed to address the rapidly developing issues associated with allergy and allergic diseases.

Newer aspects in the treatment of pediatric and adult asthma: monoclonal anti-IgE.

OBJECTIVE: To review the results of the first anti-IgE agent to undergo clinical evaluation in the treatment of allergic asthma and allergic rhinitis. DATA SOURCES: Treatment protocols conducted in Europe and the United States in moderate to severe allergic asthmatic patients who continued to show symptoms despite treatment with inhaled corticosteroids with the addition of monoclonal humanized anti-IgE treatment. STUDY SELECTION: Double-blind, placebo-controlled studies, published and in press, are reviewed. RESULTS: Treatment with anti-IgE allowed a decrease in inhaled corticosteroid and rescue medication use and significantly reduced the incidence and frequency of asthma exacerbations among these patients over a 28-week time period and a 6-month extension period. CONCLUSIONS: Anti-IgE shows great promise as an adjunctive therapy in moderate to severe asthmatic patients.

Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003.

The nomenclature proposed in the October 2003 report of the Nomenclature Review Committee of the World Allergy Organization is an update of the European Academy of Allergology and Clinical Immunology Revised Nomenclature for Allergy Position Statement published in 2001. The nomenclature can be used independently of target organ or patient age group and is based on the mechanisms that initiate and mediate allergic reactions. It is assumed that as knowledge about basic causes and mechanisms improves, the nomenclature will need further review.

Nomenclatura de alergia revisada para uso global: Relatório do Comitê de Revisão de Nomenclatura / Revised nomenclature for allergy for global use: Report of the Nomenclature

A nomenclatura proposta no relatório de outubro de 2003 do Comitê de Revisão de Nomenclatura da World Allergy Organization é uma atualização da Nomenclatura Revisada para Declaração da Situação da Alergia da Academia Européia de Alergologia e Imunologia Clínica (European Academy of Allergology and Clinical Immunology Revised Nomenclature for Allergy Position Statement), publicada em 2001. A nomenclatura pode ser usada independentemente do órgão alvo ou da faixa etária do paciente e se baseia nos mecanismos que desencadeiam e medeiam as reações alérgicas. Supõe-se que, conforme o conhecimento sobre as causas básicas e os mecanismos for se aprimorando, a nomenclatura virá a precisar de revisão