Omalizumab and the treatment of allergic rhinitis

Anti-IgE therapy affects mechanisms in the allergic response that are IgE-dependent or IgE-mediated and common to both allergic asthma and allergic rhinitis. Clinical trials of omalizumab in the treatment of patients with allergic rhinitis or comorbid allergic rhinitis and moderate to severe allergic asthma have recorded significant reductions in symptom severity scores of both conditions. This novel therapy has increased the knowledge base concerning IgE-mediated allergic responses, and, in keeping with its actions established in the treatment of asthma, appears to be useful in the treatment of moderate to severe allergic rhinitis, as well.     

Omalizumab is effective and safe in the treatment of Japanese cedar pollen-induced seasonal allergic rhinitis.

BACKGROUND: Seasonal allergic rhinitis (SAR) induced by Japanese cedar pollen is a substantial problem in Japan. Omalizumab, a novel humanized monoclonal anti-immunoglobulin E (IgE) antibody, has already been proven to reduce symptoms associated with SAR. We investigated the safety and efficacy of omalizumab in the treatment of patients with Japanese cedar pollen-induced SAR compared to placebo. METHODS: A randomized, placebo-controlled, double-blind study was conducted in 100 Japanese patients with a history of moderate-to-severe SAR induced by Japanese cedar pollens. Omalizumab (150, 225, 300, or 375mg) or placebo was administered subcutaneously every 2 or 4 weeks based on serum total IgE and body weight at baseline. The primary efficacy variable was the mean of daily nasal symptom medication scores (sum of the daily nasal symptom severity score and daily nasal rescue medication score) during the treatment period. Secondary efficacy variables included the daily ocular symptom medication score and related variables. RESULTS: Primary and all secondary efficacy variable scores were significantly lower in the omalizumab group than in the placebo group (P < .01). Serum free IgE levels markedly decreased in the omalizumab group and were associated with clinical efficacy. The overall incidence of injection site reactions was higher in the omalizumab group than in the placebo group; however, the adverse reaction profile was similar between the two groups when excluding injection site reactions. No anti-omalizumab antibodies were detected. CONCLUSIONS: Omalizumab was effective and safe in the treatment of SAR induced by Japanese cedar pollen.     

Simultaneous treatment of asthma and allergic rhinitis

Asthma and allergic rhinitis (AR) form a well-recognized comorbidity. This study aims at assessing the efficacy of nasally inhaled beclomethasone dipropionate (BDP) in their simultaneous treatment. A randomized controlled trial was conducted with 78 allergic rhinitis and asthma patients aged 5-17 years. Seventy-five individuals completed the study. During 8 weeks, 38 subjects received BDP-CFC aerosol (>or= 500 mcg/day) exclusively via nasal inhalation through a facemask attached to a plastic valved spacer. The control group (37 patients) received 200 mcg/day of aqueous intranasal beclomethasone plus oral inhalation of BDP-CFC (>or= 500 mcg/day) through a mouthpiece connected to the same spacer. Primary outcomes analyzed in order to assess the response to treatment were clinical scoring for allergic rhinitis and measurements of nasal inspiratory peak flow (NIPF). AR clinical scoring and NIPF did not differ in the two groups at admission or at nearly all follow-up visits. Nasal inhalation of beclomethasone dipropionate provides AR symptom relief while maintaining control of asthma by delivering it to the lungs. Therefore, this therapeutic strategy might be considered for patients suffering from this comorbidity, especially in low-resource countries, since it is less expensive than the conventional treatment.     

A common pathway: asthma and allergic rhinitis.

Historically, the structural and functional differences within the respiratory tract have been the basis for separating the airway into upper and lower entities. For centuries, researchers suggested similar mechanisms in asthma and rhinitis. The implications of such a connection are significant in that asthma and allergic rhinitis (AR) are associated with a high prevalence in adults and children, substantial health care costs, and, often, serious negative effects on quality of life. The importance of the unified airway hypothesis lies in the rational approach to treatment. Management approaches that consider the association between asthma and AR may improve overall outcomes in patients with both diseases. Because the treatment of AR may affect concomitant asthma, significant improvements in health status may occur in some patients. The following review discusses the epidemiology of asthma and AR, provides evidence for common pathophysiological mechanisms, and discusses a therapeutic approach that has positive effects on both diseases, and thereby may maximize benefits and outcomes for patients with concomitant asthma and AR.     

The asthma and allergic rhinitis link.

During the past 10 years, our understanding of asthma and allergic rhinitis (AR) has evolved. The historic perspective of these allergen-induced disorders as distinct and separate entities is being displaced by current thinking that they are described better as a continuum of inflammation involving one common airway. Therefore, traditional therapies originally indicated for AR and asthma are being reassessed to explore their potential value in both upper- and lower-airway diseases. Recently, there has been a renewed interest in the role that histamines play in lower-airway disease, and interest is increasing in the leukotrienes (LTs), which are far more potent inflammatory mediators than histamines, and the role they play in upper-airway disease. Given the pivotal role that LTs play as potent inflammatory mediators in the pathophysiological state of inflammation of both airways, LT receptor antagonists recently have emerged as important therapeutic advances that have potential clinical value in both asthma and allergic rhinitis. The prevalence of asthma and AR is increasing in the general population, and a high proportion of new patients have coexisting upper- and lower-airway disease. Estimates show that 60-78% of patients who have asthma have coexisting AR. The following review discusses the epidemiology of asthma and AR, provides evidence for common pathophysiological mechanisms, and discusses a therapeutic approach that has positive effects on both diseases and may maximize benefits and outcomes for patients with concomitant asthma and AR.     

Inflammatory issues in allergic rhinitis and asthma.

Allergic rhinitis and asthma are both systemic inflammatory disorders with similar pathophysiological mechanisms involving numerous cells and inflammatory mediators. Some airway remodeling also might exist in allergic rhinitis. This review has summarized selected investigative studies from our division and has addressed the effect of various therapeutic agents on nasal fluid, nasal and airway epithelial cells, and the concept of airway remodeling.     

Omalizumab and asthma control in patients with moderate-to-severe allergic asthma: a 6-year pragmatic data review

Controlled clinical trials have shown the recombinant humanized monoclonal anti-IgE antibody omalizumab to improve asthma control and reduce symptom exacerbations in patients with moderate-to-severe allergic asthma who remain clinically unstable despite optimal medical therapy. An objective retrospective review compared clinical experience with the data reported in the controlled studies. Data tracking for 167 patients progressively enrolled between 2003 and 2010 treated with omalizumab included symptoms, forced expiratory volume at 1 second (FEV(1)), systemic steroid bursts, and need for short-acting bronchodilator rescue measured at the start of therapy; 3, 6, and 12 months after starting treatment, and yearly thereafter. Exacerbations were compared for the 12 months before and the 12 months after starting treatment in a subgroup of patients. Asthma control improved with omalizumab over time (up to 6 years) as indicated by fewer symptoms and less need for rescue medication (p < 0.001 for both). FEV(1) remained stable. The number of patients reporting asthma exacerbations requiring urgent care decreased by 49% during the first 12 months of treatment (p ≤ 0.01), and significant reductions in exacerbations were also evident when measured by hospitalizations or systemic corticosteroid bursts (p < 0.001 for both). This is the first long-term pragmatic review of omalizumab. Our clinical experience (up to 6 years in some patients) supports the results of earlier controlled studies, confirming the usefulness of adding omalizumab to the long-term management of patients with difficult-to-treat disease who suffer from persistent symptoms despite optimal therapy with medications.     

A novel air filtration delivery system improves seasonal allergic rhinitis.

Twenty percent of the United States population has respiratory allergies. The preferable treatment for allergies is avoidance. Bedrooms offer the best opportunity for allergen avoidance. Most previous studies of air filtration only measured the effect on allergen particle counts, but few have addressed the clinical efficacy. This study measured the effects of a novel laminar flow air filtration device (PureNight) on seasonal ragweed allergies. Seventy-seven percent of the subjects improved significantly on symptom scores, an average of 26% improvement in the morning and 24% in the evening. Daytime sleepiness and quality of life scores also improved significantly in all subjects. Tolerability was excellent. The PureNight device provided significant clinical improvement of allergic symptoms during ragweed hay fever season.     

Experimental and seasonal exposure to birch pollen in allergic rhinitis and allergic asthma with regard to the inflammatory response

Background and Aims: Seasonal allergy is an interesting model to study the pathophysiological mechanisms involved in allergic inflammation. However, experimental allergen exposure is easier to perform and standardise. The primary aim of this study was to compare the inflammatory responses to high‐dose bronchial challenge and natural exposure during birch pollen season. The second aim was to compare the responses of patients with allergic rhinitis and allergic asthma, respectively to both types of allergen exposure. Methods: Fifteen birch pollen‐allergic patients (seven with asthma and eight with rhinitis) and five healthy individuals were studied during pollen season and after challenge with birch allergen. Symptoms, medication and peak expiratory flow rate (PEFR) were recorded, and blood samples, spirometry and induced sputum were analysed during season and after challenge. Results: Patients with allergic asthma demonstrated a greater bronchial responsiveness to bronchial provocation with birch allergen than patients with rhinitis (P = 0.04) whereas no difference was found regarding nasal challenge. No significant association was found between the level of responsiveness and the inflammatory response after seasonal exposure. Seasonal exposure was related to a more marked systemic inflammatory blood–eosinophil increase than bronchial challenge [(median) (0.25 vs 0.11 × 109/L, P = 0.03)] and after nasal challenge, respectively [(median) (0.25 vs 0.04 × 109/L, P = 0.003)]. A significant correlation in eosinophil cationic protein in induced sputum was found between the experimental and seasonal exposure (rho = 0.62, P = 0.02). Conclusions: Bronchial allergen challenge with inhalation of birch pollen gives a similar inflammatory response in the airway but less systemic inflammation than seasonal exposure in birch pollen allergic patients with asthma and rhinitis. Please cite this paper as: Kämpe M, Janson C, Stålenheim G, Stolt I and Carlson M. Experimental and seasonal exposure to birch pollen in allergic rhinitis and allergic asthma with regard to the inflammatory response. The Clinical Respiratory Journal 2009; DOI:10.1111/j.1752‐699X.2009.00140.x.     

Omalizumab provides long-term control in patients with moderate-to-severe allergic asthma.

The ability of omalizumab, an anti-immnoglobulin-E agent, to maintain long-term disease control in patients with moderate-to-severe allergic asthma was investigated in a 24-week double-blind extension to a 28-week core trial. During the extension, 483 of the initial 546 patients were maintained on randomised treatment and the lowest sustainable dose of beclomethasone dipropionate (BDP) as established during the steroid-reduction phase of the core trial. The use of concomitant asthma medication was permitted and investigators were allowed to adjust the BDP dose or switch patients from BDP to other asthma medications if deemed necessary. More omalizumab-treated patients (33.5%) than placebo-treated patients (13.5%) were able to complete the extension period without requiring inhaled corticosteroid treatment. The mean BDP equivalent dose throughout the extension was lower in the omalizumab group (25 microg x day(-1)) than in the placebo group (43 microg x day(-1)). Disease control was sustained in 76% of omalizumab patients compared with 59.4% of placebo patients free from an asthma exacerbation during the extension period. Compared with placebo, fewer patients in the omalizumab group used other concomitant asthma medication during the extension. Treatment with omalizumab was well tolerated and the incidence of adverse events was similar between groups. In conclusion, these results suggest that omalizumab is a promising new agent for the long-term control of allergic asthma.     

Biomarkers in asthma and allergic rhinitis

A biological marker (biomarker) is a physical sign or laboratory measurement that can serve as an indicator of biological or pathophysiological processes or as a response to a therapeutic intervention. An applicable biomarker possesses the characteristics of clinical relevance (sensitivity and specificity for the disease) and is responsive to treatment effects, in combination with simplicity, reliability and repeatability of the sampling technique. Presently, there are several biomarkers for asthma and allergic rhinitis that can be obtained by non-invasive or semi-invasive airway sampling methods meeting at least some of these criteria.In clinical practice, such biomarkers can provide complementary information to conventional disease markers, including clinical signs, spirometry and PC₂₀methacholine or histamine. Consequently, biomarkers can aid to establish the diagnosis, in staging and monitoring of the disease activity/progression or in predicting or monitoring of a treatment response. Especially in (young) children, reliable, non-invasive biomarkers would be valuable.Apart from diagnostic purposes, biomarkers can also be used as (surrogate) markers to predict a (novel) drug’s efficacy in target populations. Therefore, biomarkers are increasingly applied in early drug development.When implementing biomarkers in clinical practice or trials of asthma and allergic rhinitis, it is important to consider the heterogeneous nature of the inflammatory response which should direct the selection of adequate biomarkers. Some biomarker sampling techniques await further development and/or validation, and should therefore be applied as a “back up” of established biomarkers or methods. In addition, some biomarkers or sampling techniques are less suitable for (very young) children. Hence, on a case by case basis, a decision needs to be made what biomarker is adequate for the target population or purpose pursued.Future development of more sophisticated sampling methods and quantification techniques, such as – omics and biomedical imaging, will enable detection of adequate biomarkers for both clinical and research applications.     

Safety and efficacy of once-daily fexofenadine HCl in the treatment of autumn seasonal allergic rhinitis.

Fexofenadine HCl (Allegra, Telfast) is approved in the US for twice-daily dosing in the treatment of seasonal allergic rhinitis (SAR). A once-daily dose (already available in some countries outside the US) can improve patient compliance and health outcomes. This multicenter, placebo-controlled, 14-day US study was conducted to compare the safety and effectiveness of once-daily fexofenadine HCl with placebo in the treatment of patients with moderate to severe autumnal SAR symptoms. After a 1-week placebo lead-in, patients received 120 or 180 mg fexofenadine HCl or placebo at 8 A.M. Patients recorded SAR symptom severity scores instantaneously (for the 1 hour before medication; i.e., trough blood levels), and reflectively (for the previous 12 hours) at 8 A.M. and 8 P.M. The primary efficacy measure was change from baseline in average instantaneous 8 A.M. total symptom score (TSS, the sum of individual symptom scores excluding nasal congestion). In 861 intent-to-treat patients, both fexofenadine HCl doses provided significant (p < or = 0.05) improvement in 8 A.M. instantaneous TSS compared with placebo. Similarly, both fexofenadine doses were superior to placebo for reflective TSS assessments (p < or = 0.0012). There were no statistical differences in efficacy between the two fexofenadine doses, though the 180 mg dose showed a trend toward greater symptom relief. Incidence of adverse events was similar between fexofenadine and placebo groups (30.2% and 30.0%, respectively), with headache the most frequently reported adverse event (8.9% and 7.5%, respectively). In conclusion, once-daily fexofenadine HCl, 120 or 180 mg, is safe and effective in the treatment of autumnal SAR.     

Cost of illness of atopic asthma and seasonal allergic rhinitis in Germany: 1-yr retrospective study.

The purpose of this study was to evaluate the cost of illness of moderate-to-severe atopic asthma and/or seasonal allergic rhinitis (SAR) in Germany from the perspective of third-party payers (TPP) and patients. Five-hundred patients (276 children/adolescents) with moderate-to-severe asthma and/or SAR were included in this cross-sectional study. Information was collected using a specific patient questionnaire and the abstraction of patient records. Overall, annual costs per patient increased with the severity of atopic asthma and if it was associated with SAR. The average annual cost of SAR was Euro1,089 per child/adolescent and Euro1,543 per adult. Annual costs of severe asthma plus SAR increased to Euro7,928 per child/adolescent and to Euro9,287 per adult. For TPPs, the main cost drivers were medication, hospitalisation, and rehabilitation. The most significant costs for patients were household modifications. For children/adolescents, 60-78% of the expenditures were direct costs, while in adults, 58% of expenditures were indirect costs. It was also observed that patients with moderate and severe asthma used inhaled corticosteroids less frequently than recommended by treatment guidelines. In summary, the total cost for patients increases with the severity of atopic asthma and/or seasonal allergic rhinitis and indirect costs represent a large proportion of the total cost.     

The burden of allergic rhinitis and asthma

Asthma and allergic rhinitis are common health problems that cause major illness and disability worldwide. The prevalence of allergic rhinitis is estimated to range from 10% to 20% in the USA and Europe. Multiple factors contribute to the wide range of reported prevalence rates. These include type of prevalence rate reported (current or cumulative), study selection criteria, age of participants, differences in survey methods, varied geographic locations and socioeconomic status, any of which are significant enough to confound direct comparison between studies. There is no standard set of diagnostic criteria for allergic rhinitis. In most studies, the criteria for diagnosis are based on the subject's reporting, solely by questionnaire and rarely confirmed by skin testing. In addition, most studies focus on hay fever, leaving perennial allergic rhinitis underestimated. Sinus imaging is generally not performed and, therefore, rhinosinusitis not differentiated. Some investigators report 'current' prevalence while others report 'cumulative' or 'lifetime' prevalence. Epidemiologic studies have consistently shown that asthma and rhinitis often coexist in the same patients. The prevalence of asthma is <2% in subjects without rhinitis while it varies from 10% to 40% in patients with rhinitis. Furthermore, the majority of patients with asthma experience rhinitis, which is a factor in the risk for asthma. Despite recognition that allergic rhinitis and asthma are global health problems, there are insufficient epidemiologic data and more data are needed with regard to their etiologic risk factors and natural history. This aim of this review is to enable the reader to discuss prevalence, risk factors and prognosis of allergic rhinitis and asthma.     

支气管哮喘与变应性鼻炎的关系

支气管哮喘与变应性鼻炎二者常同时存在,后者先于前者发生,是哮喘的一个危险因素.研究表明二者之间存在密切联系.现通过阐述二者在流行病学、发病机制及治疗方面联系,为临床医生树立同一个呼吸道,同一种疾病理念.