Meta-analysis and cost-effectiveness analysis of intranasal corticosteroid treatment in allergic rhinitis with ocular symptoms.

BACKGROUND: Intranasal corticosteroid (INCS) has a beneficial effect on ocular symptoms in allergic rhinitis (AR). To our knowledge, the cost-effectiveness of available INCS for AR with ocular symptoms is yet to be demonstrated. OBJECTIVE: To evaluate the cost-effectiveness of INCSs including Budesonide (BANS), Mometasone furoate (MFNS), Triamcinolone (TANS), and Fluticasone furoate (FFNS) on ocular symptoms associated with AR in the Thai context. METHODS: The percentage of effectiveness in improving total ocular symptoms score (TOSS) was derived from the result of a meta-analysis that estimated the SMD of each INCS treatment compared to placebo as clinical input parameters. A cost-effectiveness analysis based on a decision-tree model to assess one-year costs and outcomes from a Thai societal perspective. The outcomes were to compare incremental cost-effectiveness ratio (ICER). Probabilistic sensitivity analyses (PSA) were also conducted to capture parameter uncertainties. RESULTS: 13 eligible RCTs with a total of 3,722 patients with SAR were included in the analysis. The percentage of effectiveness of FFNS, MFNS, TANS, and BANS was 59.89%, 45.60%, 24.89%, and 16.00%, respectively. The ICER of FFNS, MFNS, and TANS is THB-6,539.92, 4,593.83, and 1,401.24 compared to BANS. CECA result showed the probability of using FFNS is considered cost-effective in 87.50% of cases from zero value followed by MFNS (0.80%), TANS (5.40%), and BANS (6.30%). With a threshold greater than THB20,000, FFNS is considered a cost-effective strategy. CONCLUSIONS: FFNS is a cost-effective option compared to alternative INCSs in Thailand for treating AR with ocular symptoms.

Human placental extract regulates polarization of macrophages via IRGM/NLRP3 in allergic rhinitis.

Allergic rhinitis (AR) is globally prevalent and its pathogenesis remains unclear. Alternative activation of macrophages is suggested in AR and thought to be involved in natural immunoregulatory processes in AR. Aberrant activation of Nod-like receptor protein 3 (NLRP3) inflammasome is linked with AR. Human placenta extract (HPE) is widely used in clinics due to its multiple therapeutic potential carried by diverse bioactive molecules in it. We aim to investigate the effect of HPE on AR and the possible underlying mechanism. Ovalbumin (OVA)-induced AR rat model was set up and treated by HPE or cetirizine. General manifestation of AR was evaluated along with the histological and biochemical analysis performed on rat nasal mucosa. A proteomic analysis was performed on AR rat mucosa. Mouse alveolar macrophages (MH-S cells) were cultured under OVA stimulation to investigate the regulation of macrophages polarization. The morphological changes and the expression of NLRP3 inflammasome and immunity-related GTPase M (IRGM) in nasal mucosa as well as in MH-S cells were evaluated respectively. The results of our study showed the general manifestation of AR along with the histological changes in nasal mucosa of AR rats were improved by HPE. HPE suppresses NLRP3 inflammasome and the decline of IRGM in AR rats and MH-S cells. HPE regulates macrophage polarization through IRGM/NLRP3. We demonstrated that HPE had protection for AR and the protection is achieved partly through suppressing M1 while promoting M2, the process which is mediated by IRGM via inhibiting NLRP3 inflammasome in AR.

A Real-World Effectiveness of Subcutaneous Immunotherapy on the Cost of Medication, Allergic Rhinitis, and Asthma Exacerbations, as well as Upper Respiratory Tract Infection in Subjects with Allergic Rhinitis with or without Asthma: A Retrospective Pilot Study.

Background and Objectives: Real-world studies are limited regarding the effectiveness of SCIT on allergic rhinitis (AR) with and without asthma and the cost of medication in Thailand. Moreover, limited data exist regarding the effectiveness of SCIT on worldwide upper respiratory tract infection (URTI). Therefore, the objective of this study was to compare the medication costs, rate of AR and asthma exacerbations, and rate of URTI in AR with or without asthma subjects before and during three years after receiving the maintenance phase of SCIT, compared with a standard usual care (SUC) group. Materials and Methods: A real-world retrospective study was conducted in AR subjects with or without asthma. From January 2001 to December 2018, 24 subjects with or without asthma received SCIT added to SUC, and 16 subjects were treated with SUC only at the Allergy and Chest Clinic of Chiang Mai Ram Hospital, Chiang Mai, Thailand. The cost of medication was recorded. AR and asthma exacerbations and URTI events were also collected. Results: From between-group comparisons, the cost of medication (THB) in the SCIT group at the one-, two-, and three-year follow up was significantly lower (587.4 (348.3-1374.6) vs. 1562.4 (1315.1-1857.3), p < 0.001, 501.2 (302.9-839.0) vs. 1728.3 (1190.0-2236.1), p < 0.001, and 372.4 (284.8-752.4) vs. 1500.3 (1217.9-1748.9), p < 0.001, respectively)), and AR and asthma exacerbations were significantly reduced at the three-year follow-up. From within-group comparisons, the cost of medication (THB) and AR and asthma exacerbations were significantly lower in the SCIT group at the one-, two-, and three-year follow-up. The URTI event was significantly reduced in the SCIT group at the two- and three-year follow-up. Conclusions: SCIT in subjects with AR with or without asthma was associated with a significantly reduced cost of medication, rates of AR and asthma exacerbations, and URTI events in the long term.

Bioavailability assessment of fexofenadine and montelukast in a fixed-dose combination tablet versus the components administered simultaneously.

INTRODUCTION AND OBJECTIVES: Allergic rhinitis is a condition with high global prevalence most effectively treated with antihistamines and antileukotrienes. This study aimed to evaluate the bioequivalence of fexofenadine and montelukast in a fixed-dose combination tablet versus the components administered simultaneously. MATERIALS AND METHODS: An open, randomized, 2×2 crossover study was performed in 78 healthy volunteers. Fexofenadine-montelukast tablets containing 120 mg and 10 mg, respectively, were used as the test treatment, and 120 mg fexofenadine tablets and 10 mg montelukast tablets were used as the reference treatment. Concentrations of fexofenadine and montelukast in plasma were determined by protein precipitation and analysis by liquid chromatography/mass spectrometry or liquid chromatography tandem mass spectrometry. RESULTS: The 90% confidence intervals (CIs) obtained for fexofenadine were 87.612-102.144 for area under the curve of the plasma concentration after administration to the last concentration (AUC0-t), 88.471-102.282 for the AUC of the plasma concentration extrapolated to infinity (AUC0-∞), and 91.413-108.544 for the maximum plasma concentration (Cmax). For montelukast, they were 96.418-108.416 for AUC0-t, 93.273-106.642 for AUC0-∞ and 94.749-110.178 for Cmax. The ratio and CIs of the values subjected to logarithmic transformation for each parameter were within the range of acceptability of 80%-125%, demonstrating the bioequivalence of the combined fixed-dose tablet to the components administered separately at the same doses. No adverse events were recorded during the study. CONCLUSIONS: This study has shown the bioequivalence of the combined fixed-dose tablet, which may be considered a new alternative for the treatment of allergic rhinitis.

Pharmacoeconomics of allergy immunotherapy versus pharmacotherapy.

Introduction: The purpose of this review is to evaluate the cost-effectiveness of allergy immunotherapy (AIT) in the treatment of allergic rhinitis, asthma, and other allergic conditions.Area covered: An extensive search of the PubMed and Medline database (January 1996 up to June of 2020) was conducted using the search terms allergy immunotherapy, pharmacoeconomics, cost-effectiveness, allergic rhinitis, and asthma. Studies were included if they included information on the economics of AIT in comparison to pharmacotherapy in the treatment of allergic rhinitis or asthma either as actual costs or based on theoretical models. Systematic reviews were included if they included information about the cost-effectiveness of AIT.Most clinical trials found significant cost-savings with AIT. The cost-effective time-point ranged from a few months to several years after treatment initiation.. Cost savings were demonstrated as early as 3 months after treatment initiation and were as great as 80% less than SDT in some studies.Expert opinion: There is strong evidence in the collective literature that AIT is cost-effective as compared to SDT alone. The magnitude of AIT's cost-effectiveness is likely underestimated because most of the studies considered during treatment costs and not AIT's long-term benefits or preventive/prophylactic effects or its impact on co-morbid conditions.

Biologics for the Treatment of Allergic Rhinitis, Chronic Rhinosinusitis, and Nasal Polyposis.

Allergic rhinitis (AR), most presentations of nasal polyposis (NP), and many presentations of chronic rhinosinusitis are type 2high disorders characterized by expression of interleukin (IL)-4, IL-5, and IL-13. Neutralization of IgE with anti-IgE (omalizumab) has proven efficacy in AR. Similarly, in addition to anti-IgE, blockade of IL-5/IL-5 (mepolizumab, reslizumab, benralizumab) and dual blockade of IL-4 and IL-13 with anti-IL-4R (dupilumab) have demonstrated efficacy in NP. However, these agents are expensive and future studies are essential to evaluate cost effectiveness in comparison with current medical and surgical therapies. This article reviews biologics as potential interventions in AR, chronic rhinosinusitis, and NP.

Healthcare costs associated with allergic rhinitis, asthma allergy immunotherapy.

Summary: Allergic rhinitis (AR) and asthma are chronic diseases in which the airways become inflamed in response to allergens. Allergy immunotherapy (AIT) is recommended for those unable to manage symptoms using pharmacotherapy. This study estimated healthcare costs and utilisation for patients with AR and asthma. Mean annual outpatient visits, pharmaceutical costs and inpatient hospitalisations were calculated for 2010 and 2014, with pharmaceutical and inpatient costs stratified by AIT use. AR and asthma patients had a 35% higher mean number of physician visits and up to 90% higher mean pharmaceutical costs compared to controls. The cost of pharmaceuticals and inpatient hospitalisations were 54% lower in those prescribed AIT. Further research is recommended to understand the reasons for these cost differences.

Omalizumab para el tratamiento de asma alérgico mediado por IgE / Omalizumab for the treatment of allergic asthma mediated by IgE

INTRODUCCIÓN: a) Cuadro clínico: El asma alérgica (AA) se debe a la sobreexpresión de la inmunoglobulina E (IgE) en respuesta a los alérgenos ambientales, como los ácaros, el polen y moho. La severidad del asma depende del tratamiento que se requiere para llegar al control de la enfermedad. En general, se define asma severa cuando se requiere el tratamiento de corticoides inhalados en altas dosis más un controlador secundario y/o corticoides sistémicos. El AA severa se puede definir como el pobre control de los síntomas a pesar de tratamiento estándar y eliminación de los factores (alérgenos) que provocan los síntomas. b) Tecnología sanitaria: Omalizumab es un anticuerpo monoclonal IgG1κ humanizado derivado de ADN recombinante que se une selectivamente a la IgE. Al unirse a la IgE, forma complejos inmunes y disminuyendo el nivel de IgE libre en sangre, por lo tanto, disminuyendo los síntomas del AA. OBJETIVO: Evaluar la eficacia y seguridad, así como documentos relacionados a la decisión de inclusión de la tecnología sanitaria omalizumab para asma alérgica moderada a severa. METODOLOGÍA: Se realizó una búsqueda en las principales bases de datos bibliográficas: MEDLINE (PubMed), LILACS y COCHRANE; así como en buscadores genéricos de Internet incluyendo Google Académico y TRIPDATABASE. Adicionalmente, se hizo una búsqueda dentro de la información generada por las principales instituciones internacionales de asma y agencias de tecnologías sanitarias que realizan revisiones sistemáticas (RS), evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC). RESULTADOS: Se seleccionó una RS, tres GPC y cuatro ETS. No se encontraron evaluaciones económicas (EE) peruanas, ni de la región. Una RS Cochrane (2014) evaluó la eficacia y seguridad de omalizumab en asma de adultos y niños. Para pacientes con AA moderada o grave que recibían tratamiento con corticoides inhalados de altas dosis, el grupo que recibió omalizumab comparado con placebo experimentó menos exacerbación del asma (odds ratio [OR]: 0,55; IC95%: 0,42 a 0,60), mayor reducción de hospitalizaciones (OR: 0,16; IC95%: 0,06 a 0,42), probabilidad mayor de detener el uso de corticoides inhalados (OR: 2,50; IC95%: 2,00 a 3,13), y de la dosis diaria de corticoides inhalados (diferencia de medias ponderada [DMP]: -118 g de dipropionato de beclometasona, IC95%: -154 a - 84). Sin embargo, no se observaron diferencias significativas en el número de participantes que dejaron o disminuyeron el uso de corticoides orales (OR: 1,18, IC95%: 0,53 a 2,63). CONCLUSIONES: Según la evidencia reportada en una RS de ensayos clínicos aleatorizados, existen beneficios en la mejora de la sintomatología y hospitalizaciones con omalizumab frente a placebo, en pacientes con AA que no han respondido a terapias que incluyen corticoides inhalados en altas dosis. Estos beneficios fueron encontrados tanto en niños como en adultos. El omalizumab se asocia a mayores probabilidades de disminuir o dejar de usar corticoides inhalados en estos pacientes, mientras no se encuentra esta asociación con respecto a corticoides orales. Las GPC y la mayoría de ETS seleccionadas coinciden en recomendar omalizumab en pacientes con AA severa; con excepción de una ETS brasilera, que no la recomienda por no considerarla costo-efectiva.

Montelukast en pacientes con rinitis alérgica crónica sin asma / Montelukast in patients with chronic allergic rhinitis without asthma

CONTEXTO CLÍNICO: La rinitis alérgica (RA) consiste en la inflamación de la membrana mucosa de la nariz y, en algunos casos, de las mucosas de los ojos, trompas de Eustaquio, oído medio, senos paranasales y faringe. Se caracteriza por presentar una serie de síntomas como estornudos, congestión nasal, picazón nasal y rinorrea. Se desencadena ante la exposición de un alérgeno (proteína extrínseca), la cual genera una respuesta inmune mediada por inmunoglobulina E (IgE) con liberación de mediadores inflamatorios (histamina, triptasa, quininas, heparina, leucotrienos y prostaglandina D2). La RA puede clasificarse de tres maneras, sobre la base del patrón temporal de la exposición alergénica: estacional (por ejemplo, alergia a pólenes), perenne (alergia a los ácaros del polvo doméstico) o episódica (exposición a alérgenos a los cuales el enfermo no está expuesto de manera regular); de acuerdo con la frecuencia de los síntomas: intermitente (menos de cuatro días por semana o menos de cuatro semanas por año) o persistente (más de cuatro días por semana y más de cuatro semanas por año); o de acuerdo a la gravedad de los síntomas: leve (cuando las manifestaciones clínicas no comprometen la calidad de vida) o moderada/grave (cuando los síntomas interfieren con la calidad de vida). La Administración de Alimentos y Medicamentos (FDA, su sigla del inglés Food and Drug Administration) suele definir la RA como estacional o perenne para la aprobación de nuevos fármacos. TECNOLOGÍA: Los leucotrienos cisteinílicos (LTC4, LTD4, LTE4) son potentes eicosanoides inflamatorios liberados por diversas células, incluidos los mastocitos y eosinófilos. Estos mediadores plasmáticos se unen a los receptores de los leucotrienos cisteinílicos (CysLT) que se encuentran en las vías respiratorias y producen varios efectos sobre ellas, incluidos broncoespasmo, secreción mucosa, permeabilidad vascular y acumulación de eosinófilos. Montelukast es un antagonista de los receptores de leucotrienos que bloquea el efecto de los leucotrienos en las vías aéreas. OBJETIVO: El objetivo del presente informe es evaluar la evidencia disponible acerca de la eficacia, seguridad y aspectos relacionados a las políticas de cobertura del uso de montelukast para rinitis crónica alérgica en pacientes sin asma. MÉTODOS: Se realizó una búsqueda en las principales bases de datos bibliográficas, en buscadores genéricos de internet, y financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas (RS), ensayos clínicos controlados aleatorizados (ECAs), evaluaciones de tecnologías sanitarias (ETS), evaluaciones económicas, guías de práctica clínica (GPC) y políticas de cobertura de diferentes sistemas de salud. RESULTADOS: Se incluyeron cuatro RS, cinco GPC, una evaluación económica y 10 informes de políticas de cobertura de montelukast en pacientes con rinitis alérgica sin asma. CONCLUSIONES: Evidencia de moderada calidad muestra que la eficacia de montelukast monoterapia en rinitis alérgica crónica sin asma es inferior a aquella de los corticosteroides tópicos y similar o inferior a la de los antihistamínicos en monoterapia. Montelukast en combinación con antihistamínicos, comparado a los antihistamínicos administrados en monoterapia, demostró una leve mejoría clínica en reducir la intensidad de los síntomas nasales diarios, y no hubo diferencias significativas en el control de síntomas nasales nocturnos, oculares y en la calidad de vida entre ambos grupos terapéuticos. La combinación de montelukast con antihistamínicos en pacientes con rinitis alérgica crónica sin asma demostró ser inferior a corticoesteroides tópicos nasales respecto al control de síntomas nasales y calidad de vida. Existe consenso entre las diferentes guías de práctica clínica identificadas en que los inhibidores de leucotrienos no deben utilizarse como tratamiento de primera línea para la rinitis alérgica crónica. Su uso se reserva como terapia complementaria en pacientes con rinitis alérgica que no responden al tratamiento inicial con corticoides y antihistamínicos. Si bien no se encontraron estudios de costo-efectividad realizados en Argentina, el elevado costo de la tecnología en comparación a sus comparadores, junto al escaso beneficio clínico sugeriría que no es una intervención costo-efectiva.

Open-label safety assessment of bilastine in elderly patients with allergic rhinoconjunctivitis and/or urticaria.

BACKGROUND: Bilastine is an H1-antihistamine approved for symptomatic treatment of patients with allergic rhinoconjunctivitis or urticaria. The safety profile of bilastine in clinical trials of allergic rhinoconjunctivitis or urticaria, assessed by type and frequency of adverse events (AE), was similar to that of placebo. OBJECTIVE: As part of the risk management plan for bilastine, the safety profile of bilastine in the elderly was assessed. METHODS: A prospective, multicenter, observational, open-label, 3-month follow-up study was performed to assess the safety profile of bilastine 20 mg in patients aged ≥65 years with allergic rhinoconjunctivitis and/or urticaria. RESULTS: A total of 74 of 146 patients (50.7%) reported 129 treatment-emergent AEs (TEAE) during the study period. The incidence of TEAEs was low, with monthly and quarterly rates of 0.29 (95% confidence intervals [CI], 0.229-0.367) and 0.88 (95% CI, 0.688-1.100), respectively. Monthly and quarterly incidence rates were 0.04 (95% CI, 0.016-0.082) and 0.12 (95% CI, 0.048-0.246), respectively, for related TEAEs (eight TEAEs in seven patients) and were 0.02 (95% CI, 0.003-0.048) and 0.05 (95% CI, 0.010-0.143), respectively, for serious TEAEs (five TEAES in three patients). All serious TEAEs were considered to be unrelated to bilastine. CONCLUSION: Bilastine 20 mg showed a favorable safety profile with a low incidence of TEAEs in patients aged ≥65 years. The results were in accordance with the known safety profile of bilastine 20 mg and incidence of AEs reported in previous studies and described in the approved summary of product characteristics.

Causality Assessment of Olfactory and Gustatory Dysfunction Associated with Intranasal Fluticasone Propionate: Application of the Bradford Hill Criteria.

Causality assessment is crucial to post-marketing pharmacovigilance and helps optimize safe and appropriate use of medicines by patients in the real world. Self-reported olfactory and gustatory dysfunction are common in the general population as well as in patients with allergic rhinitis and nasal polyposis. Intranasal corticosteroids, including intranasal fluticasone propionate (INFP), are amongst the most effective drugs indicated in the treatment of allergic rhinitis and nasal polyposis. While intranasal corticosteroids are associated with olfactory and gustatory dysfunction and are currently labeled for these adverse events, causality assessment has not been performed to date. Although there is no single widely accepted method to assess causality in pharmacovigilance, the Bradford Hill criteria offer a robust and comprehensive approach because nine distinct aspects of an observed potential drug-event association are assessed. In this literature-based narrative review, Hill's criteria were applied to determine causal inference between INFP and olfactory and gustatory dysfunction.

Assessment of the effectiveness of cyclosporine nasal spray in an animal model of allergic rhinitis.

The aim of this study is to show if cyclosporine has an antiallergic role in a rat model of ovalbumin-induced allergic rhinitis. The 54 rats were divided into six equal groups. The first group was a negative control group without induced allergic rhinitis; the second group a positive control with induced allergic rhinitis not receiving treatment. The remaining four groups, after induction of allergic rhinitis, received intranasal cyclosporine treatment in doses of 0.05, 0.1, or 0.2% or nasal steroid treatment. In the biochemical examination, on the surface of the tissue tumor necrosis factor (TNF) interferon (IFN), interleukin (IL)-5, IL-13, as well as IL-2, IL-4, IL-17A, and IgE were studied. Histologically, ciliary loss, increase of goblet cells, vascular congestion, and the degree of eosinophil infiltration were rated. In all treatment groups, on average, a significant reduction in all histological and biochemical values was found compared to the positive control group. Comparing each of the three cyclosporine-using groups with the group of nasal corticosteroid did not show any significant difference in the average scores. Cyclosporine nasal drops are effective to be used in an animal model of experimental allergic rhinitis without systemic effects.

Do Paediatric Investigation Plans (PIPs) Advance Paediatric Healthcare?

Since 2007, new drugs need a paediatric investigation plan (PIP) for EU registration. The PIPs' justifications can be traced back to concerns expressed by Shirkey that label warnings against paediatric use made children "therapeutic orphans", and the American Academy of Pediatrics' claim that all children differ considerably from adults. US legislation first encouraged, then also required, separate, adult-style safety and efficacy studies in all paediatric subpopulations. This triggered paediatric regulatory studies by the pharmaceutical industry. There were also negative outcomes, as a result of using the legal definition of childhood as a medical/physiological term. The "therapeutic orphans" concept became dogma that supported/expanded adult-style regulatory testing into all age groups even when poorly justified in adolescents or where other methods are available to generate needed data. PIPs are especially problematic because they lack the limitations imposed on the Food and Drug Administration's (FDA's) regulatory actions and more practical approaches used in the USA. Many PIP studies are medically senseless or even questionable and/or unfeasible with poor risk/benefit ratios. For example, physiologically mature adolescents have been exposed to treatments and doses known to be suboptimal in adults. Unfeasible PIP studies in rare diseases may harm patients by preventing their participation in more beneficence-driven studies. PIP-required studies can prevent effective treatment of allergic rhinitis during years of placebo treatment, exposing minors to the risk of disease progression to asthma. The PIP system should be revised; more should be done by key players, including institutional review boards/ethics committees, to ensure that all paediatric clinical studies are medically justified, rather than legislation driven, and can produce scientifically valid results.

Clinical assessment, diagnosis and management of nasal obstruction.

BACKGROUND: Nasal obstruction is among the most common complaints to the general practitioner (GP). Causes can be divided into mucosal causes or anatomical abnormalities. Most mucosal pathologies can be managed effectively in the primary care setting, with referral to the otolaryngologist in cases that are resistant to medical therapy and in cases of structural anomaly. In cases of allergy, referral to an immunologist may be beneficial. OBJECTIVE: The aim of this article is to review the clinical assessment and management of nasal obstruction in the primary care setting. We consider the various causes of nasal obstruction, describe their management and define those cases that require specialist referral. DISCUSSION: Nasal obstruction may be acute or chronic and is a manifestation of a wide range of disease processes, most of which are managed by the GP. In patients with persistent nasal obstruction and in those with structural abnormalities, specialist referral is warranted.

Self-assessment of Allergic Rhinitis and Asthma (SACRA) Questionnaire-based Allergic Rhinitis Treatment Improves Asthma Control in Asthmatic Patients with Allergic Rhinitis.

Objective This study was conducted to investigate whether the add-on treatment of allergic rhinitis (AR) based on the Self-assessment of Allergic Rhinitis and Asthma (SACRA) questionnaire for assessing AR control improves both AR and asthma control in asthmatic patients with AR. Methods This multi-center prospective study was performed in Nagano prefecture, Japan. Two hundred five asthmatic patients and 23 respiratory physicians participated in the study. We administered add-on AR treatments based on the results of the SACRA questionnaire. After the first SACRA questionnaire, 67 asthmatic patients agreed to receive an add-on AR treatment. Three months after the AR treatment, a secondary SACRA questionnaire, asthma control test (ACT), and pulmonary function tests were performed. Results After the add-on AR treatment, the visual analogue scales (VASs) for AR and asthma, as assessed by the SACRA questionnaire and ACT score, were significantly improved in the patients of the AR+ group. With regard to the pulmonary function tests, the percent predicted vital capacity, and percent predicted forced expiratory volume in one second were also significantly improved. Regardless of whether the patients had previously undergone leukotriene receptor antagonists (LTRA) treatment, the VASs for AR and asthma and the ACT score were significantly improved in the AR+ group. However, the vital capacity (VC), forced vital capacity (FVC) and forced expiratory volume (FEV1) were only significantly improved in the AR+ group that had previously undergone LTRA treatment. Conclusion SACRA questionnaire-based add-on AR treatment would be convenient for the detection of AR by respiratory physicians and would offer improved asthma control. This questionnaire can also be used to assess the therapeutic effects.

[Clinical effects assessment of nasal cellulose powder on allergic rhinitis].

Objective:To evaluate the role of nasal cellulose powder locally applied in allergic rhinitis patients.Method:Fifty patients with allergic rhinitis were divided randomly into two groups: the study group and the control group. The study group were treated with nasal cellulose powder while the control group were treated with physiological sea water.Objective and subjective examinations (nasal airway resistance, nasal syndrome score, rhinoconjunctivitis qualityof life questionnaire and olfactory function,nasal mucus cilia clearance ) were performed before and 3 months after treatment.Result:After treatment, partial parameters in nasal syndrome store ( nasal itching, nasal discharge,sneezing and total store) and rhinoconjunctivitis qualityof life questionnaire (sleep, nasal symptom, non-hay-fever symptom, emotional function and total score) in the study group were significantly improved than those in the control group (P< 0.05). However, no significant difference was found in olfactory function, Nasal airway resistance, nasal mucus cilia clearance and the eye symptom in rhinoconjunctivitis qualityof life questionnaire between the two groups after treatment (P> 0.05). No adverse reaction was found in both groups.Conclusion:Nasal cellulose powder can help alleviate clinical symptoms and improve the quality of life in allergic rhinitis patients with no significant side effect.

Eficacia y seguridad de omalizumab en niños y adolescentes con diagnóstico de asma alérgica severa no controlada / Efficacy and safety of omalizumab in children and adolescents diagnosed with severe uncontrolled allergic asthma

INTRODUCCIÓN: En el presente dictamen se expone la evidencia relacionada a la eficacia y seguridad de omalizumab como terapia complementaria comparado con terapia estándar más placebo, en niños de 6 a 12 años y adolescentes mayores de 12 a 18 años con asma alérgica severa no controlada; es decir, que no responden al tratamiento estândar correspondiente al escalón 4 del GINA. El asma es una enfermedad caracterizada por inflamación crónica de las vías respiratorias. Clínicamente se define por la presencia de síntomas como disnea recurrente, sibilantes, tos y opresión torácica además de limitación variable del flujo aéreo espiratorio. La severidad del asma se determina retrospectivamente según el nivel de tratamiento requerido para controlar los síntomas y las exacerbaciones. Así, por ejemplo, el asma severa corresponde a aquellos pacientes cuyos síntomas persisten a pesar de recibir tratamiento con altas dosis de corticoides inhalados y agonistas beta-2 de acción prolongada, y que presentan más de dos episodios de exacerbaciones al año que requieren corticoides orales. El asma alérgica es uno de los fenotipos de asma severa más frecuente, en donde las exacerbaciones son desencadenadas por alérgenos y se debe a mecanismos mediados por Inmunoglobulina E (IgE). A nivel global, la prevalencia de asma varía entre 20% a 25%, y en Latino américa, menos del 5% de la población asmática corresponde a pacientes con asma no controlada. Además, el asma no controlada contribuye aproximadamente al 80% de los costos de atención por la enfermedad, pues es un factor de riesgo para exacerbaciones que requiere hospitalización y atención por emergencia. En el Perú, se estima que la prevalencia de los síntomas de asma varía entre 20% a 30% en niños. Asimismo, se estima que, en el Perú los síntomas compatibles con asma severa varían de 5% a 14% en adolescentes entre 13 a 15 años. Es así que, el asma es altamente prevalente durante la infancia y se asocia a morbimortalidad significativa. TECNOLOGIA SANITARIA DE INTERES: Omalizumab es un anticuerpo monoclonal anti-IgE, recombinante humanizado derivado de ADN. Omalizumab se une específicamente a la IgE circulante y bloquea su unión con el receptor IgE de alta afinidad (FcRI) ubicados en la superficie de los mastocitos y basófilos, interrumpiendo la cascada inflamatoria. Al inhibir la unión se interfiere con la síntesis y liberación de mediadores de la respuesta alérgica (por ejemplo, leucotrienos, citocinas, quimiocinas). METODOLOGÍA: Se realizó una búsqueda de la literatura con respecto a la eficacia y seguridad de omalizumab para el tratamiento de asma alérgica severa no controlada. Esta búsqueda se realizó utilizando los meta-buscadores: Translating Research into Practice (TRIPDATABASE), The Cochrane Library, National Library of Medicine (Pubmed-Medline) y Health Systems Evidence. Adicionalmente, se amplió la búsqueda revisando agencias que desarrollan evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC), como The National Institute for Health and Care Excellence (NICE), the Agency for Health Care Research and Quality (AHRQ), The Canadian Agency for Drugs and Technologies in Health (CADTH) y el Instituto de Evaluación de Tecnología en Salud (IETS); y especializados en neumología como GINA y la British Thoracic Society/Scottish Intercollegiate Guidelines Network (BTS/SIGN). RESULTADOS: En el presente dictamen se expone la evidencia relacionada a la eficacia y seguridad de omalizumab como terapia complementaria comparado con terapia estándar más placebo, en niños de 6 a 12 años y adolescentes mayores de 12 a 18 años con asma alérgica severa no controlada, es decir, que no responden al tratamiento estándar correspondiente al escalón 4 del Global Initiative for Asthma (GINA). Así, las guías de práctica clínica internacionales presentan recomendaciones homogéneas con respecto al uso de omalizumab en niños y adolescentes. En ese sentido, tanto GINA, como British Thoracic Society/Scottish Intercollegiate Guidelines Network (BTS/SIGN) e Instituto de Evaluación de Tecnología en Salud (IETS) recomiendan omalizumab en pacientes mayores de 6 años con asma alérgica severa que no logran el control de la enfermedad a pesar de tratamiento con las alternativas correspondientes al escalón 4 del GINA. En cuanto a los ensayos clínicos incluidos, estos mostraron que omalizumab es más eficaz que placebo en la reducción de exacerbaciones y en la disminución del uso de corticoides. Con respecto a la seguridad, los ensayos aleatorizados mostraron que el uso de omalizumab es seguro en este grupo etario. La evidencia proveniente de los ensayos se considera de calidad metodológica adecuada y corresponde a dos ensayos clínicos aleatorizados fase III controlados por placebo en niños de 6 a 12 años con asma alérgica moderada a severa; un ensayo aleatorizado fase III controlado por placebo en niños de 6 a 20 años con asma alérgica moderada a severa. CONCLUSIÓN: El Instituto de Evaluación de Tecnologías en Salud e Investigación- IETSI aprueba el uso de omalizumab en niños de 6 a 12 años y adolescentes de 12 a 18 años con asma alérgica severa y niveles altos de IgE, no controlada; según lo establecido en el Anexo N° 01. La vigencia del presente dictamen preliminar es de dos años, la continuación de dicha aprobación estará sujeta a los resultados obtenidos de los pacientes que se beneficien con dicho tratamiento y a la nueva evidencia que pueda surgir en el tiempo.

A Comparison of Health Care Resource Utilization and Costs for Patients with Allergic Rhinitis on Single-Product or Free-Combination Therapy of Intranasal Steroids and Intranasal Antihistamines.

BACKGROUND: Allergic rhinitis (AR) is a common condition that can be treated with a number of different therapies. Treatments such as intranasal antihistamines (INAs) and intranasal steroids (INSs) are widely used by AR patients. For some allergy sufferers, a combination of therapies, specifically an INA and an INS, is required to address their symptoms. A new treatment, the formulation of azelastine hydrochloride and fluticasone pro-pionate used as a single spray (MP-AzeFlu), has become available for AR patients who need both types of treatment. In this regard, the comparison with the alternative concomitant use of INAs and INSs is of interest. The current study examines the health care resource utilization and costs for each cohort. OBJECTIVE: To examine the resource utilization and costs associated with AR for patients treated with MP-AzeFlu or concurrent therapy with single-ingredient INA and INS sprays (free-combination therapy). METHODS: A retrospective administrative claims study for commercially insured patients from a large U.S. health plan was performed. Patients with an AR diagnosis and a prescription claim for MP-AzeFlu or free-combination therapy between September 1, 2012, and September 30, 2013, were identified. Patients were aged at least 12 years at index date (first prescription fill for intranasal therapy) and were required to have 12 months pre-index and 6 months post-index of continuous enrollment. Health care resource utilization and costs were assessed for the post-index period. The cohorts were adjusted on baseline demographic and clinical characteristics using inverse propensity treatment weights. Other covariates, prescriber specialty, product switching during the post-index period, and pre-index total costs were included in the regression models measuring outcomes. One clinical characteristic of interest was the presence of asthma as comorbidity. A subset analysis of AR patients with asthma was also performed. RESULTS: All-cause-related pharmacy fills as well as pharmacy, medical, and total costs were significantly reduced by using MP-AzeFlu (N = 810) instead of the free combination of drugs (N = 726). For AR-related health care resource utilization, the MP-AzeFlu cohort had significantly fewer pharmacy fills than the free-combination cohort (1.01 and 1.17, respectively; P < 0.001) with no significant difference in outpatient services and specialist visits (P = 0.139 and P = 0.117, respectively). Six-month AR-related pharmacy and total costs were significantly lower (P < 0.001 and P = 0.001) for the MP-AzeFlu cohort ($128 and $334, respectively) than the free-combination cohort ($268 and $458, respectively). There was no statistically significant difference in AR-related medical costs between the 2 cohorts (P = 0.454). For the subcohort of AR patients with asthma, the MP-AzeFlu cohort had lower 6-month asthma resource utilization and costs than the free-combination cohort. CONCLUSIONS: These findings suggest that, for AR patients needing INAs and INSs, the single-spray formulation MP-AzeFlu had better economic outcomes than for patients who rely on the free combination of these agents. MP-AzeFlu also appears to keep asthma-related utilization and costs down for those AR patients who also suffer from asthma. Potential explanations for these findings are explored. DISCLOSURES: This study was funded by Meda Pharmaceuticals. Authors were either employed by Meda Pharmaceuticals or received consulting fees from Meda Pharmaceuticals. Comprehensive Health Insights and Sedaghat received funding from Meda Pharmaceuticals as a consultant to participate in this study. Dufour and Caldwell-Tarr are employees of Comprehensive Health Insights. Harrow is currently employed by TESARO. This study was conceived by Harrow, Dufour, and Caldwell-Tarr. All authors contributed to the design of the study. Dufour took the lead in data collection, along with Caldwell-Tarr, and data interpretion was performed by Harrow, along with the other authors. Analyses were performed by Dufour. The manuscript was written and revised by all authors.

Eficacia y seguridad de omalizumab en el tratamiento de pacientes con asma alérgica persistente severa no controlada con el tratamiento estandar optimazado / Efficacy and safety of omalizumab in the treatment of patients with severe persistent allergic asthma uncontrolled with optimazed standard treatment

INTRODUCCIÓN: Antecedentes: El presente dictamen expone la evaluación de tecnología de la eficacia y seguridad de omalizumab en el tratamiento de pacientes con asma alérgica persistente severa no controlada con ek tratamiento estándar optimizado (refractaria). Aspectos Generales: El asma es una condición inflamatoria crónica de las vías aéreas caracterizada por producción de esputo, obstrucción del flujo aéreo y tos. Los sintomas varian en frecuencia y en gravedad, deste intermitente leve, hasta persistente severa. Existen dos forma de asma: alérgica y no alérgica. El asma alérgica es el resultado de una producción excesiva de inmunoglobulina E (IgE) en respuesta a alérgenos ambientales como los ácaros del polvo de la casa, el polen y los hongos. El asma no alérgica puede ser desencadeada por factores como la ansiedad, el estrés, el ejercício, el aire frio, el humo y la infección. Tecnología Sanitaria de Interés: El Omalizumab, también conocido como rhuMAb-E25, rhu-Mab o Xolair, es un anticuerpo IgG1 monoclonal recombinante humanizado que se une a la Ig-E. Este anticuerpo anti-IgE forma complejos con los IgE libres, y de esta manera bloquea la interacción entre la IgE y las células inflamatorias. METODOLOGÍA: Estrategia de Búsqueda: Se realizó una búsqueda de la literatura con respecto a la eficacia y seguridad de omalizumab como agente adicional al tratamiento estándar optimizado de pacientes con asma alérgica persistente severa no controlada (o refractaria) a pesar del uso de altas dosis de CE!, beta 2 agonistas de acción prolongada y corticoesteroides orales.Esta búsqueda se realizó utilizando los meta-buscadores: Translating Research into Practice (TRIPDATABASE). national Library of Medicine (Pubmed-Medline) y Health System Evidence. Adicionalmente, se amplió la búsqueda revisando la evidencia generada por grupos internacionales que realizan revisiones sistemáticas (RS), evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC), tales como la Cochrane Group, The National Institute for Helath and Care Excellence (NICE), the Agency for Helath care Research and Quality (AHRQ), The Canadian Agency for Drugs and Technologies in Helath (CADTH) y The Scottish Medicines Consortium (SMC). Esta búsqueda se completó ingresando a la página web www.clinicaltrials.gov, para así poder indentificar ensayos clínicos en elaboración o queno hayan sido publicados aún, y así disminuir el riesgo de sesgo de publicación. RESULTADOS: Sinopsis de la Evidencia: Se realizó la búsqueda bibliográfica y de evidencia científica para el sustento del uso de omalizumab como agente adicional al tratamiento estándar optimizado de pacientes con asma alérgica persistente severa no controlada (o refractaria) a pesar del uso de altas dosis de CEI, beta 2 agonistas de acción prolongada y CEO. Se presenta la evidencia disponible según el tipo de publicación en los criterios de inclusión. CONCLUSIONES: El asma alérgico es resultado de una producción excesiva de inmunoglobulina E (IgE) en respuesta a alérgenos ambientales como los ácaros del polvo de la casa, el polen y los hongos. Los pacientes con asma alérgica persistente severa no controlada tienen alto riesgo de padecer excerbaciones, hospitalizaciones y menor calidad de vida. Los pacientes que recibieron omalizumab experimentaron significativamente menos eventos adversos serios como la anafilaxia y los eventos trombólicos que aquellos que recibieron palcebo. Los eventos adversos más comunes en el grupo que uso omalizumab fueron las reacciones del sitio de la inyección. Respecto a la mortalidad, no se obervaron diferencias significativas entre el grupo de omalizumab s.c y placebo. Los pacientes de interés es esta evaluación son pacientes con el mayor grado de severidad de asma alérgica, que no consiguen el control de la enfermedad a pesar del tratamiento optimizado del último escalón del manejo del asma recomendado por las GPCs internacionales, que incluyen el uso de corticoides orales. Estos pacientes ya hicieron uso de todos los agentes disponibles recomendados, y necesitan de otros agentes para controlar la enfermedad. Omalizumab puede ser considerado como un medicamento adicional al tratamiento estándar óptimo para reducir la tasa de exacerbaciones, clinicamente significativas y severas del grupo más severo de pacientes con asma alértica, evitando así el uso de los recursos de salud y la reducción de la frecuencia de CEO. El benefício en la reuucción del uso de CEO se reflejaria en menor riesgo de exposición para desarrollar un enorme número de eventos adversos asociados. En este grupo se encuentran la fractura ósea, diabetes mellitus, ulcera péptica, infarto de miocardio, ictus cerebral, cataratas, glaucoma, disturbios del sueño y del ánimo, y ganancia de peso. El Instituto de Evaluación de Tecnologías Sanitarias-IETSI, aprueba por el período de un año a partir de la fecha de publicación del presente dictamen preliminar el uso de omalizumab para el tratamiento de pacientes con asma alérgico mediado por IgE persistente severo. Asimismo, debido a que la evidencia del benefício de omalizumab en este tipo de pacientes no es robusta, se establece que el efecto del uso de este medicamento se evaluará con datos de los pacientes que hayan recibido el tratamiento por el tiempo autorizado, incluyendo evaluación económica para determinar su impacto. Esta información servirá para una reevaluació del medicamento, incluyendo una evaluación económica al terminar la vigencia de este dictamen.