Chronic urticaria in the real-life clinical practice setting in the UK: results from the noninterventional multicentre AWARE study.

BACKGROUND: Chronic urticaria (CU) is a skin condition characterized by repeated occurrence of itchy weals and/or angio-oedema for > 6 weeks. AIM: To provide data demonstrating the real-life burden of CU in the UK. METHODS: This UK subset of the worldwide, prospective, noninterventional AWARE study included patients aged 18-75 years diagnosed with H1-antihistamine (H1-AH)-refractory chronic spontaneous urticaria (CSU) for > 2 months. Baseline characteristics, disease activity, treatments, comorbidities and healthcare resource use were documented. Quality of life (QoL), work productivity and activity impairment were assessed. RESULTS: Baseline analysis included 252 UK patients. Mean age and body mass index were 45.0 years and 29.0 kg/m2 , respectively. Most patients were female (77.8%) and had moderate/severe disease activity (mean Urticaria Activity Score over 7 days was 18.4) and a 'spontaneous' component to their CU (73.4% CSU; 24.6% CSU and chronic inducible urticaria). Common comorbidities included depression/anxiety (24.6%), asthma (23.8%) and allergic rhinitis (12.7%). A previous treatment was recorded for 57.9% of patients. Mean Dermatology Life Quality Index score was 9.5, and patients reported impairments in work productivity and activity. Healthcare resource use was high. Severity of CSU was associated with female sex, obesity, anxiety and diagnosis. Only 28.5% of patients completed all nine study visits, limiting analysis of long-term treatment patterns and disease impact. CONCLUSIONS: Adult H1-AH-refractory patients with CU in the UK reported high rates of healthcare resource use and impairment in QoL, work productivity and activity at baseline. The differing structures of UK healthcare may explain the high study discontinuation rates versus other countries.

Cost-effectiveness of omalizumab for the treatment of chronic spontaneous urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a skin disease with itchy hives and/or angio-oedema that last for at least 6 weeks without an obvious external trigger. OBJECTIVES: To determine the cost-effectiveness of omalizumab relative to standard of care (SoC; up to four times the daily dose of H1 -antihistamines) in the Netherlands from a societal perspective. METHODS: The Markov model used consisted of five health states based on Urticaria Activity Score over 7 days. Model settings and characteristics of the Dutch patient population were based on an online survey among clinical experts and were validated during an expert committee meeting. Transition probabilities were derived from the GLACIAL trial. Healthcare consumption, quality of life (using EuroQol-5D) and productivity losses were derived from a burden-of-illness study (ASSURE-CSU) among 93 Dutch patients. Healthcare consumption and productivity losses were evaluated using the Dutch costing manual. The comparator treatment was SoC, consisting of (updosed) antihistamines. A 10-year time horizon was used. RESULTS: The incremental cost-effectiveness ratio (ICER) of omalizumab vs. SoC was €17 502 per quality-adjusted life-year (QALY) gained. Productivity costs played an important role in the value of the ICER; discarding productivity costs resulted in an ICER of €85 310 per QALY. CONCLUSIONS: Omalizumab is cost-effective compared with SoC. The outcomes of this study were used to establish omalizumab as third-line therapy in the Dutch treatment guidelines for CSU.

Cost-effectiveness of omalizumab add-on to standard-of-care therapy in patients with uncontrolled severe allergic asthma in a Brazilian healthcare setting.

OBJECTIVE: Omalizumab add-on to standard-of-care therapy has proven to be efficacious in severe asthma patients for whom exacerbations cannot be controlled otherwise. Moreover, evidence from different healthcare settings suggests reduced healthcare resource utilization with omalizumab. Based on these findings, this study aimed to assess the cost-effectiveness of the addition of omalizumab to standard-of-care therapy in patients with uncontrolled severe allergic asthma in a Brazilian healthcare setting. METHODS: A previously published Markov model was adapted using Brazil-specific unit costs to compare the costs and outcomes of the addition of omalizumab to standard-of-care therapy vs standard-of-care therapy alone. Model inputs were largely based on the eXpeRience study. Costs and health outcomes were calculated for lifetime-years and were annually discounted at 5%. Both one-way and probabilistic sensitivity analyses were performed. RESULTS: An additional cost of R$280,400 for 5.20 additional quality-adjusted life-years was estimated with the addition of omalizumab to standard-of-care therapy, resulting in an incremental cost-effectiveness ratio of R$53,890. One-way sensitivity analysis indicated that discount rates, standard-of-care therapy exacerbation rates, and exacerbation-related mortality rates had the largest impact on incremental cost-effectiveness ratios. LIMITATIONS: Assumptions of lifetime treatment adherence and rate of future exacerbations, independent of previous events, might affect the findings. The lack of Brazilian patients in the eXpeRience study may affect the findings, although sample size and baseline characteristics suggest that the modeled population closely resembles Brazilian severe allergic asthma patients. CONCLUSION: Results indicate that omalizumab as an add-on therapy is more cost-effective than standard-of-care therapy alone for Brazilian patients with uncontrolled severe allergic asthma, based on the World Health Organization's cost-effectiveness threshold of up to 3-times the gross domestic product.

Longterm clinical outcomes of omalizumab therapy in severe allergic asthma: Study of efficacy and safety.

Omalizumab has been shown to be an effective add-on therapy for patients with uncontrolled severe persistent allergic asthma. There has been a steady accumulation of evidence on the long-term effectiveness of omalizumab; however, data on real-life outcomes beyond one year of treatment is limited. In this study, we report on long-term outcomes of omalizumab treatment. We collected data from our severe asthma registry on hospitalisations, exacerbations, corticosteroid sparing, asthma control, lung function, biomarkers and side effects, to determine if the benefit was sustained and treatment was safe on the long term. Forty-five patients [mean age 44.9 years (range 19-69), females 37/45 (82%), mean duration of omalizumab treatment = 60.7 ± 30.9 months (range 23-121) were included in the analysis. We observed a reduction in the annual acute asthma related hospital admissions for the total population from 207 at baseline to 40 on treatment (80.7% reduction), whilst the per patient annual hospitalisations were reduced from a mean of 4.8 to 0.89 post-omalizumab treatment (p < 0.00001). There was a 76.7% reduction in daily mean maintenance OCS dose (prednisolone equivalent) from 25.8 mg (n = 43) to 6.0 mg (p < 0.0001), associated with clinically significant improvement in asthma control questionnaire (ACQ) from mean score of 4.1 (range 3.7-4.7) to 2.27 (range 0.5-4.1) p < 0.0001. The mean % predicted FEV1 has improved from 59.2% at baseline to 75.7% on treatment (p = 0.001). There was a statistically non-significant reduction in median peripheral blood eosinophils (PBE) from 300 cells/µl (range 40-1050) at baseline to 175 cells/µl (range 0-1500) post-treatment (p = 0.068), and statistically significant reduction of median fraction exhaled nitric oxide (FeNO) level from 37 parts per billion (range 12-178) to 24 ppb (range 7-50) (p = 0.0067). The work/school missed days were reduced in 17/19 patients who were at employment or school. The overall safety profile of the treatment seemed acceptable and was consistent with published experience. In conclusion, results from this real-life study demonstrate that improved outcomes in patients with severe allergic asthma are sustained with longer-term omalizumab therapy.

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.

Pharmacokinetics, pharmacodynamics and clinical efficacy of omalizumab for the treatment of asthma.

INTRODUCTION: Omalizumab is a subcutaneously administrated monoclonal anti-IgE antibody indicated in adults, adolescents and children 6 years of age and older with moderate to severe allergic asthma uncontrolled by conventional pharmacological treatments and sensitization to at least one perennial allergen. Area covered: This drug evaluation summarizes published data on pharmacokinetic and pharmacodynamic properties of omalizumab, on clinical efficacy and safety, including real-world evidence, and provides a medico-economic evaluation of the drug. Expert opinion: Omalizumab represents an efficient therapeutic option for the management of patients with uncontrolled moderate/severe allergic asthma. It provides a significant reduction in the asthma exacerbation rate with a steroid-sparing effect, an improvement in quality of life in adults and adolescents, despite a lack of evidence about its efficacy specifically in severe allergic asthma. Clinical trials have demonstrated its efficacy in the pediatric population but further real-life evidence is expected to better characterize long-term effects in this population. There is still some debate about the optimal treatment duration but, to date, it is recommended not to stop the treatment as cessation has resulted in symptom recurrence. Omalizumab is an expensive treatment, but a key therapeutic option when used for uncontrolled severe allergic asthma.

Ethnic sensitivity assessment of pharmacokinetics and pharmacodynamics of omalizumab with dosing table expansion.

A three-part license expansion for omalizumab (Xolair(®)), humanized anti-IgE antibody, was recently made in Japan for paediatric use, additional higher doses and revised dosing frequency in allergic asthma. The dosing level and frequency of omalizumab are guided by a dosing table based on the total serum IgE and bodyweight. Nonlinear mixed-effect pharmacokinetic (PK) and pharmacodynamic (PD) modeling and simulation techniques described the binding between omalizumab and its target IgE. The population PKPD analysis was conducted using data from the nine studies included originally in the European application of dosing table expansion together with three Japanese clinical studies to assess the influence of the ethnicity. Statistically significant differences between the ethnic groups were detected. These were small, within or close to bioequivalence criteria. The model described the primary pharmacology in Caucasian and Japanese patients, both adult and paediatric, with simulations showing that the interplay between the clearance, volume and binding affinity parameters was such that there was no clinical impact of the Japanese ethnic differences on either drug PK or free IgE suppression and hence the required posology.

Omalizumabe para o tratamento da asma grave / Omalizumab for the treatment of severe asthma

A asma é uma doença inflamatória crônica das vias respiratórias, geralmente associada à hiper-reatividade das vias aéreas e obstrução do fluxo de ar e caracterizada por crises recorrentes de sibilos, dispneia, opressão torácica e tosse. Durante uma crise asmática, cuja frequência e gravidade variam de pessoa para pessoa, a membrana que envolve os brônquios se torna edemaciada, o que provoca estreitamento das vias aéreas e reduz o fluxo de ar para dentro e fora dos pulmões. Afeta tanto adultos quanto crianças e é a doença crônica mais comum entre essas últimas. A asma é um problema de saúde pública e ocorre em todos os países independentemente do seu nível de desenvolvimento econômico. Entretanto, a maior parte das mortes relacionadas a essa doença ocorrem em países de renda baixa e média baixa. A Organização Mundial de Saúde ­ OMS estima que atualmente existam 235 milhões de pessoas com asma no mundo. Considerando uma prevalência global de 10%, estima-se que no Brasil existam aproximadamente 20 milhões de asmáticos. Os medicamentos usados no tratamento da asma podem ser classificados como controladores ou de alívio. Os medicamentos controladores possuem atividade anti-inflamatória, são utilizados diariamente por um longo período de tempo para manter o controle clínico da asma e constituem a base do tratamento medicamentoso da asma persistente. Incluem os corticosteroides inalatórios (CI) e orais (CO), os beta2 - agonistas de longa ação (B2LA) em associação aos CI, os antileucotrienos, a teofilina de ação prolongada e a imunoterapia anti-IgE. Os medicamentos de alívio são usados conforme a necessidade, com o objetivo de atuar rapidamente, revertendo a broncoconstrição e aliviando os sintomas, incluem os beta-2 agonistas inalatórios de curta ação, anticolinérgicos inalatórios e teofilina de curta ação. Omalizumabe é uma imunoterapia inespecífica anti-IgE indicada para adultos e crianças (acima de 6 anos de idade) com asma alérgica persistente moderada a grave cujos sintomas são inadequadamente controlados com corticosteroides inalatórios. A segurança e a eficácia do medicamento não foram estabelecidas em outras condições alérgicas. As referências disponíveis até o momento mostram que o omalizumabe, quando adicionado à terapia padrão no tratamento de pacientes com asma moderada a grave, reduz as taxas de exacerbação da doença, em relação ao placebo ou terapia padrão isolada. O estudo de avaliação econômica apresentado pelo demandante mostrou que o medicamento é custo-efetivo. Os membros da CONITEC presentes na 3ª reunião extraordinária do plenário do dia 20/12/2012, por unanimidade, ratificaram a deliberação de não recomendar a incorporação do medicamento omalizumabe para o tratamento da asma alérgica grave não controlada mesmo com a adição de corticosteroide oral (etapa 5 das diretrizes da SBPT para o Manejo da Asma), em pacientes acima de 6 anos. Além disso, recomendaram a atualização do Protocolo Clínico e Diretrizes Terapêuticas da Asma (2010), do Ministério da Saúde, com avaliação da possibilidade de inclusão do medicamento para situações específicas. A Portaria SCTIE-MS N.º 14, de 2 de abril de 2013 - Torna pública a decisão de não incorporar o medicamento omalizumabe para o tratamento de asma grave no Sistema Único de Saúde (SUS).