Duration of the efficacy of omalizumab after treatment discontinuation in 'real life' severe asthma.

Efficacy of omalizumab in severe asthma is well documented; however, the optimal duration of the treatment remains unclear. In an open prospective study, we sought to assess the persistence of response in subjects withdrawing from omalizumab treatment. We evaluated 49 patients who voluntarily accepted to discontinue omalizumab treatment after 6 years of therapy. Asthma relapse was defined as any severe asthma exacerbation associated with loss of asthma control. Twelve patients relapsed in the first year of follow-up, and 7 within 13 and 48 months. These results suggest that the effects of 6 years of omalizumab may persist after discontinuation of therapy in 60% of patients for at least 4 years.

Effects of omalizumab in non-atopic asthma: results from a Spanish multicenter registry.

Aim. To evaluate the effectiveness of omalizumab in non-atopic asthma. Methods. Using data from a multicenter registry of severe asthma, we evaluated and compared the clinical outcome of 29 omalizumab-treated severe non-atopic asthmatics with 266 omalizumab-treated severe allergic asthmatics. Effectiveness was assessed by considering severe exacerbations, pulmonary function, the Global Evaluation of Treatment Effectiveness (GETE) scale, and Asthma Control Test (ACT). Results. Omalizumab demonstrated significant improvement in the clinical status of non-atopic asthmatics as measured by GETE, which rose from 1.6 ± 1.1 to 2.8 ± 0.9 [corrected] at 4 months (p = .0215) to 2.9 ± 0.9 at 1 year (p = .0093) and to 3.4 ± 0.6 at 2 years (p = .0078), and by the ACT, which increased from 13.3 ± 5.5 [corrected] to 17.5 ± 5.4 at 4 months (p = .0236) to 17.9 ± 4.8 at 1 year (p = .0136) and to 20.6 ± 3.9 at 2 years (p = .0024). Forced expiratory volume in 1 second (FEV1) improved from 61.0 ± 19.4% to 65.1 ± 17.2 at 4 months to 64.1 ± 24.7 at 1 year and to 67.3 ± 23.0% [corrected] at 2 years, but without significant differences between initial and follow-up measurements (p = .52, .91, and .45, respectively) and exacerbations decreased from 3.1 ± 3.5 to 1.9 ± 2.8 at 1 year (p = .1709) to 1.8 ± 4.4 at 2 years (p = .2344). The results were not significantly different from those obtained in atopic asthmatics. Conclusion. Anti-IgE therapy can be effective in non-atopic severe asthma.

Omalizumab therapy in severe asthma: experience from the Spanish registry--some new approaches.

OBJECTIVE: The efficacy of omalizumab in severe asthma has been widely demonstrated. The main objective of this study was to evaluate the efficacy and tolerability of omalizumab in a real-life setting in Spain, particularly in those patients with immunoglobulin E (IgE) levels out of range. METHODS: Totally 266 uncontrolled severe asthma patients receiving high-dose inhaled corticosteroids (ICSs) plus long-acting ß2-agonist (LABA) were recruited. Main efficacy outcomes were asthma exacerbation rate (AER), asthma control test (ACT), and global evaluation of treatment effectiveness (GETE). RESULTS: AER was reduced from 3.6 (3.6) in previous year to 0.67 (1.2) at 4 months (p < .05) and to 1.04 (1.8) at 2 years (p < .05). ACT increased significantly from 14.3 (4.7) at baseline to 18.4 (4.4) at 4 months (p < .05) and to 20.3 (4.0) (p < .05) at 2 years. After 4 months, 74.6% of patients had reached a good or excellent rate on the GETE scale (p < .05). This rate continued increasing up to 81.6% at 2 years. These efficacy results were similar for patients with "off-label" IgE > 700 IU/ml. At follow-up, maintenance treatment with oral steroids was discontinued in a considerable number of patients: from 89 to 19 (p < .05). Omalizumab was discontinued because of lack of efficacy only in 28/266 (10.5%) patients. Overall, 30 patients (11.4%) reported adverse events. Severe adverse events were not observed. CONCLUSION: This real-life study confirms that omalizumab is very efficacious and very well tolerated in patients with uncontrolled severe asthma. Results did not vary in the subgroup of patients with IgE levels >700 IU/ml.

Is asthma in the elderly different? Functional and clinical characteristics of asthma in individuals aged 65 years and older.

BACKGROUND: The prevalence of chronic diseases in the elderly (> 65 years), including asthma, is growing, yet information available on asthma in this population is scarce.Our objective is to determine the differential clinical and functional characteristics of the population > 65 years old with asthma included in the Integrated Research Programs of Asthma Databank of the Spanish Society of Pneumology and Thoracic Surgery (www.bancodatosasma.com). METHODS: Retrospective comparative descriptive study of demographic, clinical and functional variables for 1713 patients with asthma categorized into 3 age groups as follows: adults aged < 65 years (A), younger elderly aged 65-74 years (B) and older elderly aged ≥75 years (C). RESULTS: Predominant features of elderly patients with asthma (N = 471) were the female sex, fewer smokers, greater obesity, poorer lung function, and lower values of nitric oxide in exhaled air (p < 0.01). The most frequently associated comorbidity was gastroesophageal reflux. The highest doses of inhaled corticosteroids were by group A (60.8%). For the sample overall, 23.2% (N = 398) were being treated with omalizumab and 8.2% (N = 140) were corticosteroid-dependent (10.6% in group B). The highest percentage of patients receiving antileukotriene agents was in group B (42.9%). CONCLUSIONS: Asthma in adults aged> 65 is more severe and associated with greater comorbidity, which would indicate the need for a more integrated and multidimensional approach to asthma treatment for these patients.

A Simple Score for Future Risk Prediction in Patients with Controlled Asthma Who Undergo a Guidelines-Based Step-Down Strategy.

BACKGROUND: The minimum controlling dose of treatment must be established in patients with asthma, but the outcome of step-down is unpredictable. OBJECTIVE: To identify factors associated with risk of control loss when stepping down asthma treatment and to develop a score to predict this risk. METHODS: A prospective, multicenter study including adults with well-controlled asthma was performed. Treatment was stepped up or stepped down over a 12-month period to maintain asthma control. We determined associations between clinical and functional variables and step-down failure. Finally, we derived a score to predict loss of control in 1 cohort and validated it in an independent cohort. RESULTS: The derivation cohort consisted of 228 patients; 218 completed at least 1 step-down episode and a total of 495 step-down episodes were evaluated. A medical-record documented postbronchodilator spirometry result of <70% forced expiratory volume in 1 second (FEV1)/forced vital capacity (odds ratio [OR] = 2.08; 95% confidence interval [CI]: 1.26-3.43), current FEV1 < 80% (OR = 1.80; 95% CI: 1.03-3.14), ≥1 severe exacerbation in the previous 12 months (OR = 2.43; 95% CI: 1.48-4.01), and Asthma Control Test score < 25 (OR = 2.30; 95% CI: 1.35-3.92) were independently associated with failure. The score showed an area under the curve of 0.690 (95% CI: 0.633-0.747; P < .05) in the derivation cohort and 0.76 (95% CI: 0.643-0.882; P < .001) in a validation cohort of 114 patients. A score <4.5 implies a low risk of failure (<20%), whereas a score >8 implies a high risk (>40%). CONCLUSION: This score can facilitate the prediction of step-down failure before medication taper in patients with well-controlled asthma.

[Triamcinolone acetonide in the treatment of corticosteroid-resistant asthma: risks and benefits]. / Acetónido de triamcinolona en el tratamiento del asma resistente a los glucocorticoides: riesgos y beneficios.

Few therapeutic alternatives to prednisone are available for severe, corticosteroid-resistant asthma. Injectable triamcinolone acetonide (TA) has been used in this type of asthma, although its use is controversial. TA shows considerable efficacy when compared with prednisone according to nearly all studies, although the majority do not provide a high level of evidence. The use of TA has been questioned, with claims put forward that it is equivalent to increasing the corticosteroid dose, thus leading to a higher risk of adverse effects. This would mean that TA would not represent an improvement over prednisone because of the trade-offs between risks and benefits. This interpretation is questionable, however, because the data show that TA causes fewer adverse effects than prednisone, meaning that the balance of risks and benefits does favor TA. Therefore, TA can be considered a useful option for the treatment of patients with severe prednisone-resistant asthma.

Cost-Effectiveness Analysis of Omalizumab for the Treatment of Severe Persistent Asthma in Real Clinical Practice in Spain.

BACKGROUND AND OBJECTIVE: Omalizumab is a humanized monoclonal antibody that targets circulating immunoglobulin E molecules to treat severe uncontrolled asthma. The aim of this study was to determine the cost effectiveness of omalizumab compared with standard treatment for the control of severe persistent asthma according to data from patients treated in a specialized asthma unit. METHODS: This was an observational, retrospective, single-center study in the setting of the Pulmonology and Respiratory Allergy Service, Thorax Institute, Hospital Clínic de Barcelona, Barcelona, Spain. Data were collected by review of medical records of 86 uncontrolled severe persistent asthma patients treated with omalizumab from January 2005 to April 2014. Effectiveness was assessed by the reduction in asthma exacerbations and 3-point increases in the Asthma Control Test (ACT) score. The economic evaluation was performed from the societal perspective, including direct health costs (resource use and drug treatments) and indirect costs (disease impact on labor productivity) in 2016 Euros. The time horizon was 12 months before and after the initiation of treatment with omalizumab. Results were expressed using the incremental cost-effectiveness ratio (ICER). RESULTS: Taking into account only direct costs, the ICERs were €1487.46 (95 % confidence interval [CI] 1241.21-1778.34) per exacerbation avoided and €5425.13 (95 % CI 4539.30-6551.03) per 3-point increase in the ACT. When indirect costs were included, the ICERs were €1130.93 (95 % CI 909.08-1392.86) per exacerbation avoided, and €4124.79 (95 % CI 3281.69-5186.73) per 3-point increase in the ACT. CONCLUSIONS: The results of this study confirm the effectiveness of the addition of omalizumab to standard therapy in patients with uncontrolled severe persistent asthma.

Novel diagnostic approaches and biological therapeutics for intrinsic asthma.

Intrinsic asthma has been considered as a specific disease entity for a long time, although many controversies have emerged in relation to this concept. Of note, not finding specific allergen sensitization in an asthmatic patient neither excludes an allergic component nor the essential role that immunoglobulin E may play in asthma. The diagnostic approach should be similar in any patient suspected to have asthma. The atopic status is one among many other questions. Omalizumab, the only monoclonal anti-immunoglobulin E antibody commercialized for asthma, should be tried in patients with uncontrolled severe asthma independent of their atopic status.

Factors associated with severe uncontrolled asthma and the perception of control by physicians and patients.

INTRODUCTION: Despite current treatments, more than half of patients with asthma are not controlled. The objective was to evaluate the correlation between control perceived by patients and physicians, compared with control evaluated according to criteria of the Spanish Guidelines for Asthma Management (GEMA), and to investigate the factors associated with that control. METHODS: Multicenter, cross-sectional, observational study including 343 patients with severe persistent asthma according to GEMA criteria seen in the Department of Pulmonology and Allergology. The correlation between asthma control perceived by the patient, the physician and according to clinical judgment based on the GEMA criteria was calculated, and a multivariate analysis was used to determine variables related to the perception of asthma control. RESULTS: According to GEMA criteria, only 10.2% of patients were well controlled, 27.7% had partial control and 62.1% were poorly controlled. Both the physicians and the patients overestimated control: 75.8% and 59.3% of patients had controlled asthma according to the patient and the physician, respectively, and were not controlled according to GEMA (P<.0001). Patients with uncontrolled asthma according GEMA had higher body mass index (P=.006) and physical inactivity (P=.016). Factors associated with a perceived lack of control by both physicians and patients were: nocturnal awakenings (≥ 1 day/week), frequent use of rescue medication (≥ 5 days/week) and significant limitation in activities. Discrepant factors between physicians and patients were dyspnea and emergency room visits (patients only), FEV1 ≤ 80% and a poorer understanding of the disease by the patient (physicians only). CONCLUSIONS: Only 10% of patients with severe asthma evaluated in this study are controlled according to GEMA criteria. Patients and physicians overestimate control and the overestimation by patients is greater. Physical inactivity and obesity are associated with a lack of control according to GEMA.

Factores asociados con el asma grave no controlada y con la percepción del control por parte de médicos y pacientes / Factors associated with severe uncontrolled asthma and the perception of control by physicians and patients

Introducción: A pesar de los tratamientos actuales más de la mitad de pacientes con asma no están controlados. El objetivo fue evaluar la concordancia entre la percepción de control por parte de pacientes y médicos comparado con el control evaluado según criterios de la Guía española para el manejo del asma (GEMA), así como investigar los factores asociados con dicho control. Métodos: Estudio multicéntrico, observacional y transversal que incluyó 343 pacientes con asma grave persistente según criterios de la GEMA atendidos en consultas de neumología y alergología. Se calculó la concordancia entre control del asma según percepción del paciente, criterio clínico del médico y en función de criterios GEMA, y se utilizó análisis multivariante para determinar variables relacionadas con la percepción de control del asma. Resultados: Según criterios GEMA solo el 10,2% de pacientes estaba bien controlado, el 27,7% presentaba control parcial y el 62,1% estaba mal controlado. Tanto médicos como pacientes sobrestimaron el control: el 75,8 y 59,3% de individuos con asma controlada según el propio paciente y su médico, respectivamente, no estaba controlada según GEMA (p < 0,0001). Los pacientes con asma no controlada según GEMA presentaron un mayor índice de masa corporal (p = 0,006) y más sedentarismo (p = 0,016). Los factores asociados a la falta de control percibida tanto por médicos como por pacientes fueron: despertares nocturnos (≥ 1 día/semana), uso frecuente de medicación de rescate (≥ 5 días/semana) y limitación importante de actividades. Los factores discordantes entre médicos y pacientes fueron: disnea y visitas a urgencias (solo pacientes); FEV1 ≤ 80% y peor conocimiento de la enfermedad por el paciente (solo médicos). Conclusiones: Solo el 10% de pacientes con asma grave evaluados en este estudio está controlado según criterios GEMA. Tanto pacientes como médicos sobrestiman el control, con una mayor sobrestimación en pacientes. El sedentarismo y la obesidad se asocian con la falta de control según GEMA

Introduction: Despite current treatments, more than half of patients with asthma are not controlled. The objective was to evaluate the correlation between control perceived by patients and physicians, compared with control evaluated according to criteria of the Spanish Guidelines for Asthma Management (GEMA), and to investigate the factors associated with that control. Methods: Multicenter, cross-sectional, observational study including 343 patients with severe persistent asthma according to GEMA criteria seen in the Department of Pulmonology and Allergology. The correlation between asthma control perceived by the patient, the physician and according to clinical judgment based on the GEMA criteria was calculated, and a multivariate analysis was used to determine variables related to the perception of asthma control. Results: According to GEMA criteria, only 10.2% of patients were well controlled, 27.7% had partial control and 62.1% were poorly controlled. Both the physicians and the patients overestimated control: 75.8% and 59.3% of patients had controlled asthma according to the patient and the physician, respectively, and were not controlled according to GEMA (P < 0.0001). Patients with uncontrolled asthma according GEMA had higher body mass index (P = 0.006) and physical inactivity (P = 0.016). Factors associated with a perceived lack of control by both physicians and patients were: nocturnal awakenings (≥ 1 day/week), frequent use of rescue medication (≥ 5 days/week) and significant limitation in activities. Discrepant factors between physicians and patients were dyspnea and emergency room visits (patients only), FEV1≤ 80% and a poorer understanding of the disease by the patient (physicians only). Conclusions: Only 10% of patients with severe asthma evaluated in this study are controlled according to GEMA criteria. Patients and physicians overestimate control and the overestimation by patients is greater. Physical inactivity and obesity are associated with a lack of control according to GEMA

Patologías mediadas por la inmunoglobulina E: de lainmunoglobulina E al omalizumab / IgE mediated diseases: from IgE to omalizumab

Alrededor del 30-40% de la población mundial está afectada por una o más enfermedades alérgicas. La inmunoglobulina E (IgE) fue descubierta en 1967 y reconocida como un mediador fundamental en la alergia. El omalizumab es un anticuerpo monoclonal humanizado que reconoce a la IgE como molécula diana uniéndose a su fracción constante (Fc). Por su acción es capaz de limitar el desencadenamiento de la respuesta alérgica mediada por los anticuerpos IgE. Se trata del único anticuerpo monoclonal del que se dispone en la actualidad para tratar a los pacientes con asma grave refractaria al tratamiento convencional, con excelentes resultados tanto en ensayos clínicos como en pacientes de la vida real. Otras entidades IgE mediadas como la rinitis alérgica, la poliposis nasal, las enfermedades de la vía aérea asociadas a Aspergillus fumigatus y las urticarias crónicas, han mostrado también resultados muy prometedores aunque su uso no esté actualmente autorizado en estas enfermedades. Este artículo revisa el desarrollo del omalizumab, sus mecanismos de acción y los resultados observados en estudios realizados (AU)

Around 30-40% of the world population is affected by one or more allergic diseases. Immunoglobulin IgE (IgE) was discovered in 1967 and recognized as an essential mediator in allergy. Omalizumab is a humanized monoclonal antibody directed towards IgE as a molecular target by binding to the Fc region of circulating IgE, thus preventing IgE-mediated clinical responses. It is currently the only monoclonal antibody to treat severe refractory asthma, with excellent results in clinical trials and in real life patients. Other IgE mediated conditions, such as allergic rhinitis, nasal polyposis, airways diseases associated with Aspergillus fumigatus, and chronic urticaria, also demonstrated promised results, although they are not yet approved in routine clinical practice. This article reviews the development of omalizumab, its mechanisms of action, and results in Spain and other countries (AU)

Acetónido de triamcinolona en el tratamiento del asma resistente a los glucocorticoides: riesgos y beneficios / Triamcinolone acetonide in the treatment of corticosteroid-resistant asthma: risks and benefits

Las alternativas terapéuticas a la prednisona en el asma grave que no responde a los corticoides son escasas. El acetónido de triamcinolona (AT) de administración inyectada se ha utilizado en esta asma, aunque su empleo es motivo de controversia. Casi todos los estudios realizados, aunque en su mayoría son de escasa calidad, muestran una eficacia sustancial del AT comparado con la prednisona. Se ha cuestionado el uso del AT aduciéndose que equivale a aumentar la dosis del glucocorticoide, lo que comportará un mayor riesgo de efectos secundarios, de modo que el balance final de riesgos y beneficios del AT no mejoraría el de la prednisona. Los datos publicados permiten dudar de esa interpretación, ya que muestran que el AT ocasiona menos efectos secundarios que la prednisona, por lo que el balance de riesgos y beneficios es superior al de esta última. Por ello puede considerarse el AT una opción válida para tratar a los pacientes con asma grave que no responde a la prednisona

Few therapeutic alternatives to prednisone are available for severe, corticosteroid-resistant asthma. Injectable triamcinolone acetonide (TA) has been used in this type of asthma, although its use is controversial. TA shows considerable efficacy when compared with prednisone according to nearly all studies, although the majority do not provide a high level of evidence. The use of TA has been questioned, with claims put forward that it is equivalent to increasing the corticosteroid dose, thus leading to a higher risk of adverse effects. This would mean that TA would not represent an improvement over prednisone because of the trade-offs between risks and benefits. This interpretation is questionable, however, because the data show that TA causes fewer adverse effects than prednisone, meaning that the balance of risks and benefits does favor TA. Therefore, TA can be considered a useful option for the treatment of patients with severe prednisone-resistant asthma

Caso clínico: rinoconjuntivitis alérgica y asma bronquial por pancreatina y celulasa / Clinical case: allergic rhinoconjuntivitis and bronchial asthma for pancreatin and cellulase

Se presenta un paciente de 25 años, trabajador de un laboratorio farmacéutico que presenta un cuadro de asma bronquial y rinoconjuntivitis alérgicas, de 7 meses de evolución, en el que se investigó la relación con drogas de exposición laboral, por búsqueda de IgE específicas, pruebas cutáneas y de provocación nasal y bronquial. Se comprobó sensibilidad a grupos complejos de proteínas con actividad enzimática, denominadas celulasa y pancreatina, por IgE específicas y pruebas cutáneas. Las pruebas de provocación nasal y bronquial sólo fueron positivas para celulasa

Caso clínico: rinoconjuntivitis alérgica y asma bronquial por pancreatina y celulasa / Clinical case: allergic rhinoconjuntivitis and bronchial asthma for pancreatin and cellulase

Se presenta un paciente de 25 años, trabajador de un laboratorio farmacéutico que presenta un cuadro de asma bronquial y rinoconjuntivitis alérgicas, de 7 meses de evolución, en el que se investigó la relación con drogas de exposición laboral, por búsqueda de IgE específicas, pruebas cutáneas y de provocación nasal y bronquial. Se comprobó sensibilidad a grupos complejos de proteínas con actividad enzimática, denominadas celulasa y pancreatina, por IgE específicas y pruebas cutáneas. Las pruebas de provocación nasal y bronquial sólo fueron positivas para celulasa