Cost-effectiveness of benralizumab versus mepolizumab and dupilumab in patients with severe uncontrolled eosinophilic asthma in Spain.

OBJECTIVE: To assess the cost-effectiveness of benralizumab (benra) vs. mepolizumab (mepo) and dupilumab (dupi) for the treatment of patients with severe uncontrolled asthma from the Spanish Health System perspective. METHODS: Exacerbations avoided, quality-adjusted life years (QALYs) gained and costs in a 5-year period were estimated with a Markov model for a cohort of 1,000 patients in which, based on published evidence, 31% of the patients received biologics + oral corticosteroids (OCS) and 69% received only biologics. Efficacy data (exacerbation reduction and OCS elimination) were derived from a matching-adjusted indirect comparison. Published EQ-5D utilities per health state (biologic alone, biologic + OCS, standard of care + OCS, exacerbations, and post-exacerbations) were used for QALY estimation. Utility decrements associated with exacerbation management [-0.1 (OCS or emergency visits), -0.2 (hospitalization)] derived from the literature were applied. Costs (€, 2022) included drug acquisition (ex-factory price), administration and disease management. An expert panel (2 pneumologists and 1 pharmacist) validated all inputs. RESULTS: Benra was more effective (52.21 QALYs) than mepo (51.39 QALYs) and dupi (51.30 QALYs). Benra avoided more exacerbations (2.87 exacerbations) compared to mepo (4.70 exacerbations) and dupi (5.11 exacerbations) for the 5-year horizon. Total costs/patient were €56,093.77 (benra), €59,280.45 (mepo) and €62,991.76 (dupi), resulting in benra dominating (more QALYs with lower costs) vs. mepo and dupi. CONCLUSIONS: Benralizumab can be considered as a dominant treatment alternative vs. other biologic drugs for the treatment of uncontrolled severe eosinophilic asthma patients in Spain.

Response to Monoclonal Antibodies in Asthma: Definitions, Potential Reasons for Failure, and Therapeutic Options for Suboptimal Response.

Real-life data reveal that more than half of severe asthma patients treated with monoclonal antibodies (mAbs) do not achieve a complete response. Response to mAbs must be assessed holistically, considering all the clinically meaningful therapeutic goals, not only reduction of exacerbations and oral corticosteroids. There are 2 different ways of measuring the response to mAbs. One, qualitative, classifies patients according to the degree of disease control they have achieved, without explaining how much a given patient improves relative to the baseline (pre-mAb) clinical situation; the other, quantitative, scores the changes occurring after treatment. Both methods are complementary and essential to making clinical decisions on whether to continue treatment. The various potential causes of suboptimal response to mAbs include incorrect identification of the specific T2 pathways, comorbidities that reduce the room for improvement, insufficient dose, autoimmune phenomena, infections, change in the initial inflammatory endotype, and adverse events. Once a suboptimal response has been confirmed, a well-structured and multifaceted assessment of the potential causes of failure should be performed, with emphasis on the resulting inflammatory process of the airway after mAb therapy and the presence of chronic or recurrent infection. This investigation should guide the decision on the best therapeutic approach. The present review aims to help clinicians gain insights into how to measure response to mAbs and proceed in cases of suboptimal response.

Factors Affecting the Success of Step-up Therapy in Patients With Moderate-Severe Asthma: A Real-Life Study.

INTRODUCTION AND OBJECTIVE: Introduction: Clinical practice guidelines recommend regular adjustment of treatment to achieve control of asthma. A step-up approach based on the degree of disease control should be followed. Objective: To perform a real-life analysis of the factors that affect the success or failure of this therapeutic strategy and of the criteria applied by clinicians when applying a step-up approach in a representative sample of patients diagnosed with moderate-severe asthma. MATERIAL AND METHODS: We performed a multicenter retrospective cohort study involving 226 Spanish specialist physicians (98 allergologists, 127 pulmonologists, and 1 family physician). We included 1254 patients (787 women) diagnosed with moderate-severe asthma who underwent step-up therapy during 2016. RESULTS: Step-up was successful in 44% of cases. The factors associated with success were presence of <2 comorbid conditions, lower grade of severity and therapy step before modification, absence of exacerbations during the previous year, fewer daytime/nighttime symptoms, and limitation in activities, as well as type of inhaled corticosteroid/ long-acting ß2-agonist combination after modification, lower body mass index, and higher fractional exhaled nitric oxide. An early increase in the maintenance dose once a lack of control was detected (≤3 months, >3 to ≤6 months, >6 to ≤12 months) was more likely to be successful. CONCLUSION: The factors that determine whether or not this therapeutic strategy manages to control asthma are time since onset of clinical impairment, previous grade of severity, number of comorbid conditions, previous exacerbations, and frequency of symptoms.

Factors affecting quality of life of asthma patients in Spain: the importance of patient education.

OBJECTIVES: Assessment of demographic and clinical factors that have an impact on the quality of life (QoL) of patients with asthma in Spain. PATIENTS AND METHODS: Multicenter, prospective, observational, cohort study, conducted in 40 Spanish Pneumology Units during a 12-month period. Data on sociodemographic, clinical variables, asthma treatment and QoL were collected in a case report form. RESULTS: 536 patients (64.6% women, mean age: 54) were recruited. Reported QoL was better for patients from Northern and Central Spain as compared with those from the South and the East (p<0.001), students and employed patients as compared with housewives and unemployed (p<0.01), for those who had received asthma information (p<0.01), for those with milder daytime symptoms (p<0.01) and for patients with higher level of education (p<0.05). CONCLUSIONS: Among the factors that have a significant effect on patients' QoL only symptom control and patient education on asthma control are modifiable. Therefore, all the strategies should be tailored to improve such factors when managing asthma patients.

Factors that determine the loss of control when reducing therapy by steps in the treatment of moderate-severe asthma in standard clinical practice: A multicentre Spanish study. / Factores que condicionan la pérdida de control al reducir escalones terapéuticos en el tratamiento del asma moderada-grave en la práctica clínica habitual: estudio español multicéntrico.

BACKGROUND: Although the clinical practice guidelines recommend continuous adjustment of asthma treatment and reducing the maintenance drugs when achieving control (step-down), there are few studies of standard clinical practice aimed at collecting information on the factors that determine step-down failure. OBJECTIVE: To determine the factors that determine step-down failure in standard clinical practice of patients with moderate-severe asthma controlled by a combination of inhaled glucocorticoids and long-acting beta agonists. METHODS: A multicentre retrospective study included 374 patients with moderate-severe asthma controlled with inhaled glucocorticoids and long-acting beta agonists for whom the physician indicated a step-down in 2016. RESULTS: The step-down failed in 41.7% of the patients. The following factors were related to failure: greater patient age (P=.006), presence of at least 2 comorbidities (P=.016), greater severity level (severe persistent vs. moderate persistent) (P<.001), greater age at diagnosis (>40 years) (P=.045), the higher the therapeutic step before (P=.003) and after the change (P<.001), the shorter the time of improvement/control prior to the change (P=.019), lower FEV1 (P=.001) and a poorer Asthma Control Test score or Asthma Control Questionnaire score before the step-down (P<.001). The logistic regression analysis showed a higher probability of step-down failure in the more elderly patients (OR, 0.983; 95% CI 0.969-0.997) and those with severe asthma compared to those with moderate asthma (OR, 0.537; 95% CI 0.292-0.985), as well as an increased probability of success if the patients had the disease controlled for more than 6 months (OR, 2.253; 95% CI 1.235-4.112). CONCLUSION: In standard clinical practice conditions, step-down fails in a high percentage of patients, and the suggestion is to indicate step-down when the patient has had more than 6 months of disease control.

Efectos de la pandemia en una consulta de tabaquismo / Effects of the pandemic on a smoking consultation

Objetivo. Análisis de las diferencias entre pacientes atendidos en la unidad hospitalaria de tabaquismo del H. Doctor Peset de Valencia, antes de la pandemia y con posterioridad, para valorar resultados obtenidos en cuanto a abstinencia tabáquica. Material y método. Estudio retrospectivo observacional analizando las mismas variables en dos periodos temporales: pacientes atendidos por primera vez durante el año previo a la pandemia (enero-diciembre 2019) y entre junio de 2021 y junio de 2022 (postpandemia). Se valoran datos demográficos, comorbilidades, dependencia, tratamiento farmacológico prescrito y éxitos obtenidos. Resultados. Diferencias en el número de pacientes atendidos con una reducción de 645 a 115. Incremento de trastornos psiquiátricos de 16,1% a 30,4%. Entre los tratamientos prescritos hay variación en vareniclina (46% a 13,9%) y en citisina (0 a 27,8%). La tasa de abstinencia a los 12 meses disminuye de 37,6% a 8,7% y el porcentaje de abstinencia entre los que completan el seguimiento pasa de 72% a 15,62%. No hay variación significativa en el resto de las variables estudiadas. Conclusión. El impacto de la pandemia en esta consulta se ha reflejado no solo en el drástico descenso del número de pacientes atendidos, sino también en un notable aumento de la comorbilidad psiquiátrica. Además, preocupa la reducción del porcentaje de pacientes que consiguen deshabituación. (AU)

Objective. Analysis of the differences between patients seen in a hospital smoking cessation unit of the H. Doctor Peset de Valencia before and after the pandemic to evaluate the results obtained regarding smoking abstinence. Material and methods. A retrospective observational study analyzing the same variables in two time periods: patients seen for the first time during the year prior to the pandemic (January-December 2019) and between June 2021 and June 2022 (post-pandemic). Demographic data, comorbidities, dependency, drug treatment prescribed and successes obtained are evaluated. Results. Differences were found in the number of patients seen, with a reduction from 645 to 115 and an increase of psychiatric disorders from 16.1% to 30.45. Among the treatments prescribed, there were variations in varenicline (46% to 13.9%) and in cytisine (0 to 27.8%). Abstinence rate at 12 months decreased from 37.6% to 8.7% and the abstinence percentage among those who completed the follow-up from 72% to 15.62%. There are no significant variations in the rest of the variables studied. Conclusion. The impact of the pandemic in this consultation has not only been reflected in the drastic decrease in the number of patients seen but also on a notable increase in psychiatric comorbidity. In addition, the reduction in the percentage of patients who achieved cessation is of concern. (AU)

Response to Monoclonal Antibodies in Asthma: Definitions, Potential Reasons for Failure, and Therapeutic Options for Suboptimal Response

Real-life data reveal that more than half of severe asthma patients treated with monoclonal antibodies (mAbs) do not achieve a complete response. Response to mAbs must be assessed holistically, considering all the clinically meaningful therapeutic goals, not only reduction of exacerbations and oral corticosteroids. There are 2 different ways of measuring the response to mAbs. One, qualitative, classifies patients according to the degree of disease control they have achieved, without explaining how much a given patient improves relative to the baseline (pre-mAb) clinical situation; the other, quantitative, scores the changes occurring after treatment. Both methods are complementary and essential to making clinical decisions on whether to continue treatment. The various potential causes of suboptimal response to mAbs include incorrect identification of the specific T2 pathways, comorbidities that reduce the room for improvement, insufficient dose, autoimmune phenomena, infections, change in the initial inflammatory endotype, and adverse events. Once a suboptimal response has been confirmed, a well-structured and multifaceted assessment of the potential causes of failure should be performed, with emphasis on the resulting inflammatory process of the airway after mAb therapy and the presence of chronic or recurrent infection. This investigation should guide the decision on the best therapeutic approach. The present review aims to help clinicians gain insights into how to measure response to mAbs and proceed in cases of suboptimal response (AU)

Los estudios clínicos en vida real revelan que más de la mitad de los pacientes con asma grave, tratados con anticuerpos monoclonales (mAb), no logran una respuesta completa. La respuesta a los mAbs debe evaluarse de manera integral, considerando todos los objetivos terapéuticos clínicamente significativos y no solo las exacerbaciones o la reducción de corticosteroides orales. Existen dos formas diferentes de medir la respuesta a los mAbs: una, cualitativa, que clasifica a los pacientes según el grado de control de la enfermedad que han logrado, sin explicar cuánto mejora un determinado paciente con respecto a su situación clínica basal (pre-mAb); y la otra, cuantitativa, la cual puntúa los cambios ocurridos después del tratamiento. Ambos métodos son complementarios y claramente esenciales a la hora de tomar decisiones clínicas sobre la continuación del tratamiento con estos fármacos biológicos. Se han descrito varias causas posibles de respuesta subóptima a los mAbs que son: la identificación incorrecta de las vías T2 específicas, las comorbilidades que reducen el margen de mejora, una dosis insuficiente, fenómenos autoinmunes, infecciones, cambio del endotipo inflamatorio inicial y la aparición de efectos adversos. na vez que se ha confirmado una respuesta subóptima, se debe realizar una evaluación bien estructurada y polifacética de estas posibles causas del fracaso, considerando, en particular, el proceso inflamatorio residual de las vías respiratorias tras la terapia con mAb y la presencia de infecciones crónicas o recurrentes. Esta evaluación es la que debe guiar las decisiones sobre el mejor enfoque terapéutico. Esta revisión tiene como objetivo ayudar a los clínicos a obtener un conocimiento más profundo sobre cómo medir la respuesta a los mAbs y cómo proceder con los pacientes que presenten una respuesta subóptima (AU)

Empiric treatment in hospitalized community-acquired pneumonia. Impact on mortality, length of stay and re-admission.

OBJECTIVE: To evaluate adherence to guidelines when choosing an empirical treatment and its impact upon the prognosis of community-acquired pneumonia (CAP). METHODS: A prospective multicentre study was conducted in 425 CAP patients hospitalized on ward. Initial empirical treatment was classified as adhering or not to Spanish guidelines. Adherent treatment was defined as an initial antimicrobial regimen consisting of beta-lactams plus macrolides, beta-lactam monotherapy and quinolones. Non-adherent treatments included macrolide monotherapy and other regimens. Initial severity was graded according to pneumonia severity index (PSI). The end point variables were mortality, length of stay (LOS) and re-admission at 30 days. RESULTS: Overall 30-day mortality was 8.2%, the mean LOS was 8+/-5 days, and the global re-admission rate was 7.6%. Adherence to guidelines was 76.5%, and in most cases the empirical treatment consisted of beta-lactam and macrolide in combination (57.4%). Logistic regression analysis showed that other regimens were associated with higher mortality OR=3 (1.2-7.3), after adjusting for PSI and admitting hospital. Beta-lactam monotherapy was an independent risk factor for re-admission. LOS was independently associated with admitting hospital and not with antibiotics. CONCLUSIONS: A high adherence to CAP treatment guidelines was found, though with considerable variability in the empirical antibiotic treatment among hospitals. Non-adherent other regimens were associated with greater mortality. Beta-lactam monotherapy was associated with an increased re-admission rate.

[Does experience influence perception of dyspnea?]. / Influye la experiencia en la percepción de disnea?

OBJECTIVE: The perception of somatic sensations like dyspnea can be influenced by such factors as an individual s personality, experiences, or ability to adapt to stimuli. Our aim was to determine whether the perception of acute bronchoconstriction is different for patients with asthma and patients who have never experienced an episode of airway obstruction. PATIENTS AND METHOD: We studied 2 groups of patients. The first consisted of 24 subjects with intermittent rhinitis and asthma (10 females and 14 males) with a mean (SD) age of 25 (7) years. All reported not feeling dyspnea at rest on a Borg scale. The second group consisted of 24 subjects who only had rhinitis but no lung disease (no episode of asthma) or dyspnea at rest (12 females and 12 males) with a mean age of 27 (6) years. There were no significant differences between the groups with regard to sex, smoking, economic or educational level, anxiety (determined by the trait portion of the State-Trait Anxiety Inventory), depression (Beck Depression Inventory), or spirometric parameters. All took a histamine bronchial provocation test in which the patient assessed dyspnea on a modified Borg scale after each histamine dose. The provocation dose needed to produce a 20% decrease (PD20) in forced expiratory volume in the first second (FEV1) was calculated. We also recorded dyspnea perception score when FEV1 fell 5%, 10%, 15%, and 20%. RESULTS: No dyspnea was perceived at PS20 by 12.5% of the asthmatics and by 45% of nonasthmatics (P< .0001). The mean PS20 was 2.4 (2.1) (range, 0-7) in the first group and 0.37 (0.48) (range, 0-3) in the second (P< .0001). More asthma patients than nonasthmatics perceived dyspnea at all degrees of bronchial obstruction. PD20 was different in the 2 groups (1.6 [2] vs 6.03 [5] for the first and second groups, respectively; P< .003), but there was no significant relation between PD20 and PS20 (Spearman s correlation coefficient, 0.19; P= .221). CONCLUSION: Our findings support the hypothesis that appropriate perception of dyspnea is grounded in prior experience and learning.

[Evolution over time in over perceivers of dyspnea in asthma]. / Evolución temporal de la percepción exagerada de disnea en los pacientes con asma.

OBJECTIVE: In previous studies we identified a subgroup of patients whose perception of breathlessness was exaggerated during acute bronchoconstriction and who were termed "over perceivers" or "hyperperceivers". In this study we aimed to determine whether such over perception is sporadic or stable over time. We also examined whether there is an association between over perception of dyspnea and hyperventilation syndrome. PATIENTS AND METHODS: The subjects were 22 stable asthmatics (11 men, 11 women) who had been over perceivers of dyspnea in a study 9 years earlier. After a medical history was taken, a patient performed forced spirometry and a severity classification was made according to the criteria of the Global Initiative for Asthma (GINA). A bronchial histamine challenge was then administered to measure dose-related perception of dyspnea on a Borg scale, according to a procedure that was similar to the one used 9 years earlier by the same investigator. The patients were also asked for a subjective assessment of the severity of their asthma (scale, 0-10) and to respond to items on the Nijmegen hyperventilation questionnaire and the trait form of the State-Trait Anxiety Inventory. RESULTS: The overall perception of severity of disease, level of anxiety, and perception of dyspnea at rest were lower after 9 years (P<.001). No change was observed in bronchial hyperresponsiveness (dose of inhaled histamine required to provoke a 20% decline in forced expiratory volume in the first second [FEV1]-PD20) or objective parameters of severity (FEV1 and GINA classification). Fourteen asthmatics (64%) were still over perceivers and the other patients had changed: 6 were normal perceivers and 2 were "poor perceivers". Only subjective perception of disease severity improved for the patients who were still over perceivers; the other patients, on the other hand, showed improvements in subjective assessments, objective ones (except PD20), and anxiety. Finally, those who remained over perceivers had higher scores for anxiety (24 vs 15; P<.05) and hyperventilation (18 vs 13; P= not significant). CONCLUSIONS: Most over perceivers of dyspnea remain so over the years and this trait is related to anxiety. We have been unable to demonstrate an association with hyperventilation syndrome.

Factors Affecting the Success of Step-up Therapy in Patients With Moderate-Severe Asthma: A Real-Life Study

Background: Clinical practice guidelines recommend regular adjustment of treatment to achieve control of asthma. A step-up approachbased on the degree of disease control should be followed.Objective: To perform a real-life analysis of the factors that affect the success or failure of this therapeutic strategy and of the criteriaapplied by clinicians when applying a step-up approach in a representative sample of patients diagnosed with moderate-severe asthma.Material and Methods: We performed a multicenter retrospective cohort study involving 226 Spanish specialist physicians (98 allergologists,127 pulmonologists, and 1 family physician). We included 1254 patients (787 women) diagnosed with moderate-severe asthma whounderwent step-up therapy during 2016.Results: Step-up was successful in 44% of cases. The factors associated with success were presence of <2 comorbid conditions, lower gradeof severity and therapy step before modification, absence of exacerbations during the previous year, fewer daytime/nighttime symptoms,and limitation in activities, as well as type of inhaled corticosteroid/ long-acting β₂-agonist combination after modification, lower bodymass index, and higher fractional exhaled nitric oxide. An early increase in the maintenance dose once a lack of control was detected(≤3 months, >3 to ≤6 months, >6 to ≤12 months) was more likely to be successful.Conclusion: The factors that determine whether or not this therapeutic strategy manages to control asthma are time since onset of clinicalimpairment, previous grade of severity, number of comorbid conditions, previous exacerbations, and frequency of symptoms. (AU)

Antecedentes: Las guías de práctica clínica recomiendan el ajuste del tratamiento hasta alcanzar el control del asma, siguiendo un escaladoprogresivo basado en el grado de control de la enfermedad.Objetivo: Realizar un análisis en vida real de los criterios que utilizan los clínicos para realizar el escalado terapéutico y de los factoresque condicionan el éxito o el fracaso de esta estrategia terapéutica en una muestra representativa de pacientes diagnosticados de asmapersistente moderada y grave.Material y métodos: Estudio multicéntrico retrospectivo de cohorte en el que participaron 226 médicos especialistas españoles (98alergólogos, 127 neumólogos y un médico de atención primaria). Incluimos 1.254 pacientes (787 mujeres) diagnosticados de asmapersistente moderada o grave en los que se realizó un escalado de tratamiento durante 2016.Resultados: El escalado terapéutico fue exitoso en el 44% de los casos. Los factores asociados con el éxito fueron la presencia de <2comorbilidades, menor grado de gravedad y del escalón terapéutico de la terapia antes de la modificación, ausencia de exacerbacionesdurante el año anterior, menos síntomas diurnos/nocturnos y limitación en las actividades ordinarias, así como el tipo de corticosteroideinhalado (ICS) / combinación de β₂-agonista de acción prolongada (LABA) después de la modificación, índice de masa corporal inferiory fracción del óxido nítrico exhalado superior. Un aumento temprano en la dosis de mantenimiento una vez que se detectó una falta decontrol (≤ 3 meses,> 3 a ≤ 6 meses,> 6 a ≤ 12 meses) también se asoció a un aumento de probabilidad de éxito.Conclusión: Los factores que determinan si el escalado terapéutico logra controlar el asma son el tiempo transcurrido desde el inicio deldeterioro clínico, el grado previo de gravedad, el número de afecciones comórbidas, las exacerbaciones previas y la frecuencia de síntomas. (AU)

Multidisciplinary expert discussion. Uncontrolled asthma: causes, consequences and possible solutions / Debate multidisciplinar de expertos. Asma no controlada: causas, consecuencias y posibles soluciones.

Background. Numerous studies conclude that about half of the asthmatic population is not well controlled. The aim of this study was to discuss causes, consequences and possible solutions of uncontrolled asthma (UCA). Methods. Discussion amongst asthma experts from the fields of Pneumology, Allergy and Primary Care, structured in three phases: 1) survey to get the opinion of participants involved in different areas of UCA; 2) expert meeting, in which the results of the survey were discussed, and the diagnosis, treatment and monitoring of UCA were presented and discussed; and, 3) with the main findings, 83 items were formulated and subjected to consensus among all participants through the Delphi method. Results. There was consensus on 86.7% of the items in the Delphi questionnaire, mostly in terms of agreement. Conclusions. The UCA analysis results show the need for future improvement in the following areas: to incorporate clinical performance protocols into asthma CPG to identify aggravating factors and comorbidities; to develop an inexpensive and easy-to-use tool to identify adherence; to establish patient phenotype; to analyse treatment side effects and to provide personalized treatment, especially assessing its efficacy and safety (symptom control and future risks). It is necessary to generate new evidence to determine additional tests to be used to monitor these patients.