Anti-IL-5 and anti-IL-5R biologics for severe asthma. Are there any differences in their effects?

OBJECTIVE: The aim of this retrospective multicentre study is to describe the clinical characteristics of patients diagnosed with severe eosinophilic asthma receiving anti-IL-5/anti-IL-5Rα therapies and to compare their effectiveness. METHODS: We collected and analysed results separately for anti-IL-5 and anti-IL-5Rα therapies from January 2016 until December 2021 in multidisciplinary severe asthma units. We collected demographic and clinical data, treatment with previous anti-IgE and/or anti-IL-5 agents, and comorbidities. We compared the number of exacerbations and admissions to the hospital, daily oral corticosteroid intake, pulmonary function tests, and Asthma Control Test scores before and after 12 months of therapy. 261 patients were included: 176 patients in the anti-IL-5 group and 85 in the anti-IL-5Rα group. RESULTS: Both groups led to statistically significant reductions in asthma exacerbations, hospital admissions, and visits to the Emergency Room. Although both groups showed a significant reduction in blood eosinophiliccount, we found a difference, although not significant, in the magnitude of reduction as benralizumab was able to decrease eosinophil counts to zero. Patients in the anti-IL-5 group achieved higher ACT scores after treatment, although this improvement was seen in both treatment groups. CONCLUSION: The anti-IL-5 and anti-IL-5Rα biologics have shown similar effectiveness despite having different mechanisms of action. The anti-IL-5 group appeared to be better than benralizumab at improving ACT scores and FEV1/FVC and at reducing the number of inhalers. Although these differences were not statistically significant, it is not clear whether they may have clinical relevance and they might highlight the need for further head-to-head studies comparing these treatments.

Cost-effectiveness and resource use analysis of patients with asthma before and after treatment with mepolizumab in a real-life setting.

OBJECTIVE: To define the cost-effectiveness and health resource use of mepolizumab in a cohort of patients with severe eosinophilic asthma in real-life conditions in Spain. METHODS: This was an observational, retrospective, single-center study. Patients included were diagnosed with severe eosinophilic asthma and treated with mepolizumab 100 mg subcutaneous (SC) 4-weekly for 12 months. Outcomes evaluated: incremental cost-effectiveness ratio (ICER), number of exacerbations, disease control with the Asthma Control Test (ACT), Asthma Quality of Life Questionnaire (AQLQ), and direct and indirect cost per patient. RESULTS: 12 months after mepolizumab initiation, a significant decrease in exacerbations was shown, from a mean (standard deviation [SD]) of 3.1 (2.6) to 0.7 (1.5), an increase from 4.9 (0.4) to 6.1 (0.5) in AQLQ, and from 14.9 (5.7) to 21.5 (3.9) in ACT scores. The number of cortico-dependent patients significantly decreased from 53.3% to 13.3% during this period. There was a significant decrease of 94% in the cost of hospitalization, from a mean (SD) of €4063.9 (5423.9) pretreatment to €238.6 (1306.9) post-treatment (p = 0.0003). Total costs decreased significantly from a median of €2,423.1 (1,512.8; 9,320.9) pretreatment to €1,177.5 (965.0; 1,737.8) post-treatment if mepolizumab was excluded. ICER per exacerbation avoided was €3606.9, per 3-point ACT score increase €3934.8, and per 0.5-point AQLQ score increase €3606.9. CONCLUSIONS: Mepolizumab improves control of asthma and quality of life in patients with severe diseases in a cost-effectiveness range. The number of exacerbations decreased, and there was a clear reduction in primary care visits and hospitalizations. Further economic analyses of biological therapies for asthma are required.

Krebs von den Lungen-6 (KL-6) Levels in Post-COVID Follow-Up: Differences According to the Severity of COVID-19.

To evaluate KL-6 levels in medium-term post-COVID and to compare them in three groups categorised by the severity of COVID-19, we conducted a real-world, retrospective, cohort study. Data from the COVID-19 episode and follow-up during the post-COVID phase were extracted from the COVID@HULP and POSTCOVID@HULP databases, respectively. For the post-COVID period we included demographics, medical history, symptoms, quality of life, physical activity, anxiety and depression status and laboratory results. Patients were categorised into three groups based on the severity of COVID-19: Group 1 (inpatient critical), Group 2 (inpatient non-critical) and Group 3 (hospitalised at home). KL-6 was measured during the follow-up of the three groups. In all, 802 patients were included (Group 1 = 59; Group 2 = 296; Group 3 = 447 patients). The median age was 59 years (48-70), and 362 (45.2%) were males. At admission, fibrinogen and ferritin levels were lower in Group 3 than in the other groups (p < 0.001). Follow-up data were obtained 124 days (97-149) after the diagnosis of COVID-19. The median levels of fibrinogen, ferritin and KL-6 at follow-up were 336 mg/dL (276-413), 80.5 ng/mL (36-174.3) and 326 U/mL (240.3-440.3), respectively. KL-6 levels were lower in Group 3 than in the other groups (298 U/mL (231.5-398) vs. 381.5 U/mL (304-511.8) (Group 1) and 372 U/mL (249-483) (Group 2) (p < 0.001)). KL-6 was associated with ferritin (p < 0.001), fibrinogen (p < 0.001), D-dimer (p < 0.001) and gamma-glutamyl transferase (p < 0.001). KL-6 levels are less elevated at medium-term post-COVID follow-up in patients with mild COVID-19 than in those with moderate or severe disease. KL-6 is associated with systemic inflammatory, hepatic enzyme and thrombosis biomarkers.

Severe SARS-CoV-2 Pneumonia and Pneumomediastinum/Pneumothorax: A Prospective Observational Study in an Intermediate Respiratory Care Unit.

INTRODUCTION: The occurrence of pneumomediastinum (PM) and/or pneumothorax (PTX) in patients with severe pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was evaluated. METHODS: This was a prospective observational study conducted in patients admitted to the intermediate respiratory care unit (IRCU) of a COVID-19 monographic hospital in Madrid (Spain) between December 14, 2020 and September 28, 2021. All patients had a diagnosis of severe SARS-CoV-2 pneumonia and required noninvasive respiratory support (NIRS): high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), and bilevel positive airway pressure (BiPAP). The incidences of PM and/or PTX, overall and by NIRS, and their impact on the probabilities of invasive mechanical ventilation (IMV) and death were studied. RESULTS: A total of 1306 patients were included. 4.3% (56/1306) developed PM/PTX, 3.8% (50/1306) PM, 1.6% (21/1306) PTX, and 1.1% (15/1306) PM + PTX. 16.1% (9/56) of patients with PM/PTX had HFNC alone, while 83.9% (47/56) had HFNC + CPAP/BiPAP. In comparison, 41.7% (521/1250) of patients without PM and PTX had HFNC alone (odds ratio [OR] 0.27; 95% confidence interval [95% CI] 0.13-0.55; p < .001), while 58.3% (729/1250) had HFNC + CPAP/BiPAP (OR 3.73; 95% CI 1.81-7.68; p < .001). The probability of needing IMV among patients with PM/PTX was 67.9% (36/53) (OR 7.46; 95% CI 4.12-13.50; p < .001), while it was 22.1% (262/1185) among patients without PM and PTX. Mortality among patients with PM/PTX was 33.9% (19/56) (OR 4.39; 95% CI 2.45-7.85; p < .001), while it was 10.5% (131/1250) among patients without PM and PTX. CONCLUSIONS: In patients admitted to the IRCU for severe SARS-CoV-2 pneumonia requiring NIRS, incidences of PM/PTX, PM, PTX, and PM + PTX were observed to be 4.3%, 3.8%, 1.6%, and 1.1%, respectively. Most patients with PM/PTX had HFNC + CPAP/BiPAP as the NIRS device, much more frequently than patients without PM and PTX. The probabilities of IMV and death among patients with PM/PTX were 64.3% and 33.9%, respectively, higher than those observed in patients without PM and PTX, which were 21.0% and 10.5%, respectively.

Clinical Findings and Outcomes From Subjects With COVID-19 Pneumonia in an Intermediate Respiratory Care Unit.

BACKGROUND: Many patients with COVID-19 require respiratory support and close monitoring. Intermediate respiratory care units (IRCU) may be valuable to optimally and adequately implement noninvasive respiratory support (NRS) to decrease clinical failure. We aimed at describing intubation and mortality in a novel facility entirely dedicated to COVID-19 and to establish their outcomes. METHODS: This was a retrospective, observational study performed at one hospital in Spain. We included consecutive subjects age > 18 y, admitted to IRCU with COVID-19 pneumonia, and requiring NRS between December 2020-September 2021. Data collected included mode and usage of NRS, laboratory findings, endotracheal intubation, and mortality at day 30. A multivariable Cox model was used to assess risk factors associated with clinical failure and mortality. RESULTS: A total of 1,306 subjects were included; 64.6% were male with mean age of 54.7 y. During the IRCU stay, 345 subjects clinically failed NRS (85.5% intubated; 14.5% died). Cox model showed a higher clinical failure in IRCU upon onset of symptoms and hospitalization was < 10 d (hazard ratio [HR] 1.59 [95% CI 1.24-2.03], P < .001) and PaO2 /FIO2 < 100 mm Hg (HR 1.59 [95% CI 1.27-1.98], P < .001). These variables were not associated with increased 30-d mortality. CONCLUSIONS: The IRCU was a valuable option to manage subjects with COVID-19 requiring NRS, thus reducing ICU overload. Male sex, gas exchange, and blood chemistry at admission were associated with worse prognosis, whereas older age, gas exchange, and blood chemistry were associated with 30-d mortality. These findings may provide a basis for better understanding outcomes and to improve management of noninvasively ventilated patients with COVID-19.

Adherence to inhalers in patients with severe asthma treated with anti-interleukin-5 biologics.

OBJECTIVE: Given poor medication adherence in severe asthma is difficult to  evaluate in daily practice, using at least two methods concurrently is recommended. We aimed to determine the prevalence of nonadherence  to  inhalers using the Test of Adherence to Inhalers questionnaire and the medication possession ratio obtained from the pharmacy refill data in patients with severe asthma treated with anti-interleukin-5 biologics and to evaluate their concordance. METHOD: This was a cross-sectional retrospective observational study of 53  patients with severe asthma recruited from the severe asthma unit of a tertiary  hospital in Madrid from June to December 2020. We registered demographic data, comorbidities and concomitant therapy for  sthma. Nonadherence was defined as pharmacy refill data < 80% and/or Test of Adherence to Inhalers questionnaire results < 50. Concordance was assessed by determining the Cohen's kappa statistic. Results: The median age was 61 years (interquartile range 51.8-67.0), and 33  (61%) were women. According to the pharmacy refill data lack of  adherence to the primary inhaler was 58.5%. However, when using the Test of  Adherence to Inhalers questionnaire, it was 22.6%. Combining both methods,  17% of patients were considered to have nonadherence to inhalers. Likewise,  when identifying nonadherence by either of these methods, it reached a  prevalence of 64.2%. The pharmacy refill data and Test of Adherence to  Inhalers questionnaire agreed in 53.1% and disagreed in 46.9% of patients (k  = 0.137; 95% confidence interval -0.057 to 0.331; p = 0.318). CONCLUSIONS: We observed a higher prevalence of non-adherence to inhalers  in patients with severe asthma treated with anti-interleukin-5 biologics. The  agreement between the Test of Adherence to Inhalers questionnaire and the  pharmacy refill data is lower when evaluating nonadherence in patients with  severe asthma treated with anti-interleukin-5 biologics. The pharmacy refill  data detect a higher proportion of nonadherence compared with the Test of  Adherence to Inhalers questionnaire.

OBJETIVO: Dado que la mala adherencia a la medicación en el asma grave es  difícil de evaluar en la práctica diaria, se recomienda utilizar al menos dos métodos simultáneamente. El objetivo es determinar la prevalencia de la  falta de adherencia a los inhaladores mediante el cuestionario Test de  Adherencia a los Inhaladores y la ratio de posesión de la medicación obtenida a  partir de los datos de dispensación de la farmacia en pacientes con asma  grave tratados con biológicos anti interleucina 5 y evaluar su concordancia.Método: Estudio observacional retrospectivo transversal de 53 pacientes con  asma grave reclutados en la unidad de asma grave de un hospital terciario de  Madrid de junio a diciembre de 2020. Se registraron datos demográficos, comorbilidades y el tratamiento concomitante para el asma. La  falta de adherencia se definió como una ratio de posesión de la medicación <  80% y/o un valor en los resultados del cuestionario Test de Adherencia a los  Inhaladores < 50. La concordancia se evaluó con el coeficiente kappa de  Cohen. RESULTADOS: La mediana de edad fue de 61 años (rango intercuartílico 51,8- 67,0), y 33 (61%) eran mujeres. Según la ratio de posesión de la medicación,  la falta de adherencia al inhalador primario fue del 58,5%. Sin embargo, al  utilizar el cuestionario Test de Adherencia a los Inhaladores, ésta fue del  22,6%. Combinando ambos métodos, se consideró que el 17% de los  pacientes presentaban no adherencia a los inhaladores. Asimismo, al identificar  la no adherencia por cualquiera de estos métodos, se alcanzó una  prevalencia del 64,2%. El cuestionario Test de Adherencia a los Inhaladores y  la ratio de posesión de la medicación coincidieron en el 53,1% y discreparon en  el 46,9% de los pacientes (k = 0,137; intervalo de confianza del 95% ­0,057 a 0,331; p = 0,318). CONCLUSIONES: Se observó una alta prevalencia de no adherencia a los inhaladores en los pacientes con asma grave tratados con biológicos anti interleucina 5. La concordancia entre el cuestionario Test de Adherencia a los Inhaladores y la ratio de posesión de la medicación es menor cuando se  evalúa la no adherencia en pacientes con asma grave tratados con biológicos  anti interleucina 5. La ratio de posesión de la medicación detecta una mayor  proporción de no adherencia en comparación con el cuestionario Test de  Adherencia a los Inhaladores.

El neumomediastino como complicación de la neumonía por SARS-CoV-2 / Pneumomediastinum as a complication of SARS-CoV-2 pneumonia

La incidencia de neumomediastino en los pacientes hospitalizados con diagnóstico de neumonía por coronavirus 2 delsíndrome respiratorio agudo grave (SARS-CoV-2) no es para nada desdeñable, muy superior en comparación con la pobla-ción general. La fisiopatología del neumomediastino en la neumonía por SARS-CoV-2 viene explicada por el aumento delgradiente de presión alveolo-intersticio (accesos de tos seca, trabajo respiratorio, barotrauma por soporte ventilatorio) sobreunos pulmones especialmente «frágiles» debido al daño alveolo-intersticial difuso de origen infeccioso-inflamatorio, todo locual aumenta significativamente el riesgo de rotura de la pared alveolar. Cuanta mayor gravedad revista la neumonía porSARS-CoV-2, más probable será la aparición de neumomediastino. El desarrollo de neumomediastino en pacientes conneumonía por SARS-CoV-2 se asocia a unas frecuencias mayores de exitus letalis, ingreso en unidad de cuidados intensi-vos (UCI) y traqueostomía y a unos tiempos mayores de estancia hospitalaria y en UCI. En la mayoría de los casos, elneumomediastino producido en el seno de la neumonía por SARS-CoV-2 es un proceso benigno y autolimitado que seresuelve con tratamiento conservador.(AU)

The incidence of pneumomediastinum in hospitalised patients diagnosed with SARS-CoV-2 pneumonia is by no means ne-gligible, much higher compared to the general population. The pathophysiology of pneumomediastinum in severe acute res-piratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia is explained by the increase in alveolar-interstitial pressure gradient(dry coughing spells, respiratory work, barotrauma from ventilatory support) in the context of particularly “fragile” lungs due todiffuse alveolar-interstitial damage from infectious-inflammatory origin, all of which significantly increases the risk of alveolarwall rupture. The more severe the SARS-CoV-2 pneumonia, the more likely it is that pneumomediastinum will occur. The deve-lopment of pneumomediastinum in patients with SARS-CoV-2 pneumonia is associated with higher frequencies of death,intensive care unit (ICU) admission and tracheostomy and longer hospital and ICU lengths of stay. In most cases, pneumo-mediastinum in SARS-CoV-2 pneumonia is a benign and self-limiting process that resolves with conservative treatment.(AU)

Successful Long-Term Treatment Combining Omalizumab and Anti-IL-5 Biologics in Allergic Bronchopulmonary Aspergillosis

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Adherencia a los inhaladores en pacientes con asmagrave tratados con biológicos anti interleucina 5 / Adherence to inhalers in patients with severe asthma treated with anti-interleukin-5 biologics

Objetivo: Dado que la mala adherencia a la medicación en el asma gravees difícil de evaluar en la práctica diaria, se recomienda utilizar al menos dosmétodos simultáneamente. El objetivo es determinar la prevalencia de la faltade adherencia a los inhaladores mediante el cuestionario Test de Adherenciaa los Inhaladores y la ratio de posesión de la medicación obtenida a partirde los datos de dispensación de la farmacia en pacientes con asma gravetratados con biológicos anti interleucina 5 y evaluar su concordancia.Método: Estudio observacional retrospectivo transversal de 53 pacientescon asma grave reclutados en la unidad de asma grave de un hospital terciario de Madrid de junio a diciembre de 2020. Se registraron datos demográficos, comorbilidades y el tratamiento concomitante para el asma. La faltade adherencia se definió como una ratio de posesión de la medicación< 80% y/o un valor en los resultados del cuestionario Test de Adherencia alos Inhaladores < 50. La concordancia se evaluó con el coeficiente kappade Cohen.Resultados: La mediana de edad fue de 61 años (rango intercuartílico51,8-67,0), y 33 (61%) eran mujeres. Según la ratio de posesión de lamedicación, la falta de adherencia al inhalador primario fue del 58,5%.Sin embargo, al utilizar el cuestionario Test de Adherencia a los Inhaladores, ésta fue del 22,6%. Combinando ambos métodos, se consideróque el 17% de los pacientes presentaban no adherencia a los inhaladores. Asimismo, al identificar la no adherencia por cualquiera de estos métodos, se alcanzó una prevalencia del 64,2%. El cuestionario Test deAdherencia a los Inhaladores y la ratio de posesión de la medicacióncoincidieron en el 53,1% y discreparon en el 46,9% de los pacientes(k = 0,137; intervalo de confianza del 95% –0,057 a 0,331; p = 0,318).Conclusiones: Se observó una alta prevalencia de no adherencia a losinhaladores en los pacientes con asma grave tratados con biológicos antiinterleucina 5. (AU)

Objective: Given poor medication adherence in severe asthma is difficult to evaluate in daily practice, using at least two methods concurrently isrecommended. We aimed to determine the prevalence of nonadherenceto inhalers using the Test of Adherence to Inhalers questionnaire and themedication possession ratio obtained from the pharmacy refill data inpatients with severe asthma treated with anti-interleukin-5 biologics and toevaluate their concordance.Method: This was a cross-sectional retrospective observational study of53 patients with severe asthma recruited from the severe asthma unit of atertiary hospital in Madrid from June to December 2020. We registereddemographic data, comorbidities and concomitant therapy for asthma.Nonadherence was defined as pharmacy refill data < 80% and/or Testof Adherence to Inhalers questionnaire results < 50. Concordance wasassessed by determining the Cohen’s kappa statistic.Results: The median age was 61 years (interquartile range 51.8-67.0),and 33 (61%) were women. According to the pharmacy refill data lackof adherence to the primary inhaler was 58.5%. However, when usingthe Test of Adherence to Inhalers questionnaire, it was 22.6%. Combiningboth methods, 17% of patients were considered to have nonadherenceto inhalers. Likewise, when identifying nonadherence by either of thesemethods, it reached a prevalence of 64.2%. The pharmacy refill data andTest of Adherence to Inhalers questionnaire agreed in 53.1% and disagreed in 46.9% of patients (k = 0.137; 95% confidence interval −0.057to 0.331; p = 0.318). (AU)