Patient and clinician preferences for biologic treatments for severe uncontrolled asthma: a discrete choice experiment (DCE).

OBJECTIVES: To estimate the preferences of patients with asthma and asthma-treating clinicians for attributes of biologic treatments, to compare patients' and clinicians' preferences, and to better understand the reasons for their preferences. METHODS: Adults with moderate-to-severe asthma and clinicians who treat asthma in the US completed a cross-sectional, online survey including a discrete choice experiment (DCE) that consisted of seven attributes spanning treatment efficacy, risk and convenience. Marginal utilities were estimated using a mixed logit model, and relative attribute importance scores calculated. Clinicians were also asked about the value of biomarker agnostic biologic treatments. The survey was followed by qualitative interviews targeting a sub-sample of survey participants, in which the rationale behind their survey responses was discussed. RESULTS: In the DCE, both patients and clinicians placed the most importance on exacerbation and hospitalization rate reduction, and risk of injection site reaction. Patients valued location of administration more than clinicians. Rationale for individual-level preferences varied, with patients and clinicians reporting their preference depended on event frequency and anticipated quality of life impacts. Clinicians mentioned compliance and financial impacts, while patients mentioned personal experience, particularly around site reactions. Most patients and clinicians would value a biomarker agnostic asthma treatment. CONCLUSIONS: Asthma treatment preferences are largely driven by treatment efficacy and minimizing the risk of site reactions, although preferences differ between patients and clinicians across other attributes, highlighting the need for shared decision-making and individualized care.

Early response to Tezepelumab in type-2 severe asthma patients non-responders to other biological treatments: a real-life study.

BACKGROUND: Biologic therapies play a crucial role in the treatment of severe asthma. Tezepelumab, a human monoclonal antibody (mAb), inhibits thymic stromal lymphopoietin, a pivotal factor in the pathophysiology of asthma. Although randomized clinical trials have demonstrated the efficacy of Tezepelumab, evidence gaps remain in real-world scenarios. OBJECTIVE: We sought investigate Tezepelumab's response in a clinical setting, focusing on patients who previously failed to other asthma mAbs. METHODS: Real-life study with severe uncontrolled asthma patients despite mAb treatment, requiring a switch to Tezepelumab. Follow-up was done four to six months after initiation of Tezepelumab. The primary endpoint was to evaluate the response in patients with poor response or intolerance to other mAbs. RESULTS: Nine patients were followed up during 7 months. Patients were predominantly middle-aged females with eosinophilic or eosinophilic-allergic phenotypes. Patients had a median failure rate of 2 mAbs (IQR 2-3), with an uncontrolled asthma (median of 2 severe exacerbations the previous year, airflow obstruction and 78% corticosteroid dependence). Tezepelumab demonstrated after 4 to 6 months of treatment reduce corticosteroid dependence (complete withdrawal in 2/7 patients), no exacerbations in 6/9, symptoms control improvement (Asthma Control Test score improved in 5/9) and modulate lung function (improving in 3/9 patients). These findings align with clinical trial results, suggesting Tezepelumab's potential in real-world settings. CONCLUSION: In real-world scenarios, despite the study's limitations, our results underscore Tezepelumab's promise as a therapeutic option for uncontrolled severe asthma, and may be useful for non-responders to other mAbs. Further studies are needed to corroborate these findings.

Influence of Genetics on the Response to Omalizumab in Patients with Severe Uncontrolled Asthma with an Allergic Phenotype.

Omalizumab is a monoclonal antibody indicated for the treatment of severe uncontrolled asthma with an allergic phenotype. Its effectiveness could be influenced by clinical variables and single nucleotide polymorphisms (SNPs) in one or more of the genes involved in the mechanism of action and process of response to omalizumab, and these could be used as predictive biomarkers of response. We conducted an observational retrospective cohort study that included patients with severe uncontrolled allergic asthma treated with omalizumab in a tertiary hospital. Satisfactory response after 12 months of treatment was defined as (1) Reduction ≥ 50% of exacerbations or no exacerbations, (2) Improvement of lung function ≥ 10% FEV1, and (3) Reduction ≥ 50% of OCS courses or no OCS. Polymorphisms in the FCER1A (rs2251746, rs2427837), FCER1B (rs1441586, rs573790, rs1054485, rs569108), C3 (rs2230199), FCGR2A (rs1801274), FCGR2B (rs3219018, rs1050501), FCGR3A (rs10127939, rs396991), IL1RL1 (rs1420101, rs17026974, rs1921622), and GATA2 (rs4857855) genes were analyzed by real-time polymerase chain reaction (PCR) using TaqMan probes. A total of 110 patients under treatment with omalizumab were recruited. After 12 months of treatment, the variables associated with a reduction in exacerbations were the absence of polyposis (odds ratio [OR] = 4.22; 95% confidence interval [CI] = 0.95-19.63), IL1RL1 rs17026974-AG (OR = 19.07; 95% CI = 1.27-547), and IL1RL1 rs17026974-GG (OR = 16.76; 95% CI = 1.22-438.76). Reduction in oral corticosteroids (OCS) was associated with age of starting omalizumab treatment (OR = 0.95; 95% CI = 0.91-0.99) and blood eosinophil levels > 300 cells/µL (OR = 2.93; 95% CI = 1.01-9.29). Improved lung function showed a relationship to the absence of chronic obstructive pulmonary disease (COPD) (OR = 12.16; 95% CI = 2.45-79.49), FCGR2B rs3219018-C (OR = 8.6; 95% CI = 1.12-117.15), GATA2 rs4857855-T (OR = 15.98; 95% CI = 1.52-519.57) and FCGR2A rs1801274-G (OR = 13.75; 95% CI = 2.14-142.68; AG vs. AA and OR = 7.46; 95% CI = 0.94-89.12; GG vs. AA). Meeting one response criterion was related to FCER1A rs2251746-TT (OR = 24; 95% CI = 0.77-804.57), meeting two to age of asthma diagnosis (OR = 0.93; 95% CI = 0.88-0.99), and meeting all three to body mass index (BMI) < 25 (OR = 14.23; 95% CI = 3.31-100.77) and C3 rs2230199-C (OR = 3; 95% CI = 1.01-9.92). The results of this study show the possible influence of the polymorphisms studied on the response to omalizumab and the clinical benefit that could be obtained by defining predictive biomarkers of treatment response.

Impact of Anti-IL5 Therapies on Patients with Severe Uncontrolled Asthma and Possible Predictive Biomarkers of Response: A Real-Life Study.

Severe Uncontrolled Asthma (SUA) counts for more than 25% of cases of severe asthma. The main factors that impair the quality of life of these patients are high doses of oral corticosteroids, the presence of exacerbations, and reduced lung function. The objective of this study was to evaluate, in real life, the clinical improvement of patients with SUA treated with anti-interleukin 5 (IL5) therapies: mepolizumab and benralizumab, together with the search for biomarkers associated with the response. We conducted a retrospective observational cohort study that included patients with severe uncontrolled eosinophilic asthma in a tertiary hospital receiving biological therapies. Three types of response were evaluated: improvement in lung function, reduction in exacerbations, and decrease in the use of oral corticosteroids. After 12 months of treatment, significant reductions were found in the number of exacerbations, the use of oral corticosteroids, and blood eosinophil levels for both biological therapies (p < 0.001). Lung function improved, achieving a significant improvement in %FEV1 (p < 0.001), as well as asthma control, with a significant increase in asthma control test (ACT) scores in both therapies. The markers associated with the corticosteroid-saving effect were the low doses of oral corticosteroids and absence of exacerbations for mepolizumab, and higher blood eosinophilia, absence of chronic obstructive pulmonary disease (COPD), and reduction in oral corticosteroid cycles for benralizumab. The greatest improvement in lung function in both therapies was linked to lower previous FEV1 levels and absence of other respiratory diseases. The reduction in exacerbations was associated with absence of exacerbations the previous year for mepolizumab and never smokers for benralizumab. The results of this real-life study confirm the clinical benefit obtained after the introduction of an anti-IL5 biological therapy and the possible predictive biomarkers of response to treatment.

Destruction of the bronchial epithelium in patients with severe asthma according to different patterns of inflammation and cold airway hyperresponsiveness.

AIM: The aim of the research was to study the state of the bronchial mucosa epi-thelium in relation to the severity of clinical manifestations in severe uncon-trolled asthma depending on the pattern of inflammation and the presence of cold airway hyperresponsiveness. MATERIALS AND METHODS: In 48 patients with severe uncontrolled asthma, there were assessed asthma symptoms, clinical signs of cold airway hyperre-sponsiveness, and lung function; the samples of slides were analyzed in the cytological examination of the sputum; the degree of damage to epithelial cells and granulocytes was estimated using the total cell destruction index (CDI). RESULTS: According to the analysis of sputum cytograms, the patients were divided into two groups: group I (22 patients) included persons with eosin-ophilic inflammation pattern (31.0±3.1% of eosinophils and 22.0±2.2% of neutrophils), group II (26 patients) was with mixed inflammation pattern (7.2±1.4 and 71.8±4.2%, respectively). The patients of group II had lower disease control according to Asthma Control Test (ACT; 12.1±0.7 and 17.8±0.2 points, respectively; р<0.05), a greater frequency of exacerbations (4.1±0.3 and 3.2±0.2 per year, respectively; р<0.05), greater incidence of clinical signs of cold airway hyperresponsiveness (79 and 19%, respectively; χ2=14.18; р<0.001); lower lung function (midexpiratory flow rate MEF25-75 was 14.6±1.6 and 20.7±1.9%, respectively; р<0.05); they received a higher dose of the combined medications of inhaled glucocorticosteroid in controller anti-inflammatory therapy (salmeterol/fluticasone at a dose of 705.3±19.7 and 650.7±14.8 µg/day for fluticasone propionate; р<0.05) In patients of group II the correlations of epithelial CDI with neutrophil CDI (r=0.61; p<0.01) and eosinophil CDI (r=0.48; p<0.05), as well as correlation of ACT with neutrophil CDI (r=-0.71; p<0.01) and eosinophil CDI (r=-0.53; p<0.05) were found. CONCLUSION: The degree of destruction of the epithelium and granulocytes in the inflammatory patterns has diagnostic relevance for the assessment of the severity of the disease, clinical manifestations of the airway response to the cold trigger, and the inertia of achieving control in patients with severe un-controlled asthma.

Healthcare resource use and costs of severe, uncontrolled eosinophilic asthma in the UK general population.

BACKGROUND: Little is known about the prevalence of severe, uncontrolled eosinophilic asthma (SUEA) and associated costs. AIMS: We sought to determine the prevalence of SUEA and compare asthma-related healthcare resource use (HCRU) and associated costs with overall means for a general asthma population. METHODS: This cohort study evaluated anonymised medical record data (December 1989 through June 2015) from the Clinical Practice Research Datalink and the Optimum Patient Care Research Database to study UK patients with active asthma (diagnostic code and one or more drug prescriptions in the baseline year), aged 5 years and older, without concomitant COPD, and with recorded eosinophil count. SUEA was defined as two or more asthma attacks during 1 baseline year preceding a high blood eosinophil count (≥0.3×109/L) for patients prescribed long-acting ß2-agonist (LABA) and high-dosage inhaled corticosteroids (ICS) during baseline plus 1 follow-up year. We compared asthma-related HCRU and associated direct costs (2015 pounds sterling, £) during the follow-up year for SUEA versus the general asthma population. RESULTS: Of 363 558 patients with active asthma and recorded eosinophil count, 64% were women, mean (SD) age was 49 (21) years; 43% had high eosinophil counts, 7% had two or more attacks in the baseline year and 10% were prescribed high-dosage ICS/LABA for 2 study years. Overall, 2940 (0.81%; 95% CI 0.78% to 0.84%) patients had SUEA. Total mean per-patient HCRU and associated costs were four times greater for SUEA versus all patients (HCRU and cost ratios 3.9; 95% CI 3.7 to 4.1). CONCLUSIONS: Less than 1% of patients in a general asthma population had SUEA. These patients accounted for substantially greater asthma-related HCRU and costs than average patients with asthma.

RItA: The Italian severe/uncontrolled asthma registry.

BACKGROUND: The Italian severe/uncontrolled asthma (SUA) web-based registry encompasses demographic, clinical, functional, and inflammatory data; it aims to raise SUA awareness, identifying specific phenotypes and promoting optimal care. METHODS: Four hundred and ninety three adult patients from 27 Italian centers (recruited in 2011-2014) were analyzed. RESULTS: Mean age was 53.8 years. SUA patients were more frequently female (60.6%), with allergic asthma (83.1%). About 30% showed late onset of asthma diagnosis/symptoms (>40 years); the mean age for asthma symptoms onset was 30.2 years and for asthma diagnosis 34.4 years. 97.1% used ICS (dose 2000 BDP), 93.6% LABA in association with ICS, 53.3% LTRAs, 64.1% anti-IgE, 10.7% theophylline, and 16.0% oral corticosteroids. Mean FEV1 % pred of 75.1%, median values of 300/mm3 of blood eosinophil count, 323 kU/L of serum total IgE, and 24 ppb of FENO were shown. Most common comorbidities were allergic rhinitis (62.4%), gastroesophageal reflux (42.1%), sinusitis (37.9%), nasal polyposis (30.2%), and allergic conjunctivitis (30.2%). 55.7% of SUA patients had exacerbations in the last 12 months, 9.7% emergency department visits, and 7.3% hospitalizations. Factors associated with exacerbation risk were obesity (OR, 95% CI 2.46, 1.11-5.41), psychic disorders (2.87, 0.89-9.30-borderline), nasal polyps (1.86, 0.88-3.89-borderline), partial/poor asthma treatment adherence (2.54, 0.97-6.67-borderline), and anti-IgE use in a protective way (0.26, 0.12-0.53). Comparisons to severe asthma multicenter studies and available registries showed data consistency across European and American populations. CONCLUSIONS: An international effort in the implementation of SUA patients' registries could help to better understand the clinical features and to manage severe asthma, representing a non-negligible socioeconomic burden for health services.

The frequency of asthma exacerbations and healthcare utilization in patients with asthma from the UK and USA.

BACKGROUND: Asthma exacerbations are frequent in patients with severe disease. This report describes results from two retrospective cohort studies describing exacerbation frequency and risk, emergency department (ED)/hospital re-admissions, and asthma-related costs by asthma severity in the US and UK. METHODS: Patients with asthma in the US-based Clinformatics™ DataMart Multiplan IMPACT (2010-2011; WEUSKOP7048) and the UK-based Clinical Practice Research Datalink (2009-2011; WEUSKOP7092) databases were categorized by disease severity (Global Initiative for Asthma [GINA]; Step and exacerbation history) during the 12 months pre-asthma medical code (index date). Outcomes included: frequency of exacerbations (asthma-related ED visit, hospitalization, or oral corticosteroid use with an asthma medical code recorded within ±2 weeks) 12 months post-index, asthma-related ED visits/hospitalization, and asthma-related costs 30 days post-index. Risk of a subsequent exacerbation was determined by proportional hazard model. RESULTS: Of the 222,817 and 211,807 patients with asthma included from the US and UK databases, respectively, 12.5 and 8.4% experienced ≥1 exacerbation during the follow-up period. Exacerbation frequency increased with disease severity. Among the 5,167 and 2,904 patients with an asthma-related ED visit/hospitalization in the US and UK databases, respectively, 9.2 and 4.7% had asthma-related re-admissions within 30 days. Asthma-related re-admission rates and costs increased with disease severity, approximately doubling between GINA Step 1 and 5 and in patients with ≥2 versus <2 exacerbations in the previous year. Risk of a subsequent exacerbation increased 32-35% for an exacerbation requiring ED visit/hospitalization versus oral corticosteroids. CONCLUSION: Increased disease severity was associated with higher exacerbation frequency, ED/hospitalization re-admission, costs and risk of subsequent exacerbation, indicating that these patients require high-intensity post-exacerbation management.

Healthcare Resource Utilisation of Severe Uncontrolled T2low and Non-T2low Asthma in Finland During 2018-2021.

Purpose: Patients with asthma and low levels of type 2 inflammatory biomarkers (T2 low) have limited effective treatment options. Such biomarkers include eg blood eosinophils (b-eos) and fractional exhaled nitric oxide (FeNO). The healthcare resource utilisation (HCRU) of severe uncontrolled T2 low asthma remains unexplored. Thus, this study aimed to estimate the HCRU of T2 low and non-T2 low severe uncontrolled asthma patients using real-world data in Finland. Patients and Methods: Adult patients with an asthma diagnosis during baseline (2012-2017) at the pulmonary department of Turku University Hospital were included and followed during 2018-2021, or until death. Total HCRU costs and respiratory-related HCRU costs were evaluated. The main drivers for the HCRU and costs were assessed with gamma and negative binomial regression models. Results: Of the severe uncontrolled asthma patients with T2 status available, 40% (N=66) were identified with T2 low and 60% (N=103) with non-T2 low asthma. The average cumulative cost per patient was similar in patients with T2 low compared with non-T2 low, with all-cause costs cumulating in four years of follow-up to 37,524€ (95% CI: 27,160, 47,888) in T2 low compared to 34,712€ (25,484, 43,940) in non-T2 low. The corresponding average cumulative respiratory-related costs were 5178€ (3150, 7205) in T2 low compared to 5209€ (4104, 6313) in non-T2 low. Regression modelling identified no differences between the T2-status groups when assessing all-cause healthcare costs per patient-year (PPY). On the other hand, the regression modelling predicted more inpatient days PPY for severe uncontrolled patients with T2 low status compared to the patients with non-T2 low status. Conclusion: Patients with uncontrolled severe T2 low asthma use equal healthcare resources as corresponding non-T2 low patients. This study brought new insights into the HCRU of severe uncontrolled asthma patients per T2 status, which has not previously been investigated.

Analysis of Patients Admitted for Asthma Exacerbation in a Tertiary Hospital in Spain.

OBJECTIVES: To analyze the characteristics of adult patients admitted for asthma exacerbation and determine optimization, treatment adherence, and follow-up in clinics. METHODS: Patients ≥ 18 years old admitted from May 2021 to June 2023 with a primary diagnosis of asthma exacerbation were included. Patients with a secondary diagnosis of asthma exacerbation and those without a confirmed diagnosis were excluded. RESULTS: A total of 186 patients were analyzed, 63% were female, with a mean age of 49 ± 34 years, mean body mass index (BMI) of 26.4 ± 5 kg/m2, mean immunoglobulin E level of 132 ± 235 IU/mL (range: 25-2041), mean eosinophils count of 180 ± 443, and length of stay of 8.6 ± 5 days. Comparing patients with one admission to those with multiple admissions, differences were observed in age (39 ± 15 vs. 58 ± 20, p < 0.0001), BMI (25.2 ± 3 vs. 27.4 ± 4, p < 0.0003), comorbidity (15% vs. 60%, p < 0.0001), and length of stay (4.5 ± 2 vs. 11 ± 3, p < 0.0001). Of the patients, 15% had undiagnosed asthma, 28% had known asthma without maintenance therapy, 23% were managed by primary care, and 34% were followed by pneumology. The mean Test of Adherence to Inhalers (TAI) score was 42.5 ± 8 points, with 70% showing erratic non-adherence, 46% showing deliberate non-adherence, and 21% showing unconscious non-adherence. CONCLUSIONS: The young population represents a significant percentage of admissions for asthma exacerbation due to poor follow-up in pulmonology clinics, inadequate treatment optimization, and low adherence. This study adds that it is necessary to improve the approach to asthma in primary care to optimize treatment, reduce under-diagnosis, and avoid hospital admissions.

Comparison of Long-term Response and Remission to Omalizumab and Anti-IL-5/IL-5R Using Different Criteria in a Real-life Cohort of Severe Asthma Patients.

BACKGROUND: Evaluation of biologic therapy response is vital to monitor its effectiveness. Authors have proposed various response criteria including good responder, super-responder, non-responder, and clinical remission. OBJECTIVES: To ascertain the prevalence of response and clinical remission after long-term treatment (>6 months) of anti-IgE and anti-IL-5/IL-5Rα biologics, compare these results with existing criteria, and identify predictors for non-responders and clinical remission. METHODS: A multicenter, real-life study involving severe asthma patients in Spain. Various outcomes were assessed to gauge response and clinical remission against established criteria. RESULTS: The study included 429 patients, 209 (48.7%) omalizumab, 112 (26.1%) mepolizumab, 19 (4.4%) reslizumab and 89 (20.7%) benralizumab, with a mean treatment duration of 55.3±38.8 months. In the final year of treatment, 218 (50.8%) were super-responders, 173 (40.3%) responders, 38 (8.9%) non-responders, and clinical remission in 116 (27%), without differences among biologics. The short-term non-responders (<6 months) were 25/545 (4.6%). Substantial variations in response and clinical remission were observed when applying different published criteria. Predictors of non-response included higher BMI (OR:1.14; 95% CI:1.06-1.23; p<0.001), admissions at ICU (2.69; 1.30-5.56; p=0.01), high count of SAE (1.21; 1.03-1.42; p=0.02) before biologic treatment. High FEV1% (0.96; 0.95-0.98; p<0.001), a high ACT score (0.93; 0.88-0.99; p=0.01) before biologic treatment or NSAID-ERD (0.52; 0.29-0.91; p=0.02) showed strong associations with achieving clinical remission. CONCLUSION: A substantial proportion of severe asthma patients treated long-term with omalizumab or anti-IL5/IL-5Rα achieved a good response. Differences in response criteria highlight the need for harmonization in defining response and clinical remission in biologic therapy to enable meaningful cross-study comparisons.

Clinical and Economic Burden of Severe Asthma With Low Blood Eosinophil Counts.

BACKGROUND: Type 2 low-severe asthma phenotype is often a result of corticosteroid-overtreated type 2 disease owing to persistent symptoms, often unrelated to asthma and unlikely to respond to high-dose corticosteroid treatment. OBJECTIVE: This study aimed to characterize patients with severe asthma with low eosinophil counts (<300 cells/µL) and describe their disease burden and treatment across health care settings in the United Kingdom. METHODS: A retrospective cohort study of patients with severe asthma using linked Clinical Practice Research Datalink (CPRD) Aurum-Hospital Episode Statistics (HES) and UK Severe Asthma Registry (UKSAR) data indexed patients according to the latest blood eosinophil count (BEC). Clinical characteristics, treatment patterns, outcomes, and health care resource use were described by baseline BEC (≤150 and >150 to <300 cells/µL). RESULTS: Analysis included 701 (CPRD-HES) and 1,546 (UKSAR) patients; 60.5% and 59.4% had BECs 150 cells/µL or less at baseline, respectively. Across BEC groups, the proportion with uncontrolled asthma (two or more exacerbations) at follow-up (12 months after the index) was 5.4% in CPRD-HES and 45.2% in UKSAR. Maintenance oral corticosteroid use remained high across BEC groups (CPRD-HES: 29.4%; UKSAR: 51.7%), symptom control remained poor (>200 µg short-acting ß2 agonist or >500 µg terbutaline/d in CPRD-HES: 48.8%; median Asthma Control Questionnaire-6 score in UKSAR: 2.0 [range, 1.0-3.3]). Health care resource use was similar across BEC groups. CONCLUSIONS: Most patients managed in primary care experienced infrequent exacerbations, whereas UKSAR patients had frequent exacerbations. Large proportions of both patient groups had poor symptom control and continued to receive high levels of maintenance oral corticosteroids, increasing the risk of corticosteroid-induced morbidity. These data highlight the need for rigorous assessment of underlying disease pathology to guide appropriate treatment.

Real-World Safety and Effectiveness of Benralizumab in Japanese Patients with Severe Asthma: A Multicenter Prospective Observational Study.

Introduction: This study aimed to demonstrate whether benralizumab maintained the safety and effectiveness profiles established in randomized controlled trials among all patients with severe uncontrolled asthma initially prescribed benralizumab in the real-world setting in Japan. Methods: This was a prospective, observational, multicenter post-marketing study (ClinicalTrial.gov, NCT03588546). The safety and tolerability of benralizumab over 1 year were assessed by the incidence of adverse events (AEs), serious AEs, adverse drug reactions (ADRs), and serious ADRs. Patient background characteristics indicating a more frequent onset of ADRs with benralizumab were explored. The main effectiveness assessment was the change in Asthma Control Questionnaire-5 (ACQ-5) score from baseline. Patients with baseline ACQ-5 scores ≥1.5 were defined as having severe uncontrolled asthma. Results: In total, 632 patients were evaluated for safety and 274 for effectiveness; 139 patients were included in the severe uncontrolled asthma subgroup. ADRs were reported in 12.7% and serious AEs in 13.0% of patients. Serious infections occurred in 3.8%, serious hypersensitivity in 0.3%, and malignancy in 0.3% of patients. No helminthic infections occurred. In the effectiveness population, benralizumab improved the mean (standard deviation [95% confidence interval]) ACQ-5 score by -1.16 (1.40 [-1.36, -0.96]) from baseline; forced expiratory volume in 1 second by 0.151 (0.440 [0.09, 0.21]) L; and Mini-Asthma Quality of Life questionnaire score by 1.16 (1.29 [0.94, 1.38]) at the last observation. The annual asthma exacerbation rate was 0.42. A greater ACQ-5 score improvement was observed among patients with eosinophilic asthma characteristics. Conclusion: No new safety concerns were raised, and patients experienced benefits consistent with previous studies of benralizumab, thus supporting the use of benralizumab for the add-on maintenance treatment of patients with eosinophilic severe uncontrolled asthma.

Impact of Omalizumab in Patients with Severe Uncontrolled Asthma and Possible Predictive Biomarkers of Response: A Real-Life Study.

Most patients with asthma can control their symptoms with a basic standard of medical care and with maintenance and rescue medication. However, between 5% and 10% of asthmatics worldwide do not achieve control of their symptoms and have recurrent exacerbations and respiratory difficulties. The objective of the study was the real-life evaluation of the clinical improvement of patients with severe eosinophilic asthma treated with omalizumab, together with the search for biomarkers associated with the response. An observational retrospective cohort study was conducted that included patients with severe uncontrolled allergic asthma being treated with omalizumab. Three types of response were evaluated: lower use of oral corticosteroids, improvement in lung function, and reduction in exacerbations. A total of 110 patients under treatment with omalizumab were included, with a mean age of 48 ± 16 years. After 12 months had elapsed, significant reductions were found in the number of exacerbations, use of oral cortico-steroids and doses of inhaled corticosteroids (p < 0.001). Lung function and asthma control improved significantly (p < 0.001; p = 0.004) and eosinophil levels were significantly reduced (p = 0.004). Low scores in the Asthma Control Test were associated with the oral corticosteroid-saving effect; lower previous FEV1 levels and absence of chronic obstructive pulmonary disease (COPD) were related to improvement in lung function, and prior FEV1 values higher than 80% and absence of gastroesophageal reflux disease (GERD) with a reduction in exacerbations. The results of this study confirm the clinical benefit obtained after the introduction of omalizumab and the possible predictive biomarkers of response to the treatment.

Treatment Patterns of Monoclonal Antibodies in Patients With Severe Uncontrolled Asthma Treated by Pulmonologists in Spain.

Introduction and objectives: The use of monoclonal antibody (mAb)-based therapies is becoming the new standard of care for severe uncontrolled asthma (SUA). Even though patients may qualify for one or more of these targeted treatments, based on different clinical criteria, a global vision of mAb prescription management in a large sample of hospitals is not well characterised in Spain.The objective was to give a global vision of mAb prescription management in a large sample of hospitals in Spain. Materials and methods: We used an aggregate data survey method to interview pulmonology specialists in a large sample of Spanish centres (90). The following treatment-related information was obtained on patients treated with mAbs: specific mAbs prescribed, treatment interruption, switch and restart and the reasons for these treatment changes. Results: mAb prescription was more frequent in females (13.3% females vs 7.4% males; p < 0.001). There were no differences in prevalence by hospital complexity level. In contrast, there were differences by geographical area. Omalizumab was the most prescribed mAb (6.2%), followed by mepolizumab (2.9%). Discontinuation of Omalizumab (due to a lack of effectivity) and switches from this mAb to mepolizumab were more frequent. Very few restarts to the first treatment were observed after a switch from ≥2 mAbs. Conclusions: Omalizumab appeared as the most prescribed mAb in SUA but was also the most withdrawn; a specific and objective characterisation of patients with SUA, along with asthma phenotyping, and together with further evaluation of safety and effectiveness profiles, will lead to future progress in the management of SUA with mAbs.

Introducción y objetivos: El uso de terapias basadas en anticuerpos monoclonales (mAb) se está convirtiendo en el nuevo estándar de atención para el asma grave no controlada (AGNC). A pesar de que los pacientes pueden optar a uno o varios de estos tratamientos dirigidos, con base en diferentes criterios clínicos, en España no se ha caracterizado bien una visión global de la gestión de la prescripción de mAb en una gran muestra de hospitales.El objetivo fue dar una visión global de la gestión de la prescripción de mAB en una amplia muestra de hospitales en España. Materiales y métodos: Se utilizó un método basado en una encuesta de datos agregados para entrevistar a especialistas en Neumología en una amplia muestra de centros españoles (90). Se obtuvo la siguiente información relacionada con el tratamiento de los casos tratados con mAbs: mAbs específicos prescritos, interrupción del tratamiento, cambio y reinicio, y las razones de estos cambios de tratamiento en consultas de Neumología. Resultados: La prescripción de mAB fue más frecuente en mujeres (13,3% mujeres vs. 7,4% hombres; p < 0,001). No hubo diferencias de prevalencia por nivel hospitalario. En cambio, hubo diferencias por área geográfica. Omalizumab fue el mAb más prescrito (6,2%), seguido de mepolizumab (2,9%). La interrupción y los cambios (debido a la falta de efectividad) también fueron más frecuentes para omalizumab. Conclusiones: Omalizumab fue el mAb más prescrito en el manejo de AGNC, pero también fue el mAB que presentó más retiradas; una caracterización específica y objetiva de los pacientes con AGNC, mediante fenotipificación de asma, junto con una evaluación adicional de los perfiles de seguridad y efectividad, conducirá a nuevos avances en el manejo del AGNC con mABs.

Type 2 Low Biomarker Stability and Exacerbations in Severe Uncontrolled Asthma.

We investigated the stability of T2 low status, based on low levels of T2 biomarkers, and exacerbation rates in T2 low and non-T2 low asthma from clinical retrospective data of severe uncontrolled asthma patients. Knowledge of the T2 low biomarker profile is sparse and biomarker stability is uncharted. Secondary care patients with severe uncontrolled asthma and at least two blood eosinophil counts (BEC) and fractional exhaled nitric oxide (FeNO) measured for determination of type 2 inflammation status were evaluated from a follow-up period of 4 years. Patients were stratified into four groups: T2 low150 (n = 31; BEC < 150 cells/µL and FeNO < 25 ppb), non-T2 low150 (n = 138; BEC > 150 cells/µL and/or FeNO > 25 ppb), T2 low300 (n = 66; BEC < 300 cells/µL and FeNO < 25 ppb), and non-T2 low300 (n = 103; BEC > 300 cells/µL and/or FeNO > 25 ppb). Exacerbation rates requiring hospital care, stability of biomarker status, and cumulative OCS and ICS doses were assessed during follow-up. Among patients with severe uncontrolled asthma, 18% (n = 31) were identified as T2 low150, and 39% (n = 66) as T2 low300. In these groups, the low biomarker profile was stable in 55% (n = 11) and 72% (n = 33) of patients with follow-up measures. Exacerbation rates were different between the T2 low and non-T2 low groups: 19.7 [95% CI: 4.3-45.6] in T2 low150 vs. 8.4 [4.7-13.0] in non-T2 low150 per 100 patient-years. BEC and FeNO are useful biomarkers in identifying T2 low severe uncontrolled asthma, showing a stable follow-up biomarker profile in up to 72% of patients. Repeated monitoring of these biomarkers is essential in identifying and treating patients with T2 low asthma.

[Translated article] Advances in the work of multidisciplinary teams for the care of patients with severe uncontrolled asthma. A post-COVID vision (TEAM 2.0 project).

Asthma is a chronic respiratory disease with a high health, social and economic impact, particularly in the case of Severe Uncontrolled Asthma (SUA). For this reason, new strategies are especially necessary to improve its approach, with a personalized approach to each patient and from a multidisciplinary perspective, in addition to integrating the new telemedicine and telepharmacy practices promoted as a result of the COVID-19 pandemic. In this context, the TEAM 2.0 project ("Work in Multidisciplinary Asthma Teams") has been developed, following the TEAM project carried out in 2019, with the aim of updating and prioritizing good multidisciplinary work practices in SUA in a post pandemic context and analyze the progress made. A coordinating group, made up of eight multidisciplinary teams of hospital pharmacists, pulmonologists, and allergists, carried out an updated bibliographic review, sharing of good multidisciplinary practices, and analysis of advances. Through five regional meetings with other experts with experience in SUA, the good practices identified were shared and subjected to debate, evaluation and prioritization. In total, 23 good multidisciplinary work practices in SUA, grouped into five work areas: 1) Organization of work in multidisciplinary teams, 2) Patient education, self-management and adherence, 3) Health results, data monitoring and persistence, 4) Telepharmacy and experiences implemented during the COVID-19 pandemic and 5) Training and research, were evaluated and prioritized by 57 professionals from the field of Hospital Pharmacy, Pulmonology, Allergology and Nursing. This work has made it possible to update the roadmap of priority actions to continue advancing in optimal models of care for patients with AGNC in a post-COVID-19 context.

Spanish multidisciplinary consensus on the characteristics of severe asthma patients on biologic treatment who are candidates for at-home administration.

BACKGROUND AND OBJECTIVE: Biologic therapies are known to reduce exacerbations and improve severe uncontrolled asthma management. The at-home administration of biologics has increased during the COVID-19 pandemic, but the characteristics of severe uncontrolled asthma patients who may benefit from at-home administration of biologic therapy have yet to be identified. MATERIALS AND METHODS: This project is based on the Delphi method, designed to reach an expert consensus through a multidisciplinary scientific committee addressing the following questions: clinical characteristics, treatment adherence, patient or caregiver administration ability, patient self-care, relationship with the healthcare professional, patient preference, and access to the hospital. RESULTS: One hundred and thirty-one healthcare professionals (pulmonologists, allergists, nurses, and hospital pharmacists) completed two Delphi consensus questionnaires. Fourteen items were identified as priority characteristics, the first five being: 1. The patient follows the healthcare team's indications/recommendations to control their disease, 2. The patient is capable of detecting any deterioration in their disease and of identifying exacerbation triggers, 3. The patient receives biologic therapy and has stable disease with no vital risk, 4. The patient takes responsibility for their self-care, 5. The patient has occupational/educational obligations that prevent them from going to the hospital regularly. CONCLUSION: Disease stability and control plus the ability to identify exacerbation triggers are the most important characteristics when opting for at-home administration for a patient with severe uncontrolled asthma on biologic therapy. These recommendations could be applicable in clinical practice.

Advances in the work of multidisciplinary teams for the care of patients with severe uncontrolled asthma. A post-COVID vision (TEAM 2.0 project). / Avances en el trabajo de equipos multidisciplinares para la atención al paciente con asma grave no controlada. Una visión post-COVID (Proyecto TEAM 2.0).

Asthma is a chronic respiratory disease with a high health, social and economic impact, particularly in the case of Severe Uncontrolled Asthma (SUA). For this reason, new strategies are especially necessary to improve its approach, with a personalized approach to each patient and from a multidisciplinary perspective, in addition to integrating the new telemedicine and telepharmacy practices promoted as a result of the COVID-19 pandemic. In this context, the TEAM 2.0 project ("Work in Multidisciplinary Asthma Teams") has been developed, following the TEAM project carried out in 2019, with the aim of updating and prioritizing good multidisciplinary work practices in SUA in a post pandemic context and analyze the progress made. A coordinating group, made up of eight multidisciplinary teams of hospital pharmacists, pulmonologists, and allergists, carried out an updated bibliographic review, sharing of good multidisciplinary practices, and analysis of advances. Through five regional meetings with other experts with experience in SUA, the good practices identified were shared and subjected to debate, evaluation and prioritization. In total, 23 good multidisciplinary work practices in SUA, grouped into five work areas: 1) Organization of work in multidisciplinary teams, 2) Patient education, self-management and adherence, 3) Health results, data monitoring and persistence, 4) Telepharmacy and experiences implemented during the COVID-19 pandemic and 5) Training and research, were evaluated and prioritized by 57 professionals from the field of Hospital Pharmacy, Pulmonology, Allergology and Nursing. This work has made it possible to update the roadmap of priority actions to continue advancing in optimal models of care for patients with AGNC in a post-COVID-19 context.

Effectiveness of Switching to Benralizumab in Severe Refractory Eosinophilic Asthma.

Purpose: Benralizumab is a monoclonal antibody that targets the α subunit of the IL-5 receptor. Clinical trials have demonstrated the efficacy of this agent with respect to lung function and symptom control in patients with refractory eosinophilic asthma. However, few studies have evaluated the efficacy of benralizumab after switching previous treatment with other monoclonal antibodies. Patients and Methods: We performed a multicenter retrospective study under conditions of daily clinical practice. The study population comprised consecutively included patients with severe refractory eosinophilic asthma whose initial treatment with omalizumab or mepolizumab was switched to benralizumab. Patients were evaluated at 4 and 12 months after starting treatment with benralizumab. We analyzed asthma control, number of severe exacerbations, corticosteroid cycles, visits to the emergency department, and hospital admissions, as well as lung function. Similarly, we evaluated the response to treatment according to previously established criteria. Results: We evaluated 40 patients who switched from omalizumab (n=16) or mepolizumab (n=24) to benralizumab. The reasons for switching were lack of response in 30 cases, adverse effects in 9, and patient request in 1. Switching was followed by a significant decrease in the number of exacerbations, visits to the emergency department, and corticosteroid cycles, as well as improved ACT both at 4 and 12 months. However, no significant improvement in lung function was observed. Asthma control (including complete response and control) was achieved in 55% of patients (n=22) at 12 months. Specifically, a complete response was achieved in 30% of patients at 12 months (66.7% switching from omalizumab and 33.3% from mepolizumab). Conclusion: Patients diagnosed with severe refractory eosinophilic asthma who experience a partial response with omalizumab or mepolizumab could benefit from switching to benralizumab. This approach can reduce the number of exacerbations, visits to the emergency department, and corticosteroid cycles and improve control of asthma.