Uncontrolled Eosinophilic Asthma Research Articles

Geographic and economic influences on benralizumab prescribing for severe asthma in Japan

Benralizumab, a monoclonal antibody targeting IL-5 receptors, reduces exacerbations and oral corticosteroid requirements for severe, uncontrolled eosinophilic asthma. In Japan, geographic disparities in asthma outcomes suggest differential prescribing and access. This study aimed to quantify regional prescribing variations for benralizumab nationwide. Using Japan’s National Database (NDB) of insurance claims (2009–2019), benralizumab standardized claim ratios (SCRs) were calculated for 47 prefectures. Correlations between SCRs and other biologics’ SCRs, economic variables like average income, and physician densities were evaluated through univariate analysis and multivariate regressions. Income-related barriers to optimal prescribing were examined. Wide variation emerged in benralizumab SCRs, from 40.1 to 184.2 across prefectures. SCRs strongly correlated with omalizumab (r = 0.61, p < 0.00001) and mepolizumab (r = 0.43, p = 0.0024). Average monthly income also positively correlated with benralizumab SCRs (r = 0.45, p = 0.0016), whereas lifestyle factors were insignificant. Respiratory specialist density modestly correlated with SCRs (r = 0.29, p = 0.047). In multivariate regressions, average income remained the most robust predictor (B = 0.74, p = 0.022). Benralizumab SCRs strongly associate with income metrics more than healthcare infrastructure/population factors. Many regions show low SCRs, constituting apparent prescribing gaps. Access barriers for advanced asthma therapies remain inequitable among Japan’s income strata. Addressing affordability alongside specialist allocation can achieve better prescribing quality and asthma outcomes.

Clinical Remission in Patients Affected by Severe Eosinophilic Asthma on Dupilumab Therapy: A Long-Term Real-Life Study.

Background. Nowadays, highly selective biological drugs offer the possibility of treating severe type 2 asthma. However, in the real-life setting, it is crucial to confirm the validity of the chosen biological treatment by evaluating the achievement of clinical remission. Study purpose. The main aims of this real-life study were to evaluate the efficacy of dupilumab in terms of clinical, functional, and inflammatory outcomes at 6, 12, 18, and 24 months of treatment and to estimate the percentage of patients achieving partial or complete clinical remission at 12 and 24 months of treatment. In addition, we attempted to identify whether baseline clinical characteristics of patients could be associated with clinical remission at 24 months of treatment. Materials and methods. In this observational prospective study, 20 outpatients with severe uncontrolled eosinophilic asthma were prescribed dupilumab and followed-up after 6, 12, 18, and 24 months of treatment. At each patient visit, the need for oral corticosteroids (OCS) and corticosteroid required dose, number of exacerbations during the previous year or from the previous visit, asthma control test (ACT) score, pre-bronchodilator forced expiratory volume in the 1st second (FEV1), fractional exhaled nitric oxide at a flow rate of 50 mL/s (FeNO50), and blood eosinophil count were assessed. Results. The number of OCS-dependent patients was reduced from 10 (50%) at baseline to 5 (25%) at one year (T12) and 2 years (T24). The average dose of OCS required by patients demonstrated a significant reduction at T12 (12.5 ± 13.75 mg vs. 2.63 ± 3.94 mg, p = 0.015), remaining significant even at T24 (12.5 ± 13.75 mg vs. 2.63 ± 3.94 mg, p = 0.016). The number of exacerbators showed a statistically significant decrease at T24 (10 patients, 50% vs. 3 patients, 15%, p = 0.03). The mean number of exacerbations demonstrated a statistically significant reduction at T24 (1.45 ± 1.58 vs. 0.25 ± 0.43, p = 0.02). The ACT score improved in a statistically significant manner at T12 (15.30 ± 4.16 vs. 21.40 ± 2.35, p < 0.0001), improving further at T24 (15.30 ± 4.16 vs. 22.10 ± 2.59, p < 0.0001). The improvement in pre-bronchodilator FEV1 values reached statistical significance at T24 (79.5 ± 14.4 vs. 87.7 ± 13.8, p = 0.03). The reduction in flow at the level of the small airways (FEF25-75%) also demonstrated an improvement, although it did not reach statistical significance either at T12 or T24. A total of 11 patients (55%) showed clinical remission at T12 (6 complete + 5 partial) and 12 patients (60%) reached clinical remission at T24 (9 complete + 3 partial). Only obesity was associated with a negative odds ratio (OR) for achieving clinical remission at T24 (OR: 0.03, 95% CI: 0.002-0.41, p = 0.004). No other statistically significant differences in baseline characteristics emerged between patients who reached clinical remission at T24 and the group of patients who did not achieve this outcome. Conclusion. Dupilumab appears to be an effective drug in promoting achievement of clinical remission in patients with severe uncontrolled eosinophilic asthma. The achievement of clinical remission should be continuously evaluated during treatment. Further studies are needed to clarify whether certain baseline clinical characteristics can help predict dupilumab favorable outcomes.

EE101 Assessing the Cost-Effectiveness of Introducing Benralizumab in the Treatment of Severe Uncontrolled Eosinophilic Asthma Patients in Prince Sultan Military Medical City (PSMMC) - Kingdom of Saudi Arabia (KSA)

EE101 Assessing the Cost-Effectiveness of Introducing Benralizumab in the Treatment of Severe Uncontrolled Eosinophilic Asthma Patients in Prince Sultan Military Medical City (PSMMC) - Kingdom of Saudi Arabia (KSA)

A real-life cohort of mepolizumab treatment in severe eosinophilic asthma.

Background. Mepolizumab, a monoclonal antibody that interacts with IL-5, was the first anti-IL-5 approved for uncontrolled severe eosinophilic asthma. In several randomised, placebo-controlled trials, treatment with mepolizumab has shown a significant improvement in asthma symptoms and the need to use of oral corticosteroids (OCS). Several studies have correlated blood levels of eosinophil cationic protein (ECP) with the degree of eosinophilic inflammation, which could make it an indirect marker of eosinophilic activity. Methods. This was a single-centre retrospective study that included all patients diagnosed with severe eosinophilic asthma under treatment with mepolizumab. We recorded the number of exacerbations, daily prednisone intake, asthma control test scores and forced expiratory volume in the first second. Results. We followed 22 patients, 14 of whom were OCS-dependent with a mean daily dose of 15.85 ± 15.62 mg prednisone. After 12 months, only five continued taking OCS and the mean daily dose was reduced by up to 2.50 ± 3.84 mg (p less than 0.007). The exacerbation rate at baseline was 2.91 ± 2.27 and decreased to 0.82 ± 1.14 in the following year (p less than 0.001). ACT scores increased significantly from 16.00 ± 5.85 to 20.71 ± 4.45 after six months (p = 0.003). We also observed a decrease in ECP from 81.46 ± 43.99 µg/L to 19.12 ± 18.80 µg/L (p > 0.001). Conclusions. These real-life results are consistent with previous clinical trials demonstrating the efficacy and safety of mepolizumab in routine clinical practice for severe uncontrolled eosinophilic asthma. We observed a significant decrease in blood eosinophil counts and in ECP levels, suggesting a reduction in eosinophil activity following mepolizumab treatment.

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.

A Case Study Showing Benralizumab’s Effectiveness in Treating Uncontrolled Severe Eosinophilic Asthma that is Resistant to Omalizumab

Asthma is a diverse illness that can range in severity. Because it has a significant impact on patients' quality of life and because people with severe asthma have symptoms, exacerbations, and drug side effects. Although first disregarded, eosinophils have since been directly linked to characteristics of the continuous inflammatory process in asthma, especially in the severe form. We present of the case of a 50year old female patient who presented with complaints of cough, breathing difficult on exertion and history of fever, chest pain and tiredness. The chest x ray showed left lower zone haziness. Patient was successfully treated with IV antibiotics, IV Proton pump inhibitor, Nebulised bronchodilators, IV Steroids, Anti-Hypertensive therapy and all other supportive medications along with pulmonary rehabilitations. In view of uncontrolled Eosinophilic asthma patient was treated with monoclonal antibody. Patient improved symptomatically better. This case study describes how benralizumab treatment for a patient with uncontrolled severe eosinophilic asthma resulted in significant improvements in lung function, asthma control, steroid use, and quality of life. Keywords: Benralizumab, Severe eosinophilic asthma, Omalizumab, Monoclonal antibodies

Eosinophil depletion with benralizumab is associated with attenuated mannitol airway hyperresponsiveness in severe uncontrolled eosinophilic asthma

Airway hyperresponsiveness (AHR) and eosinophilia are hallmarks of persistent asthma. We investigated whether eosinophil depletion with benralizumab might attenuate indirect mannitol AHR in severe uncontrolled asthma using a pragmatic open-label design. After a 4-week run-in period with provision of usual inhaled corticosteroids and/or long-acting β-agonist (baseline), adults with mannitol-responsive uncontrolled severe eosinophilic asthma received 3 doses of open-label benralizumab 30 mg every 4 weeks, followed by 16 weeks' washout after the last dose. The primary outcome was doubling difference (DD) in provocative dose of mannitol required to decrease FEV1 by 10% (PD10) at the end point after 12 weeks, powered at 90% with 18 patients required to detect 1 DD. Secondary outcomes included measures assessed by the asthma control questionnaire and mini-asthma quality of life questionnaire. Twenty-one patients completed 12 weeks' benralizumab therapy at the end point at week 12. Mean (SEM) age was 53 (4) years, and FEV1 80.2% (4.1%) inhaled corticosteroid dose was 1895 (59) μg, with 12 receiving long-acting muscarinic antagonist and 13 leukotriene receptor antagonists. Improvement in AHR was significant by 8 weeks, with a mean 2.1 DD (95% confidence interval 1.0, 3.3; P< .01) change in PD10 at week 12, while mean changes in asthma control questionnaire and mini-asthma quality of life questionnaire were significant by week 2 and sustained over 12 weeks, both exceeding the minimal important difference. Peripheral blood eosinophils were depleted by 2 weeks (439 to 6 cells/μL). No significant improvement occurred in lung function after 12 weeks. Domiciliary peak flow and symptoms also improved with benralizumab. Eosinophil depletion results in clinically meaningful attenuated AHR in severe uncontrolled asthma patients.

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.

POSB21 Monoclonal Antibodies in the Treatment of Persistent, Uncontrolled Eosinophilic Asthma: Systematic Review, Meta-Analysis and Indirect Comparison

Eosinophilic asthma is a phenotype of severe asthma, characterized by elevated blood eosinophils. Monoclonal antibody therapies targeting interleukin (IL)-4/IL-13 and IL-5 cytokine pathways, seem to reduce asthma exacerbations, improve lung function and asthma symptoms.

Integrated Safety and Efficacy Among Patients Receiving Benralizumab for Up to 5 Years

Benralizumab is an IL-5Rα-directed monoclonal antibody indicated for patients with severe, uncontrolled eosinophilic asthma. To evaluate the long-term safety and tolerability of benralizumab among adults treated for up to 5 years. This analysis included adults treated with placebo or subcutaneous benralizumab 30 mg every 4 or 8 weeks in the 48-week SIROCCO, 56-week CALIMA, and 28-week ZONDA pivotal trials, who were subsequently enrolled in the 56-week double-blind BORA extension and continued assigned regimens or initiated benralizumab (if previously on placebo) for 16 to 40 weeks, before entering the open-label MELTEMIextension. Safety was measured by adverse and serious adverse event rates. Exacerbations were evaluated in patients with blood eosinophils greater than or equal to 300cells/μL receiving high-dose inhaled corticosteroids atbaseline. Overall, 446 received treatment and 384 (86.1%) completed the study; 157 (35.2%) received benralizumab for 4 or more years. Adverse and serious adverse event rates (28.5-32.4 and 6.3-8.4 per 100 patient-years, respectively) were low, stable over time, and did not increase with exposure; few (n= 8) discontinued because of adverse events. Serious infections and hypersensitivity event rates were consistent with those in previous studies. Among patients with blood eosinophils greater than or equal to 300 cells/μL-high-dosage inhaled corticosteroids receiving benralizumab every 8 weeks, at least 75% had zero exacerbations annually during the integrated analysis period. In patients with severe, uncontrolled eosinophilic asthma, long-term benralizumab was safe and well tolerated for up to 5 years. There were no new safety signals, and exacerbations were eliminated in similar percentages of patients as in predecessor studies.

Efficacy of mepolizumab in usual clinical practice and characteristics of responders

BackgroundSevere eosinophilic asthma is a high-burden disease. Mepolizumab has been effective in several randomized clinical trials. However, such success might not be applicable to patients treated in usual clinical practice. The objectives of this article are to evaluate the efficacy of mepolizumab in severe uncontrolled eosinophilic asthma under usual clinical practice, and to determine characteristics associated with the response to this treatment. MethodsWe have conducted a retrospective, multicentre study, including all adult patients with severe uncontrolled eosinophilic asthma in Galicia, Spain, on whom mepolizumab treatment was started before June 2020, at least 6 months before the time of inclusion, and had received at least one dose of the drug. Patient characteristics, clinical data, respiratory function and comorbidities were collected at baseline and at the 6-month-follow-up. Responders and super-responders were defined according to clinical response and requirement of systemic corticosteroids. Results122 patients (mean age 58 years old) were included. In the follow-up treatment 6 months later, 75.4% of the patients were well-controlled, displaying a significant reduction in blood eosinophil counts (p < 0.001), hospital admissions and disease exacerbations (p < 0.001), and had their systemic glucocorticosteroid dose significantly reduced (p < 0.001). The inhaled corticosteroid dose was also lowered (p < 0.01) after 6 months of treatment. Around two-thirds had a clinically significant increase in FEV1, 95% of the patients were considered responders and 43% super-responders. ConclusionIn routine clinical practice, mepolizumab is effective in patients with severe eosinophilic asthma and it has a good safety profile.

Results in clinical practice in the treatment of severe eosinophilic asthma with mepolizumab: a real-life study

Objective Add-on therapy with monoclonal antibodies is the recommended therapy for severe asthmatic patients refractory to maintenance treatment. In randomized control trials, mepolizumab reduced the number of exacerbations, the need of oral corticosteroids (OCS), increased asthma control, and lung function in a population of uncontrolled severe eosinophilic asthmatic patients. In this piece of work, we aimed to assess mepolizumab efficacy and safety in a cohort of patients with severe eosinophilic asthma in real-life conditions. Methods A retrospective study was carried out at eight hospitals from Asturias (Spain). The sample included patients treated with mepolizumab from 1 January 2016 to 31 March 2019. Demographic and clinical variables were collected, including OCS use, asthma control, lung function, and exacerbation rate. Results Sixty-nine patients (72% women) with mean age 56 ± 13 years were included. Annual exacerbation rate decreased from 4.7 (SD 3.7) to 1.3 (SD 2.5) (p < 0.001). The number of patients requiring OCS treatment decreased from 25 patients (36%, mean prednisone dose = 18 mg/day) to 13 patients (19%, mean prednisone dose = 9 mg/day) (p < 0.001). Twelve patients (48%) stopped OCS treatment. Forced expired volume in one second (FEV1) as percentage increased from 68% (SD 20) to 76% (SD 21) (p < 0.001). Fifty-six patients (81%) were considered responders to mepolizumab. No serious adverse events were detected during the study period. Conclusions Overall, this study demonstrates mepolizumab efficacy and safety in a cohort of patients with uncontrolled severe eosinophilic asthma in routine clinical practice.

Clinical and economic consequences of switching from omalizumab to mepolizumab in uncontrolled severe eosinophilic asthma

Severe asthma is burdened by frequent exacerbations and use of oral corticosteroids (OCS), which worsen patients’ health and increase healthcare spending. The aim of this study was to assess the clinical and economic impact of switching from omalizumab (OMA) to mepolizumab (MEP) in patients eligible for both biologics, but not optimally controlled by omalizumab. We retrospectively enrolled uncontrolled severe asthmatic patients who switched from OMA to MEP during the last two years. Information included blood eosinophil count, asthma control test (ACT), spirometry, serum IgE, fractional exhaled nitric oxide (FeNO), OCS intake, drugs, exacerbations/hospitalizations, visits and diagnostic exams. Within the perspective of Italian National Health System, a pre- and post-MEP 12-month standardized total cost per patient was calculated. 33 patients were enrolled: five males, mean age 57 years, disease onset 24 years. At OMA discontinuation, 88% were OCS-dependent with annual mean rate of 4.0 clinically significant exacerbations, 0.30 exacerbations needing emergency room visits or hospitalization; absenteeism due to disease was 10.4 days per patient. Switch to MEP improved all clinical outcomes, reducing total exacerbation rate (RR = 0.06, 95% CI 0.03–0.14), OCS-dependent patients (OR = 0.02, 95% CI 0.005–0.08), and number of lost working days (Δ = − 7.9, 95% CI − 11.2 to − 4.6). Pulmonary function improved, serum IgE, FeNO and eosinophils decreased. Mean annual costs were €12,239 for OMA and €12,639 for MEP (Δ = €400, 95% CI − 1588–2389); the increment due to drug therapy (+ €1,581) was almost offset by savings regarding all other cost items (− €1,181). Patients with severe eosinophilic asthma, not controlled by OMA, experienced comprehensive benefits by switching to MEP with only slight increases in economic costs.

Rapid effect of benralizumab in exacerbation of severe eosinophilic asthma associated with eosinophilic granulomatosis with polyangiitis

BackgroundEosinophilic granulomatosis with polyangiitis (EGPA) is a disease that is associated with severe uncontrolled eosinophilic asthma. Eosinophils play an important pathogenic role in the development of both diseases. Benralizumab is an antieosinophilic monoclonal antibody that binds to the α subunit of the human interleukin 5 receptor that is expressed on the surface of the eosinophil and basophil. We present the first case of rapid improvement in symptoms and lung function during admission for exacerbation of a severe eosinophilic asthma associated with EGPA.Case presentationA 57-year-old man diagnosed with severe eosinophilic asthma associated to EGPA was admitted to the Pulmonology Department due to severe bronchospasm. At admission he presented 2300 eosinophils/µl. Despite intensive bronchodilator treatment, intravenous methylprednisolone at a dose of 80 mg/d, oxygen therapy, and budesonide nebulization, the patient continued to present daily episodes of bronchospasm. Ten days after admission, with blood eosinophil levels of 1700 cells/µl, benralizumab 30 mg sc was administered. That day, the Forced Expiratory Volume in the first second (FEV1) was 28% of the theoretical value (1150 ml). AT three days, FEV1 increased to 110 ml (31%). On the 9th day FEV1 was 51% (2100 ml). The blood eosinophil level on the 9th day was 0 cells/µl.ConclusionsThe rapid improvement of FEV1 is in line with studies based on clinical trials that found improvement after two days in peak flow and one phase II study that showed rapid response in exacerbation of asthma in the emergency room. The antieosinophilic effect at 24 h and the effect in different tissues determine the rapid improvement and the potential advantage of benralizumab in the treatment of EGPA. This case suggests the usefulness of benralizumab in patients with EGPA and eosinophilic severe asthma who show bronchospasm refractory to conventional treatment during a hospitalization due to asthma exacerbation.

Targeted therapy in eosinophilic chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a common and preventable airway disease causing significant worldwide mortality and morbidity. Lifetime exposure to tobacco smoking and environmental particles are the two major risk factors. Over recent decades, COPD has become a growing public health problem with an increase in incidence. COPD is defined by airflow limitation due to airway inflammation and small airway remodelling coupled to parenchymal lung destruction. Most patients exhibit neutrophil-predominant airway inflammation combined with an increase in macrophages and CD8+ T-cells. Asthma is a heterogeneous chronic inflammatory airway disease. The most studied subtype is type 2 (T2) high eosinophilic asthma, for which there are an increasing number of biologic agents developed. However, both asthma and COPD are complex and share common pathophysiological mechanisms. They are known as overlapping syndromes as approximately 40% of patients with COPD present an eosinophilic airway inflammation. Several studies suggest a putative role of eosinophilia in lung function decline and COPD exacerbation. Recently, pharmacological agents targeting eosinophilic traits in uncontrolled eosinophilic asthma, especially monoclonal antibodies directed against interleukins (IL-5, IL-4, IL-13) or their receptors, have shown promising results. This review examines data on the rationale for such biological agents and assesses efficacy in T2-endotype COPD patients.

Assessing the cost-effectiveness of mepolizumab as add-on therapy to standard of care for severe eosinophilic asthma in Singapore

Objective To evaluate the cost-effectiveness of mepolizumab added to standard of care (SOC) compared with SOC alone among patients with severe uncontrolled eosinophilic asthma in the Singapore setting. Methods A Markov model with three health states (asthma on mepolizumab and SOC, asthma on SOC alone, and death) was developed from a healthcare system perspective over a lifetime horizon. During each 4-week cycle, patients in the non-death health states could experience asthma exacerbations requiring oral corticosteroid burst, emergency department visit, or hospitalization. Asthma-related mortality following an exacerbation or all-cause mortality could also occur at each cycle. The model was populated using local costs while utilities were derived from international literature. Transition probabilities were obtained from a mixture of Singapore-specific and internationally published data. Results The base-case analysis comparing mepolizumab plus SOC with SOC alone resulted in an incremental cost-effectiveness ratio (ICER) of SGD335 486 (USD238 195) per quality-adjusted life-year (QALY) gained. Sensitivity analysis demonstrated that the ICER was most sensitive to the price of mepolizumab, followed by the proportion of exacerbations which required hospital intensive care. Despite restricting mepolizumab use to patients with a higher baseline exacerbation rate (3 in the past year) in a scenario analysis, the ICER remained high at SGD238 876 (USD 169 602) per QALY gained. Conclusion At its current price, mepolizumab is not considered a cost-effective use of healthcare resources in Singapore. Substantial price reductions for mepolizumab are required to improve its cost-effectiveness to an acceptable range. These results will be useful to inform national funding decisions.

Severe asthma: adding new evidence – Latin American Thoracic Society

This document constitutes a summary of the clinical practice guidelines (CPGs) prepared at the initiative of the Latin American Thoracic Society (ALAT). Due to new evidence in the treatment of severe asthma, it was agreed to select six clinical questions, and the corresponding recommendations are provided herein. After considering the quality of the evidence, the balance between desirable and undesirable impacts and the feasibility and acceptance of procedures, the following recommendations were established. 1) We do not recommend the use of an inhaled corticosteroid (ICS) plus formoterol as rescue medication in the treatment of severe asthma. 2) We suggest performing many more high-quality randomised studies to evaluate the efficacy and safety of tiotropium in patients with severe asthma. 3) Omalizumab is recommended in patients with severe uncontrolled allergic asthma with serum IgE levels above 30 IU. 4) Anti-interleukin (IL)-5 drugs are recommended in patients with severe uncontrolled eosinophilic asthma (cut-off values above 150 cells·µL−1 for mepolizumab and above 400 cells·µL−1 for reslizumab). 5) Benralizumab is recommended in adult patients with severe uncontrolled eosinophilic asthma (cut-off values above 300 cells·µL−1). 6) Dupilumab is recommended in adult patients with severe uncontrolled allergic and eosinophilic asthma and in adult patients with severe corticosteroid-dependent asthma.

Benralizumabo veiksmingumas ir saugumas gydant sunkią nekontroliuojamą astmą

Astma sergantiems pacientams dažnai nustatoma eozinofilija, kuri susijusi su ligos sunkumu, pablogėjusia plaučių funkcija ir padidėjusiu paūmėjimų dažniu. Benralizumabas – taimonokloninis antikūnas, kuris jungiasi prie eozinofilų paviršiujeesančių interleukino-5 (IL-5) receptorių ir sukelia tiesioginį, greitą ir beveik visišką eozinofilų išeikvojimą. Benralizumabas patvirtintas sunkia eozinofiline astma sergantiems pacientams, kuriems, skiriant gydymą didelėmis įkvepiamųjų gliukokortikoidų dozėmis ir ilgo veikimo β2 agonistais, liga yra nekontroliuojama. Šioje apžvalgoje apibendrinami benralizumabo veiksmingumo ir saugumo duomenys iš SIROCCO, CALIMA, BORA, ZONDA ir ALIZE klinikinių tyrimų. Vertinant jų rezultatus, benralizumabas žymiai sumažino astmos paūmėjimų dažnį ir geriamųjų gliukokortikoidų dozę, pagerino plaučių funkciją ir ligos simptomų kontrolę. Benralizumabas yra veiksmingas ir gerai toleruojamas vaistas. Dažniausiai pasireiškianti nepageidaujama reakcija, susijusi su benralizumabo vartojimu, yra virusinė viršutinių kvėpavimo takų infekcija.

Mepolizumabo veiksmingumo vertinimas gydant sunkią nekontroliuojamą eozinofilinę astmą pagal pradinį eozinofilų kiekį kraujyje: Kauno klinikų Sunkios astmos centro patirtis

Mepolizumabas – pridėtinis biologinis vaistas sunkiai nekontroliuojamai eozinofilinei astmai gydyti. Atsitiktinių imčių tyrimai įrodė šio vaisto veiksmingumą, tačiau klinikinės praktikos tyrimų metu išlieka neatsakytų klausimų apie sunkios astmos (SA) natūralią eigą, predikcinius atsako į gydymą veiksnius. Tyrimo tikslas. Įvertinti pridėtinio astmos gydymo mepolizumabu veiksmingumą, priklausomai nuo pradinio eozinofilų kiekio kraujyje, gydant sunkia nekontroliuojama eozinofiline astma sergančius pacientus (Lietuvos sveikatos mokslų universiteto Kauno klinikų (toliau – Kauno klinikos) SA centro patirtis). Tyrimo metodika. Atlikta retrospektyvioji 34 pacientų, sergančių sunkia nekontroliuojama eozinofiline astma ir gydytų mepolizumabu, duomenų analizė. Tiriamieji buvo suskirstyti į dvi grupes pagal pradinį eozinofilų kiekį kraujyje: 9 pacientai, kurių pradinis eozinofilų kiekis kraujyje – ≤0,30×109/l, ir 25 pacientai, kurių kraujo eozinofilų kiekis – &gt;0,30×109/l). Gydymo mepolizumabu veiksmingumas vertintas pagal metinį ligos paūmėjimų skaičių, geriamųjų gliukokortikoidų (GKK) vartojimą, astmos kontrolės testo (AKT) balų ir plaučių funkcijos rodiklių kitimą po 4 ir 12 mėnesių nuo gydymo pradžios. Rezultatai. AKT balų skaičius po 4 mėn. gydymo mepolizumabu reikšmingai padidėjo abiejose grupėse (≤0,30×109/l eozinofilų skaičiaus grupėje 11,1±3,8 vs 15,3±4,5, p=0,016, esant kraujo eozinofilams &gt;0,30×109/l – 11,8±4,5 vs 18,4±5,3, p=0,001). Po 12 mėn. (palyginus su pradiniais duomenimis) taip pat reikšmingai padidėjo AKT balų skaičius (grupėje ≤0,30×109/l 11,1±3,8 vs 17,1±4,6, p=0,007, grupėje &gt;0,30×109/l – 11,8±4,5 vs 19,5±3,1, p=0,001). GKK dozė reikšmingai sumažėjo po 4 mėn. (16,0±10,2 vs 5,5±9,3 mg/d, p=0,045) ir po 12 mėn. (16,0±10,2 vs 0,5±1,6 mg/d, p=0,007) toje grupėje, kai pradinis eozinofilų kiekis kraujyje buvo &gt;0,30×109/l. FEV 1reikšmingas padidėjimas stebėtas tik po 12 mėn. gydymo mepolizumabu (1,86±1,00 vs 2,31±1,00 l, p=0,017)toje grupėje, kai pradinis eozinofilų kiekis kraujyje buvo &gt;0,30×109/l. Metinis ligos paūmėjimų dažnis reikšmingai sumažėjo abiejose grupėse (grupėje ≤0,30×109/l – 3,2±0,8 vs 0,6±1,0, p=0,011, grupėje &gt; 0,30 x 109/l – 3,8±2,7 vs 0,6±1,4, p=0,001). Išvados. Kauno klinikų SA centro patirtis parodė, kad 12 mėn. gydant sunkią nekontroliuojamą eozinofilinę astmą mepolizumabu, reikšmingai pagerėja plaučių funkcija, sumažėja GKK dozė, kai pradinis eozinofilų kiekis kraujyje yra didesnis nei 0,3×109/l.

Ciężka, niekontrolowana astma alergiczna eozynofilowa – w poszukiwaniu najlepszej opcji terapeutycznej

ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA Kupryś-Lipinska I, Kuna P. Severe uncontrolled allergic eosinophilic asthma – looking for the best therapeutic option. Alergologia Polska - Polish Journal of Allergology. 2020;7(4):180-189. doi:10.5114/pja.2020.101997. APA Kupryś-Lipinska, I., & Kuna, P. (2020). Severe uncontrolled allergic eosinophilic asthma – looking for the best therapeutic option. Alergologia Polska - Polish Journal of Allergology, 7(4), 180-189. https://doi.org/10.5114/pja.2020.101997 Chicago Kupryś-Lipinska, Izabela, and Piotr Kuna. 2020. "Severe uncontrolled allergic eosinophilic asthma – looking for the best therapeutic option". Alergologia Polska - Polish Journal of Allergology 7 (4): 180-189. doi:10.5114/pja.2020.101997. Harvard Kupryś-Lipinska, I., and Kuna, P. (2020). Severe uncontrolled allergic eosinophilic asthma – looking for the best therapeutic option. Alergologia Polska - Polish Journal of Allergology, 7(4), pp.180-189. https://doi.org/10.5114/pja.2020.101997 MLA Kupryś-Lipinska, Izabela et al. "Severe uncontrolled allergic eosinophilic asthma – looking for the best therapeutic option." Alergologia Polska - Polish Journal of Allergology, vol. 7, no. 4, 2020, pp. 180-189. doi:10.5114/pja.2020.101997. Vancouver Kupryś-Lipinska I, Kuna P. Severe uncontrolled allergic eosinophilic asthma – looking for the best therapeutic option. Alergologia Polska - Polish Journal of Allergology. 2020;7(4):180-189. doi:10.5114/pja.2020.101997.