scholarly journals Serum microRNAs as Tool to Predict Early Response to Benralizumab in Severe Eosinophilic Asthma

2021 ◽  
Vol 11 (2) ◽  
pp. 76
Author(s):  
José A. Cañas ◽  
Marcela Valverde-Monge ◽  
José M. Rodrigo-Muñoz ◽  
Beatriz Sastre ◽  
Marta Gil-Martínez ◽  
...  
Keyword(s):  
Target Genes ◽  
Early Response ◽  
Mapk Signaling ◽  
Economic Problem ◽  
Biological Drugs ◽  
Eosinophilic Asthma ◽  
Altered Expression ◽  
Asthmatic Patients ◽  
Severe Eosinophilic Asthma ◽  
Before And After

Severe eosinophilic asthma poses a serious health and economic problem, so new therapy approaches have been developed to control it, including biological drugs such as benralizumab, which is a monoclonal antibody that binds to IL-5 receptor alpha subunit and depletes peripheral blood eosinophils rapidly. Biomarkers that predict the response to this drug are needed so that microRNAs (miRNAs) can be useful tools. This study was performed with fifteen severe eosinophilic asthmatic patients treated with benralizumab, and serum miRNAs were evaluated before and after treatment by semi-quantitative PCR (qPCR). Patients showed a clinical improvement after benralizumab administration. Additionally, deregulation of miR-1246, miR-5100 and miR-338-3p was observed in severe asthmatic patients after eight weeks of therapy, and a correlation was found between miR-1246 and eosinophil counts, including a number of exacerbations per year in these severe asthmatics. In silico pathway analysis revealed that these three miRNAs are regulators of the MAPK signaling pathway, regulating target genes implicated in asthma such as NFKB2, NFATC3, DUSP1, DUSP2, DUSP5 and DUSP16. In this study, we observed an altered expression of miR-1246, miR-5100 and miR-338-3p after eight weeks of benralizumab administration, which could be used as early response markers.

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

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Giovanna Elisiana Carpagnano ◽  
Emanuela Resta ◽  
Massimiliano Povero ◽  
Corrado Pelaia ◽  
Mariella D’Amato ◽  
...  
Keyword(s):  
Disease Onset ◽  
National Health System ◽  
Healthcare Spending ◽  
Blood Eosinophil ◽  
Asthma Control Test ◽  
Eosinophilic Asthma ◽  
Exacerbation Rate ◽  
Serum Ige ◽  
Asthmatic Patients ◽  
Severe Eosinophilic Asthma

AbstractSevere 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.

scholarly journals Adherence to corticosteroids and clinical outcomes in mepolizumab therapy for severe asthma

2020 ◽  
Vol 55 (5) ◽  
pp. 1902259 ◽  
Author(s):  
Gráinne d'Ancona ◽  
Joanne Kavanagh ◽  
Cris Roxas ◽  
Linda Green ◽  
Mariana Fernandes ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Biologic Therapy ◽  
Inhaled Corticosteroids ◽  
Final Analysis ◽  
Good Adherence ◽  
Eosinophilic Asthma ◽  
Exacerbation Rate ◽  
Asthmatic Patients ◽  
Severe Eosinophilic Asthma ◽  
Asthma Patients

IntroductionInhaled corticosteroids (ICS) achieve disease control in the majority of asthmatic patients, although adherence to prescribed ICS is often poor. Patients with severe eosinophilic asthma may require treatment with oral corticosteroids (OCS) and/or biologic agents such as mepolizumab. It is unknown if ICS adherence changes on, or alters clinical response to, biologic therapy.MethodsWe examined ICS adherence and clinical outcomes in OCS-dependent severe eosinophilic asthma patients who completed 1 year of mepolizumab therapy. The ICS medicines possession ratio (MPR) was calculated (the number of doses of ICS issued on prescription/expected number) for the year before and the year after biologic initiation. Good adherence was defined as MPR >0.75, intermediate 0.74–0.51 and poor <0.5. We examined outcomes after 12 months of biologic therapy, including OCS reduction and annualised exacerbation rate (AER), stratified by adherence to ICS on mepolizumab.ResultsOut of 109 patients commencing mepolizumab, 91 who had completed 12 months of treatment were included in the final analysis. While receiving mepolizumab, 68% had good ICS adherence, with 16 (18%) having poor ICS adherence. ICS use within the cohort remained similar before (MPR 0.81±0.32) and during mepolizumab treatment (0.82±0.32; p=0.78). Patients with good adherence had greater reductions in OCS dose (median (interquartile range) OCS reduction 100 (74–100)% versus 60 (27–100)%; p=0.031) and exacerbations (AER change −2.1±3.1 versus 0.3±2.5; p=0.011) than those with poor adherence. Good ICS adherence predicted the likelihood of stopping maintenance OCS (adjusted OR 3.19, 95% CI 1.02–9.94; p=0.045).ConclusionICS nonadherence is common in severe eosinophilic asthma patients receiving mepolizumab, and is associated with a lesser reduction in OCS requirements and AER.

scholarly journals Integrated analyses of early responses to radiation in glioblastoma identify new alterations in RNA processing and candidate target genes to improve treatment outcomes

2019 ◽  
Author(s):  
Saket Choudhary ◽  
Suzanne C. Burns ◽  
Hoda Mirsafian ◽  
Wenzheng Li ◽  
Dat T. Vo ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Target Genes ◽  
Early Response ◽  
Radiation Sensitivity ◽  
Integrated Analysis ◽  
High Dose ◽  
Transcriptional Level ◽  
Altered Expression ◽  
Improve Treatment ◽  
Main Component

AbstractBackgroundHigh-dose radiation is the main component of glioblastoma therapy. Unfortunately, radio-resistance is a common problem and a major contributor to tumor relapse. Understanding the molecular mechanisms driving response to radiation is critical for identifying regulatory routes that could be targeted to improve treatment response.MethodsWe conducted an integrated analysis in the U251 and U343 glioblastoma cell lines to map early alterations in the expression of genes at three levels: transcription, splicing, and translation in response to ionizing radiation.ResultsChanges at the transcriptional level were the most prevalent response. Downregulated genes are strongly associated with cell cycle and DNA replication and linked to a coordinated module of expression. Alterations in this group are likely driven by decreased expression of the transcription factor FOXM1 and members of the E2F family. Genes involved in RNA regulatory mechanisms were affected at the mRNA, splicing, and translation levels, highlighting their importance in radiation-response. We identified a number of oncogenic factors, with an increased expression upon radiation exposure, including BCL6, RRM2B, IDO1, FTH1, APIP, and LRIG2 and lncRNAs NEAT1 and FTX. Several of these targets have been previously implicated in radio-resistance. Therefore, antagonizing their effects post-radiation could increase therapeutic efficacy.ConclusionsOur integrated analysis provides a comprehensive view of early response to radiation in glioblastoma. We identify new biological processes involved in altered expression of various oncogenic factors and suggest new target options to increase radiation sensitivity and prevent relapse.

Late Breaking Abstract - Early response to benralizumab in Canadians with severe eosinophilic asthma

2021 ◽  
Author(s):  
Stephen G Noorduyn ◽  
Brett Lancaster ◽  
Alain Gendron ◽  
Lawrence Mbuagbaw ◽  
Erika Penz
Keyword(s):  
Early Response ◽  
Eosinophilic Asthma ◽  
Severe Eosinophilic Asthma

Comparison of early and late responses to antigen of sensitized guinea pig parenchymal lung strips

2006 ◽  
Vol 100 (5) ◽  
pp. 1610-1616 ◽  
Author(s):  
Tatiana Lanças ◽  
David I. Kasahara ◽  
Carla M. Prado ◽  
Iolanda F. L. C. Tibério ◽  
Milton A. Martins ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Lung Parenchyma ◽  
Early Response ◽  
Control Group ◽  
Late Response ◽  
Asthmatic Patients ◽  
Tissue Resistance ◽  
Before And After ◽  
Response Group ◽  
L1 And L2

The peripheral lung parenchyma has been studied as a component of the asthmatic inflammatory response. During induced constriction, tissue resistance increases in different asthma models. Approximately 60% of the asthmatic patients show early and late responses. The late response is characterized by more severe airway obstruction. In the present study, we evaluated lung parenchymal strips mechanics in ovalbumin-sensitized guinea pigs, trying to reproduce both early and late inflammatory responses. Oscillatory mechanics of lung strips were performed in a control group (C), in an early response group (ER), and in two late response groups: 17 h (L1) and 72 h (L2) after the last ovalbumin challenge. Measurements of resistance and elastance were obtained before and after ovalbumin challenge in C and ER groups and before and after acetylcholine challenge in all groups. Using morphometry, we assessed the density of eosinophils and smooth muscle cells, as well as collagen and elastin content in lung strips. The baseline and postagonist values of resistance and elastance were increased in ER, L1, and L2 groups compared with C ( P ≤ 0.001). The morphometric analysis showed an increase in alveolar eosinophil density in ER and L2 groups compared with C ( P < 0.05). There was a significant correlation between eosinophil density in parenchymal strips of C, L1, and L2 groups and values of resistance and elastance postacetylcholine ( r = 0.71, P = 0.001 and r = 0.74, P < 0.001, respectively). The results show that the lung parenchyma is involved in the late response, and the constriction response in this phase is related to the eosinophilic inflammation.

scholarly journals Anti-Interleukin 5 (IL-5) and IL-5Ra Biological Drugs: Efficacy, Safety, and Future Perspectives in Severe Eosinophilic Asthma

2017 ◽  
Vol 4 ◽  
Author(s):  
Diego Bagnasco ◽  
Matteo Ferrando ◽  
Gilda Varricchi ◽  
Francesca Puggioni ◽  
Giovanni Passalacqua ◽  
...  
Keyword(s):  
Future Perspectives ◽  
Biological Drugs ◽  
Eosinophilic Asthma ◽  
Interleukin 5 ◽  
Severe Eosinophilic Asthma

Determining early response to anti-IL5/IL5R monoclonal antibodies in severe eosinophilic asthma

2020 ◽  
Author(s):  
Joanne Kavanagh ◽  
Cris Roxas ◽  
Linda Green ◽  
Mariana Fernandes ◽  
Louise Thomson ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Early Response ◽  
Eosinophilic Asthma ◽  
Severe Eosinophilic Asthma

Effect of Benralizumab in Patients With Severe Eosinophilic Asthma and Chronic Rhinosinusitis With Nasal Polyps: A Case Series

2020 ◽  
pp. 194589242097835
Author(s):  
Chandala Chitguppi ◽  
Prachi Patel ◽  
Alan Gandler ◽  
Kira Murphy ◽  
Tawfiq Khoury, MD ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Case Series ◽  
Act Scores ◽  
Eosinophilic Asthma ◽  
Severe Eosinophilic Asthma ◽  
Before And After ◽  
The Mean ◽  
Snot 22 ◽  
Sinonasal Symptoms

Objective To analyze the effect of benralizumab in severe eosinophilic asthma (SA) and chronic rhinosinusitis with polyps (CRSwP). Methods Retrospective review of patients with both SA and CRSwP that were treated with benralizumab. Asthma controlled test (ACT), pulmonary function metrics (FEV1), Meltzer endoscopic polyp scores, SNOT-22 scores, were collected before and after at least 4 months of benralizumab therapy. Results 23 patients were included. The mean age at the time of enrollment into benralizumab therapy was 50.47 ± 17.3 years and majority (65.2%, n = 15) were males. Pulmonary Effects: In comparison to baseline ACT, scores at four months showed significant improvement (p = 0.03). In those with pre and post spirometry measurements, mean FEV1 showed significant increase following benralizumab therapy (p = 0.04) with a mean increase of 547 mL ± 597 mL following therapy. Sinonasal Effects: 78.5% of subjects on benralizumab had a significant improvement in sinonasal symptoms (p = 0.009) based on their SNOT-22 scores. Additionally, there was an improvement in endoscopic polyp scores, although not statistically significant, following benralizumab therapy (p = 0.2) with 54.5% patients showing improvement. Conclusion Usage of benralizumab in patients with SA and CRSwNP can lead to significantly improved asthma control, lung function, and sinonasal quality of life. Additionally, in this patient population, there was a subset of patients that showed a significant reduction in polyp burden.

A new delivery device for benralizumab (autoinjector, pen-injector device) in the clinical practice of treating severe eosinophilic asthma: Conclusion of the Expert Council

2021 ◽  
Vol 31 (6) ◽  
pp. 776-781
Author(s):  
Sergey N. Avdeev ◽  
Alexandr V. Emelyanov ◽  
Oksana M. Kurbacheva ◽  
Irina M. Marusenko ◽  
Pavel I. Novikov ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Biological Therapy ◽  
Genetically Engineered ◽  
Delivery Device ◽  
Self Administration ◽  
Biological Drugs ◽  
Eosinophilic Asthma ◽  
Severe Eosinophilic Asthma ◽  
Real Practice

The emergence of new means of administering genetically-engineered biological drugs, such as an autoinjector (pen injector device), can positively affect the organizational aspects of treating patients with severe eosinophilic asthma (SA) who need biological therapy.The aim. To determine the place of a new delivery device for benralizumab (autoinjector, pen injector device) in the clinical practice of treating eosinophilic SA.Results. The expert council considered the results of the latest clinical studies and real practice data on the use of genetically-engineered biological drugs in the form of an autoinjector. The experts discussed the safety and efficacy of this delivery device and recommended considering the possibility of switching eosinophilic SA patients to self-administration of genetically-engineered biological drugs (autoinjector form) at home. This treatment tactic is especially relevant in the current epidemiological situation since it will reduce the risks of infection compared to planned medical care in inpatient or outpatient treatment settings and reduce the burden for healthcare workers.Conclusion. The practice of switching eosinophilic SA patients to self-administration of biologics in the form of an autoinjector (pen injector device) can improve the adherence to biological therapy and quality of life of this group of patients.

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