scholarly journals Saudi Arabian real-life experience with biologic therapy in severe asthma

2021 ◽  
Vol 16 ◽  
Author(s):  
Safwat Eldaboussi ◽  
Ahmed Qabil ◽  
Ahmed Lotfi ◽  
Amgad Awad ◽  
Eman Abdel Salam ◽  
...  

Background: Severe asthma (SA) is a common health problem associated with increased morbidity and mortality and high medical costs. Biological therapies have emerged in recent decades as promising treatment options for patients with high type 2 (T2) SA. This retrospective observational study from Saudi Arabia aimed to investigate the effects of additional biologics therapy on reducing oral corticosteroid (OCS) consumption, frequency of asthma exacerbations, improvement in lung function, and asthma control.Methods: This multicenter observational study enrolled a cohort of 97 patients from Mach 2019 to February 2021. Outcomes of anti-IgE, anti-IL5/IL5R, and anti-IL4R therapies in severe type 2 asthma were recorded and analyzed in terms of number of exacerbations (emergency visits or hospitalizations required), asthma symptoms, and use of oral corticosteroids, blood eosinophil count, asthma control according to GINA classification, and FEV1 before and during biologic therapy.Results:  Ninety-seven patients were included in the analysis The mean age was 46.7±14.1 years, and 69.1% of them were female. The average duration of biological treatment was 16.4±6.8 months. At the time of data collection, the four biologic therapies reduced the exacerbation rate per year from 82/97 (84.5%) to 14/97 (14.4%) with a percent improvement of 83% from 2.9 per year in the year before biologic treatment to 1.6 per year (p<0.001). OCS was reduced from 75/97 (77.3%) to 10/97 (10.3%) for a percent improvement of 86.7%, and the average OCS dose decreased from 7.12 mg to 6.8 mg. Mean blood eosinophil count also decreased after biologic therapy from 750.5±498.5 to 188.0±122.4 cells/μl, most significant result achieved with benralizumab, and mean FEV1 improved from 59.0±12.9% to 76.0±10.2%, most significant result achieved with omalizumab.  ll patients had uncontrolled asthma before biologics therapy, but asthma control improved by 91.8% after treatment.Conclusions: Biologic as add-on therapy for high T2 SA was found to reduce asthma exacerbations, systemic glucocorticoid doses, and SA symptoms.

2017 ◽  
Vol 119 (1) ◽  
pp. 16-20 ◽  
Author(s):  
Enrico Heffler ◽  
Giovanni Terranova ◽  
Carlo Chessari ◽  
Valentina Frazzetto ◽  
Claudia Crimi ◽  
...  

2021 ◽  
pp. 1-12
Author(s):  
Hirofumi Watanabe ◽  
Toshihiro Shirai ◽  
Keita Hirai ◽  
Taisuke Akamatsu ◽  
Hiromasa Nakayasu ◽  
...  

2020 ◽  
Vol 181 (11) ◽  
pp. 862-870
Author(s):  
Yoshihiro Kanemitsu ◽  
Ryota Kurokawa ◽  
Junya Ono ◽  
Kensuke Fukumitsu ◽  
Norihisa Takeda ◽  
...  

<b><i>Background:</i></b> Eosinophilic nasal polyps (NPs) are associated with the presence of asthma in chronic rhinosinusitis (CRS) patients. Serum periostin has been considered a relevant biomarker for unified airway diseases. <b><i>Objective:</i></b> To determine the utility of biomarkers including serum periostin that reflects reduction of exacerbations of comorbid asthma in CRS patients. <b><i>Methods:</i></b> We prospectively recruited 56 CRS patients who were subjected to undergo endoscopic sinus surgery (ESS) (20 with asthma) between October 2015 and December 2017 and followed them for 1 year after ESS. Blood eosinophil count, serum periostin, and fractional nitric oxide (FeNO) were measured at enrollment. How these type 2-driven biomarkers reflect comorbid asthma was determined using receiver operating characteristic (ROC) analysis. The frequency of asthma exacerbations during 1 year was counted both before and after ESS. Associations between preoperative biomarkers including eosinophils in NPs and asthma exacerbations were evaluated. <b><i>Results:</i></b> Blood eosinophil count, FeNO, and serum periostin levels were significantly higher in CRS patients with asthma than in those without (<i>p</i> &#x3c; 0.01 for all) and discriminated comorbid asthma among CRS patients (<i>p</i> &#x3c; 0.05; AUC &#x3e; 0.80 for all). The increased preoperative serum periostin correlated with lower absolute number of postoperative exacerbations (ρ = −0.49, <i>p</i> = 0.03) and its relative reduction after ESS (ρ = 0.53, <i>p</i> = 0.03) in asthmatic patients. Increased eosinophils in NPs were also associated with reduced asthma exacerbations. <b><i>Conclusion:</i></b> Preoperative increased serum periostin and eosinophils in NPs are associated with the preventive effect of ESS for asthma exacerbations in CRS patients comorbid with asthma.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Andrew Menzies-Gow ◽  
Michael E. Wechsler ◽  
Chris E. Brightling

Abstract Despite treatment with standard-of-care medications, including currently available biologic therapies, many patients with severe asthma have uncontrolled disease, which is associated with a high risk of hospitalization and high healthcare costs. Biologic therapies approved for severe asthma have indications limited to patients with either eosinophilic or allergic phenotypes; there are currently no approved biologics for patients with eosinophil-low asthma. Furthermore, existing biologic treatments decrease exacerbation rates by approximately 50% only, which may be because they target individual, downstream elements of the asthma inflammatory response, leaving other components untreated. Targeting an upstream mediator of the inflammatory response may have a broader effect on airway inflammation and provide more effective asthma control. One such potential target is thymic stromal lymphopoietin (TSLP), an epithelial-derived cytokine released in response to multiple triggers associated with asthma exacerbations, such as viruses, allergens, pollutants and other airborne irritants. Mechanistic studies indicate that TSLP drives eosinophilic (including allergic) inflammation, neutrophilic inflammation and structural changes to the airway in asthma through actions on a wide variety of adaptive and innate immune cells and structural cells. Tezepelumab is a first-in-class human monoclonal antibody that blocks the activity of TSLP. In the phase 2b PATHWAY study (NCT02054130), tezepelumab reduced asthma exacerbations by up to 71% compared with placebo in patients with severe, uncontrolled asthma across the spectrum of inflammatory phenotypes, and improved lung function and asthma control. Phase 3 trials of tezepelumab are underway. NAVIGATOR (NCT03347279), a pivotal exacerbation study, aims to assess the potential efficacy of tezepelumab further in patients with a broad range of severe asthma phenotypes, including those with low blood eosinophil counts. SOURCE (NCT03406078) aims to evaluate the oral corticosteroid-sparing potential of tezepelumab. DESTINATION (NCT03706079) is a long-term extension study. In addition, an ongoing phase 2 bronchoscopy study, CASCADE (NCT03688074), aims to evaluate the effect of tezepelumab on airway inflammation and airway remodelling in patients across the spectrum of type 2 airway inflammation. Here, we summarize the unmet therapeutic need in severe asthma and the current treatment landscape, discuss the rationale for targeting TSLP in severe asthma therapy and describe the current development status of tezepelumab.


2020 ◽  
Vol 34 ◽  
pp. 205873842095085 ◽  
Author(s):  
Nicola Lombardo ◽  
Corrado Pelaia ◽  
Marco Ciriolo ◽  
Marcello Della Corte ◽  
Giovanna Piazzetta ◽  
...  

The aim of this study has been to evaluate the efficacy of the IL-5 receptor blocker benralizumab on chronic rhinosinusitis with nasal polyposis (CRSwNP), associated with severe eosinophilic allergic asthma. Ten patients with severe eosinophilic allergic asthma and CRSwNP were enrolled. Sino-nasal outcome test (SNOT-22), numerical rating scale (NRS), endoscopic nasal polyp score, Lund Mackey CT (computed tomography) score, and blood eosinophil count were measured at baseline and after 24 weeks of treatment with benralizumab. All the above clinical, endoscopic, imaging, and hematological parameters significantly improved after 24 weeks of treatment with benralizumab. In particular, SNOT-22 decreased from 61.10 ± 17.20 to 26.30 ± 19.74 ( P < 0.001), NRS decreased from 7.20 ± 1.55 to 3.40 ± 2.22 ( P < 0.001), the endoscopic polyp nasal score decreased from 4.20 ± 1.32 to 2.50 ± 1.78 ( P < 0.001), the Lund-Mackay CT score decreased from 16.60 ± 5.50 to 6.90 ± 5.99 ( P < 0.001), and blood eosinophil count decreased from 807.3 ± 271.1 cells/μL to 0 cells/μL ( P < 0.0001). These results strongly suggest that benralizumab exerted a very effective therapeutic action on CRSwNP associated with severe asthma, thus improving nasal symptoms and decreasing polyp size.


2021 ◽  
Author(s):  
Hyonsoo Joo ◽  
So-Young Park ◽  
So Young Park ◽  
Seo Young Park ◽  
Sang-Heon Kim ◽  
...  

Abstract Background: Asthma and chronic obstructive pulmonary disease (COPD) are airway diseases with similar clinical manifestations, despite differences in pathophysiology. Asthma-COPD overlap (ACO) is a condition characterized by overlapping clinical features of both diseases. There have been few reports regarding the prevalence of ACO in COPD and severe asthma cohorts. ACO is heterogeneous; patients can be classified on the basis of phenotype differences. This study was performed to analyze the prevalence of ACO in COPD and severe asthma cohorts. In addition, this study compared baseline characteristics among ACO patients according to phenotype.Methods: Patients with COPD were prospectively enrolled into the Korean COPD subgroup study (KOCOSS) cohort. Patients with severe asthma were prospectively enrolled into the Korean Severe Asthma Registry (KoSAR). ACO was defined in accordance with the updated Spanish criteria. In the COPD cohort, ACO was defined as bronchodilator response (BDR) ≥ 15% and ≥ 400 mL from baseline or blood eosinophil count ≥ 300 cells/μL. In the severe asthma cohort, ACO was defined as age ≥ 35 years, smoking ≥ 10 pack-years, and post-bronchodilator forced expiratory volume in 1 s/forced vital capacity < 0.7. Patients with ACO were divided into four groups according to smoking history (threshold: 20 pack-years) and blood eosinophil count (threshold: 300 cells/μL).Results: The prevalence of ACO significantly differed between the COPD and severe asthma cohorts (19.8% [365/1839] vs. 12.5% [104/832], respectively, P < 0.001). The numbers of patients in each group were as follows: Group A (smoking 10–20 pack-years and blood eosinophil count ≥ 300 cells/μL), 42 (9.1%); Group B (smoking 10–20 pack-years and eosinophil count < 300 cells/μL), 17 (3.7%); Group C (smoking ≥ 20 pack-years and eosinophil count ≥ 300 cells/μL), 341 (73.8%); and Group D (smoking ≥ 20 pack-years and eosinophil count < 300 cells/μL), 62 (13.4%). Age, sex, BDR, comorbidities, and medications significantly differed among the four groups.Conclusion: The prevalence of ACO differed between COPD and severe asthma cohorts. ACO patients can be classified into four phenotype groups, such that each phenotype exhibits distinct characteristics.


2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
L. Brussino ◽  
E. Heffler ◽  
C. Bucca ◽  
S. Nicola ◽  
G. Rolla

Asthma is a chronic and heterogeneous disease, which is defined as severe disease whenever it requires treatment with a high dose of inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming ‘‘uncontrolled’’ or if it remains ‘‘uncontrolled’’ despite this therapy. Severe asthma is a heterogeneous condition consisting of phenotypes such as eosinophilic asthma, which is characterized by sputum eosinophilia, associated with mild to moderate increase in blood eosinophil count, frequently adult-onset, and associated with chronic rhinosinusitis with nasal polyps in half of the cases. Eosinophilic asthma is driven by T2 inflammation, characterized, among the others, by interleukin-5 production. IL-5 plays a key role in the differentiation, survival, migration, and activation of eosinophils, and it has become an appealing therapeutic target for eosinophilic asthma. In recent years two monoclonal antibodies (mepolizumab and reslizumab) directed against IL-5 and one monoclonal antibody directed against the alpha-subunit of the IL-5 receptor (benralizumab) have been developed. All these IL-5 target drugs have been shown to reduce the number of exacerbation in patients with severe asthma selected on the basis of peripheral blood eosinophil count. There are still a number of unresolved issues related to the anti-IL5 strategy in eosinophilic asthma, which are here reviewed. These issues include the effects of such therapy on airway obstruction and asthmatic symptoms, the level of baseline eosinophils that predicts a response to treatment, the relationship between blood and airway eosinophilia, and, perhaps most importantly, how to elucidate the pathogenetic role played by eosinophils in the individual patient with severe eosinophilic asthma.


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