Free Serum IgE In Patients With Severe Allergic Asthma Treated With Omalizumab

Effects of long-acting bronchodilators in COPD patients according to COPD severity and ICS use

SummaryBackgroundIndacaterol is a once-daily, long-acting β2-agonist bronchodilator that improves dyspnoea and health status in patients with moderate-to-severe COPD. While its bronchodilator effects have been shown to be maintained in different patient subgroups, effects on clinical outcomes in certain subgroups are not yet defined.MethodsPost-hoc analysis of pooled clinical study data to investigate efficacy and safety of indacaterol compared with placebo and other long-acting bronchodilators (formoterol, salmeterol, open-label tiotropium) in patient subgroups defined by COPD severity (GOLD stage II or III; n = 4082) and ICS use at baseline (no/yes; n = 4088). Efficacy outcomes were troug…

Reslizumab Treatment for Moderate to Severe Asthma with Elevated Blood Eosinophil Levels

Monitoring free serum IgE in severe asthma patients treated with omalizumab

SummaryBackgroundBenefit of treatment with the monoclonal anti-IgE-antibody omalizumab in severe IgE-dependent asthma requires a significant reduction of serum free IgE concentrations. It is unclear if monitoring free serum IgE is clinically meaningful once omalizumab treatment is initiated.MethodsFree IgE and omalizumab serum concentrations were quantified in 22 patients with severe asthma (68% female, 47 ± 11 yrs, mean (±SD) pre-bronchodilator FEV1 62 ± 13%, baseline mean (±SEM) free serum IgE 652 ± 136 ng/ml) treated with omalizumab for 4 months using a Recovery-ELISA.ResultsOmalizumab treatment reduced free serum IgE prior to the second omalizumab injection by 73%, after 16 weeks by 81%…

Disease-Modifikation und Dauer einer Omalizumab-Therapie bei Patienten mit schwerem allergischen Asthma

Hintergrund und Methodik: Omalizumab ist ein monoklonaler Anti-IgE-Antikorper zur Behandlung des schweren allergischen Asthma bronchiale. Ziel dieser Arbeit war die Bewertung der vorhandenen Evidenz durch ein Expertengremium und die Formulierung daraus resultierender Empfehlungen zu moglichen krankheitsmodifizierenden Effekten und der Dauer der Behandlung mit Omalizumab. Ergebnisse: Eine direkte oder indirekte Interaktion zwischen Omalizumab und der IgE-Produktion ist wahrscheinlich. Die aufgrund eines pharmakokinetisch-pharmakodynamischen Modells erwarteten IgE-modulierenden Eigenschaften von Omalizumab werden derzeit in der klinischen Anwendung uberpruft. Therapieentscheidungen auf Grundl…

Cytokine Production Profile Of T-lymphocytes In Patients With Allergic Asthma Receiving Anti-IgE Therapy

Once-daily QVA149 improves dyspnoea and health status compared with tiotropium plus formoterol in patients without ICS use: A post-hoc analysis of the QUANTIFY study

Rationale: The QUANTIFY study compared the approved dual bronchodilator QVA149 with the free-dose combination of tiotropium plus formoterol (TIO+FOR) regarding lung function, dyspnoea and health status in patients with moderate-to-severe COPD. This post-hoc analysis reported on the subgroup of pts without ICS background therapy. Methods: This blinded, triple-dummy 26-week study randomised patients to QVA149 110/50 µg OD or TIO 18 µg OD plus FOR 12 µg b.i.d. (1:1). ICS was allowed as background therapy. Endpoints included lung function (trough FEV1), dyspnoea (TDI) and health status (COPD Assessment Test, CAT). Results: Of the 934 pts randomised (QVA149 [N=476] or TIO+FOR [N=458]); 87.9% com…

Prospective evaluation of current asthma control using ACQ and ACT compared with GINA criteria

Background The goal of asthma treatment is to achieve and maintain current best control and reduce future risk of exacerbations and long-term morbidity. Objective To prospectively compare current asthma control as defined by ACQ (asthma control questionnaire) and ACT (asthma control test) criteria with the GINA (Global Initiative for Asthma) classification in treated patients in a real-life setting. Methods In 150 adult patients (48% male, age 46.3 ± 14.4 years., forced expiratory volume in 1 second [FEV 1 ], 2.3 ± 0.9 L or 78.5 ± 21.8% pred.), asthma control was evaluated using the GINA classification as the "true" and ACQ-7, ACQ-5, and ACT as "predictor" criteria. The relationship between…

Effect of QVA149 on lung volumes and exercise tolerance in COPD patients: The BRIGHT study

Summary Introduction QVA149 is a novel, inhaled, once-daily dual bronchodilator containing a fixed-dose combination of the long-acting β 2 -agonist indacaterol and the long-acting muscarinic antagonist glycopyrronium (NVA237), for the treatment of chronic obstructive pulmonary disease (COPD). This study evaluated the effects of QVA149 on exercise tolerance, hyperinflation, lung function and lung volumes versus placebo and tiotropium. Methods Patients with moderate-to-severe COPD were randomized to QVA149 110/50 μg, placebo or tiotropium 18 μg once daily in a blinded, 3-period crossover study for 3 weeks. The primary endpoint was exercise endurance time at Day 21 for QVA149 versus placebo. R…

The German COPD cohort COSYCONET: Aims, methods and descriptive analysis of the study population at baseline

Abstract Background The German COPD cohort study COSYCONET (" CO PD and SY stemic consequences- CO morbidities NET work") investigates the interaction of lung disease, comorbidities and systemic inflammation. Recruitment took place from 2010 to 2013 in 31 study centers. In addition to the baseline visit, follow-up visits are scheduled at 6, 18, 36 and 54 months after baseline. The study also comprises a biobank, image bank, and includes health economic data. Here we describe the study design of COSYCONET and present baseline data of our COPD cohort. Methods Inclusion criteria were broad in order to cover a wide range of patterns of the disease. In each visit, patients undergo a large panel …

Individual and Synergistic Effects of IL-5 and IL-13 on Trans-Compartmental Activation and Migration of Eosinophils and Murine Asthma Features

Prospective, Single-Arm, Longitudinal Study of Biomarkers in Real-World Patients with Severe Asthma.

ARIETTA was a prospective, single-arm, noninterventional, multicenter study in patients with severe asthma.To examine the predictive and prognostic abilities of type 2 biomarkers for severe asthma outcomes.Adult patients with severe asthma receiving daily inhaled corticosteroids (fluticasone propionate ≥500 μg or equivalent) and ≥1 second controller medication were enrolled. Biomarker, clinical, and safety data were collected over 52 weeks. The primary endpoint was the asthma exacerbation rate over 52 weeks in serum periostin-high (≥50 ng/mL at baseline) versus periostin-low subgroups (50 ng/mL). Correlations between biomarker levels (periostin, blood eosinophils, IgE, and fractional exhale…

GARP inhibits allergic airway inflammation in a humanized mouse model

Background Regulatory T cells (Treg) represent a promising target for novel treatment strategies in patients with inflammatory/allergic diseases. A soluble derivate of the Treg surface molecule glycoprotein A repetitions predominant (sGARP) has strong anti-inflammatory and regulatory effects on human cells in vitro as well as in vivo through de novo induction of peripheral Treg. The aim of this study was to investigate the immunomodulatory function of sGARP and its possible role as a new therapeutic option in allergic diseases using a humanized mouse model. Methods To analyze the therapeutic effects of sGARP, adult NOD/Scidγc−/− (NSG) mice received peripheral blood mononuclear cells (PBMC) …

Patients with allergic and eosinophilic asthma in the German severe asthma registry

Targeted treatment strategies for asthma require a precise diagnosis of phenotypes. 308 adult patients (age mean±SD: 50.3±13.5yrs) with severe asthma from the German Severe Asthma Registry (www.german-asthma-net.de) were evaluated based on history of allergy symptoms, results of skin prick tests, total/specific IgE, and blood cell differentials. 121 patients (39%) showed typical signs of allergic asthma including allergic symptoms and a positive skin prick test and/or specific IgE with no elevated blood eosinophils (median total IgE: 222 (range 4-4023) IU/ml, eosinophils: 128 (0-295)/µl, FeNO: 23 (7-300) ppb). 53 (43.8%) of these patients were treated with omalizumab. 50 patients (16%) had …

Effectiveness of omalizumab in patients 50 years and older with severe persistent allergic asthma.

Omalizumab is approved for the treatment of severe allergic asthma.To compare the efficacy of omalizumab therapy in patients 50 years or older with patients younger than 50 years.Between November 2005 and November 2007 a total of 174 asthma patients 50 years or older (40.7% male, 51.1% taking oral corticosteroids, and mean [SD] serum IgE level of 315 [353] U/L) and 297 asthma patients younger than 50 years (40.0% male, 50.5% taking oral corticosteroids, and mean [SD] serum IgE level of 363 [431] U/L) who met the European Union criteria for add-on therapy with anti-IgE were treated prospectively with omalizumab for 4 months as part of 2 postmarketing surveillance trials.Compared with the pre…

Late Breaking Abstract - Efficacy of CSJ117 on allergen-induced asthmatic responses in mild atopic asthma patients

Introduction: CSJ117 is a potent neutralizing antibody fragment against human Thymic stromal lymphopoietin (TSLP), formulated as a PulmoSol™ engineered powder in hard capsules for delivery to the lungs via dry powder inhaler. Methods: In this double-blind, placebo-controlled study, 28 mild, atopic asthmatics meeting elibility criteria were randomized to receive 4mg CSJ117 (n = 15) or placebo (n = 13) inhaled daily for 12 weeks. Allergen inhalation challenge (AIC) was conducted at screening, day 42 and day 84. The primary efficacy variable was the late asthmatic response (LAR), measured 3 to 7 hours after AIC at day 84. Other outcomes included the early asthmatic response (EAR) measured with…

Reduction Of Pulmonary Inflammation Through HIV-1 Envelope Protein GP120 In A Humanized Mouse Model Of Allergic Asthma Depends On Regulatory T Cells

Change in measured Patient-Reported Outcomes in severe eosinophilic asthma patients treated with benralizumab under real life conditions in Germany (imPROve asthma study) – Study Design

Tralokinumab did not demonstrate oral corticosteroid-sparing effects in severe asthma

Long-term oral corticosteroid (OCS) use in patients with severe asthma is associated with significant adverse effects.This 40-week, randomised, double-blind trial evaluated the OCS-sparing potential of tralokinumab in patients with severe, uncontrolled asthma requiring maintenance OCS treatment plus inhaled corticosteroids/long-acting β2-agonists. Overall, 140 patients were randomised to tralokinumab 300 mg or placebo (n=70 in each group) administered subcutaneously every 2 weeks. The primary end-point was percentage change from baseline in average OCS dose at week 40, while maintaining asthma control. Secondary end-points included proportion of patients with a prescribed maintenance OCS do…

Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials

Elevated numbers of blood eosinophils are a risk factor for asthma exacerbations. Reslizumab is a humanised anti-interleukin 5 monoclonal antibody that disrupts eosinophil maturation and promotes programmed cell death. We aimed to assess the efficacy and safety of reslizumab in patients with inadequately controlled, moderate-to-severe asthma.We did two duplicate, multicentre, double-blind, parallel-group, randomised, placebo-controlled phase 3 trials. Both trials enrolled patients with asthma aged 12-75 years (from 128 clinical research centres in study 1 and 104 centres in study 2) from Asia, Australia, North America, South America, South Africa, and Europe, whose asthma was inadequately c…

Effects of Reslizumab on Asthma Outcomes in a Subgroup of Eosinophilic Asthma Patients with Self-Reported Chronic Rhinosinusitis with Nasal Polyps.

Background An estimated 7% of patients with asthma have chronic rhinosinusitis with nasal polyps (CRSwNP), and more than 80% have at least some radiographic evidence of sinonasal inflammation. Aspirin sensitivity is strongly associated with elevated blood eosinophil levels and increased asthma severity. Intravenous (IV) reslizumab has been shown to improve asthma control in patients with nasal polyps. Objective These post hoc analyses of pooled data from 2 BREATH phase 3 clinical trials, studies 1 and 2 (NCT01287039 and NCT01285323), examined asthma-related outcomes in patients with comorbid, self-reported CRSwNP with and without aspirin sensitivity. Methods Patients aged 12-75 years with e…

Reductions in Inflammatory Biomarkers in Patients with Oral Corticosteroid-Dependent Asthma Treated with Tezepelumab

The Severe Asthma Registry – German data

Patients with severe persistent asthma represent the highest unmet medical need among the asthmatic population. To improve the understanding of underlying mechanisms and disease progression the German Asthma Net (GAN, www.german-asthma-net.de) launched a Severe Asthma Registry in December 2011. Enrolled patients undergo detailed clinical and physiologic evaluations, including patients’ medical history, allergy and lung function tests, blood analyses as well as past and concomitant medication and comorbidities. Patients are followed up every year. As of February 2018, 1097 subjects were recruited in Germany, Austria, and Slovenia. The mean age±SEM of the 839 German adult patients is 50.6±0.5…

S2k-Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma

ZusammenfassungDie vorliegende Leitlinie ist eine Neufassung und Aktualisierung der Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma, welche die bisher für den deutschen Sprachraum gültige Version aus dem Jahr 2006 ablöst. Die Fülle an neuen Erkenntnissen zur Pathophysiologie und zu den Phänotypen von Asthma und das erweiterte Spektrum an diagnostischen und therapeutischen Möglichkeiten bei dieser Erkrankung machte eine Neufassung und Aktualisierung notwendig. Es werden sowohl für Kinder und Jugendliche als auch für Erwachsene mit Asthma die aktuellen, Evidenz-basierten diagnostischen und therapeutischen Empfehlungen dargelegt.

Age- and sex-dependent differences in patients with severe asthma included in the German Asthma Net cohort.

Severe asthma affects less than 5% of asthmatics, but is associated with high costs and increased mortality. The aim of this study was to assess age- and sex-dependent differences in this patient group.Retrospective analysis of 1317 children and adults with severe asthma who are included in the German Asthma Net registry.There were more adults than children in the registry and patients' mean age was 52. Apart from children18 years, there were more women (57%) than men. The age of first diagnosis ranged from 0 to 76 years. 38% of patients had a positive bronchial reversibility after short acting bronchodilators. Quality of life, FEV1 and MEF 25 decreased with older age whereas treatment with…

Dupilimab Efficacy in Patients with Uncontrolled, Moderate-to-Severe Asthma by Body Mass Index

Introduction: Obesity is associated with increased asthma severity, poor asthma control, and poor response to inhaled corticosteroids. Dupilumab (DPL), a fully human monoclonal antibody blocks the shared receptor component for interleukin (IL)-4/IL-13, key drivers of type 2 inflammation. In the phase 3 QUEST trial (NCT02414854), add-on DPL 200/300 mg every 2 wks (q2w) vs placebo (PBO) reduced severe exacerbations and improved pre-bronchodilator (BD) FEV1 in patients (pts) with uncontrolled, moderate-to-severe asthma. Aim: To assess the effect of baseline (BL) body mass index (BMI) on DPL efficacy in uncontrolled, moderate-to-severe asthma pts. Methods: Annualized rate of severe exacerbation…

A Non-Interventional Study of Tiotropium/Olodaterol versus Any Triple Combination Therapy for Chronic Obstructive Pulmonary Disease: The EVELUT® Study Protocol

Roland Buhl,1 Michael Dreher,2 Stephanie Korn,1 Christian Taube,3 Christian Stock,4 Christoph M Zehendner,5 Anke Kondla,5 Claus F Vogelmeier6 1Pulmonary Department, Johannes Gutenberg University Mainz, Mainz, Germany; 2Clinic of Cardiology, Pneumology, Angiology and Internal Medicine Intensive Care, University Hospital RWTH Aachen, Aachen, Germany; 3Clinic for Pneumonology, University Medicine Essen – Ruhrlandklinik, Essen, Germany; 4Biostatistics + Data Sciences Corp, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany; 5HP Country Medical Affairs, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany; 6Department of Pneumology,…

Use of a portable device to record maximum inspiratory flow in relation to dyspnoea in patients with COPD

SummaryForced inspiratory measures have been described to reflect the reduction in dyspnoea upon bronchodilation in severe COPD. Based on this we evaluated the applicability and usefulness of a portable device for the assessment of forced inspiration. In 37 patients with COPD (GOLD II/II/IV n = 16/15/6, mean ± SD FEV1 46.2 ± 15.4%pred) lung function was recorded prior to inhalation of 24 μg formoterol and 30 min later. Assessments comprised spirometry including forced inspiration, body plethysmography, maximum inspiratory flow (InCheck, Clement Clarke), and changes in dyspnoea via visual analogue scale (VAS). The sequence was repeated on a second day to assess reproducibility. Bronchodilati…

S61 Analysis of the efficacy and safety of the combination of tiotropium + olodaterol in patients with COPD by previous usage of inhaled corticosteroids: Abstract S61 Table 1

Rationale Tiotropium (T), a long-acting muscarinic antagonist, and olodaterol (O), a long-acting β 2 -agonist (both administered once daily), have been studied as a once-daily combination. Two Phase III studies have demonstrated that T+O significantly improved lung function and symptoms over T and O monotherapy treatments in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). 1 During these studies, patients were allowed to continue existing treatment with inhaled corticosteroids (ICS); this analysis was conducted to determine the effects of study treatment in patients receiving or not receiving ICS as reported at baseline. Methods A total of 5162 patients we…

Real-World Multicenter Experience with Mepolizumab and Benralizumab in the Treatment of Uncontrolled Severe Eosinophilic Asthma Over 12 Months

Moritz Z Kayser,1 Nora Drick,1 Katrin Milger,2,3 Jan Fuge,1,4 Nikolaus Kneidinger,2,3 Stephanie Korn,5 Roland Buhl,6 Jürgen Behr,2,3 Tobias Welte,1,4 Hendrik Suhling1 1Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany; 2Department of Medicine V, University Hospital, LMU, Munich, Germany; 3Comprehensive Pneumology Center-Munich (CPC‐M), Member of the German Center for Lung Research (DZL), Munich, Germany; 4Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany; 5Clinical Research Centre for Respiratory Medicine, Mainz, Germany; 6Pulmonary Department, Mainz Universit…

Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial

BACKGROUND: Some patients with severe asthma have recurrent asthma exacerbations associated with eosinophilic airway inflammation. Early studies suggest that inhibition of eosinophilic airway inflammation with mepolizumab-a monoclonal antibody against interleukin 5-is associated with a reduced risk of exacerbations. We aimed to establish efficacy, safety, and patient characteristics associated with the response to mepolizumab. METHODS: We undertook a multicentre, double-blind, placebo-controlled trial at 81 centres in 13 countries between Nov 9, 2009, and Dec 5, 2011. Eligible patients were aged 12-74 years, had a history of recurrent severe asthma exacerbations, and had signs of eosinophil…

The Arietta Study: Exploring Severe Asthma Biomarkers in a Real-World Setting

Quantification Of Total Serum IgE In Patients With Asthma Using 3 Different Methods

Fractional exhaled nitric oxide is associated with more severe asthma

Fractional exhaled nitric oxide (FeNO) levels are used as a marker of airway inflammation. The aim of the present work was to evaluate a possible relationship between FeNO and parameters of asthma control and severity in different asthma phenotypes. FeNO was evaluated in 200 asthma patients (37% male, mean age ± SD 54±15 years, 19% controlled (GINA), 30% treated with oral corticosteroids (OCS), median FEV1 (interquartile range) 2,05 L (1,49-2,70), 74% pred. (56-90%)), together with other asthma characteristics (lung function, asthma control, allergies, serum IgE, serum ECP, and blood eosinophils). Patients with poorly controlled asthma had significantly higher FeNO values (ACQ-5≥1.5 vs. 70%…

P131 Efficacy of tiotropium and olodaterol combination in patients with COPD on β-blockers: Abstract P131 Table 1

Rationale The efficacy and safety of a new once-daily combination with tiotropium (T), a long-acting muscarinic antagonist, and olodaterol (O), a long-acting β2-agonist, was established for the treatment of chronic obstructive pulmonary disease (COPD) in the TONADO studies ([NCT01431274][1]; [NCT01431287][2]). This analysis evaluates the efficacy of the combination in a subpopulation of patients receiving β-blockers in these studies. Methods Two replicate, randomised, double-blind, parallel-group, 52-week, Phase III trials assessed the efficacy and safety of T+O (2.5/5 μg; 5/5 μg; via Respimat® inhaler) once daily compared to the monocomponents. Key primary end-point data for the combined a…

Severe and uncontrolled adult asthma is associated with vitamin D insufficiency and deficiency

Background Vitamin D has effects on the innate and adaptive immune system. In asthmatic children low vitamin D levels are associated with poor asthma control, reduced lung function, increased medication intake, and exacerbations. Little is known about vitamin D in adult asthma patients or its association with asthma severity and control. Methods Clinical parameters of asthma control and 25-hydroxyvitamin D (25(OH)D) serum concentrations were evaluated in 280 adult asthma patients (mean ± SD: 45.0 ± 13.8 yrs., 40% male, FEV1 74.9 ± 23.4%, 55% severe, 51% uncontrolled). Results 25(OH)D concentrations in adult asthmatics were low (25.6 ±11.8 ng/ml) and vitamin D insufficiency or deficiency (vi…

Aortopexy in esophageal atresia: Long-term experience of a parent support group

Abstract Purpose: The aim of this study was to obtain the parents' view of aortopexy after esophageal atresia. Methods: A questionnaire was completed by the parents of 24 former patients, now aged from 1 to 15 years (average, 8.9; median, 9.0 years). The respondents were all members of a support group. Results: The median age of the patients receiving aortopexy was 4 months. The 24 procedures were performed in 16 different hospitals. The subjects had experienced a median of 3 apneic attacks. Technical complications occurred in 4 of the 24 children. In 71%, aortopexy was an immediate success. Conclusion: Despite its low success rate compared with centers with large cumulative experience, 90%…

S2k-Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma – Addendum 2020

ZusammenfassungDas vorliegende Addendum zur Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma (2017) ergänzt wichtige neue Erkenntnisse zur Diagnostik und Therapie von Asthma sowie zu neu für die Therapie des Asthmas zugelassenen Medikamenten. Es werden sowohl für Kinder und Jugendliche als auch für Erwachsene mit Asthma die aktuellen, Evidenz-basierten diagnostischen und therapeutischen Empfehlungen dargelegt.

Reslizumab as add-on therapy in patients with refractory asthma

### Key messages #### What is the key question? #### What is the bottom line? #### Why read on? Asthma is a common disease, affecting an estimated 334 million people worldwide, with considerable impact on quality of life and high associated costs.1–3 Asthma severity is assessed retrospectively from the level of treatment required to control symptoms and exacerbations. Approximately 5%–10% of patients with asthma are believed to suffer from severe disease.4 Patients with severe asthma typically require ongoing maintenance therapy with high-dose inhaled corticosteroid (ICS)/long-acting beta-agonist (LABA).2 Furthermore, systemic corticosteroids (SCS) are often required for potentially life-th…

Anti-type2-Antibodies Specifically Inhibit Murine Asthma Features Induced By Intranasal Application of IL-5 and IL-13

Measurement of exhaled nitric oxide: comparison of 3 different analyzers

Exhaled nitric oxide (FeNO) is used as a surrogate marker to monitor airway inflammation. Aim of this study was to compare the new FeNO analyzer Vivatmo pro from Bosch (BV) with the Niox Vero from Circassia (CN) and the CLD from Ecomedics (EC). In 106 asthma patients (median age 54 years (range 20-87), 60 % female, median ACT of 16, 85 % on inhaled corticosteroids (mean 1300 μg BDP), 36 % on therapy with biologics) 2 FeNO measurements per patient and per device were performed using each analyzer in a random sequence according to the ATS / ERS guidelines. Additionally, the success rate to achieve a valid NO value was evaluated. 70 % of the patients had FeNO values In conclusion, for the rang…

Benefits of Tiotropium + Olodaterol Over Tiotropium at Delaying Clinically Significant Events in Patients with COPD Classified as GOLD B

Long-term efficacy of omalizumab (OMA) for patients with severe allergic asthma (SAA). Clinical assessment and relationship to serum IgE concentrations

Background: OMA is an effective treatment option in SAA. However, little data are available on the long-term-efficacy oft the drug. Objective: To determine the long-term efficacy of OMA in respect to clinical parameters and IgE serum levels. Methods: This was a retrospective, open-label, uncontrolled, multi-center observational study according to the definition of non-interventional studies. 22 non-smoking patients (10 m, 12 f; mean age 47,9 yrs) with SAA were enrolled. Pat were treated with OMA up to for 4 years and total serum IgE levels were assessed at initiation of therapy, after 2-6 ms and 3-5 yrs. Data were recorded on standardized CRFs by the treating physician. Results: The average…

Reslizumab for uncontrolled eosinophilic asthma in patients who experienced a single exacerbation in the previous year: sub-analysis of two phase 3 trials

Background: Reslizumab (RES), a humanized anti-interleukin-5 monoclonal antibody, has been demonstrated to significantly reduce the risk of clinical asthma exacerbation (CAE), and improve lung function, asthma symptoms and quality of life (QOL) in patients (pts) with inadequately controlled eosinophilic asthma (ICEA) and ≥1 CAE in the prior 12 mos despite standard of care therapy (Castro et al., Lancet Respir Med 2015; 3:355-366). Aims/Objectives: To assess the efficacy of RES in a subgroup of pts with ICEA who experienced only 1 CAE in the 12 mos prior to trial enrolment. Methods: This was a post-hoc analysis of the two duplicate 52-wk, placebo (PBO)-controlled phase 3 trials of RES (3 mg/…

Reslizumab (RES) in patients (pts) with inadequately controlled asthma and elevated blood eosinophils (EOS): Analysis of two phase 3, placebo-controlled trials

Background: RES reduced exacerbation frequency and improved lung function and asthma control in pts with inadequately controlled asthma and elevated blood EOS in two placebo (PBO)-controlled, phase 3 studies (Castro et al. Lancet Resp Med 2015). Aims/objectives: To determine the efficacy of RES in the subset of pts in these studies meeting the definition of ATS/ERS-defined inadequately controlled asthma. Methods: This was a post-hoc analysis of pooled data from two replicate, 52-week, PBO-controlled studies of RES (3mg/kg IV Q4W) in pts with inadequately controlled asthma and blood EOS ≥400/µL who were using medium-to-high dose inhaled corticosteroids; primary results have been reported. As…

Real-life effectiveness of anti-IL-5(-receptor) antibody treatment in patients with severe eosinophilic asthma

In patients with uncontrolled, severe eosinophilic asthma treatment with anti-IL-5(-receptor) (anti-IL5(R)) antibodies is a promising therapeutic approach. Results of clinical trials demonstrate a very good effectiveness and safety profile of these drugs. However, there is limited data on real-life effectiveness because the drugs have been approved for just a few years. Aim of the present study was to evaluate the real-life effectiveness of the anti-IL5(R) antibodies mepolizumab, reslizumab and benralizumab in severe eosinophilic asthma shortly after approval in Germany. In 119 patients (n=44 male, mean age 54±14 yrs., BMI 27.5±6.2, FEV1 1.9±0.8L (64±21%), 5±3 exacerbations in the last 12 m…

Efficacy of tiotropium and olodaterol fixed-dose combination in patients with COPD on β-blockers

Introduction: The efficacy and safety of a new once-daily (QD) fixed-dose combination (FDC) with tiotropium (T), a long-acting muscarinic antagonist, and olodaterol (O), a long-acting β 2 -agonist, was established for the treatment of COPD in the TONADO studies (NCT01431274; NCT01431287). This analysis evaluates the efficacy of the FDC in a subpopulation of patients receiving β-blockers (BBs) in these studies. Methods: Two replicate, randomised, double-blind, parallel-group, 52-week, Phase III trials assessed the efficacy and safety of T+O FDC (2.5/5 μg; 5/5 μg; Respimat ® inhaler) QD compared to the monocomponents. Key primary end point data for the combined analysis of the replicate trial…

Efficacy and safety of once-daily QVA149 compared with the free combination of once-daily tiotropium plus twice-daily formoterol in patients with moderate-to-severe COPD (QUANTIFY): a randomised, non-inferiority study

Background QVA149 is a once-daily (o.d.) inhaled dual bronchodilator containing a fixed-dose combination of the long-acting β2-agonist indacaterol and the long-acting muscarinic antagonist glycopyrronium for the treatment of COPD. The QUANTIFY study compared QVA149 with a free-dose bronchodilator combination of tiotropium plus formoterol (TIO+FOR) in improving health-related quality of life (HRQoL) of patients with COPD. Methods This multicentre, blinded, triple-dummy, parallel-group, non-inferiority study randomised patients aged ≥40 years with moderate-to-severe COPD (post-bronchodilator forced expiratory volume in 1 s (FEV1) ≥30% to <80% predicted) to QVA149 110/50 µg o.d. or TIO 18 µg o…

Onset of Effect, Changes in Airflow Obstruction and Lung Volume, and Health-Related Quality of Life Improvements with Benralizumab for Patients with Severe Eosinophilic Asthma: Phase IIIb Randomized, Controlled Trial (SOLANA)

Reynold A Panettieri Jr,1 Tobias Welte,2 Kartik V Shenoy,3 Stephanie Korn,4 Margret Jandl,5 Edward M Kerwin,6 Rosa Feijoo,7 Peter Barker,8 Richard F Olsson,9 Ubaldo J Martin8 On behalf of the SOLANA Study Investigators1Pulmonary, Allergy and Critical Care Division, University of Pennsylvania, Philadelphia, PA, USA; 2Department of Respiratory Medicine, Member of the German Center of Lung Research, Medizinische Hochschule Hannover, Hannover, Germany; 3Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA; 4Pulmonary Department, Universit&amp;auml;tsmedizin Mainz, Langenbeckstr, Mainz, Germany; 5Hamburger Institut F&amp;uuml;r Th…

Reply to the Letter Entitled "FeNO Variability when Using Different Analyzers at the Joint ATS/ERS Guideline Cutoff".

Short-Term Reproducibility Of Non-Invasive Clinical And Inflammatory Parameters In Asthma

The ARIETTA study: baseline demographics in a real-world setting in patients with severe asthma

Introduction and Aim: As recognition of asthma heterogeneity increases and targeted treatment options are introduced, the future role of biomarkers (BM) in patient (pt) selection, monitoring and risk prediction will be important. We report baseline demographic and clinical characteristics from ARIETTA, an ongoing, prospective, longitudinal study assessing the relationship between BM and disease-related health outcomes in the real world. Methods: Pts with severe asthma (GINA steps 4-5) receiving daily inhaled corticosteroids (CS; fluticasone propionate ≥500 μg or equivalent) and ≥1 second controller medication were enrolled. Study enrollment is now complete. BM, clinical characteristics and …

Type 2-High and Type 2-Low Airway Inflammation in Severe Asthma

CD4-mediated regulatory T-cell activation inhibits the development of disease in a humanized mouse model of allergic airway disease

Background Based on their potency to control allergic diseases, regulatory T (Treg) cells represent a promising target for novel strategies to interfere with allergic airway inflammation. We have previously demonstrated that stimulation of the CD4 molecule on human Treg cells activates their suppressive activity in vitro and in vivo . Objective We sought to determine the effect of CD4-mediated Treg-cell activation on pulmonary inflammation in a humanized mouse model of allergic airway inflammation. Methods PBMCs obtained from donors allergic to birch pollen or from healthy donors were injected into NOD-severe combined immunodeficiency γc −/− mice, followed by allergen airway challenges and …

Efficacy of Reslizumab with Asthma, Chronic Sinusitis with Nasal Polyps and Elevated Blood Eosinophils

Characterization of the interstitial lung and peripheral blood T cell receptor repertoire in cigarette smokers.

T lymphocytes modulate the pulmonary inflammatory response. The aim of this study was to evaluate the clonality within the interstitial lung and peripheral blood T cell receptor (TCR) repertoire in smokers. Interstitial T lymphocytes were isolated from surplus tissue of 16 patients (63 +/- 9 [+/- SD] yr old, 11 male) undergoing surgery due to lung cancer (n = 15) or emphysema. TCR clonality was assessed by PCR amplification followed by spectratyping. Nearly all TCR of interstitial lung lymphocytes showed oligoclonal bands (CD4(+) subset 13/16 patients, 81%; CD8(+) 100%) indicating a specific differentiation. Peripheral blood T lymphocytes (PBL) TCR (especially CD4(+)) had less oligoclonal b…

Efficacy of a fixed combination of ciclesonide and formoterol: the EXCITED-study.

SummaryRecommended treatment for moderate to severe asthma is the combination of an inhaled corticosteroid and a long-acting beta2-agonist. The present study was designed to evaluate the efficacy of a newly developed fixed combination of ciclesonide and formoterol in comparison to the marketed fixed combination of fluticasone and salmeterol in patients with moderate asthma.This was a phase II, multi-centre, randomized, parallel-group, double-blind, double-dummy study. After a 2-week run-in period, 160 patients with moderate asthma were randomized to a 6-week treatment with ciclesonide/formoterol 320/9 μg bid (CIC/F) or fluticasone propionate/salmeterol 250/50 μg bid (FP/S), both delivered a…

Measurement of Fractional Exhaled Nitric Oxide: Comparison of Three Different Analysers

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Fractional exhaled nitric oxide (FeNO) is a surrogate marker for airway inflammation, supporting the diagnostic pathway and treatment decisions for asthma patients. &lt;b&gt;&lt;i&gt;Objectives:&lt;/i&gt;&lt;/b&gt; Aim of this study was to compare the new analyser Vivatmo pro (Bosch, BV) with NIOX VERO (Circassia, CN) and CLD (Ecomedics, EC). &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; In 100 asthmatics (median 53 years [range 20–87], 62% female, 86% on inhaled corticosteroids [mean 1,300 μg beclomethasone dipropionate or equivalent], 35% treated with biologics) 2 FeNO measurements per device were performed. Additionally, the success rate…

P121 Characteristics of COPD patients with and without maintenance treatment at baseline, by GOLD stage: TONADO: Abstract P121 Table 1

Rationale The efficacy and safety of the once-daily combination of tiotropium (T), a long-acting muscarinic antagonist (LAMA), and olodaterol (O), a long-acting β 2 -agonist (LABA), for the treatment of chronic obstructive pulmonary disease (COPD) has been established. We investigated whether there was a difference in the characteristics of COPD patients with and without baseline maintenance treatment. Methods Two replicate, randomised, 52-week, double-blind, parallel-group, Phase III trials (NCT01431274; NCT01431287; n = 5162) assessed the efficacy and safety of once-daily treatment with T+O (2.5/5 μg; 5/5 μg; Respimat® inhaler) compared to the individual components. Baseline characteristi…

THE RECOVERY-ELISA—A NOVEL ASSAY TECHNIQUE TO MONITOR THERAPY WITH HUMANIZED ANTIBODIES: THE EXAMPLE OF OMALIZUMAB

The therapeutic use of antibodies has grown exponentially, providing new treatment options for various diseases. Monitoring treatment with therapeutic antibodies is a particular challenge because often the target antigen is no longer measurable or the results are unreliable. To overcome this problem, a recovery-ELISA was developed to quantify therapeutic antibody and antigen by a modification of the traditional sandwich immunoassay using omalizumab as an example. Standard serum samples were spiked with IgE and omalizumab in a certain concentration range to create standard curves. After incubation and washout procedures, the reaction was stopped and the plate read with bichromatic absorbance…

Mepolizumab for eosinophilic chronic obstructive pulmonary disease

BACKGROUNDPatients with chronic obstructive pulmonary disease (COPD) with an eosinophilic phenotype may benefit from treatment with mepolizumab, a monoclonal antibody directed against interleukin-5.METHODSWe performed two phase 3, randomized, placebo-controlled, double-blind, parallel-group trials comparing mepolizumab (100 mg in METREX, 100 or 300 mg in METREO) with placebo, given as a subcutaneous injection every 4 weeks for 52 weeks in patients with COPD who had a history of moderate or severe exacerbations while taking inhaled glucocorticoid-based triple maintenance therapy. In METREX, unselected patients in the modified intention-to-treat population with an eosinophilic phenotype were …

A New Dosimeter Methacholine Challenge Protocol Based On A Single Methacholine Concentration

Analysis Of Pulmonary Inflammation Using Humanized Mouse Models

Comparison of Exhaled Nitric Oxide (eNO) Measurements with 5 Different Analyzers.

P191 QVA149 once daily improves exercise tolerance and lung function in patients with moderate to severe COPD: the BRIGHT study: Abstract P191 Table 1

Introduction QVA149 is a novel once-daily fixed-dose combination of the long-acting β 2 -agonist indacaterol and the long-acting muscarinic antagonist glycopyrronium (NVA237) in development for the treatment of chronic obstructive pulmonary disease (COPD). The BRIGHT study evaluated the effects of QVA149 versus placebo and tiotropium on exercise tolerance and lung function in patients with moderate-to-severe COPD. Methods In a double-blind, double-dummy, 3-period crossover study, patients with moderate-to-severe COPD were randomised to QVA149 110/50 µg, placebo or tiotropium 18 µg once daily for 3 weeks. The primary endpoint was exercise endurance time for QVA149 versus placebo during a sub…

Omalizumab in patients with severe persistent allergic asthma in a real-life setting in Germany

Omalizumab is a humanized monoclonal anti-immunoglobulin E (IgE) antibody indicated in Europe for the treatment of uncontrolled severe persistent allergic (IgE-mediated) asthma despite optimal therapy with inhaled corticosteroids and long-acting beta(2) agonists. Between 2005 and 2007 280 patients (58% female, mean age 44+/-16 yrs., 46% on oral corticosteroids, median serum IgE level 235IU/ml) who met the EU criteria for add-on therapy with anti-IgE were treated prospectively with omalizumab by 134 physicians as part of a post-marketing surveillance trial and were followed-up for 6 months. The median follow-up time was 195 days, the patients were treated with a median dose of 450mg omalizum…

An open-label, prospective phase I/II study evaluating the immunogenicity and safety of a ras peptide vaccine plus GM-CSF in patients with non-small cell lung cancer.

Mutations of the ras gene have been reported in 20-40% of NSCLC patients. If present, they are critical for the malignant phenotype of these tumors. Therefore, targeting them by specific vaccination is a promising therapeutic approach. In a clinical trial we screened for ras mutations in patients with NSCLC. Patients with ras-positive tumors were immunized six times intradermally with a mixture of seven peptides representing the most common ras mutations. Objectives of the study were the feasibility, efficacy and safety of the vaccination. In addition, the induction of a specific immune reaction was investigated by DTH tests, and the induction of peptide-specific T cells was tested in ex vi…

Late Breaking Abstract - Dose-ranging study of mepolizumab in eosinophilic COPD

Background: Patients with eosinophilic COPD & frequent exacerbations may benefit from mepolizumab (MEP) treatment. Objective: Assess efficacy & safety of 2 MEP doses vs placebo (PBO) in COPD with blood eosinophils ≥150 cells/µL [screening] or ≥300 cells/µL [prior yr], history of ≥2 moderate/≥1 severe exacerbations & ICS+≥2 bronchodilator maintenance therapies (ICS+MT). Methods: Phase III, randomised, PBO-controlled, double-blind, parallel-group trial (METREO); patients received SC MEP 100mg, MEP 300mg or PBO plus ICS+MT, every 4 wks for 52 wks. Primary endpoint: rate/yr of moderate (systemic corticosteroids/antibiotics)/severe(hospitalisation or death) exacerbations. Secondary endpoints inc…

Measurement of exhaled nitric oxide: Comparison of different analysers

Background and objective:  Exhaled nitric oxide (NO) is used as a surrogate marker to monitor eosinophilic airway inflammation, assist in diagnosis, and support treatment decisions for asthma patients. The aim of this study was to compare five NO analysers: Medisoft (M), Aerocrine Niox (N), Aerocrine Niox flex (NF), Aerocrino Niox mino (NM) and EcoMedics (E). Methods:  In 85 subjects (25 asthma patients, 25 COPD patients, 35 healthy volunteers; median age 36.5 years, range 23–79, 47% female), three NO measurements per individual were performed, using each analyser according to the American Thoracic Society/European Respiratory Society guidelines. Subjects evaluated the devices on the basis …

The Treatment of Mild and Moderate Asthma in Adults

BACKGROUND: Asthma is a chronic inflammatory airway disease that usually causes variable airway obstruction. It affects 5–10% of the German population. METHODS: This review is based on relevant publications retrieved by a selective search, as well as on national and international guidelines on the treatment of mild and moderate asthma in adults. RESULTS: The goal of treatment is to attain optimal asthma control with a minimal risk of exacerbations and mortality, loss of pulmonary function, and drug side effects. This can be achieved with a combination of pharmacotherapy and non-drug treatment including patient education, exercise, smoking cessation, and rehabilitation. Pharmacohterapy is ba…

New fixed bronchodilator combinations of a long-acting β2-agonist and a long-acting anticholinergic

Specific IgE against Staphylococcus aureus enterotoxins: an independent risk factor for asthma.

The role of IgE in patients with severe asthma is not fully understood.We sought to investigate whether IgE to Staphylococcus aureus enterotoxins might be relevant to disease severity in adult asthmatic patients.Specific IgE antibody concentrations in serum against enterotoxins, grass pollen (GP), and house dust mite allergens and total IgE levels were measured in adult cohorts of 69 control subjects, 152 patients with nonsevere asthma, and 166 patients with severe asthma. Severe asthma was defined as inadequately controlled disease despite high-dose inhaled corticosteroids plus at least 2 other controller therapies, including oral steroids.Enterotoxin IgE positivity was significantly great…

Efficacy and safety of tralokinumab in patients with severe uncontrolled asthma: a randomised, double-blind, placebo-controlled, phase 2b trial

Summary Background Interleukin 13 is a central mediator of asthma. Tralokinumab is a human interleukin-13 neutralising monoclonal antibody. We aimed to assess the efficacy and safety of two dosing regimens of tralokinumab in patients with severe uncontrolled asthma. Methods We did a randomised, double-blind, placebo-controlled, parallel-group, multicentre, phase 2b study at 98 sites in North America, South America, Europe, and Asia. Patients aged 18–75 years with severe asthma and two to six exacerbations in the previous year were randomly assigned (1:1), via an interactive voice-response or web-response system, to one of two dosing regimen groups (every 2 weeks, or every 2 weeks for 12 wee…

Vitamin D Insufficiency In Adult Asthma Is Associated With Asthma Severity And Control

Data in asthmatic children suggest that low vitamin D levels are associated with poor asthma control, reduced lung function, and increased medication intake. To investigate the role of vitamin D insufficiency in adult asthmatics 25-hydroxyvitamin D was measured in 280 adult patients with asthma (mean±SEM: 45.0±0.8 yrs., 40% male, FEV1 74.9±1.4%) and correlated with clinical parameters of asthma control. The majority of patients had severe asthma (n=155, 55%) and were uncontrolled (n=144, 51%). Serum levels of vitamin D were significantly related to asthma severity (mean±SEM: intermittent 31.1±3.2 ng/ml, mild 27.3±1.6 ng/ml, moderate 26.5±1.5, severe 24.0±0.9, p=0.046) and asthma control (co…

Against all odds: anti-IgE for intrinsic asthma?

For many years, pathogenetic concepts and the results of clinical trials supported the view that anti-IgE treatment is specifically effective in allergic asthma. However, there is now growing clinical and mechanistic evidence suggesting that treatment with the anti-IgE antibody omalizumab can be effective in patients with intrinsic asthma. Therefore, large and well-controlled clinical trials with anti-IgE are urgently warranted in patients with intrinsic asthma. In addition, there is a need to find new biomarkers which can identify patients with asthma who respond to anti-IgE treatment.

&lt;p&gt;Switch from IL-5 to IL-5-Receptor α Antibody Treatment in Severe Eosinophilic Asthma&lt;/p&gt;

Background Anti-IL-5 antibodies represent an established therapy for severe eosinophilic asthma (SEA), but some patients show inadequate response. The objective of this study was to assess the effects of a switch to anti-IL-5Rα therapy in patients with inadequate response to anti-IL-5 therapy. Methods In this retrospective multi-centre, real-life study, we analysed all SEA patients switched from anti-IL-5 to anti-IL-5Rα therapy due to inadequate response or intolerability. Pulmonary function tests, blood gas analyses, asthma control tests (ACT) and oral corticosteroid (OCS) usage were analysed and compared at three timepoints: baseline (BL, before anti-IL-5 therapy), timepoint 1 (T1, under …

P294 Benefits of tiotropium/olodaterol over tiotropium at delaying clinically significant events in patients with copd classified as gold B

Rationale The once-daily combination of tiotropium (T), a long-acting muscarinic antagonist, and olodaterol (O), a long-acting β 2 -agonist, has demonstrated efficacy and safety in COPD. Two large clinical studies (TONADO ® 1 + 2) have also demonstrated the benefits of T/O compared to the monocomponents in patients with moderate to very severe COPD. This post hoc analysis investigated whether T/O is more effective than T at delaying clinically significant events in patients with GOLD stage B COPD. Methods A total of 5162 patients were randomised to O 5 µg, T 2.5 µg, T 5 µg, T/O 2.5/5 µg or T/O 5/5 µg (delivered via Respimat ® inhaler) in two 52-week, parallel-group, double-blind studies (NC…

Assessing biomarkers in a real-world severe asthma study (ARIETTA)

AbstractThe prognostic value of asthma biomarkers in routine clinical practice is not fully understood. ARIETTA (NCT02537691) is an ongoing, prospective, longitudinal, international, multicentre real-world study designed to assess the relationship between asthma biomarkers and disease-related health outcomes. The trial aims to enrol and follow for 52 weeks approximately 1200 severe asthma patients from approximately 160 sites in more than 20 countries. Severe asthmatics, treated with daily inhaled corticosteroid (≥500 μg of fluticasone propionate or equivalent) and at least 1 second controller medication are to be included. In this real-world study, patients will be treated according to the…

Indacaterol once-daily provides superior efficacy to salmeterol twice-daily in COPD: A 12-week study

SummaryBackgroundIndacaterol is a novel, inhaled once-daily ultra-long-acting β2-agonist for the treatment of COPD.MethodsThis 12-week randomised, parallel-group study compared the efficacy of indacaterol 150 μg once-daily to salmeterol 50 μg twice-daily in patients with moderate-to-severe COPD. Assessments included FEV1 standardised area under curve (AUC) from 5 min to 11 h 45 min at Week 12 (primary endpoint), 24-h trough FEV1 (mean of 23 h 10 min and 23 h 45 min post-dose) at Week 12 (key secondary endpoint), FEV1 and FVC measured over 24-h, transition dyspnoea index (TDI) and rescue medication use.ResultsOf 1123 patients randomised 92.1% completed. Mean ± SD age was 62.8 ± 8.78 years, p…

Tiotropium Respimat® in asthma: a double-blind, randomised, dose-ranging study in adult patients with moderate asthma

Tiotropium, a once-daily long-acting anticholinergic bronchodilator, when administered via Respimat® SoftMist™ inhaler (tiotropium Respimat®) significantly reduces the risk of severe exacerbations and improves lung function in patients with severe persistent asthma that is not fully controlled despite using inhaled corticosteroids (ICS) and long-acting β2-agonists. To further explore the dose–response curve in asthma, we investigated the efficacy and safety of three different doses of tiotropium Respimat® as add-on to ICS in symptomatic patients with moderate persistent asthma. In this randomised, double-blind, placebo-controlled, four-way crossover study, patients were randomised to tiotro…