Symptomatic Asthma

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Michael Engel - One of the best experts on this subject based on the ideXlab platform.

  • Tiotropium add-on therapy is safe and reduces seasonal worsening in paediatric Asthma patients.
    The European respiratory journal, 2019
    Co-Authors: Christian Vogelberg, Stanley J Szefler, Attilio L. Boner, Michael Engel, P. Moroni-zentgraf, Georges El Azzi, Sebastian D. Vulcu, Elianne J.l.e. Vrijlandt, Olaf Eickmeier, Eckard Hamelmann
    Abstract:

    There remains an unmet need for effective, well tolerated therapeutic options in paediatric patients with not fully controlled Asthma, for whom safety is of paramount importance. Data were pooled from five randomised, double-blind, placebo-controlled studies evaluating tiotropium 5 or 2.5 µg versus placebo add-on therapy in patients with Symptomatic Asthma aged 1–17 years. Analysis included adverse events (AEs) and serious AEs (SAEs) reported throughout and for 30 days following treatment. Of 1691 patients treated, 1119 received tiotropium. Reporting of AEs was low and comparable across all groups: tiotropium 5 µg (51%), 2.5 µg (51%) and placebo (54%). Reporting of drug-related AEs, those leading to discontinuation and SAEs was also low and balanced between treatment groups, irrespective of age, disease severity or gender. The number of AEs related to Asthma symptoms and exacerbations was lower with tiotropium (5 µg) than with placebo, particularly during the seasonal peaks of these AEs. This comprehensive analysis of a large safety database allowed subgroup analyses that are often impractical with individual trials and provides further support for the safety of once-daily tiotropium Respimat® add-on therapy in paediatric patients with Symptomatic Asthma. Clinical Trial Registration: NinoTinA-Asthma® (NCT01634113), CanoTinA-Asthma® (NCT01634139), VivaTinA-Asthma® (NCT01634152), RubaTinA-Asthma® (NCT01257230), PensieTinA-Asthma® (NCT01277523).

  • Tiotropium add-on therapy improves lung function in children and adolescents with moderate and severe Symptomatic Asthma, independent of markers of allergic status
    Pediatrics, 2018
    Co-Authors: Eckard Hamelmann, Ralf Sigmund, Christian Vogelberg, Michael Engel, Georges El Azzi, Birgit Voelker, Stanley J Szefler
    Abstract:

    Purpose: Tiotropium add-on therapy has demonstrated efficacy and safety in 6–17 year-old patients with moderate and severe Symptomatic Asthma despite inhaled corticosteroid (ICS) treatment ± other controllers. Since allergic Asthma is the most common phenotype, we assessed whether the allergic status impacts lung function improvements with tiotropium add-on therapy in these patients. Methods: Analyses involved four Phase III, randomized, double-blind, placebo-controlled, parallel-group trials in patients aged 6–11 years and 12–17 years. Two were 12-week …

  • P172 Safety profile of tiotropium add-on therapy in paediatric patients by gender
    Optimising inhalers for optimal asthma control, 2018
    Co-Authors: Christian Vogelberg, Michael Engel, Sebastian D. Vulcu, Eckard Hamelmann
    Abstract:

    Introduction Tiotropium Respimat® has a safety profile comparable with placebo when given as add-on therapy to at least inhaled corticosteroids (ICS) in paediatric patients with Symptomatic Asthma. We aimed to determine whether the safety and tolerability of tiotropium add-on in paediatric patients is independent of gender. Methods Data were pooled from all parallel-group, randomised, double-blinded, placebo-controlled studies of ≥12 weeks’ duration in 1–17 year-olds (n=1691) with Symptomatic Asthma treated with tiotropium 5 µg or 2.5 µg or placebo (as two puffs once daily) as add-on to ICS ±other controllers. This analysis includes adverse events (AEs) and serious AEs (SAEs) recorded throughout treatment, and for 30 days after. Results Baseline characteristics and exposure to study medication were comparable between treatment groups within each trial. Of 1691 patients treated, 1119 received tiotropium. Overall, the proportion of patients reporting AEs was comparable for tiotropium 5 µg, 2.5 µg and placebo (table 1). This was true for both genders, although slightly fewer female than male patients in the tiotropium 5 µg group reported AEs. Reporting of drug-related AEs, AEs leading to discontinuation and SAEs was low and balanced between treatment groups, irrespective of gender. Conclusion The safety and tolerability profile of once-daily tiotropium as add-on to ICS ±additional controllers is comparable with placebo among paediatric patients with Symptomatic Asthma, irrespective of gender. Please refer to page A267 for declarations of interest related to this abstract.

  • Once-daily tiotropium Respimat add-on therapy improves lung function in children with moderate Symptomatic Asthma, independent of the degree of airflow obstruction
    Paediatric Asthma and Allergy, 2017
    Co-Authors: Christian Vogelberg, Michael Engel, David M.g. Halpin, Birgit Voelker, Reinhold Luehmann, Eckard Hamelmann
    Abstract:

    Introduction: Tiotropium Respimat® add-on therapy is well tolerated and improves lung function in children with persistent Asthma despite inhaled corticosteroid (ICS) treatment ± other controllers. Aims and Objectives: To determine whether this efficacy varies in children with moderate persistent Asthma with different degrees of airflow obstruction. Methods: CanoTinA-Asthma® (NCT01634139) was a Phase III, randomised, double-blind, placebo-controlled 48-week trial in children (6–11y) with moderate persistent Asthma. Patients received once-daily tiotropium Respimat® 5 or 2.5 µg (as 2 puffs) or placebo, as add-on to at least ICS. This post hoc analysis stratified patients by FEV1 % predicted at screening (80– Results: 401 patients were treated. Baseline characteristics were balanced between treatment arms. At Week 24, tiotropium Respimat® add-on therapy improved peak and trough FEV1 responses (Table 1) and FEF25–75% response vs. placebo, independent of FEV1 % predicted at screening. Conclusion: In children (6–11y) with moderate Symptomatic Asthma, once-daily tiotropium Respimat® add-on therapy improves lung function compared with placebo, irrespective of the degree of airflow obstruction at screening.

  • Tiotropium Respimat Add-on Is Efficacious in Symptomatic Asthma, Independent of T2 Phenotype
    The journal of allergy and clinical immunology. In practice, 2017
    Co-Authors: Thomas B. Casale, Mark Vandewalker, Petra Moroni-zentgraf, Michael Engel, Eric D. Bateman, Hendrik Schmidt, J. Christian Virchow, Huib A. M. Kerstjens
    Abstract:

    Background Adding tiotropium to existing inhaled corticosteroid (ICS) maintenance therapy with or without a long-acting β 2 -agonist (LABA) has been shown to be beneficial in patients with Symptomatic Asthma. Objective To assess whether responses to tiotropium Respimat add-on therapy were influenced by patients' T2 status. Methods In this exploratory study, data from 4 phase III trials were analyzed: once-daily tiotropium 5 μg or placebo as add-on to ICS + LABA (PrimoTinA-Asthma; 2 replicate trials; NCT00772538/NCT00776984; n = 912); once-daily tiotropium 5 μg or 2.5 μg, twice-daily salmeterol 50 μg, or placebo as add-on to ICS (MezzoTinA-Asthma; 2 replicate trials; NCT01172808/NCT01172821; n = 2100). The prespecified efficacy outcomes of these studies have been reported previously. Here, further exploratory subgroup analyses were performed to study whether these coprimary end points were influenced by serum IgE levels, blood eosinophil counts, and clinician judgment of allergic Asthma. In addition, for the continuous parameters, namely, IgE and blood eosinophils, their influence on the treatment effect was modeled over the whole range of values. Results Tiotropium was efficacious in improving peak FEV 1 within 3 hours postdose and trough FEV 1 , independent of T2 status. Tiotropium significantly reduced the risk of severe Asthma exacerbations and Asthma worsening, independent of T2 phenotype; Cox regression modeling supported a beneficial effect of tiotropium on exacerbations, independent of IgE levels or eosinophil counts. Numerical improvements in the 7-question Asthma Control Questionnaire (ACQ-7) responder rate with tiotropium versus placebo were observed in T2 high and T2 low patients; logistic regression modeling provided further evidence for improvement in ACQ-7 responder rates with tiotropium, independent of IgE levels or eosinophil counts. Conclusions The results of our exploratory analyses suggest that the improvements seen with tiotropium Respimat as add-on to ICS ± LABA in patients with Symptomatic Asthma on lung function, exacerbation risk, and symptom control are independent of T2 phenotype.

Hendrik Schmidt - One of the best experts on this subject based on the ideXlab platform.

  • Tiotropium Respimat Add-on Is Efficacious in Symptomatic Asthma, Independent of T2 Phenotype
    The journal of allergy and clinical immunology. In practice, 2017
    Co-Authors: Thomas B. Casale, Mark Vandewalker, Petra Moroni-zentgraf, Michael Engel, Eric D. Bateman, Hendrik Schmidt, J. Christian Virchow, Huib A. M. Kerstjens
    Abstract:

    Background Adding tiotropium to existing inhaled corticosteroid (ICS) maintenance therapy with or without a long-acting β 2 -agonist (LABA) has been shown to be beneficial in patients with Symptomatic Asthma. Objective To assess whether responses to tiotropium Respimat add-on therapy were influenced by patients' T2 status. Methods In this exploratory study, data from 4 phase III trials were analyzed: once-daily tiotropium 5 μg or placebo as add-on to ICS + LABA (PrimoTinA-Asthma; 2 replicate trials; NCT00772538/NCT00776984; n = 912); once-daily tiotropium 5 μg or 2.5 μg, twice-daily salmeterol 50 μg, or placebo as add-on to ICS (MezzoTinA-Asthma; 2 replicate trials; NCT01172808/NCT01172821; n = 2100). The prespecified efficacy outcomes of these studies have been reported previously. Here, further exploratory subgroup analyses were performed to study whether these coprimary end points were influenced by serum IgE levels, blood eosinophil counts, and clinician judgment of allergic Asthma. In addition, for the continuous parameters, namely, IgE and blood eosinophils, their influence on the treatment effect was modeled over the whole range of values. Results Tiotropium was efficacious in improving peak FEV 1 within 3 hours postdose and trough FEV 1 , independent of T2 status. Tiotropium significantly reduced the risk of severe Asthma exacerbations and Asthma worsening, independent of T2 phenotype; Cox regression modeling supported a beneficial effect of tiotropium on exacerbations, independent of IgE levels or eosinophil counts. Numerical improvements in the 7-question Asthma Control Questionnaire (ACQ-7) responder rate with tiotropium versus placebo were observed in T2 high and T2 low patients; logistic regression modeling provided further evidence for improvement in ACQ-7 responder rates with tiotropium, independent of IgE levels or eosinophil counts. Conclusions The results of our exploratory analyses suggest that the improvements seen with tiotropium Respimat as add-on to ICS ± LABA in patients with Symptomatic Asthma on lung function, exacerbation risk, and symptom control are independent of T2 phenotype.

  • tiotropium improves lung function exacerbation rate and Asthma control independent of baseline characteristics including age degree of airway obstruction and allergic status
    Respiratory Medicine, 2016
    Co-Authors: Huib A. M. Kerstjens, Petra Moronizentgraf, Mark Vandewalker, Michael Engel, Pierluigi Paggiaro, Hendrik Schmidt, Ronald Dahl, Donald P Tashkin, Eric D. Bateman
    Abstract:

    Abstract Background Many patients with Asthma remain Symptomatic despite treatment with inhaled corticosteroids (ICS) with or without long-acting β 2 -agonists (LABAs). Tiotropium add-on to ICS plus a LABA has been shown to improve lung function and reduce exacerbation risk in patients with Symptomatic Asthma. Objective To determine whether the efficacy of tiotropium add-on therapy is dependent on patients' baseline characteristics. Methods Two randomized, double-blind, parallel-group, twin trials (NCT00772538 and NCT00776984) of once-daily tiotropium Respimat ® 5 μg add-on to ICS plus a LABA were performed in parallel in patients with severe Symptomatic Asthma. Exploratory subgroup analyses of peak forced expiratory volume in 1 s (FEV 1 ), trough FEV 1 , time to first severe exacerbation, time to first episode of Asthma worsening, and seven-question Asthma Control Questionnaire responder rate were performed to determine whether results were influenced by baseline characteristics. Results 912 patients were randomized: 456 received tiotropium and 456 received placebo. Tiotropium improved lung function, reduced the risk of Asthma exacerbations and Asthma worsening, and improved Asthma symptom control, compared with placebo, independent of baseline characteristics including gender, age, body mass index, disease duration, age at Asthma onset, and FEV 1 % predicted at screening and reversibility. Conclusion Once-daily tiotropium 5 μg compared with placebo improved lung function, reduced the risk of Asthma exacerbations and Asthma worsening, and improved Asthma symptom control, independent of a broad range of baseline characteristics, as add-on to ICS plus LABAs in patients with severe Symptomatic Asthma. Trial registry ClinicalTrials.gov; numbers NCT00772538 and NCT00776984 URL: www.clinicaltrials.gov.

  • P150 Once-daily tiotropium Respimat® reduces risk of severe Asthma exacerbation and Asthma worsening in Symptomatic Asthma, independent of allergic and inflammatory status
    Thorax, 2015
    Co-Authors: Ronald Dahl, Mark Vandewalker, Michael Engel, P. Moroni-zentgraf, Thomas B. Casale, Hendrik Schmidt, Ham Kerstjens
    Abstract:

    Background Four trials explored whether tiotropium Respimat® add-on to at least ICS is effective in the T H 2 phenotype, determined by high serum immunoglobulin E (IgE) and blood eosinophil values, in reducing risk of severe Asthma exacerbation and Asthma worsening in adult patients with moderate or severe Symptomatic Asthma. Methods Four Phase III, double-blind, placebo-controlled, parallel-group trials. PrimoTinA-Asthma® (two 48-week trials; NCT00776984/NCT00772538; n = 912): tiotropium Respimat® 5 µg or placebo Respimat® add-on to ICS + LABA (≥800 µg budesonide or equivalent); MezzoTinA-Asthma® (two 24-week trials; NCT01172808/NCT01172821; n = 2100): tiotropium Respimat® 5 µg, tiotropium Respimat® 2.5 µg or placebo add-on to ICS (400–800 µg budesonide or equivalent). Patients had Symptomatic Asthma requiring treatment with at least ICS for ≥4 weeks before screening; COPD was excluded. Subgroups of allergic and inflammatory status (IgE and eosinophils) were used to analyse risk of severe exacerbation and Asthma worsening, post hoc . Cox regression modelling analyses, adjusted for treatment, IgE or eosinophils and treatment by IgE or eosinophil interaction, were applied to calculate hazard ratios and 95% confidence intervals across IgE (2–2000 μg/L) and eosinophil (0.05–7.00 × 10 9 /L) values. Results Severe exacerbation: in PrimoTinA-Asthma®, tiotropium Respimat® 5 µg reduced risk in terms of hazard ratio versus placebo Respimat® up to an IgE level of ~1000 µg/L, and consistently across all eosinophil values. In MezzoTinA-Asthma®, tiotropium Respimat® 5 µg and 2.5 µg reduced risk versus placebo consistently across all IgE and eosinophil levels. Asthma worsening: in PrimoTinA-Asthma®, tiotropium Respimat® 5 µg reduced risk in terms of hazard ratio versus placebo Respimat®, independent of IgE and eosinophils. In MezzoTinA-Asthma®, tiotropium Respimat® 5 µg reduced risk versus placebo across all IgE and eosinophil values. Tiotropium Respimat® 2.5 µg reduced risk versus placebo across all IgE values and at eosinophil values 9 /L. Conclusion Tiotropium Respimat® add-on to ICS ± LABA reduces risk of severe exacerbation and Asthma worsening in patients across severities of Symptomatic Asthma and a broad range of IgE and eosinophil values, suggesting efficacy independent of underlying allergic/eosinophilic inflammation. Once-daily tiotropium Respimat® may have potential as add-on to at least ICS maintenance therapy in patients with Symptomatic Asthma, independent of T H 2 phenotype.

  • tiotropium respimat add on therapy reduces airflow obstruction in patients with Symptomatic moderate Asthma independent of th2 inflammatory status
    Allergy Asthma & Clinical Immunology, 2014
    Co-Authors: W H Yang, Petra Moronizentgraf, Mark Vandewalker, Michael Engel, Thomas B. Casale, Eric D. Bateman, Emilio Pizzichini, Ronald Dahl, Johann Christian Virchow, Hendrik Schmidt
    Abstract:

    S A T U R D A Y 16 Tiotropium Respimat Add-On Therapy Reduces Airflow Obstruction In Patients With Symptomatic Moderate Asthma, Independent Of TH2 Inflammatory Status Dr. Thomas B. Casale, MD, FAAAAI, Dr. Eric Donn Bateman, MD, Prof. Ronald Dahl, MD, Dr. Emilio Pizzichini, Dr. Mark L. Vandewalker, MD, Dr. Johann Christian Virchow, Dr. Michael Engel, MD, Dr. Petra Moroni-Zentgraf, Dr. Hendrik Schmidt, Huib A. M. Kerstjens; Univeristy Of South Florida Morsani College Of Medicine, Tampa, FL, University of Cape Town Lung Institute, Cape Town, South Africa, Odense University Hospital, Odense, Denmark, NUPAIVA (Asthma Research Centre), Universidade Federal de Santa Catarina, Florian opolis, Brazil, Clinical Research of the Ozarks, Columbia, MO, University Clinic Rostock, Rostock, Germany, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim Am Rhein, Germany, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany, University Medical Center Groningen, University of Groningen, Groningen, Netherlands. RATIONALE: In patients with Symptomatic Asthma receiving ICS or ICS+LABA, Phase III studies have demonstrated improved lung function with tiotropium Respimat , a once-daily long-acting anticholinergic bronchodilator. The efficacy of some treatments (e.g. ICS and omalizumab) appears higher in TH2-high phenotypes, but no specific treatments are available that work equally well in both TH2-high and TH2-low phenotypes. We explored whether TH2 biomarker status influenced responses to tiotropium in patients with moderate Symptomatic Asthma. METHODS: In two replicate Phase III, randomized, double-blind, placebo-controlled, parallel-group trials (NCT01172808/NCT01172821), patients with moderate Symptomatic Asthma, using medium-dose ICS (400-800 mg budesonide equivalent), were administered once-daily tiotropium Respimat 5 mg or 2.5 mg, placebo, or salmeterol (active comparator without inferential analysis). Co-primary endpoints included peak and trough FEV1 response (difference from baseline) at 24 weeks. Pre-planned analyses (pooled population) were performed in TH2-low and TH2-high subgroups defined at baseline as total serum IgE 430 mg/L or blood eosinophils 0.6310/L. RESULTS: Of 1545 patients in the full analysis set who received tiotropium or placebo, 915/1455 were reported with IgE >430 mg/L and 300/1461 with an eosinophil count of >0.6310/L. Peak FEV1 improved with tiotropium versus placebo, independent of IgE (p<0.0001 both doses) and eosinophil count (p<0.0001 both doses). Trough FEV1 also improved with tiotropium versus placebo, independent of IgE (p<0.0001 both doses) and eosinophil count (p<0.005 both doses). CONCLUSIONS: Once-daily tiotropium Respimat as add-on to ICS reduces airflow obstruction in patients withmoderate Symptomatic Asthma, independent of TH2 phenotype, and thus may potentially provide an important therapeutic option.

  • Tiotropium respimat® add-on therapy reduces airflow obstruction in patients with Symptomatic moderate Asthma, independent of TH2 inflammatory status
    Allergy Asthma & Clinical Immunology, 2014
    Co-Authors: W H Yang, Mark Vandewalker, Michael Engel, P. Moroni-zentgraf, Thomas B. Casale, Eric D. Bateman, Emilio Pizzichini, Ronald Dahl, Johann Christian Virchow, Hendrik Schmidt
    Abstract:

    S A T U R D A Y 16 Tiotropium Respimat Add-On Therapy Reduces Airflow Obstruction In Patients With Symptomatic Moderate Asthma, Independent Of TH2 Inflammatory Status Dr. Thomas B. Casale, MD, FAAAAI, Dr. Eric Donn Bateman, MD, Prof. Ronald Dahl, MD, Dr. Emilio Pizzichini, Dr. Mark L. Vandewalker, MD, Dr. Johann Christian Virchow, Dr. Michael Engel, MD, Dr. Petra Moroni-Zentgraf, Dr. Hendrik Schmidt, Huib A. M. Kerstjens; Univeristy Of South Florida Morsani College Of Medicine, Tampa, FL, University of Cape Town Lung Institute, Cape Town, South Africa, Odense University Hospital, Odense, Denmark, NUPAIVA (Asthma Research Centre), Universidade Federal de Santa Catarina, Florian opolis, Brazil, Clinical Research of the Ozarks, Columbia, MO, University Clinic Rostock, Rostock, Germany, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim Am Rhein, Germany, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany, University Medical Center Groningen, University of Groningen, Groningen, Netherlands. RATIONALE: In patients with Symptomatic Asthma receiving ICS or ICS+LABA, Phase III studies have demonstrated improved lung function with tiotropium Respimat , a once-daily long-acting anticholinergic bronchodilator. The efficacy of some treatments (e.g. ICS and omalizumab) appears higher in TH2-high phenotypes, but no specific treatments are available that work equally well in both TH2-high and TH2-low phenotypes. We explored whether TH2 biomarker status influenced responses to tiotropium in patients with moderate Symptomatic Asthma. METHODS: In two replicate Phase III, randomized, double-blind, placebo-controlled, parallel-group trials (NCT01172808/NCT01172821), patients with moderate Symptomatic Asthma, using medium-dose ICS (400-800 mg budesonide equivalent), were administered once-daily tiotropium Respimat 5 mg or 2.5 mg, placebo, or salmeterol (active comparator without inferential analysis). Co-primary endpoints included peak and trough FEV1 response (difference from baseline) at 24 weeks. Pre-planned analyses (pooled population) were performed in TH2-low and TH2-high subgroups defined at baseline as total serum IgE 430 mg/L or blood eosinophils 0.6310/L. RESULTS: Of 1545 patients in the full analysis set who received tiotropium or placebo, 915/1455 were reported with IgE >430 mg/L and 300/1461 with an eosinophil count of >0.6310/L. Peak FEV1 improved with tiotropium versus placebo, independent of IgE (p

Mark Vandewalker - One of the best experts on this subject based on the ideXlab platform.

  • Tiotropium Respimat Add-on Is Efficacious in Symptomatic Asthma, Independent of T2 Phenotype
    The journal of allergy and clinical immunology. In practice, 2017
    Co-Authors: Thomas B. Casale, Mark Vandewalker, Petra Moroni-zentgraf, Michael Engel, Eric D. Bateman, Hendrik Schmidt, J. Christian Virchow, Huib A. M. Kerstjens
    Abstract:

    Background Adding tiotropium to existing inhaled corticosteroid (ICS) maintenance therapy with or without a long-acting β 2 -agonist (LABA) has been shown to be beneficial in patients with Symptomatic Asthma. Objective To assess whether responses to tiotropium Respimat add-on therapy were influenced by patients' T2 status. Methods In this exploratory study, data from 4 phase III trials were analyzed: once-daily tiotropium 5 μg or placebo as add-on to ICS + LABA (PrimoTinA-Asthma; 2 replicate trials; NCT00772538/NCT00776984; n = 912); once-daily tiotropium 5 μg or 2.5 μg, twice-daily salmeterol 50 μg, or placebo as add-on to ICS (MezzoTinA-Asthma; 2 replicate trials; NCT01172808/NCT01172821; n = 2100). The prespecified efficacy outcomes of these studies have been reported previously. Here, further exploratory subgroup analyses were performed to study whether these coprimary end points were influenced by serum IgE levels, blood eosinophil counts, and clinician judgment of allergic Asthma. In addition, for the continuous parameters, namely, IgE and blood eosinophils, their influence on the treatment effect was modeled over the whole range of values. Results Tiotropium was efficacious in improving peak FEV 1 within 3 hours postdose and trough FEV 1 , independent of T2 status. Tiotropium significantly reduced the risk of severe Asthma exacerbations and Asthma worsening, independent of T2 phenotype; Cox regression modeling supported a beneficial effect of tiotropium on exacerbations, independent of IgE levels or eosinophil counts. Numerical improvements in the 7-question Asthma Control Questionnaire (ACQ-7) responder rate with tiotropium versus placebo were observed in T2 high and T2 low patients; logistic regression modeling provided further evidence for improvement in ACQ-7 responder rates with tiotropium, independent of IgE levels or eosinophil counts. Conclusions The results of our exploratory analyses suggest that the improvements seen with tiotropium Respimat as add-on to ICS ± LABA in patients with Symptomatic Asthma on lung function, exacerbation risk, and symptom control are independent of T2 phenotype.

  • a randomised controlled trial of tiotropium in adolescents with severe Symptomatic Asthma
    European Respiratory Journal, 2017
    Co-Authors: Eckard Hamelmann, Daniela Verri, Petra Moronizentgraf, Jonathan A. Bernstein, Mark Vandewalker, Anna Unseld, Michael Engel, Attilio L. Boner
    Abstract:

    We present results from the first phase III trial of once-daily tiotropium add-on to inhaled corticosteroids (ICS) plus one or more controller therapies in adolescents with severe Symptomatic Asthma. In this double-blind, parallel-group trial (NCT01277523), 392 patients aged 12–17 years were randomised to receive once-daily tiotropium 5 µg or 2.5 µg, or placebo, as an add-on to ICS plus other controller therapies over 12 weeks. The primary and key secondary end-points were change from baseline (response) in peak forced expiratory volume in 1 s (FEV 1 ) within 3 h post-dosing (FEV 1(0–3h) ) and trough FEV 1 , respectively, after 12 weeks of treatment. Tiotropium 5 µg provided numerical improvements in peak FEV 1(0–3h) response, compared with placebo (90 mL; p=0.104), and significant improvements were observed with tiotropium 2.5 µg (111 mL; p=0.046). Numerical improvements in trough FEV 1 response and Asthma control were observed with both tiotropium doses, compared with placebo. The safety and tolerability of tiotropium were comparable with those of placebo. Once-daily tiotropium Respimat add-on to ICS plus one or more controller therapies in adolescents with severe Symptomatic Asthma was well tolerated. The primary end-point of efficacy was not met, although positive trends for improvements in lung function and Asthma control were observed.

  • p155 safety of tiotropium respimat add on therapy in patients aged 6 17 years with Symptomatic Asthma
    Thorax, 2016
    Co-Authors: Christian Vogelberg, Petra Moronizentgraf, Eckard Hamelmann, Stanley J Szefler, Attilio L. Boner, Michael Engel, Helen Finnigan, El G Azzi, Mark Vandewalker
    Abstract:

    Introduction and objectives Two Phase II trials have shown tiotropium Respimat® (tioR) to be a well-tolerated bronchodilator in patients aged 12–17 1 and 6–11 2 years with Symptomatic Asthma. Here, we further assessed the safety and tolerability of once-daily (QD) tioR add-on therapy in Phase III trials in patients aged 6–17 years with Symptomatic Asthma. Methods Data was analysed from three completed Phase III, randomised, double-blind, placebo-controlled, parallel-group trials: VivaTinA (NCT01634152), 12-week trial, patients aged 6–11 years; PensieTinA (NCT01277523), 12-week trial, patients aged 12–17 years; RubaTinA (NCT01257230), 48-week trial, patients aged 12–17 years. Patients received QD tioR 5 μg (2 puffs, 2.5 µg), QD tioR 2.5 μg (2 puffs, 1.25 µg) or QD placebo Respimat® (pboR; 2 puffs) as add-on to background therapy. Adverse events (AEs) were recorded and analysed descriptively by age: 6–11 years; 12–17 years. Results 1189 patients were treated: 6–11 years, n = 400; 12–17 years, n = 789. The frequency of patients with AEs was similar across all treatment arms, with a low incidence of drug-related and serious AEs; Asthma and decreased peak expiratory flow rate were the most common AEs (Table). No deaths occurred. Conclusion The AE profile and AE incidences were similar between tioR 5 µg, tioR 2.5 µg and pboR, as add-on to inhaled corticosteroid ± other controllers, in patients aged 6–17 years with Symptomatic Asthma. References Vogelberg C, et al . Respir Med 2014; 108 :1268–76. Vogelberg C, et al . Respir Res 2015; 16 :20.

  • P156 Efficacy, safety and tolerability of once-daily tiotropium respimat® add-on therapy in children with moderate Symptomatic Asthma
    Thorax, 2016
    Co-Authors: Olaf Schmidt, Eckard Hamelmann, Christian Vogelberg, Michael Engel, P. Moroni-zentgraf, Helen Finnigan, Istvan Laki, G El Azzi, Mark Vandewalker
    Abstract:

    Introduction and objectives A Phase II trial has shown that tiotropium Respimat® (tioR) is an effective, safe, and well-tolerated bronchodilator in patients aged 6–11 years with moderate Symptomatic Asthma.1 To further assess the efficacy and safety of once-daily tioR add-on therapy, a Phase III trial was carried out in patients aged 6–11 years with moderate Symptomatic Asthma. Methods This 48-week, Phase III, randomised, double-blind, placebo-controlled, parallel-group study (CanoTinA-Asthma®; NCT01634139) was performed in patients aged 6–11 years with moderate Symptomatic Asthma. Patients received once-daily tioR 5μg (2 puffs, 2.5 µg), tioR 2.5 μg (2 puffs, 1.25 µg) or placebo Respimat® (pboR; 2 puffs) as add-on to maintenance treatment of at least medium-dose inhaled corticosteroid (ICS) (200–400 µg budesonide or equivalent) alone or in combination with another controller medication. The primary end point was peak FEV1 within 3 hours post-dosing (FEV1(0–3 h)). Secondary end points included trough FEV1 (key end point), FEV1 area under the curve (AUC) (0–3 h), and peak FVC (0–3 h); all measured as response (change from baseline) at Week 24. Adverse events (AEs) were analysed descriptively. Results Of 403 patients randomised, 401 were treated. Baseline demographics and disease characteristics were balanced between treatment groups. TioR 5 µg and 2.5 µg provided statistically significant improvements in lung function versus pboR at Week 24 (Table) with adjusted mean difference ± standard error peak FEV1 (0–3 h) improvements of 164 ± 31 ml (p Conclusion In patients aged 6–11 years with moderate Symptomatic Asthma, once-daily tioR add-on to ICS with or without other maintenance therapy significantly improves lung function compared with pboR. The safety profile of tioR was similar to that of pboR. Reference Vogelberg C, et al. Respir Res 2015;16(1):20. Please refer to page A272 for declarations of interest in relation to abstract P156.

  • P155 Safety of tiotropium respimat® add-on therapy in patients aged 6–17 years with Symptomatic Asthma
    Thorax, 2016
    Co-Authors: Christian Vogelberg, Eckard Hamelmann, Stanley J Szefler, Attilio L. Boner, Michael Engel, P. Moroni-zentgraf, Helen Finnigan, G El Azzi, Mark Vandewalker
    Abstract:

    Introduction and objectives Two Phase II trials have shown tiotropium Respimat® (tioR) to be a well-tolerated bronchodilator in patients aged 12–17 1 and 6–11 2 years with Symptomatic Asthma. Here, we further assessed the safety and tolerability of once-daily (QD) tioR add-on therapy in Phase III trials in patients aged 6–17 years with Symptomatic Asthma. Methods Data was analysed from three completed Phase III, randomised, double-blind, placebo-controlled, parallel-group trials: VivaTinA (NCT01634152), 12-week trial, patients aged 6–11 years; PensieTinA (NCT01277523), 12-week trial, patients aged 12–17 years; RubaTinA (NCT01257230), 48-week trial, patients aged 12–17 years. Patients received QD tioR 5 μg (2 puffs, 2.5 µg), QD tioR 2.5 μg (2 puffs, 1.25 µg) or QD placebo Respimat® (pboR; 2 puffs) as add-on to background therapy. Adverse events (AEs) were recorded and analysed descriptively by age: 6–11 years; 12–17 years. Results 1189 patients were treated: 6–11 years, n = 400; 12–17 years, n = 789. The frequency of patients with AEs was similar across all treatment arms, with a low incidence of drug-related and serious AEs; Asthma and decreased peak expiratory flow rate were the most common AEs (Table). No deaths occurred. Conclusion The AE profile and AE incidences were similar between tioR 5 µg, tioR 2.5 µg and pboR, as add-on to inhaled corticosteroid ± other controllers, in patients aged 6–17 years with Symptomatic Asthma. References Vogelberg C, et al . Respir Med 2014; 108 :1268–76. Vogelberg C, et al . Respir Res 2015; 16 :20.

P. Moroni-zentgraf - One of the best experts on this subject based on the ideXlab platform.

  • Tiotropium add-on therapy is safe and reduces seasonal worsening in paediatric Asthma patients.
    The European respiratory journal, 2019
    Co-Authors: Christian Vogelberg, Stanley J Szefler, Attilio L. Boner, Michael Engel, P. Moroni-zentgraf, Georges El Azzi, Sebastian D. Vulcu, Elianne J.l.e. Vrijlandt, Olaf Eickmeier, Eckard Hamelmann
    Abstract:

    There remains an unmet need for effective, well tolerated therapeutic options in paediatric patients with not fully controlled Asthma, for whom safety is of paramount importance. Data were pooled from five randomised, double-blind, placebo-controlled studies evaluating tiotropium 5 or 2.5 µg versus placebo add-on therapy in patients with Symptomatic Asthma aged 1–17 years. Analysis included adverse events (AEs) and serious AEs (SAEs) reported throughout and for 30 days following treatment. Of 1691 patients treated, 1119 received tiotropium. Reporting of AEs was low and comparable across all groups: tiotropium 5 µg (51%), 2.5 µg (51%) and placebo (54%). Reporting of drug-related AEs, those leading to discontinuation and SAEs was also low and balanced between treatment groups, irrespective of age, disease severity or gender. The number of AEs related to Asthma symptoms and exacerbations was lower with tiotropium (5 µg) than with placebo, particularly during the seasonal peaks of these AEs. This comprehensive analysis of a large safety database allowed subgroup analyses that are often impractical with individual trials and provides further support for the safety of once-daily tiotropium Respimat® add-on therapy in paediatric patients with Symptomatic Asthma. Clinical Trial Registration: NinoTinA-Asthma® (NCT01634113), CanoTinA-Asthma® (NCT01634139), VivaTinA-Asthma® (NCT01634152), RubaTinA-Asthma® (NCT01257230), PensieTinA-Asthma® (NCT01277523).

  • P156 Efficacy, safety and tolerability of once-daily tiotropium respimat® add-on therapy in children with moderate Symptomatic Asthma
    Thorax, 2016
    Co-Authors: Olaf Schmidt, Eckard Hamelmann, Christian Vogelberg, Michael Engel, P. Moroni-zentgraf, Helen Finnigan, Istvan Laki, G El Azzi, Mark Vandewalker
    Abstract:

    Introduction and objectives A Phase II trial has shown that tiotropium Respimat® (tioR) is an effective, safe, and well-tolerated bronchodilator in patients aged 6–11 years with moderate Symptomatic Asthma.1 To further assess the efficacy and safety of once-daily tioR add-on therapy, a Phase III trial was carried out in patients aged 6–11 years with moderate Symptomatic Asthma. Methods This 48-week, Phase III, randomised, double-blind, placebo-controlled, parallel-group study (CanoTinA-Asthma®; NCT01634139) was performed in patients aged 6–11 years with moderate Symptomatic Asthma. Patients received once-daily tioR 5μg (2 puffs, 2.5 µg), tioR 2.5 μg (2 puffs, 1.25 µg) or placebo Respimat® (pboR; 2 puffs) as add-on to maintenance treatment of at least medium-dose inhaled corticosteroid (ICS) (200–400 µg budesonide or equivalent) alone or in combination with another controller medication. The primary end point was peak FEV1 within 3 hours post-dosing (FEV1(0–3 h)). Secondary end points included trough FEV1 (key end point), FEV1 area under the curve (AUC) (0–3 h), and peak FVC (0–3 h); all measured as response (change from baseline) at Week 24. Adverse events (AEs) were analysed descriptively. Results Of 403 patients randomised, 401 were treated. Baseline demographics and disease characteristics were balanced between treatment groups. TioR 5 µg and 2.5 µg provided statistically significant improvements in lung function versus pboR at Week 24 (Table) with adjusted mean difference ± standard error peak FEV1 (0–3 h) improvements of 164 ± 31 ml (p Conclusion In patients aged 6–11 years with moderate Symptomatic Asthma, once-daily tioR add-on to ICS with or without other maintenance therapy significantly improves lung function compared with pboR. The safety profile of tioR was similar to that of pboR. Reference Vogelberg C, et al. Respir Res 2015;16(1):20. Please refer to page A272 for declarations of interest in relation to abstract P156.

  • P155 Safety of tiotropium respimat® add-on therapy in patients aged 6–17 years with Symptomatic Asthma
    Thorax, 2016
    Co-Authors: Christian Vogelberg, Eckard Hamelmann, Stanley J Szefler, Attilio L. Boner, Michael Engel, P. Moroni-zentgraf, Helen Finnigan, G El Azzi, Mark Vandewalker
    Abstract:

    Introduction and objectives Two Phase II trials have shown tiotropium Respimat® (tioR) to be a well-tolerated bronchodilator in patients aged 12–17 1 and 6–11 2 years with Symptomatic Asthma. Here, we further assessed the safety and tolerability of once-daily (QD) tioR add-on therapy in Phase III trials in patients aged 6–17 years with Symptomatic Asthma. Methods Data was analysed from three completed Phase III, randomised, double-blind, placebo-controlled, parallel-group trials: VivaTinA (NCT01634152), 12-week trial, patients aged 6–11 years; PensieTinA (NCT01277523), 12-week trial, patients aged 12–17 years; RubaTinA (NCT01257230), 48-week trial, patients aged 12–17 years. Patients received QD tioR 5 μg (2 puffs, 2.5 µg), QD tioR 2.5 μg (2 puffs, 1.25 µg) or QD placebo Respimat® (pboR; 2 puffs) as add-on to background therapy. Adverse events (AEs) were recorded and analysed descriptively by age: 6–11 years; 12–17 years. Results 1189 patients were treated: 6–11 years, n = 400; 12–17 years, n = 789. The frequency of patients with AEs was similar across all treatment arms, with a low incidence of drug-related and serious AEs; Asthma and decreased peak expiratory flow rate were the most common AEs (Table). No deaths occurred. Conclusion The AE profile and AE incidences were similar between tioR 5 µg, tioR 2.5 µg and pboR, as add-on to inhaled corticosteroid ± other controllers, in patients aged 6–17 years with Symptomatic Asthma. References Vogelberg C, et al . Respir Med 2014; 108 :1268–76. Vogelberg C, et al . Respir Res 2015; 16 :20.

  • P150 Once-daily tiotropium Respimat® reduces risk of severe Asthma exacerbation and Asthma worsening in Symptomatic Asthma, independent of allergic and inflammatory status
    Thorax, 2015
    Co-Authors: Ronald Dahl, Mark Vandewalker, Michael Engel, P. Moroni-zentgraf, Thomas B. Casale, Hendrik Schmidt, Ham Kerstjens
    Abstract:

    Background Four trials explored whether tiotropium Respimat® add-on to at least ICS is effective in the T H 2 phenotype, determined by high serum immunoglobulin E (IgE) and blood eosinophil values, in reducing risk of severe Asthma exacerbation and Asthma worsening in adult patients with moderate or severe Symptomatic Asthma. Methods Four Phase III, double-blind, placebo-controlled, parallel-group trials. PrimoTinA-Asthma® (two 48-week trials; NCT00776984/NCT00772538; n = 912): tiotropium Respimat® 5 µg or placebo Respimat® add-on to ICS + LABA (≥800 µg budesonide or equivalent); MezzoTinA-Asthma® (two 24-week trials; NCT01172808/NCT01172821; n = 2100): tiotropium Respimat® 5 µg, tiotropium Respimat® 2.5 µg or placebo add-on to ICS (400–800 µg budesonide or equivalent). Patients had Symptomatic Asthma requiring treatment with at least ICS for ≥4 weeks before screening; COPD was excluded. Subgroups of allergic and inflammatory status (IgE and eosinophils) were used to analyse risk of severe exacerbation and Asthma worsening, post hoc . Cox regression modelling analyses, adjusted for treatment, IgE or eosinophils and treatment by IgE or eosinophil interaction, were applied to calculate hazard ratios and 95% confidence intervals across IgE (2–2000 μg/L) and eosinophil (0.05–7.00 × 10 9 /L) values. Results Severe exacerbation: in PrimoTinA-Asthma®, tiotropium Respimat® 5 µg reduced risk in terms of hazard ratio versus placebo Respimat® up to an IgE level of ~1000 µg/L, and consistently across all eosinophil values. In MezzoTinA-Asthma®, tiotropium Respimat® 5 µg and 2.5 µg reduced risk versus placebo consistently across all IgE and eosinophil levels. Asthma worsening: in PrimoTinA-Asthma®, tiotropium Respimat® 5 µg reduced risk in terms of hazard ratio versus placebo Respimat®, independent of IgE and eosinophils. In MezzoTinA-Asthma®, tiotropium Respimat® 5 µg reduced risk versus placebo across all IgE and eosinophil values. Tiotropium Respimat® 2.5 µg reduced risk versus placebo across all IgE values and at eosinophil values 9 /L. Conclusion Tiotropium Respimat® add-on to ICS ± LABA reduces risk of severe exacerbation and Asthma worsening in patients across severities of Symptomatic Asthma and a broad range of IgE and eosinophil values, suggesting efficacy independent of underlying allergic/eosinophilic inflammation. Once-daily tiotropium Respimat® may have potential as add-on to at least ICS maintenance therapy in patients with Symptomatic Asthma, independent of T H 2 phenotype.

  • P149 Once-daily tiotropium Respimat® add-on to at least ICS in adult patients with Symptomatic Asthma: pooled safety analysis
    Thorax, 2015
    Co-Authors: Daniel Dusser, Anna Unseld, Michael Engel, Pierluigi Paggiaro, P. Moroni-zentgraf, Ham Kerstjens, Roland Buhl, Mario Castro, Eric D. Bateman
    Abstract:

    Background A high proportion of patients with Asthma are Symptomatic despite at least ICS maintenance therapy. Five trials aimed to evaluate the safety of tiotropium Respimat® compared with placebo Respimat®, each as add-on to at least ICS in adult patients with Symptomatic Asthma. Methods Five Phase III and one Phase II randomised, double-blind, placebo-controlled, parallel-group trials. PrimoTinA-Asthma® (48 weeks): tiotropium Respimat® 5 µg add-on to ICS + LABA (≥800 µg budesonide or equivalent); MezzoTinA-Asthma® (24 weeks): tiotropium Respimat® 5 µg or 2.5 µg add-on to ICS (400–800 µg budesonide or equivalent); GraziaTinA-Asthma® (12 weeks): tiotropium Respimat® 5 µg or 2.5 µg add-on to ICS (200–400 µg budesonide or equivalent); Study 342 (16 weeks): tiotropium Respimat® 5 µg add-on to ICS (400–800 µg budesonide or equivalent). Pooled safety data are presented. Results 1929 patients received tiotropium Respimat® (PrimoTinA-Asthma®, n = 456; MezzoTinA-Asthma®, n = 1036; GraziaTinA-Asthma®, n = 309; Study 342, n = 128). Frequency of AEs in >2% of patients was comparable in the tiotropium Respimat® 5 µg, tiotropium Respimat® 2.5 µg and placebo Respimat® groups (Table 1). No deaths occurred. 110 (5.7%) and 55 (4.4%) patients receiving tiotropium Respimat® and placebo Respimat®, respectively, reported drug-related AEs (cardiac AEs were rare: tiotropium Respimat®, 7 [0.4%]; placebo Respimat®, 3 [0.2%]). One drug-related serious AE (Asthma) was reported with tiotropium Respimat®. Conclusion Once-daily tiotropium Respimat® add-on to at least ICS maintenance therapy in adult patients demonstrates a safety profile comparable with that of placebo and is well tolerated across severities of Symptomatic Asthma.

Ham Kerstjens - One of the best experts on this subject based on the ideXlab platform.

  • P150 Once-daily tiotropium Respimat® reduces risk of severe Asthma exacerbation and Asthma worsening in Symptomatic Asthma, independent of allergic and inflammatory status
    Thorax, 2015
    Co-Authors: Ronald Dahl, Mark Vandewalker, Michael Engel, P. Moroni-zentgraf, Thomas B. Casale, Hendrik Schmidt, Ham Kerstjens
    Abstract:

    Background Four trials explored whether tiotropium Respimat® add-on to at least ICS is effective in the T H 2 phenotype, determined by high serum immunoglobulin E (IgE) and blood eosinophil values, in reducing risk of severe Asthma exacerbation and Asthma worsening in adult patients with moderate or severe Symptomatic Asthma. Methods Four Phase III, double-blind, placebo-controlled, parallel-group trials. PrimoTinA-Asthma® (two 48-week trials; NCT00776984/NCT00772538; n = 912): tiotropium Respimat® 5 µg or placebo Respimat® add-on to ICS + LABA (≥800 µg budesonide or equivalent); MezzoTinA-Asthma® (two 24-week trials; NCT01172808/NCT01172821; n = 2100): tiotropium Respimat® 5 µg, tiotropium Respimat® 2.5 µg or placebo add-on to ICS (400–800 µg budesonide or equivalent). Patients had Symptomatic Asthma requiring treatment with at least ICS for ≥4 weeks before screening; COPD was excluded. Subgroups of allergic and inflammatory status (IgE and eosinophils) were used to analyse risk of severe exacerbation and Asthma worsening, post hoc . Cox regression modelling analyses, adjusted for treatment, IgE or eosinophils and treatment by IgE or eosinophil interaction, were applied to calculate hazard ratios and 95% confidence intervals across IgE (2–2000 μg/L) and eosinophil (0.05–7.00 × 10 9 /L) values. Results Severe exacerbation: in PrimoTinA-Asthma®, tiotropium Respimat® 5 µg reduced risk in terms of hazard ratio versus placebo Respimat® up to an IgE level of ~1000 µg/L, and consistently across all eosinophil values. In MezzoTinA-Asthma®, tiotropium Respimat® 5 µg and 2.5 µg reduced risk versus placebo consistently across all IgE and eosinophil levels. Asthma worsening: in PrimoTinA-Asthma®, tiotropium Respimat® 5 µg reduced risk in terms of hazard ratio versus placebo Respimat®, independent of IgE and eosinophils. In MezzoTinA-Asthma®, tiotropium Respimat® 5 µg reduced risk versus placebo across all IgE and eosinophil values. Tiotropium Respimat® 2.5 µg reduced risk versus placebo across all IgE values and at eosinophil values 9 /L. Conclusion Tiotropium Respimat® add-on to ICS ± LABA reduces risk of severe exacerbation and Asthma worsening in patients across severities of Symptomatic Asthma and a broad range of IgE and eosinophil values, suggesting efficacy independent of underlying allergic/eosinophilic inflammation. Once-daily tiotropium Respimat® may have potential as add-on to at least ICS maintenance therapy in patients with Symptomatic Asthma, independent of T H 2 phenotype.

  • P149 Once-daily tiotropium Respimat® add-on to at least ICS in adult patients with Symptomatic Asthma: pooled safety analysis
    Thorax, 2015
    Co-Authors: Daniel Dusser, Anna Unseld, Michael Engel, Pierluigi Paggiaro, P. Moroni-zentgraf, Ham Kerstjens, Roland Buhl, Mario Castro, Eric D. Bateman
    Abstract:

    Background A high proportion of patients with Asthma are Symptomatic despite at least ICS maintenance therapy. Five trials aimed to evaluate the safety of tiotropium Respimat® compared with placebo Respimat®, each as add-on to at least ICS in adult patients with Symptomatic Asthma. Methods Five Phase III and one Phase II randomised, double-blind, placebo-controlled, parallel-group trials. PrimoTinA-Asthma® (48 weeks): tiotropium Respimat® 5 µg add-on to ICS + LABA (≥800 µg budesonide or equivalent); MezzoTinA-Asthma® (24 weeks): tiotropium Respimat® 5 µg or 2.5 µg add-on to ICS (400–800 µg budesonide or equivalent); GraziaTinA-Asthma® (12 weeks): tiotropium Respimat® 5 µg or 2.5 µg add-on to ICS (200–400 µg budesonide or equivalent); Study 342 (16 weeks): tiotropium Respimat® 5 µg add-on to ICS (400–800 µg budesonide or equivalent). Pooled safety data are presented. Results 1929 patients received tiotropium Respimat® (PrimoTinA-Asthma®, n = 456; MezzoTinA-Asthma®, n = 1036; GraziaTinA-Asthma®, n = 309; Study 342, n = 128). Frequency of AEs in >2% of patients was comparable in the tiotropium Respimat® 5 µg, tiotropium Respimat® 2.5 µg and placebo Respimat® groups (Table 1). No deaths occurred. 110 (5.7%) and 55 (4.4%) patients receiving tiotropium Respimat® and placebo Respimat®, respectively, reported drug-related AEs (cardiac AEs were rare: tiotropium Respimat®, 7 [0.4%]; placebo Respimat®, 3 [0.2%]). One drug-related serious AE (Asthma) was reported with tiotropium Respimat®. Conclusion Once-daily tiotropium Respimat® add-on to at least ICS maintenance therapy in adult patients demonstrates a safety profile comparable with that of placebo and is well tolerated across severities of Symptomatic Asthma.

  • P151 Tiotropium Respimat® add-on therapy reduces exacerbation risk in patients with moderate or severe Symptomatic Asthma, independent of TH2 status
    Thorax, 2015
    Co-Authors: Thomas B. Casale, Michael Engel, P. Moroni-zentgraf, Ronald Dahl, Johann Christian Virchow, Reinhold Lühmann, Ham Kerstjens
    Abstract:

    Background Phase III studies have demonstrated reduced exacerbation rates with tiotropium Respimat® (tioR) add-on to ICS + LABA in patients with Symptomatic Asthma (Kerstjens et al . NEJM 2012;367:1198–207). There are currently no reported specific treatments for Asthma that work equally well in both TH2-low and TH2-high phenotypes. We explored, in patients with moderate or severe Symptomatic Asthma, whether TH2 status influenced tioR responses, assessed by time to first exacerbation. Methods In two 48-week trials (PrimoTinA-Asthma®: [NCT00776984][1]/NCT00772538), patients on ICS + LABA (≥800 µg budesonide or equivalent) received once-daily tioR 5 µg or placebo Respimat®. In two 24-week trials (MezzoTinA-Asthma®: [NCT01172808][2]/NCT01172821), patients on ICS (400–800 µg budesonide or equivalent) received once-daily tioR 5 µg or 2.5 µg, twice-daily salmeterol 50 µg via hydrofluoroalkane metered-dose inhaler (active comparator) or placebo (identical devices in a double-dummy protocol). Pre-planned analyses (pooled data) of time to first severe exacerbation and time to first episode of Asthma worsening were performed in TH2-low and TH2-high subgroups: total serum immunoglobulin (IgE) ≤ or >430 µg/L (179.2 IU/L); blood eosinophils ≤ or >0.6 × 109/L (600/μL). Results 912 patients with severe Asthma received tioR 5 µg or placebo Respimat®: 205/182 were reported with IgE >430 µg/L and 99/87 with an eosinophil count of >0.6 × 109/L. 2100 patients with moderate Asthma received tioR 5 µg or 2.5 µg, salmeterol or placebo: 319/320/319/326 were reported with IgE >430 µg/L and 104/103/111/107 with an eosinophil count of >0.6 × 109/L. Time to first severe exacerbation was longer with tioR versus placebo ([Table 1][3]) in patients with severe or moderate Asthma, independent of IgE and eosinophils (interaction p values [Cox regression] 0.169 and 0.754, respectively, for PrimoTinA-Asthma®; analyses not performed for MezzoTinA-Asthma® because of low incidence of severe exacerbations). Time to first Asthma worsening was longer with tioR versus placebo (Table 1) in patients with moderate or severe Asthma, independent of IgE (interaction p values 0.998 [PrimoTinA-Asthma®] and 0.041 [MezzoTinA-Asthma®]) and eosinophils (interaction p values 0.251 [PrimoTinA-Asthma®] and 0.125 [MezzoTinA-Asthma®]). View this table: Abstract P151 Table 1 Risk of severe Asthma exacerbation and Asthma worsening in PrimoTinA-Asthma® and MezzoTinA-Asthma® Conclusion Once-daily tiotropium Respimat® add-on to at least ICS reduced the risk of severe exacerbation and Asthma worsening in patients with moderate or severe Symptomatic Asthma, independent of TH2 phenotype. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00776984&atom=%2Fthoraxjnl%2F70%2FSuppl_3%2FA152.2.atom [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01172808&atom=%2Fthoraxjnl%2F70%2FSuppl_3%2FA152.2.atom [3]: #T1

  • s91 once daily tiotropium respimat add on to ics laba improves symptom control and reduces exacerbations in patients with Symptomatic Asthma
    Thorax, 2014
    Co-Authors: David Price, Petra Moronizentgraf, Mark Vandewalker, Michael Engel, Pierluigi Paggiaro, Hendrik Schmidt, Ham Kerstjens, Ronald Dahl, A Kaplan
    Abstract:

    Background We evaluated the effect of once-daily tiotropium Respimat® 5 µg on lung function, Asthma exacerbation and Asthma symptom control among patients with Symptomatic Asthma receiving inhaled corticosteroids (ICS; ≥800 μg/day budesonide or equivalent) + long-acting β2-agonist (LABA). Methods Data were pooled from two replicate, double-blind, placebo-controlled, 48-week, parallel-group studies of once-daily tiotropium 5 µg versus placebo, both delivered via the Respimat® SoftMist™ inhaler (PrimoTinA-Asthma®: [NCT00772538][1], [NCT00776984][2]). Eligible patients had: ≥5-year history of Asthma diagnosed before the age of 40 years; seven-question Asthma Control Questionnaire (ACQ-7) score of ≥1.5; experienced ≥1 exacerbation during the previous year. Patients were either lifelong non-smokers, or ex-smokers (<10 pack-years) who quit smoking ≥1 year before study enrolment. Exclusion criteria included diagnosis of chronic obstructive pulmonary disease. Co-primary end points in individual trials: peak forced expiratory volume in 1 second (FEV1) within 3 h post-dose (0–3 h) and trough FEV1. A co-primary end point in pooled data was time to first severe exacerbation; secondary end points included time to first episode of Asthma worsening and ACQ-7 response. Post hoc efficacy analyses were performed. Results 912 patients were randomised to receive tiotropium Respimat® (n = 456) or placebo Respimat® (n = 456). At Week 48, tiotropium Respimat® was associated with statistically significant improvements versus placebo Respimat® in peak FEV1(0–3h) (adjusted mean difference 100 mL; 95% confidence interval: 52, 148; p < 0.0001) and trough FEV1 (adjusted mean difference 62 mL; 95% confidence interval: 18, 106; p = 0.006). Time to first severe Asthma exacerbation was significantly longer with tiotropium Respimat® versus placebo Respimat® (282 vs 226 days, respectively; hazard ratio 0.79; p = 0.034), as was time to first episode of Asthma worsening (315 vs 181 days, respectively; hazard ratio 0.69; p < 0.0001). At Week 24, ACQ-7 responder rate was significantly higher with tiotropium Respimat® (53.9%) versus placebo Respimat® (46.9%; odds ratio 1.32; p = 0.0427). Conclusion Once-daily tiotropium Respimat® add-on to ICS + LABA improves lung function, reduces risk of severe Asthma exacerbation and Asthma worsening, and significantly improves Asthma symptom control compared with placebo Respimat® in patients with Symptomatic Asthma. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00772538&atom=%2Fthoraxjnl%2F69%2FSuppl_2%2FA49.3.atom [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00776984&atom=%2Fthoraxjnl%2F69%2FSuppl_2%2FA49.3.atom

  • S92 Efficacy Of Once-daily Tiotropium Respimat® 5 µg From Five Phase Iii Trials In Adults With Symptomatic Asthma
    Thorax, 2014
    Co-Authors: David Price, Michael Engel, Pierluigi Paggiaro, P. Moroni-zentgraf, Eric D. Bateman, A Kaplan, Hendrik Schmidt, Ham Kerstjens
    Abstract:

    Background Recent clinical trials have indicated that the long-acting antimuscarinic agent tiotropium, a once-daily long-acting bronchodilator, may provide benefit to patients with Symptomatic Asthma. We investigated primary efficacy data (lung function, risk of severe exacerbation and seven-question Asthma Control Questionnaire [ACQ-7] response) from five Phase III, randomised, double-blind, parallel-group trials that evaluated the efficacy and safety of once-daily tiotropium add-on versus placebo add-on (all tiotropium doses delivered via the Respimat ® SoftMist™ inhaler) in adults with Symptomatic Asthma on inhaled corticosteroid (ICS) ± long-acting β 2 -agonist (LABA) maintenance therapy. Methods Two 48-week trials of tiotropium Respimat ® 5 µg (PrimoTinA-Asthma ® : NCT00776984, NCT00772538) in patients on high-dose ICS (≥800 µg budesonide or equivalent) + LABA; two 24-week trials of tiotropium Respimat ® 5 µg and 2.5 µg (MezzoTinA-Asthma ® : NCT01172808, NCT01172821) in patients on moderate-dose ICS (400–800 µg budesonide or equivalent); one 12-week trial of tiotropium Respimat ® 5 µg and 2.5 µg (GraziaTinA-Asthma ® : NCT01316380) in patients on low-dose ICS (200–400 µg budesonide or equivalent). Results 3476 patients were treated, of whom 1128 received tiotropium Respimat ® 5 µg. Once-daily tiotropium Respimat ® 5 µg significantly improved lung function (Table) in patients with not fully controlled Asthma receiving low- to high-dose ICS. In addition, tiotropium Respimat ® 5 µg reduced the risk of severe exacerbations versus placebo (co-primary end point) in patients on high-dose ICS + LABA (hazard ratio 0.79; p = 0.0343), and there was an increase in ACQ-7 responder rate (co-primary end point) with the5 µg dose (odds ratio 1.32; p = 0.0308) compared with placebo in patients on moderate-dose ICS. Conclusion Once-daily tiotropium Respimat ® significantly improves lung function in adult patients with Symptomatic Asthma receiving a range of doses of ICS, including even high-dose ICS + LABA, suggesting a potential role for this treatment as add-on to ICS in adults with Symptomatic Asthma.

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