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Huib A. M. Kerstjens - One of the best experts on this subject based on the ideXlab platform.

  • tiotropium Respimat efficacy and safety in asthma relationship to age
    The Journal of Allergy and Clinical Immunology: In Practice, 2020
    Co-Authors: Dennis E Doherty, Petra Moronizentgraf, Eugene R. Bleecker, Liliana Zarembapechmann, Huib A. M. Kerstjens
    Abstract:

    Background Data are limited on the differential response to long-acting bronchodilators in older versus younger adults with asthma. Objective To determine whether the response to tiotropium Respimat differed in older versus younger patients with asthma. Methods Post hoc analyses of 4 randomized, double-blind, placebo-controlled studies in adults with asthma were carried out. Two studies compared tiotropium Respimat 5 μg once daily with placebo, both added to high-dose inhaled corticosteroid (ICS) plus long-acting β2-agonist (ie, severe asthma). The other 2 evaluated tiotropium Respimat 2.5 or 5 μg once daily, salmeterol 50 μg twice daily, or placebo, all added to medium-dose ICS (moderate asthma). Data were analyzed in 2 pools: (1) severe and (2) moderate asthma. Efficacy end points: trough and peak FEV1; trough forced vital capacity; Asthma Control Questionnaire total score and responder percentage, all at week 24. One set of analyses was performed with age as a continuous covariate; the second was conducted in categories less than 40, 40 to 60, and more than 60 years, with treatment-by-age subgroup interaction P values obtained. Safety was analyzed in age categories. Results Across the age categories, treatment-by-age subgroup interaction P values for trough FEV1 were .13 and .77 for patients with severe and moderate asthma, respectively, not indicating significant impact of age on overall treatment effect, with this observation replicated in the 2 continuum analyses. The other end points (including safety) were also not impacted by age. Conclusions Once-daily tiotropium Respimat add-on to ICS or ICS/long-acting β2-agonist therapy was effective and well tolerated in patients with asthma independent of age.

  • efficacy of once daily tiotropium Respimat in adults with asthma at gina steps 2 5
    Pulmonary Pharmacology & Therapeutics, 2020
    Co-Authors: Roland Buhl, Ralf Sigmund, Eli O. Meltzer, Alberto De La Hoz, Huib A. M. Kerstjens, J M Fitzgerald, Eugene R. Bleecker
    Abstract:

    Abstract Tiotropium Respimat is an efficacious add-on to maintenance treatment in patients with symptomatic asthma. Currently, the Global Initiative for Asthma (GINA) strategy recommends tiotropium for patients at Steps 4–5. To assess the clinical benefits of tiotropium Respimat across asthma severities, GINA Steps 2–5, a post hoc analysis of five double-blind trials (12–48-weeks; patients aged 18–75 years) investigated the effect of tiotropium Respimat, 5 μg or 2.5 μg, versus placebo, on peak forced expiratory volume in 1 s (FEV1) within 3 h post-dose (FEV1(0–3h)) response, and Asthma Control Questionnaire-7 (ACQ-7) responder rate. GINA step grouping was based on patients’ background treatment regimen. Baseline characteristics of patients (N = 2926) were balanced between treatments. Tiotropium Respimat showed consistent improvements in lung function across GINA steps; placebo-corrected peak FEV1(0–3h) improvements after tiotropium Respimat 5 μg and 2.5 μg were: Step 2 (Week 8), 135 mL (95% confidence interval: 84, 187) and 155 mL (103, 206); Step 3 (Week 24), 187 mL (139, 235) and 235 mL (187, 283); Step 4 (Week 24), 111 mL (63, 159) and 181 mL (35, 326); Step 5 (Week 24; 5 μg only), 164 mL (5, 323). Asthma control improved with tiotropium Respimat versus placebo, showing statistical significance (nominal P value) with tiotropium Respimat 5 μg at Step 4 (odds ratio 1.36 [1.03, 1.78]). Safety profiles were similar between treatments. In conclusion, tiotropium Respimat add-on therapy improves lung function, and may improve asthma control, in adults across disease severities.

  • Tiotropium Respimat® add-on therapy to inhaled corticosteroids in patients with symptomatic asthma improves clinical outcomes regardless of baseline characteristics
    Respiratory medicine, 2019
    Co-Authors: Thomas B. Casale, René Aalbers, Eugene R. Bleecker, Eli O. Meltzer, Liliana Zaremba-pechmann, Alberto De La Hoz, Huib A. M. Kerstjens
    Abstract:

    Abstract Background Despite currently available therapies and detailed treatment guidelines, many patients with asthma remain symptomatic. Tiotropium delivered by the soft mist inhaler Respimat®, as add-on therapy to medium-dose inhaled corticosteroids (ICS), has been shown to improve lung function and asthma control in patients with symptomatic moderate asthma. Objective To determine whether the efficacy of tiotropium Respimat® in asthma differs by patients’ study baseline characteristics. Methods Two replicate Phase III, randomized, double-blind, placebo-controlled, parallel-group studies (MezzoTinA-asthma®; NCT01172808 and NCT01172821 ) of once-daily tiotropium Respimat 5 μg and 2.5 μg add-on to ICS were conducted in patients with symptomatic asthma despite treatment with medium-dose ICS with or without additional controllers. Subgroup analyses of peak forced expiratory volume in 1 s (FEV1), trough FEV1, risk of severe asthma exacerbation and Asthma Control Questionnaire responder rate were performed to determine whether results were influenced by patients’ baseline characteristics. Results In this analysis, 523 patients received placebo while 517 and 519 patients received the 5 μg and 2.5 μg dose of tiotropium Respimat, respectively. The magnitude of the improvements in lung function and asthma control, as well as the reduced risk of severe exacerbation with both doses of tiotropium Respimat versus placebo, was independent of a broad range of baseline characteristics. Conclusions Once-daily tiotropium Respimat as add-on to ICS is a beneficial treatment option for patients with asthma who remain symptomatic despite at least medium-dose ICS, regardless of baseline characteristics.

  • Safety of tiotropium Respimat® in black or African-American patients with symptomatic asthma.
    Respiratory medicine, 2019
    Co-Authors: Leroy Graham, Anna Unseld, Eckard Hamelmann, Christian Vogelberg, Stanley J Szefler, Michael Engel, Huib A. M. Kerstjens, Wendelgard Pisternick-ruf, Georges El Azzi, Michael Foggs
    Abstract:

    Abstract Background Black patients with asthma have a higher disease burden and greater morbidity compared with other racial/ethnic groups. Tiotropium Respimat®, as add-on to at least inhaled corticosteroids (ICS), improves lung function and asthma control and reduces asthma exacerbation risk in patients, with a safety profile comparable with placebo. This study aimed to assess the safety of tiotropium Respimat®, compared with placebo, in black or African-American patients. Methods Data were pooled from 12 randomized, placebo-controlled, parallel-group, Phase II or III trials from the global Boehringer Ingelheim program with once-daily tiotropium Respimat® (5 μg or 2.5 μg). Trial participants had symptomatic persistent asthma with a broad range of severities and were aged 1–75 years. The safety results of black or African-American patients were compared with the overall trial population. Results Of the 5165 patients treated with tiotropium or placebo, 3.2% were black or African American. For both doses of tiotropium, the proportion of patients reporting adverse events (AEs) was approximately 10% lower compared with placebo and was generally comparable with the proportion of patients reporting AEs in all groups of the overall population. The number of investigator-assessed drug-related AEs, AEs leading to trial drug discontinuation or serious AEs reported by patients was low and comparable between treatment groups and with the overall population. Conclusion Tiotropium Respimat® appears to be a generally safe add-on bronchodilator treatment option to ICS with or without other controllers in pediatric and adult black or African-American patients with asthma. Clinical trial identifiers NCT01634113, NCT01634139, NCT01634152, NCT01257230, NCT01277523, NCT01316380, NCT00350207, NCT01172808, NCT01172821, NCT01340209, NCT00772538, NCT00776984.

  • efficacy of once daily tiotropium Respimat in adults with asthma based on gina steps 2 5
    European Respiratory Journal, 2017
    Co-Authors: Eugene R. Bleecker, Ralf Sigmund, Eli O. Meltzer, Alberto De La Hoz, Roland Buhl, Mark Fitzgerald, Huib A. M. Kerstjens
    Abstract:

    Introduction: Tiotropium Respimat® is well tolerated and efficacious as add-on therapy to maintenance low-dose ICS to high-dose ICS/LABA in adults with symptomatic asthma. Aims: We examined if these clinical benefits were consistent across groups classified as GINA Steps 2–5. Methods: Data were from 5 double-blind, placebo-controlled trials (patients 18–75 years) of the effect of tiotropium Respimat® on peak (within 3h post-dose FEV1(0-3h)) and trough (pre-dose) FEV1 response vs placebo. GINA Guidelines Step grouping was based on treatments in: GraziaTinA-asthma® (12wks, tiotropium 2.5μg, 5μg or placebo, as 2 puffs QD, added-on to ICS 200–400μg budesonide/equivalent), MezzoTinA-asthma® (2x 24wk trials, tiotropium, 2.5μg or 5μg, as 2 puffs QD, salmeterol 50μg bid or placebo added-on to ICS 400–800μg budesonide/equivalent) and PrimoTinA-asthma® (2x 48wk trials, tiotropium 5μg, as 2 puffs QD or placebo added-on to ICS ≥800μg budesonide/equivalent + LABA ± additional controller medications). Results: Baseline characteristics were balanced across treatment groups in each trial (N>3400). Tiotropium Respimat® provided improvements in peak and trough FEV1 across GINA Steps 2–5 vs placebo (Table 1); safety profiles were similar between tiotropium and placebo groups. Conclusion: Addition of tiotropium Respimat® to maintenance therapy in adult asthma patients provides significant and sustained improvements in lung function across GINA Steps 2–5.

Ronald Dahl - One of the best experts on this subject based on the ideXlab platform.

  • a systematic review of comparative studies of tiotropium Respimat and tiotropium handihaler in patients with chronic obstructive pulmonary disease does inhaler choice matter
    BMC Pulmonary Medicine, 2016
    Co-Authors: Ronald Dahl, Alan Kaplan
    Abstract:

    In many countries worldwide, the long-acting anticholinergic drug tiotropium is available as a dry powder formulation delivered by means of the HandiHaler® inhalation device and as an aqueous solution delivered via the Respimat® Soft Mist™ Inhaler. Tiotropium HandiHaler® is a single-dose, dry powder, breath-actuated inhaler that provides delivered doses and lung deposition of tiotropium that are, over a wide range, not influenced by the severity of chronic obstructive pulmonary disease (COPD). Tiotropium Respimat® is a propellant-free, multi-dose inhaler that delivers a metered dose of medication as a fine, slow-moving, long-lasting soft mist, independently of patient inspiratory effort. The high fine-particle fraction of droplets produced by the Respimat® inhaler optimizes the efficiency of drug delivery to the lungs. To help inform the choice of tiotropium inhaler for prescribers and patients, this systematic review summarizes the available pharmacokinetic, efficacy and safety data from comparative studies of tiotropium Respimat® and tiotropium HandiHaler® in COPD, focusing on the licensed once-daily doses of 5 and 18 μg, respectively. Data sources reviewed include publications and abstracts identified from database searches. Published evidence from comparative studies suggests that tiotropium Respimat® 5 μg and tiotropium HandiHaler® 18 μg provide similar clinical outcomes in patients with COPD. The findings indicate that physicians can base their decision about an inhaler for tiotropium on factors other than efficacy or safety. These could be patient preference for a particular inhaler, ease of use and the efficiency of drug delivery, with the aim of optimizing adherence and clinical outcomes with long-term tiotropium maintenance therapy.

  • tiotropium safety in real world populations response to schmiedl et al in the british journal of clinical pharmacology
    British Journal of Clinical Pharmacology, 2016
    Co-Authors: Robe A Wise, Antonio Anzueto, Ronald Dahl, Daniel Dusse, Pete M A Calverley
    Abstract:

    We read with interest the publication of Schmiedl et al. 1describing the characteristics of patients treated with tiotropium HandiHaler® or Respimat® in the Tiotropium Safety and Performance in Respimat (TIOSPIR®) study compared with their ‘real‐world’ database 2. The authors noted that patients starting either treatment had similar characteristics but suggest that we may have included a selected population with chronic obstructive pulmonary disease (COPD), who might react differently to treatment (and be at lower risk of cardiac adverse effects) than a ‘real‐world’ population.

  • safety and efficacy of tiotropium in patients switching from handihaler to Respimat in the tiospir trial
    BMJ Open, 2015
    Co-Authors: Ronald Dahl, Achim Mueller, Norbert Metzdorf, Andy Fowler, Antonio Anzueto, Peter M A Calverley, Robert A Wise, Daniel Dusser
    Abstract:

    Objectives This post hoc analysis of TIOtropium Safety and Performance In Respimat (TIOSPIR) evaluated safety and exacerbation efficacy in patients with stable (≥2 months) use of tiotropium HandiHaler 18 µg (HH18) prior to study entry, to evaluate whether there was a difference in risk for patients who switched from HH18 to tiotropium Respimat 2.5 µg (R2.5) or 5 µg (R5). Setting TIOSPIR (n=17 135) was an international, Phase IIIb/IV, randomised, double-blind, parallel-group, event-driven trial. Participants Patients from TIOSPIR with chronic obstructive pulmonary disease (COPD) and postbronchodilator ratio of forced expiratory volume in 1 s to forced vital capacity ≤0.70, receiving HH18 before study entry, were analysed (n=2784). Interventions Patients were randomised to once-daily tiotropium R2.5 (n=914), R5 (n=918) or HH18 (n=952) for 2–3 years. Primary and secondary outcome measures Primary outcomes: time to death (safety) and time to first COPD exacerbation (efficacy). Secondary outcomes: number of exacerbations and time to first major adverse cardiovascular event (MACE). Results Baseline characteristics were similar in all groups. Respimat had a similar mortality risk versus HH18 (vital status follow-up, HR; 95% CI R2.5: 0.87; 0.64 to 1.17; R5: 0.79; 0.58 to 1.07) with no significant differences in the risk and rates of exacerbations and severe exacerbations across treatment groups. Risk of MACE and fatal MACE was similar for Respimat versus HH18 (HR; 95% CI MACE R2.5: 0.73; 0.47 to 1.15; R5: 0.69; 0.44 to 1.08; fatal MACE R2.5: 0.57; 0.27 to 1.19; R5: 0.67; 0.33 to 1.34). Overall risk of a fatal event (on treatment) was lower for R5 versus HH18 (HR; 95% CI R2.5: 0.78; 0.55 to 1.09; R5: 0.62; 0.43 to 0.89). Conclusions This analysis indicates that it is safe to switch patients from tiotropium HandiHaler to tiotropium Respimat, and that the efficacy is maintained over the switch. Trial registration number NCT01126437; Post-results.

  • safety and efficacy of tiotropium Respimat versus handihaler in patients naive to treatment with inhaled anticholinergics a post hoc analysis of the tiospir trial
    npj Primary Care Respiratory Medicine, 2015
    Co-Authors: Robert A Wise, Daniel Dusser, Norbert Metzdorf, Andy Fowler, Peter M A Calverley, Ronald Dahl, Achim Muller, Antonio Anzueto
    Abstract:

    Patients with chronic obstructive pulmonary disease (COPD) who were naive to anticholinergics before the TIOtropium Safety and Performance In Respimat (TIOSPIR) trial may reflect patients seen in practice, in particular in primary care. In addition, investigating safety in these patients avoids the potential bias in patients who previously received anticholinergics and may be tolerant of their effects. The aim of this study was to evaluate whether patients naive to anticholinergic therapy who were treated with tiotropium Respimat 2.5 or 5 μg had different safety and efficacy outcomes than patients treated with tiotropium HandiHaler 18 μg. A post hoc analysis of patients who were not receiving anticholinergics before TIOSPIR (N=6,966/17,135) was conducted. Primary end points were risk of death from any cause and risk of COPD exacerbation. Secondary outcomes included severe exacerbation and major adverse cardiovascular events (MACE). Additional analysis of exacerbations was carried out in anticholinergic-naive patients with moderate (GOLD II) disease. Anticholinergic-naive patients had less severe disease than the total TIOSPIR population. Discontinuations because of anticholinergic side effects were infrequent (0.9% overall). Similar to the primary study, patients in the tiotropium Respimat groups had no difference in the risk of death or risk of any or severe exacerbation than patients treated with tiotropium HandiHaler. Risk of MACE was similar across the Respimat and HandiHaler groups. Rates of exacerbations in the subgroup of patients with moderate disease were similar across the Respimat and HandiHaler groups. Tiotropium Respimat and HandiHaler have similar safety and efficacy profiles in patients who are naive to anticholinergic therapy. Inhaled forms of the drug tiotropium are safe and effective for patients with chronic lung disease. Breathing difficulties caused by chronic obstructive pulmonary disease (COPD) can be treated using the 'anticholinergic' drug tiotropium, which works by enlarging the patient's airways. Tiotropium is available as a dry powder or aqueous solution inhaler. The inhaler was recently confirmed as safe in randomized trials, however, there were concerns that the trials did not verify safety and efficacy for patients new to anticholinergic therapy. Robert Wise at Johns Hopkins University School of Medicine in Baltimore, USA, and co-workers tested two inhaled forms of tiotropium on 6,966 COPD patients new to anticholinergics. Their results indicated both inhalers were effective and presented low risks of death, heart problems or other side effects, regardless of previous exposure to anticholinergics.

  • the tiotropium safety and performance in Respimat tiospir trial spirometry outcomes
    Respiratory Research, 2015
    Co-Authors: Antonio Anzueto, Daniel Dusser, Norbert Metzdorf, Peter M A Calverley, Robert A Wise, Wenbo Tang, Ronald Dahl
    Abstract:

    Tiotropium Safety and Performance in Respimat® (TIOSPIR®) compared the safety and efficacy of tiotropium Respimat® and tiotropium HandiHaler® in patients with chronic obstructive pulmonary disease (COPD). A prespecified spirometry substudy compared the lung function efficacy between treatment groups. TIOSPIR® was a large-scale, long-term (2.3-year), event-driven, randomized, double-blind, parallel-group trial of 17,135 patients with COPD. In the spirometry substudy, trough forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were measured at baseline and every 24 weeks for the duration of the trial. The substudy included 1370 patients who received once-daily tiotropium Respimat® 5 μg (n = 461), 2.5 μg (n = 464), or tiotropium HandiHaler® 18 μg (n = 445). Adjusted mean trough FEV1 (average 24–120 weeks) was 1.285, 1.258, and 1.295 L in the Respimat® 5 μg, 2.5 μg, and HandiHaler® 18 μg groups (difference versus HandiHaler® [95 % CI]: −10 [−38, 18] mL for Respimat® 5 μg and, −37 [−65, −9] mL for Respimat® 2.5 μg); achieving noninferiority to tiotropium HandiHaler® 18 μg for tiotropium Respimat® 5 but not for 2.5 μg (prespecified analysis). Adjusted mean trough FVC was 2.590, 2.544, and 2.593 L in the Respimat® 5 μg, 2.5 μg, and HandiHaler® 18 μg groups. The rates of FEV1 decline over 24 to 120 weeks were similar for the three treatment arms (26, 40, and 34 mL/year for the tiotropium Respimat® 5-μg, 2.5-μg, and HandiHaler® 18-μg groups). The rate of FEV1 decline in GOLD I + II patients was greater than in GOLD III + IV patients (46 vs. 23 mL/year); as well as in current versus ex-smokers, in patients receiving combination therapies at baseline versus not, and in those experiencing an exacerbation during the study versus not. The TIOSPIR® spirometry substudy showed that tiotropium Respimat® 5 μg was noninferior to tiotropium HandiHaler® 18 μg for trough FEV1, but Respimat® 2.5 μg was not. Tiotropium Respimat® 5 μg provides similar bronchodilator efficacy to tiotropium HandiHaler® 18 μg with comparable rates of FEV1 decline. The rate of FEV1 decline varied based on disease severity, with a steeper rate of decline observed in patients with moderate airway obstruction. NCT01126437 .

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

  • Safety of tiotropium Respimat® in black or African-American patients with symptomatic asthma.
    Respiratory medicine, 2019
    Co-Authors: Leroy Graham, Anna Unseld, Eckard Hamelmann, Christian Vogelberg, Stanley J Szefler, Michael Engel, Huib A. M. Kerstjens, Wendelgard Pisternick-ruf, Georges El Azzi, Michael Foggs
    Abstract:

    Abstract Background Black patients with asthma have a higher disease burden and greater morbidity compared with other racial/ethnic groups. Tiotropium Respimat®, as add-on to at least inhaled corticosteroids (ICS), improves lung function and asthma control and reduces asthma exacerbation risk in patients, with a safety profile comparable with placebo. This study aimed to assess the safety of tiotropium Respimat®, compared with placebo, in black or African-American patients. Methods Data were pooled from 12 randomized, placebo-controlled, parallel-group, Phase II or III trials from the global Boehringer Ingelheim program with once-daily tiotropium Respimat® (5 μg or 2.5 μg). Trial participants had symptomatic persistent asthma with a broad range of severities and were aged 1–75 years. The safety results of black or African-American patients were compared with the overall trial population. Results Of the 5165 patients treated with tiotropium or placebo, 3.2% were black or African American. For both doses of tiotropium, the proportion of patients reporting adverse events (AEs) was approximately 10% lower compared with placebo and was generally comparable with the proportion of patients reporting AEs in all groups of the overall population. The number of investigator-assessed drug-related AEs, AEs leading to trial drug discontinuation or serious AEs reported by patients was low and comparable between treatment groups and with the overall population. Conclusion Tiotropium Respimat® appears to be a generally safe add-on bronchodilator treatment option to ICS with or without other controllers in pediatric and adult black or African-American patients with asthma. Clinical trial identifiers NCT01634113, NCT01634139, NCT01634152, NCT01257230, NCT01277523, NCT01316380, NCT00350207, NCT01172808, NCT01172821, NCT01340209, NCT00772538, NCT00776984.

  • 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, Petra Moroni-zentgraf, Anna Unseld, Michael Engel, Pierluigi Paggiaro, Huib A. M. 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.

  • Tiotropium Respimat® add-on therapy in children with symptomatic asthma
    5.3 Allergy and Immunology, 2015
    Co-Authors: Christian Vogelberg, Migle Leonaviciute-klimantaviciene, Ralf Sigmund, Petra Moroni-zentgraf, Eckard Hamelmann, Michael Engel, Stanley J Szefler
    Abstract:

    Background: A considerable number of children with asthma remain symptomatic despite available therapies, resulting in significant morbidity, increased healthcare costs and lost school days. Aims and objectives: To examine the efficacy and safety of QD tiotropium Respimat ® (tioR) add-on therapy in children aged 6-11 years with moderate symptomatic asthma. Methods: A Phase II, randomised, double-blind, incomplete-crossover study with 3×4-week treatment periods (NCT01383499). Patients (pts) received 3 of 4 treatments: QD (evening) tioR 5 µg, 2.5 µg, 1.25 µg or placebo Respimat ® (pboR) add-on to at least medium-dose ICS (200-400 µg budesonide or equivalent). Primary efficacy end point: peak FEV 1(0-3h) ; secondary end points included: trough FEV 1 response and morning and evening PEF. All end points were measured as a response at the end of each treatment period. AEs were recorded to assess safety. Results: 100 pts (99%) completed all 3 treatment periods: 68.3% male; mean age 8.8 years. TioR improved lung function compared with pboR (Table). The frequency of AEs was comparable between treatment groups: 9.2%, 9.5%, 9.3% and 10.5% for tioR 5 µg, 2.5 µg, 1.25 µg and pboR, respectively. No deaths, serious AEs, AEs leading to discontinuation or drug-related AEs were reported. Conclusions: QD tiotropium Respimat ® add-on therapy was efficacious and had comparable safety and tolerability with placebo Respimat ® in children with moderate symptomatic asthma.

  • A randomised dose-ranging study of tiotropium Respimat® in children with symptomatic asthma despite inhaled corticosteroids
    Respiratory Research, 2015
    Co-Authors: Christian Vogelberg, Migle Leonaviciute-klimantaviciene, Ralf Sigmund, Petra Moroni-zentgraf, Eckard Hamelmann, Michael Engel, Stanley J Szefler
    Abstract:

    Background: A considerable number of children with asthma remain symptomatic despite treatment with inhaled corticosteroids, resulting in significant morbidity, reduced quality of life, increased healthcare costs and lost school days. The aim of our study was to assess the efficacy, safety and tolerability of once-daily tiotropium Respimat® 5 μg, 2.5 μg and 1.25 μg add-on to medium-dose inhaled corticosteroids, with or without a leukotriene modifier, in children aged 6–11 years with symptomatic asthma. Methods: In this Phase II, double-blind, placebo-controlled, incomplete-crossover, dose-ranging study, patients were randomised to receive three of the four treatments evaluated: once-daily tiotropium Respimat® 5 μg, 2.5 μ go r 1.25 μg or placebo Respimat®, in the evening during the 12-week (three × 4-week) treatment period. Results: In total, 76, 74, 75 and 76 patients aged 6–11 years received tiotropium Respimat® 5 μg, 2.5 μg, 1.25 μg and placebo Respimat®, respectively. For the primary end point (peak forced expiratory volume in 1 second measured within 3 hours post-dosing), the adjusted mean responses with tiotropium Respimat® 5 μg (272 mL), 2.5 μg (290 mL) and 1.25 μg (261 mL) were significantly greater than with placebo Respimat® (185 mL; p = 0.0002, p < 0.0001 and p = 0.0011, respectively). The safety and tolerability of all doses of tiotropium Respimat® were comparable with those of placebo Respimat®, with no serious adverse events and no events leading to discontinuation. Conclusions: Tiotropium Respimat® add-on to medium-dose inhaled corticosteroids, with or without a leukotriene modifier, was efficacious in paediatric patients with symptomatic asthma and had comparable safety and tolerability with placebo Respimat®.

  • 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, Mark Vandewalker, Ronald Dahl, Michael Engel, Pierluigi Paggiaro, Petra Moronizentgraf, Huib A. M. Kerstjens, Hendrik Schmidt, 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

Antonio Anzueto - One of the best experts on this subject based on the ideXlab platform.

  • tiotropium safety and performance in Respimat tiospirtm analysis of asian cohort of copd patients
    Respirology, 2016
    Co-Authors: Nanshan Zhong, Achim Mueller, Norbert Metzdorf, Hwa S Moon, Kwan H Lee, Aziah Mahayiddin, Watchara Boonsawat, Marie Isidro, Chunxue Bai, Antonio Anzueto
    Abstract:

    Background and objective The TIOtropium Safety and Performance In Respimat (TIOSPIR) trial showed similar safety and exacerbation efficacy profiles for tiotropium Respimat and HandiHaler in patients with COPD. The TIOSPIR results for patients in Asia are presented here. Methods TIOSPIR evaluated once-daily tiotropium Respimat 5 and 2.5 µg with HandiHaler 18 µg in patients with COPD. Primary endpoints included time to death and time to first COPD exacerbation. Safety and exacerbation efficacy profiles were determined for the Asian region, and for Asia (all treatment arms pooled) versus the rest of the world (RoW). Results In Asia (n = 2356), time to death was similar for Respimat 5 and 2.5 µg versus HandiHaler 18 µg (hazard ratio (HR) (95% CI): 0.96 (0.67, 1.38) and 1.23 (0.87, 1.73)). Risk of COPD exacerbation was similar for Respimat 5 µg, but increased for 2.5 µg versus HandiHaler 18 µg (HR (95% CI): 0.99 (0.85, 1.15) and 1.17 (1.00, 1.35)). Time to death in Asia and RoW was similar (HR (95% CI): 1.15 (0.99, 1.35)). Time to first COPD exacerbation was longer (HR (95% CI): 0.84 (0.78, 0.89)) and exacerbation rates were lower in Asia, but severe exacerbations were more frequent than in the RoW. Risk of major adverse cardiovascular events was similar for both regions. Conclusion Similar safety and exacerbation efficacy profiles were observed for tiotropium Respimat 5 µg and HandiHaler 18 µg in patients with COPD from Asia, analogous to the global analysis. Asian patients had lower risk of, and fewer exacerbations overall, but a higher proportion of severe exacerbations than in the RoW.

  • tiotropium safety in real world populations response to schmiedl et al in the british journal of clinical pharmacology
    British Journal of Clinical Pharmacology, 2016
    Co-Authors: Robe A Wise, Antonio Anzueto, Ronald Dahl, Daniel Dusse, Pete M A Calverley
    Abstract:

    We read with interest the publication of Schmiedl et al. 1describing the characteristics of patients treated with tiotropium HandiHaler® or Respimat® in the Tiotropium Safety and Performance in Respimat (TIOSPIR®) study compared with their ‘real‐world’ database 2. The authors noted that patients starting either treatment had similar characteristics but suggest that we may have included a selected population with chronic obstructive pulmonary disease (COPD), who might react differently to treatment (and be at lower risk of cardiac adverse effects) than a ‘real‐world’ population.

  • safety and efficacy of tiotropium in patients switching from handihaler to Respimat in the tiospir trial
    BMJ Open, 2015
    Co-Authors: Ronald Dahl, Achim Mueller, Norbert Metzdorf, Andy Fowler, Antonio Anzueto, Peter M A Calverley, Robert A Wise, Daniel Dusser
    Abstract:

    Objectives This post hoc analysis of TIOtropium Safety and Performance In Respimat (TIOSPIR) evaluated safety and exacerbation efficacy in patients with stable (≥2 months) use of tiotropium HandiHaler 18 µg (HH18) prior to study entry, to evaluate whether there was a difference in risk for patients who switched from HH18 to tiotropium Respimat 2.5 µg (R2.5) or 5 µg (R5). Setting TIOSPIR (n=17 135) was an international, Phase IIIb/IV, randomised, double-blind, parallel-group, event-driven trial. Participants Patients from TIOSPIR with chronic obstructive pulmonary disease (COPD) and postbronchodilator ratio of forced expiratory volume in 1 s to forced vital capacity ≤0.70, receiving HH18 before study entry, were analysed (n=2784). Interventions Patients were randomised to once-daily tiotropium R2.5 (n=914), R5 (n=918) or HH18 (n=952) for 2–3 years. Primary and secondary outcome measures Primary outcomes: time to death (safety) and time to first COPD exacerbation (efficacy). Secondary outcomes: number of exacerbations and time to first major adverse cardiovascular event (MACE). Results Baseline characteristics were similar in all groups. Respimat had a similar mortality risk versus HH18 (vital status follow-up, HR; 95% CI R2.5: 0.87; 0.64 to 1.17; R5: 0.79; 0.58 to 1.07) with no significant differences in the risk and rates of exacerbations and severe exacerbations across treatment groups. Risk of MACE and fatal MACE was similar for Respimat versus HH18 (HR; 95% CI MACE R2.5: 0.73; 0.47 to 1.15; R5: 0.69; 0.44 to 1.08; fatal MACE R2.5: 0.57; 0.27 to 1.19; R5: 0.67; 0.33 to 1.34). Overall risk of a fatal event (on treatment) was lower for R5 versus HH18 (HR; 95% CI R2.5: 0.78; 0.55 to 1.09; R5: 0.62; 0.43 to 0.89). Conclusions This analysis indicates that it is safe to switch patients from tiotropium HandiHaler to tiotropium Respimat, and that the efficacy is maintained over the switch. Trial registration number NCT01126437; Post-results.

  • safety and efficacy of tiotropium Respimat versus handihaler in patients naive to treatment with inhaled anticholinergics a post hoc analysis of the tiospir trial
    npj Primary Care Respiratory Medicine, 2015
    Co-Authors: Robert A Wise, Daniel Dusser, Norbert Metzdorf, Andy Fowler, Peter M A Calverley, Ronald Dahl, Achim Muller, Antonio Anzueto
    Abstract:

    Patients with chronic obstructive pulmonary disease (COPD) who were naive to anticholinergics before the TIOtropium Safety and Performance In Respimat (TIOSPIR) trial may reflect patients seen in practice, in particular in primary care. In addition, investigating safety in these patients avoids the potential bias in patients who previously received anticholinergics and may be tolerant of their effects. The aim of this study was to evaluate whether patients naive to anticholinergic therapy who were treated with tiotropium Respimat 2.5 or 5 μg had different safety and efficacy outcomes than patients treated with tiotropium HandiHaler 18 μg. A post hoc analysis of patients who were not receiving anticholinergics before TIOSPIR (N=6,966/17,135) was conducted. Primary end points were risk of death from any cause and risk of COPD exacerbation. Secondary outcomes included severe exacerbation and major adverse cardiovascular events (MACE). Additional analysis of exacerbations was carried out in anticholinergic-naive patients with moderate (GOLD II) disease. Anticholinergic-naive patients had less severe disease than the total TIOSPIR population. Discontinuations because of anticholinergic side effects were infrequent (0.9% overall). Similar to the primary study, patients in the tiotropium Respimat groups had no difference in the risk of death or risk of any or severe exacerbation than patients treated with tiotropium HandiHaler. Risk of MACE was similar across the Respimat and HandiHaler groups. Rates of exacerbations in the subgroup of patients with moderate disease were similar across the Respimat and HandiHaler groups. Tiotropium Respimat and HandiHaler have similar safety and efficacy profiles in patients who are naive to anticholinergic therapy. Inhaled forms of the drug tiotropium are safe and effective for patients with chronic lung disease. Breathing difficulties caused by chronic obstructive pulmonary disease (COPD) can be treated using the 'anticholinergic' drug tiotropium, which works by enlarging the patient's airways. Tiotropium is available as a dry powder or aqueous solution inhaler. The inhaler was recently confirmed as safe in randomized trials, however, there were concerns that the trials did not verify safety and efficacy for patients new to anticholinergic therapy. Robert Wise at Johns Hopkins University School of Medicine in Baltimore, USA, and co-workers tested two inhaled forms of tiotropium on 6,966 COPD patients new to anticholinergics. Their results indicated both inhalers were effective and presented low risks of death, heart problems or other side effects, regardless of previous exposure to anticholinergics.

  • the tiotropium safety and performance in Respimat tiospir trial spirometry outcomes
    Respiratory Research, 2015
    Co-Authors: Antonio Anzueto, Daniel Dusser, Norbert Metzdorf, Peter M A Calverley, Robert A Wise, Wenbo Tang, Ronald Dahl
    Abstract:

    Tiotropium Safety and Performance in Respimat® (TIOSPIR®) compared the safety and efficacy of tiotropium Respimat® and tiotropium HandiHaler® in patients with chronic obstructive pulmonary disease (COPD). A prespecified spirometry substudy compared the lung function efficacy between treatment groups. TIOSPIR® was a large-scale, long-term (2.3-year), event-driven, randomized, double-blind, parallel-group trial of 17,135 patients with COPD. In the spirometry substudy, trough forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were measured at baseline and every 24 weeks for the duration of the trial. The substudy included 1370 patients who received once-daily tiotropium Respimat® 5 μg (n = 461), 2.5 μg (n = 464), or tiotropium HandiHaler® 18 μg (n = 445). Adjusted mean trough FEV1 (average 24–120 weeks) was 1.285, 1.258, and 1.295 L in the Respimat® 5 μg, 2.5 μg, and HandiHaler® 18 μg groups (difference versus HandiHaler® [95 % CI]: −10 [−38, 18] mL for Respimat® 5 μg and, −37 [−65, −9] mL for Respimat® 2.5 μg); achieving noninferiority to tiotropium HandiHaler® 18 μg for tiotropium Respimat® 5 but not for 2.5 μg (prespecified analysis). Adjusted mean trough FVC was 2.590, 2.544, and 2.593 L in the Respimat® 5 μg, 2.5 μg, and HandiHaler® 18 μg groups. The rates of FEV1 decline over 24 to 120 weeks were similar for the three treatment arms (26, 40, and 34 mL/year for the tiotropium Respimat® 5-μg, 2.5-μg, and HandiHaler® 18-μg groups). The rate of FEV1 decline in GOLD I + II patients was greater than in GOLD III + IV patients (46 vs. 23 mL/year); as well as in current versus ex-smokers, in patients receiving combination therapies at baseline versus not, and in those experiencing an exacerbation during the study versus not. The TIOSPIR® spirometry substudy showed that tiotropium Respimat® 5 μg was noninferior to tiotropium HandiHaler® 18 μg for trough FEV1, but Respimat® 2.5 μg was not. Tiotropium Respimat® 5 μg provides similar bronchodilator efficacy to tiotropium HandiHaler® 18 μg with comparable rates of FEV1 decline. The rate of FEV1 decline varied based on disease severity, with a steeper rate of decline observed in patients with moderate airway obstruction. NCT01126437 .

Daniel Dusser - One of the best experts on this subject based on the ideXlab platform.

  • safety and efficacy of tiotropium in patients switching from handihaler to Respimat in the tiospir trial
    BMJ Open, 2015
    Co-Authors: Ronald Dahl, Achim Mueller, Norbert Metzdorf, Andy Fowler, Antonio Anzueto, Peter M A Calverley, Robert A Wise, Daniel Dusser
    Abstract:

    Objectives This post hoc analysis of TIOtropium Safety and Performance In Respimat (TIOSPIR) evaluated safety and exacerbation efficacy in patients with stable (≥2 months) use of tiotropium HandiHaler 18 µg (HH18) prior to study entry, to evaluate whether there was a difference in risk for patients who switched from HH18 to tiotropium Respimat 2.5 µg (R2.5) or 5 µg (R5). Setting TIOSPIR (n=17 135) was an international, Phase IIIb/IV, randomised, double-blind, parallel-group, event-driven trial. Participants Patients from TIOSPIR with chronic obstructive pulmonary disease (COPD) and postbronchodilator ratio of forced expiratory volume in 1 s to forced vital capacity ≤0.70, receiving HH18 before study entry, were analysed (n=2784). Interventions Patients were randomised to once-daily tiotropium R2.5 (n=914), R5 (n=918) or HH18 (n=952) for 2–3 years. Primary and secondary outcome measures Primary outcomes: time to death (safety) and time to first COPD exacerbation (efficacy). Secondary outcomes: number of exacerbations and time to first major adverse cardiovascular event (MACE). Results Baseline characteristics were similar in all groups. Respimat had a similar mortality risk versus HH18 (vital status follow-up, HR; 95% CI R2.5: 0.87; 0.64 to 1.17; R5: 0.79; 0.58 to 1.07) with no significant differences in the risk and rates of exacerbations and severe exacerbations across treatment groups. Risk of MACE and fatal MACE was similar for Respimat versus HH18 (HR; 95% CI MACE R2.5: 0.73; 0.47 to 1.15; R5: 0.69; 0.44 to 1.08; fatal MACE R2.5: 0.57; 0.27 to 1.19; R5: 0.67; 0.33 to 1.34). Overall risk of a fatal event (on treatment) was lower for R5 versus HH18 (HR; 95% CI R2.5: 0.78; 0.55 to 1.09; R5: 0.62; 0.43 to 0.89). Conclusions This analysis indicates that it is safe to switch patients from tiotropium HandiHaler to tiotropium Respimat, and that the efficacy is maintained over the switch. Trial registration number NCT01126437; Post-results.

  • 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, Petra Moroni-zentgraf, Anna Unseld, Michael Engel, Pierluigi Paggiaro, Huib A. M. 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.

  • safety and efficacy of tiotropium Respimat versus handihaler in patients naive to treatment with inhaled anticholinergics a post hoc analysis of the tiospir trial
    npj Primary Care Respiratory Medicine, 2015
    Co-Authors: Robert A Wise, Daniel Dusser, Norbert Metzdorf, Andy Fowler, Peter M A Calverley, Ronald Dahl, Achim Muller, Antonio Anzueto
    Abstract:

    Patients with chronic obstructive pulmonary disease (COPD) who were naive to anticholinergics before the TIOtropium Safety and Performance In Respimat (TIOSPIR) trial may reflect patients seen in practice, in particular in primary care. In addition, investigating safety in these patients avoids the potential bias in patients who previously received anticholinergics and may be tolerant of their effects. The aim of this study was to evaluate whether patients naive to anticholinergic therapy who were treated with tiotropium Respimat 2.5 or 5 μg had different safety and efficacy outcomes than patients treated with tiotropium HandiHaler 18 μg. A post hoc analysis of patients who were not receiving anticholinergics before TIOSPIR (N=6,966/17,135) was conducted. Primary end points were risk of death from any cause and risk of COPD exacerbation. Secondary outcomes included severe exacerbation and major adverse cardiovascular events (MACE). Additional analysis of exacerbations was carried out in anticholinergic-naive patients with moderate (GOLD II) disease. Anticholinergic-naive patients had less severe disease than the total TIOSPIR population. Discontinuations because of anticholinergic side effects were infrequent (0.9% overall). Similar to the primary study, patients in the tiotropium Respimat groups had no difference in the risk of death or risk of any or severe exacerbation than patients treated with tiotropium HandiHaler. Risk of MACE was similar across the Respimat and HandiHaler groups. Rates of exacerbations in the subgroup of patients with moderate disease were similar across the Respimat and HandiHaler groups. Tiotropium Respimat and HandiHaler have similar safety and efficacy profiles in patients who are naive to anticholinergic therapy. Inhaled forms of the drug tiotropium are safe and effective for patients with chronic lung disease. Breathing difficulties caused by chronic obstructive pulmonary disease (COPD) can be treated using the 'anticholinergic' drug tiotropium, which works by enlarging the patient's airways. Tiotropium is available as a dry powder or aqueous solution inhaler. The inhaler was recently confirmed as safe in randomized trials, however, there were concerns that the trials did not verify safety and efficacy for patients new to anticholinergic therapy. Robert Wise at Johns Hopkins University School of Medicine in Baltimore, USA, and co-workers tested two inhaled forms of tiotropium on 6,966 COPD patients new to anticholinergics. Their results indicated both inhalers were effective and presented low risks of death, heart problems or other side effects, regardless of previous exposure to anticholinergics.

  • the tiotropium safety and performance in Respimat tiospir trial spirometry outcomes
    Respiratory Research, 2015
    Co-Authors: Antonio Anzueto, Daniel Dusser, Norbert Metzdorf, Peter M A Calverley, Robert A Wise, Wenbo Tang, Ronald Dahl
    Abstract:

    Tiotropium Safety and Performance in Respimat® (TIOSPIR®) compared the safety and efficacy of tiotropium Respimat® and tiotropium HandiHaler® in patients with chronic obstructive pulmonary disease (COPD). A prespecified spirometry substudy compared the lung function efficacy between treatment groups. TIOSPIR® was a large-scale, long-term (2.3-year), event-driven, randomized, double-blind, parallel-group trial of 17,135 patients with COPD. In the spirometry substudy, trough forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were measured at baseline and every 24 weeks for the duration of the trial. The substudy included 1370 patients who received once-daily tiotropium Respimat® 5 μg (n = 461), 2.5 μg (n = 464), or tiotropium HandiHaler® 18 μg (n = 445). Adjusted mean trough FEV1 (average 24–120 weeks) was 1.285, 1.258, and 1.295 L in the Respimat® 5 μg, 2.5 μg, and HandiHaler® 18 μg groups (difference versus HandiHaler® [95 % CI]: −10 [−38, 18] mL for Respimat® 5 μg and, −37 [−65, −9] mL for Respimat® 2.5 μg); achieving noninferiority to tiotropium HandiHaler® 18 μg for tiotropium Respimat® 5 but not for 2.5 μg (prespecified analysis). Adjusted mean trough FVC was 2.590, 2.544, and 2.593 L in the Respimat® 5 μg, 2.5 μg, and HandiHaler® 18 μg groups. The rates of FEV1 decline over 24 to 120 weeks were similar for the three treatment arms (26, 40, and 34 mL/year for the tiotropium Respimat® 5-μg, 2.5-μg, and HandiHaler® 18-μg groups). The rate of FEV1 decline in GOLD I + II patients was greater than in GOLD III + IV patients (46 vs. 23 mL/year); as well as in current versus ex-smokers, in patients receiving combination therapies at baseline versus not, and in those experiencing an exacerbation during the study versus not. The TIOSPIR® spirometry substudy showed that tiotropium Respimat® 5 μg was noninferior to tiotropium HandiHaler® 18 μg for trough FEV1, but Respimat® 2.5 μg was not. Tiotropium Respimat® 5 μg provides similar bronchodilator efficacy to tiotropium HandiHaler® 18 μg with comparable rates of FEV1 decline. The rate of FEV1 decline varied based on disease severity, with a steeper rate of decline observed in patients with moderate airway obstruction. NCT01126437 .

  • p261 tiotropium safety and performance in Respimat tiospir safety and efficacy in patients naive to treatment with anticholinergics
    Thorax, 2014
    Co-Authors: Robert A Wise, Achim Mueller, Daniel Dusser, Norbert Metzdorf, Andy Fowler, Ronald Dahl, P M A Calverley, Antonio Anzueto
    Abstract:

    Introduction The TIOSPIR™ trial showed similar safety and exacerbation efficacy profiles for tiotropium Respimat ® and HandiHaler ® in patients with chronic obstructive pulmonary disease (COPD). We present here the results for patients who were naive to anticholinergic treatment at baseline. Methods TIOSPIR™ (n = 17,135), a 2–3 year, randomised, double-blind, parallel-group, event-driven trial, compared safety and efficacy of once-daily tiotropium Respimat ® 5 and 2.5 µg with HandiHaler ® 18 µg in patients with COPD. Primary endpoints were time to death (noninferiority of Respimat ® 5 or 2.5 μg versus HandiHaler ® ) and time to first COPD exacerbation (superiority of Respimat ® 5 μg versus HandiHaler ® ). Safety, including cardiovascular safety, was assessed. Results Overall, 6966 patients from TIOSPIR™, naive to anticholinergic treatment at baseline, were randomised and treated (n = 2345, n = 2312 and n = 2309 for tiotropium Respimat ® 2.5 and 5 µg and HandiHaler ® 18 µg). There was similar risk of death (vital status follow up) (measured as time to death) for the Respimat ® groups versus HandiHaler ® (Respimat ® 5 µg: hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.75–1.17; Respimat ® 2.5 µg: HR, 1.05; 95% CI, 0.84–1.30) with similar results for the on-treatment sensitivity analysis (Respimat ® 5 µg: HR, 0.91; 95% CI, 0.71–1.17; Respimat ® 2.5 µg: HR, 1.11; 95% CI, 0.87–1.40). Risk of exacerbation was also similar for the Respimat ® groups versus HandiHaler ® (measured as time to first exacerbation) (Respimat ® 5 µg: HR, 0.99; 95% CI, 0.90–1.08; Respimat ® 2.5 µg: HR, 1.04; 95% CI, 0.95–1.14). Risk of major adverse cardiovascular event (MACE) or fatal MACE were similar for the Respimat ® groups versus HandiHaler ® (MACE: Respimat ® 5 µg: HR, 1.20; 95% CI, 0.88–1.63; Respimat ® 2.5 µg: HR, 1.11; 95% CI, 0.81–1.51; fatal MACE: Respimat ® 5 µg: HR, 1.14; 95% CI, 0.75–1.71, Respimat ® 2.5 µg: HR, 1.12; 95% CI, 0.75–1.69). Conclusions Analogous to the global analysis, patients naive to anticholinergic treatment and treated with tiotropium Respimat ® 2.5 or 5 µg or HandiHaler ® in the TIOSPIR™ trial exhibited similar safety and exacerbation efficacy profiles.

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