Safety Of Tiotropium Research Articles

Efficacy and safety of tiotropium and olodaterol in COPD: a systematic review and meta-analysis

BackgroundLong-acting bronchodilators are the cornerstone of pharmacologic treatment of COPD. The new combination of long-acting muscarinic antagonist (LAMA) tiotropium (TIO) and long acting beta-agonists (LABA) olodaterol (OLO) has been introduced as fist line therapy for COPD. This article analyses the evidence of efficacy and safety of the TIO/OLO combination.MethodsA systematic review and metaanalysis of randomized controlled trials (RCT) with a period of treatment of at least 6 weeks, in patients with COPD confirmed by spirometry, comparing combined treatment with TIO/OLO (approved doses only), with any of the mono-components or any other active comparator administered as an inhalator.ResultsA total of 10 Randomized controlled trials (RCT) were identified (N = 10,918). TIO/OLO significantly improved trough FEV1 from baseline to week 12 versus TIO, OLO and LABA/ICS (0.06 L, 0.09 L and between 0.04 and 0.05 L, respectively). TIO/OLO improved transitional dyspnea index (TDI) and St. George’s Respiratory Questionnaire (SGRQ) compared with mono-components, with patients more likely to achieve clinically important improvements in TDI (risk ratio [RR]: 1.17, 95% confidence interval [CI]: [1.07, 1.28] versus TIO and RR: 1.14, 95%CI: [1.01, 1.28] versus OLO) and in SGRQ (RR: 1.21, 95%CI: [1.12, 1.30] versus TIO and RR: 1.28, 95%CI: [1.18, 1.40] versus OLO). Patients treated with TIO/OLO showed a significant reduction in the use of rescue medication and no significant differences in frequency of general and serious adverse events were observed between TIO/OLO and mono-components.ConclusionsTreatment with TIO/OLO provided significant improvements in lung function versus mono-components and LABA/ICS with more patients achieving significant improvements in dyspnea and health status. No differences in adverse events were observed compared with other active treatments.Clinical trial registrationPROSPERO register of systematic reviews (CRD42016040162).

The Effect of Defining Chronic Obstructive Pulmonary Disease by the Lower Limit of Normal of FEV1/FVC Ratio in Tiotropium Safety and Performance in Respimat Participants.

There is continuing debate about whether to define airflow obstruction by a post-bronchodilator ratio of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) below 0.70, or by ratio values falling below the age-dependent lower limit of normal (LLN) derived from general population data. To determine whether using the LLN criterion affects the classification and outcomes of patients previously defined as having chronic obstructive pulmonary disease by the fixed FEV1/FVC ratio. We applied the LLN definition to pooled data from the Tiotropium Safety and Performance in Respimat study that used the fixed FEV1/FVC ratio for the clinical diagnosis of chronic obstructive pulmonary disease. A total of 17,072 patients were analyzed; of these, 1,807 (10.6%) patients had a ratio greater than or equal to LLN. Patients with a ratio greater than or equal to LLN had similar risks of death from any cause and fatal major adverse cardiovascular (CV) event as those below LLN. Patients with a ratio below LLN had a significantly lower risk of major adverse CV events (hazard ratio = 0.69; 95% confidence interval [CI] = 0.55-0.86; P = 0.001), and had significantly greater risks of moderate to severe exacerbation (rate ratio = 1.48; 95% CI = 1.36-1.61; P < 0.0001) and severe exacerbation (rate ratio = 2.01; 95% CI = 1.68-2.40; P < 0.0001) when compared with patients greater than or equal to LLN. Study outcomes by treatment arm (5 μg tiotropium Respimat vs. 18 μg HandiHaler) were comparable. Using the LLN to define airflow obstruction would have excluded patients in the Tiotropium Safety and Performance in Respimat study with a higher risk of nonfatal major adverse CV events and a lower risk of exacerbation; study outcomes by treatment arm (2.5 μg/5 μg tiotropium Respimat vs. 18 μg HandiHaler) remained similar. Clinical trial registered with www.clinicaltrials.gov (NCT01126437).

Efficacy and safety of tiotropium in school-age children with moderate-to-severe symptomatic asthma: A systematic review.

Recently published data support the benefits and safety of the once-daily (OD) long-acting anticholinergic tiotropium bromide bronchodilator for the treatment of uncontrolled moderate-to-severe asthma in adults and adolescents. However, its role for the treatment of school-age asthmatics has not yet been clearly defined. The aim of this systematic review was to assess the efficacy and safety of tiotropium Respimat® in children aged 6-11years with moderate-to-severe symptomatic asthma. Randomized, placebo-controlled trials were included. Primary outcomes were peak forced expiratory volume in 1s measured within 3h post-dosing) [FEV1 (0-3h) ] and trough FEV1 measured at the end of the dosing interval. Three studies (more than 900 patients) were selected. Tiotropium was associated with significant improvements in FEV1 peak (mean change from baseline) by 102mL (P<.0001) and trough by 82mL (P<.0001) compared with placebo. Tiotropium 5μg dose presented a trend (statistically non-significant) toward a greater bronchodilation in comparison with 2.5μg dose. Tiotropium significantly increased the rate of the Asthma Control Questionnaire (ACQ-7) responders compared with placebo (82.2% vs 75.4%, number needed to treat for benefit [NNTB]=15) and significantly decreased the number of patients with at least one exacerbation in comparison with placebo (29.1% vs. 39.8%, with a NNTB of 10). There were no significant differences in rescue medication use, withdrawals, and adverse events. OD tiotropium Respimat® is efficacious and well tolerated as an add-on to inhaled corticosteroids plus one or more controller medications in school-age symptomatic asthmatics.

Dofetilide exposure during pregnancy is associated with high blood pressure in the adult offspring

The efficacy and safety of once-daily tiotropium+olodaterol (T+O) (2.5/5 µg or 5/5 µg) for treating chronic obstructive pulmonary disease (COPD) have been demonstrated in the large, multinational, randomized, Phase III studies TONADO® 1 and 2, which included 413 Japanese patients (~80 in each group). This study was conducted to supplement the TONADO® study data to assess long-term safety in ≥100 Japanese patients treated for 1 year in compliance with International Conference on Harmonisation guidelines. Efficacy was evaluated descriptively as a secondary end point.Patients were randomized to 52 weeks of double-blind treatment with once-daily T+O (2.5/5 or 5/5 µg) or O (5 µg) monotherapy via the Respimat® inhaler. We report the safety and efficacy data descriptively.The incidence of adverse events (AEs) was comparable in the T+O 2.5/5 µg (75.0%), T+O 5/5 µg (85.4%), and O 5 µg (80.5%) groups, with drug-related AEs being reported in 5.0%, 7.3%, and 4.9% of patients, respectively. Serious AEs were reported in 14 patients (11.5%). The change from baseline in forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h and trough FEV1 were numerically higher in the T+O treatment groups than in the O monotherapy group throughout the study period. Overall safety of T+O was comparable to that in the TONADO® studies.No safety concerns for long-term T+O treatment were identified in Japanese patients with COPD. A numerical improvement in lung function was observed with T+O treatment compared to O monotherapy.

A phase III randomized controlled trial of tiotropium add-on therapy in children with severe symptomatic asthma

Studies in adults and adolescents have demonstrated that tiotropium is efficacious as an add-on therapy to inhaled corticosteroids (ICSs) with or without other maintenance therapies in patients with moderate or severe symptomatic asthma. We sought to assess the efficacy and safety of once-daily tiotropium Respimat add-on therapy to high-dose ICS with 1 or more controller medications, or medium-dose ICS with 2 or more controller medications, in the first phase III trial of tiotropium in children with severe symptomatic asthma. In this 12-week, double-blind, placebo-controlled, parallel-group trial, 401 participants aged 6 to 11years were randomized to receive once-daily tiotropium 5μg (2 puffs of 2.5μg) or 2.5μg (2 puffs of 1.25μg), or placebo (2 puffs), administered through the Respimat device as add-on to background therapy. Compared with placebo, tiotropium 5μg, but not 2.5μg, add-on therapy improved the primary end point, peak FEV1 within 3hours after dosing (5μg, 139mL [95% CI, 75-203; P<.001]; 2.5μg, 35mL [95% CI, -28 to 99; P=.27]), and the key secondary end point, trough FEV1 (5μg, 87mL [95% CI, 19-154; P=.01]; 2.5μg, 18mL [95% CI, -48 to 85; P=.59]). The safety and tolerability of tiotropium were comparable with those of placebo. Once-daily tiotropium Respimat 5μg improved lung function and was well tolerated as add-on therapy to ICSwith other maintenance therapies in children with severesymptomatic asthma.

Efficacy and safety of tiotropium + olodaterol maintenance treatment in patients with COPD in the TONADO® and OTEMTO® studies: a subgroup analysis by age.

BackgroundIncreasing age is associated with poor prognosis in patients with COPD.ObjectiveThis analysis from the replicate Phase III OTEMTO® and TONADO® studies examined the efficacy and safety of tiotropium, a long-acting anticholinergic, combined with olodaterol, a long-acting β2-agonist, compared to monotherapies and placebo in patients with COPD aged 40 years to <65 years, 65 years to <75 years, 75 years to <85 years, and ≥85 years.MethodsIn these double-blind, parallel-group, active-controlled, multicenter, randomized studies, patients received tiotropium + olodaterol 2.5/5 μg or 5/5 μg, tiotropium 5 μg or 2.5 μg (TONADO only), olodaterol 5 μg (TONADO only), or placebo (OTEMTO only). This analysis used the approved doses of tiotropium + olodaterol 5/5 μg, tiotropium 5 μg, and olodaterol 5 μg. Primary end points at 12 weeks (OTEMTO) or 24 weeks (TONADO) included St George’s Respiratory Questionnaire (SGRQ) total score, forced expiratory volume in 1 second (FEV1) area under the curve from 0 hour to 3 hours (AUC0–3) response, and trough FEV1 response.ResultsA total of 1,621 patients were randomized (40 years to <65 years, n=749; 65 years to <75 years, n=674; 75 years to <85 years, n=186; ≥85 years, n=12) in OTEMTO and 5,162 patients (40 years to <65 years, n=2,654; 65 years to <75 years, n=1,967; 75 to <85 years, n=528; ≥85 years, n=13) in TONADO. FEV1 AUC0–3 and trough FEV1 responses improved with tiotropium + olodaterol 5/5 μg at 12 weeks and 24 weeks compared to monotherapies or placebo for all age groups. SGRQ scores generally improved with tiotropium + olodaterol 5/5 μg after 12 weeks in OTEMTO and improved after 24 weeks in all age groups in TONADO. In all age groups receiving tiotropium + olodaterol 5/5 μg compared to monotherapies or placebo, transition dyspnea index scores generally improved, while rescue medication usage improved.ConclusionNo differences were noted in relative responses to treatment or safety when using tiotropium + olodaterol 5/5 μg compared to monotherapies or placebo across all age groups.

Time to COPD Exacerbation in the TONADO Studies by Disease Severity (Global Initiative for Chronic Obstructive Lung Disease [GOLD]) and Baseline Inhaled Corticosteroid (ICS) Use

SESSION TITLE: Airways 5 SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, October 26, 2016 at 01:30 PM - 02:30 PM PURPOSE: Reducing exacerbations is a key goal of COPD treatment due to their detrimental effects on lung function and health status. The Phase III, TONADO studies assessed efficacy and safety of tiotropium + olodaterol (T+O) in patients with moderate to very severe COPD. We investigated if GOLD stage and baseline ICS use are prognostic for the number of patients with, and time to first, COPD exacerbation, irrespective of treatment arm. METHODS: TONADO 1 and 2 were replicate, 52-week, double-blind, parallel-group studies (1237.5, NCT01431274; 1237.6, NCT01431287). Patients received once-daily T+O 2.5/5 or 5/5 µg, T 2.5 or 5 µg, or O 5 µg, via the Respimat inhaler. Continuation of prescribed ICS was permitted. We analyzed time to first moderate or severe exacerbation using pooled data from the two studies. RESULTS: Of 5162 treated patients, 2588 (50.1%), 1989 (38.5%), and 581 (11.3%) were GOLD 2, 3, and 4 at baseline, respectively. Fewer GOLD 2 patients had a moderate/severe on-study exacerbation: 584 (22.6%) compared to 688 (34.6%) GOLD 3 and 211 (36.3%) GOLD 4. The 25th percentile for time to first moderate/severe exacerbation was not reached within the 52 week study period for GOLD 2, and was 201 days for GOLD 3 and 182 days for GOLD 4 patients; hazard ratios (HRs) (95% CI) were 0.59 (0.53, 0.66) for GOLD 2 vs GOLD 3, 0.55 (0.47, 0.64) for GOLD 2 vs GOLD 4, and 0.93 (0.80, 1.09) for GOLD 3 vs GOLD 4. At baseline, 2446 patients (47.4%) used ICS and 2716 (52.6%) did not. More patients with baseline ICS use had an exacerbation compared to those without ICS: 879 (35.9%) vs 605 (22.3%), respectively. The 25th percentile for time to first moderate/severe exacerbation was 191 days with ICS and was not reached in the 52 week study in patients without ICS; HR (95% CI) 1.78 (1.61, 1.98). In patients stratified by baseline ICS use within GOLD groups, ICS use was associated with shorter time to exacerbation vs no ICS: HR 1.66 (1.41, 1.95) in GOLD 2 and 1.69 (1.47, 1.93) in GOLD 3/4. CONCLUSIONS: In this population, unselected by exacerbation history, more severe COPD by GOLD stage and ICS use were associated with increased exacerbation risk. The association between ICS use and increased exacerbation risk is likely to represent a confounding by indication bias. CLINICAL IMPLICATIONS: This analysis confirms separation in exacerbation risk in patients with GOLD 2 versus GOLD 3/4 lung function impairment. Funding: Boehringer Ingelheim. Editorial assistance: Complete HealthVizion. DISCLOSURE: Gary Ferguson: Consultant fee, speaker bureau, advisory committee, etc.: Boehringer-Ingelheim, AstraZeneca, Pearl Therapeutics, Novartis, Forest, Sunovion, Verona, Receptos, GlaxoSmithKline, Other: Boehringer-Ingelheim, AstraZeneca, Pearl Therapeutics, Sunovion, Sunovion, Theravance, Sanofi, Forest, GlaxoSmithKline Eric Derom: Consultant fee, speaker bureau, advisory committee, etc.: Actellion, Boehringer, AstraZeneca, Cipla, Chiesi, CSL Behring, Other: GlaxoSmithKline, Boehringer François Maltais: Consultant fee, speaker bureau, advisory committee, etc.: Boehringer-Ingelheim, GlaxoSmithKline, AstraZeneca, Novartis, Other: Boehringer-Ingelheim, GlaxoSmithKline, AstraZeneca, Nycomed, Novartis Florian Voss: Employee: Boehringer-Ingelheim Carlos Tafur: Employee: Boehringer-Ingelheim Roland Buhl: Consultant fee, speaker bureau, advisory committee, etc.: Boehringer-Ingelheim, AstraZeneca, Chiesi, GlaxoSmithKline, Novartis, TEVA, Roche, Other: Boehringer-Ingelheim, GlaxoSmithKline, Novartis, Roche No Product/Research Disclosure Information

Characteristics of Patients With and Without COPD Exacerbations During the Tiotropium + Olodaterol TONADO Studies

SESSION TITLE: Airways 3 SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, October 26, 2016 at 01:30 PM - 02:30 PM PURPOSE: The efficacy and safety of once-daily tiotropium + olodaterol (T+O) in moderate to very severe COPD were demonstrated in the pivotal, Phase III TONADO studies. Preventing exacerbations is a key aim of COPD management due to their adverse effects on lung function and patients’ health status. We investigated characteristics of patients with/without COPD exacerbations in the TONADO studies. METHODS: TONADO 1 and 2 were replicate, 52-week, double-blind, parallel-group studies (1237.5, NCT01431274; 1237.6, NCT01431287). Patients received once-daily T+O 2.5/5 or 5/5 µg, T 2.5 or 5 µg, or O 5 µg via the Respimat® inhaler. Continuation of prescribed ICS was permitted. Characteristics of patients with/without a moderate or severe COPD exacerbation during the study are presented. RESULTS: Of 5162 patients, there were 1484/3678 (28.7%/71.3%) with/without a moderate or severe on-study COPD exacerbation: T+O 5/5 µg (285/744), T 5 µg (297/736), and O 5 µg (331/707). Demographics were generally similar including mean age (64.4/63.8 years) and the proportions of current smokers (35.7%/37.5%) and their mean pack-years (46.9/45.9), but there were more women (32.5%/25.0%) and fewer Asian patients (18.2%/28.2%) in the exacerbation group. Patients who had an on-study exacerbation were more likely to have had an exacerbation in the past year (804/1392 [54.2%/37.8%]), and have received at least one course of antibiotics (52.5%/37.1%) and oral or intravenous steroids (39.8%/22.1%) in the past year. The exacerbation group had longer median (range) duration of COPD (6.0 [0-43.0]/4.8 [0-45.3] years), had lower post-bronchodilator mean FEV1 (1.238/1.429 L) and a higher proportion were GOLD 3/4 (60.6%/45.4%). Pulmonary medication use at baseline was higher in the exacerbation group (87.6%/76.3%), including ICS use at baseline (59.2%/42.6%). CONCLUSIONS: While demographics were similar in patients with and without on-study exacerbations, patients with exacerbations had longer duration of COPD and more severe COPD in terms of lung function, prior exacerbations, and use of baseline pulmonary and other medications. CLINICAL IMPLICATIONS: Analysis of this population, in which approximately one-third of patients had an exacerbation, confirms earlier findings that prior exacerbations are the major risk factor for future events. Funding: Boehringer Ingelheim. Editorial assistance: Complete HealthVizion. DISCLOSURE: Roger Abrahams: Other: Boehringer-Ingelheim Gary Ferguson: Consultant fee, speaker bureau, advisory committee, etc.: Boehringer-Ingelheim, AstraZeneca, Pearl Therapeutics, Novartis, Forest, Sunovion, Verona, Receptos, GlaxoSmithKline, Other: Boehringer-Ingelheim, AstraZeneca, Pearl Therapeutics, Sunovion, Sunovion, Theravance, Sanofi, Forest, GlaxoSmithKline Florian Voss: Employee: Boehringer-Ingelheim Pharma GmbH & Co. KG Carlos Tafur: Employee: Boehringer-Ingelheim Roland Buhl: Consultant fee, speaker bureau, advisory committee, etc.: AstraZeneca, Boehringer-Ingelheim, Chiesi, GlaxoSmithKline, Novartis, TEVA, Roche, Other: Boehringer-Ingelheim, GlaxoSmithKline, Novartis, Roche The following authors have nothing to disclose: Leif Bjermer, Emilio Pizzichini No Product/Research Disclosure Information

TIOtropium Safety and Performance In Respimat® (TIOSPIRTM): Analysis of Asian cohort of COPD patients

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. 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). 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. 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.

Safety and tolerability of once-daily tiotropium Respimat® as add-on to at least inhaled corticosteroids in adult patients with symptomatic asthma: A pooled safety analysis

BackgroundTiotropium, a long-acting anticholinergic bronchodilator, has demonstrated efficacy and safety as add-on therapy to inhaled corticosteroids (ICS), with or without other maintenance therapies, in patients with symptomatic asthma. ObjectiveTo evaluate safety and tolerability of tiotropium delivered via the Respimat® device, compared with placebo, each as add-on to at least ICS therapy, in a pooled sample of adults with symptomatic asthma at different treatment steps. MethodsData were pooled from seven Phase II and III, randomised, double-blind, parallel-group trials of 12–52 weeks’ treatment duration, which investigated once-daily tiotropium Respimat® (5 μg, 2.5 μg) versus placebo as add-on to different background maintenance therapy including at least ICS. Adverse events (AEs) including serious AEs were assessed throughout treatment + 30 days after the last dose of trial medication. ResultsOf 3474 patients analysed, 2157 received tiotropium. The percentage of patients with AEs was comparable between treatment groups: tiotropium 5 μg, 60.8%; placebo 5 μg pool, 62.5%; tiotropium 2.5 μg, 57.1%; placebo 2.5 μg pool, 55.1%. Consistent with the disease profile, the most frequent AEs overall were asthma, decreased peak expiratory flow rate (both less frequent with tiotropium) and nasopharyngitis. Overall incidence of dry mouth, commonly associated with use of anticholinergics, was low: tiotropium 5 μg, 1.0%; placebo 5 μg pool, 0.5%; tiotropium 2.5 μg, 0.4%; placebo 2.5 μg pool, 0.5%. The percentage of cardiac disorder AEs was comparable between tiotropium and placebo: tiotropium 5 μg, 1.4%; placebo 5 μg pool, 1.4%; tiotropium 2.5 μg, 1.4%; placebo 2.5 μg pool, 1.1%. The proportions of patients with serious AEs were balanced across groups: tiotropium 5 μg, 4.0%; placebo 5 μg pool, 4.9%; tiotropium 2.5 μg, 2.0%; placebo 2.5 μg pool, 3.3%. ConclusionTiotropium Respimat® demonstrated safety and tolerability comparable with those of placebo, as add-on to at least ICS therapy, at different treatment steps in adults with symptomatic asthma.

Tiotropium for the treatment of asthma: a drug safety evaluation

ABSTRACTIntroduction: Tiotropium, a once-daily long-acting anticholinergic bronchodilator, has recently been approved for use in the treatment of asthma in a number of countries, including the EU and the USA, and was incorporated into the 2015 update of the Global Initiative for Asthma treatment guidelines. Here we review safety data from published clinical trials to help inform the use of tiotropium in the treatment of patients with asthma.Areas covered: Safety data from recently published clinical trials, which compared tiotropium with placebo or an active control, were reviewed. Trials included children, adolescents, and adults across severities of symptomatic asthma, and assessed tiotropium delivered via the Respimat and HandiHaler devices.Expert opinion: Based on the reviewed scientific evidence, tiotropium is a safe and well-tolerated long-acting anticholinergic bronchodilator for use in the treatment of asthma. In the trials assessed, the safety of tiotropium was found to be comparable with that of placebo and alternative therapeutic options, including a doubling in the dose of inhaled corticosteroids and the long-acting β2-agonist salmeterol.

Tiotropium safety in ‘real‐world’ populations

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.

Tiotropium Safety and Performance in Respimat (TIOSPIR) Study: Analysis of Demographic Characteristics and Clinical Outcomes in Patients Enrolled in Asia Countries (Excluding China) Versus Rest of the World

Tiotropium Safety and Performance in Respimat (TIOSPIR) Study: Analysis of Demographic Characteristics and Clinical Outcomes in Patients Enrolled in Asia Countries (Excluding China) Versus Rest of the World

Tiotropium Safety and Performance in Respimat (TIOSPIR) Study: Analysis of Demographic Characteristics and Clinical Outcomes in Patients Enrolled in China Versus Rest of the World

Tiotropium Safety and Performance in Respimat (TIOSPIR) Study: Analysis of Demographic Characteristics and Clinical Outcomes in Patients Enrolled in China Versus Rest of the World

Efficacy and Safety of Tiotropium in the Treatment of Severe Persistent Asthma:Meta-analysis.

To evaluate the efficacy and safety of tiotropium in treatment of severe persistent asthma. Reports of randomized controlled trials (RCTs) describing tiotropium for treatment of severe persistent asthma published from January 1946 to February 2015 were searched in Cochrane Library, ClinicalTrials.gov, PubMed, Ovid Medline, CNKI, and CSJD. The data of the included RCTs were extracted and the data quality was evaluated. Meta-analyses were performed with Revman 5.3 software. Five RCTs including 1433 patients were analyzed. Meta-analysis of the data showed that compared with the placebo group, tiotropium treatment significantly improved the patients' peak forced expiratory volume in one second (FEV1) [weighted mean difference (WMD): 0.13 L, 95% confidence interval (CI): 0.10-0.16 L, P<0.00001], trough FEV1 (WMD: 0.09 L, 95%CI: 0.06-0.12 L, P<0.00001), peak forced vital capacity (FVC) (WMD: 0.10 L, 95%CI: 0.06-0.14 L, P<0.00001), trough FVC (WMD: 0.12 L, 95%CI: 0.08-0.17 L, P<0.00001), morning peak expiratory flow (PEF) (WMD: 9.21 L/min, 95%CI: 4.2-14.23 L/min, P=0.0003), evening PEF (WMD: 22.06 L/min, 95%CI 13.05-31.08 L/min, P<0.00001). The scores of asthma control questionnaire (ACQ) (WMD: 0.01, 95% CI: -0.07-0.09, P=0.86) or asthma quality of life questionnaire (AQLQ)(WMD: 0.06, 95% CI:-0.18-0.06, P=0.33) were not affected by tiotropium. No significant difference with adverse events between tiotropium group and placebo group were reported in these included studies (P>0.05). Tiotropium for severe persistent asthma treatment can improve FEV1, FVC, and PEF but may not improve the quality of life of the patients. Tiotropium is well tolerated and can be an add-on therapy for severe persistent asthma.

Safety and efficacy of tiotropium in patients switching from HandiHaler to Respimat in the TIOSPIR trial

ObjectivesThis 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)...

Current role of anticholinergic drugs in the treatment of asthma: key messages for clinical practice

Anticholinergic bronchodilators such as tiotropium, a potent long-acting drug, are central to the symptomatic treatment of chronic obstructive pulmonary disease. Its role in asthma treatment has been recently investigated. This review critically evaluates documented evidence of clinical trials and assesses the therapeutic implications of anticholinergic drugs in asthma management. So far, the results of 10 Phases II and III randomized controlled trials evaluating the effect of adding tiotropium to the treatment of mild-to-moderate or severe asthma have been published. These trials had a duration of 4 to 52 weeks and involved 3368 subjects with mild-to-moderate asthma and 1019 subjects with severe asthma [corrected]. Also, 1 systematic review and 6 meta-analyses have appraised the results of published and unpublished trials investigating the role of tiotropium in asthma. The results of the trials in mild to moderate asthma showed that adding tiotropium to inhaled corticosteroids (ICSs) was not inferior to adding long-acting β2-agonists (LABAs). In addition, the safety and efficacy of tiotropium were similar to those of salmeterol. The results of studies on severe asthma showed that adding tiotropium to a treatment with high doses of an ICS plus LABA results in further improvement in lung function, increases the time to the first severe exacerbation of asthma and to worsening of asthma, and improves asthma control. Except for dry mouth, the safety profile of tiotropium was similar to placebo both in moderate and in severe asthma. Adding tiotropium to an ICS or ICS plus LABA improves lung function, symptoms, and asthma control, and in severe asthma, it increases the time to exacerbations, with good safety profile. The effect seems independent of baseline characteristics such as age, level of bronchial obstruction, smoking status, allergic status, and bronchial reversibility.

Combined bronchodilators (tiotropium plus olodaterol) for patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD), a respiratory disease characterized by a progressive decline in lung function, is considered to be a leading cause of morbidity and mortality. Long-acting inhaled bronchodilators, such as long-acting β2 agonists (LABAs) or long-acting muscarinic antagonists (LAMAs), are the cornerstone of maintenance therapy for patients with moderate-to-very-severe COPD. For patients not sufficiently controlled on a single long-acting bronchodilator, a combination of different bronchodilators has shown a significant increase in lung function. Tiotropium, a once-daily dosing LAMA, demonstrated sustained improvements in lung function as well as improved health-related quality of life, reduced exacerbations, and increased survival without altering the rate of decline in the mean forced expiratory volume in 1 second (FEV1) with fairly tolerable side effects. Olodaterol is a once-daily dosing LABA that has proven to be effective in improving lung function, reducing rescue medication use, and improving dyspnea and health-related quality of life, as well as improving exercise endurance with an acceptable safety profile. The combination of olodaterol and tiotropium provided additional improvements in lung function greater than monotherapy with each drug alone. Several well-designed randomized trials confirmed that the synergistic effect of both drugs in combination was able to improve lung function and health-related quality of life without a significant increase in adverse effects. The objective of this paper is to review available evidence on the clinical efficacy and safety of tiotropium, olodaterol, and their combination in patients with COPD.

COMPARATIVE EFFICACY AND SAFETY OF INHALED INDACATEROL AND TIOTROPIUM IN GOLD STAGE-2 PATIENTS OF COPD

Background:Current treatment guidelines, such as those from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) describe bronchodilators as the first-line therapy for patients with moderate to very severe COPD (stage 2-4 of GOLD Spirometric Criteria for COPD Severity). Indacaterol is a new once daily inhaled bronchodilator, recently approved for the treatment of COPD. Once daily dosing is an important step to improve the adherence and compliance of the patients. Methods: In this prospective, parallel group and open labelled study we compared Efficacy and Safety of Indacaerol and Tiotropium in Patients of Satge-2 GOLD. Total 60 patients were finally evaluated in the study. They were divided in two groups, group-1 (Indacaterol group) and group-2 (Tiotropium group) receiving 150 mcg/daily of Indacaterol and 18 mcg/daily of Tiotropium in each group respectively. All patients were evaluated by measuring FEV1 at zero day (before therapeutic intervention), 2, 4, 6, 8, 10 and 12 weeks. Results: Patients in both group showed gradual improvement at 2, 4, 6, 8, 10 and 12 weeks, but there was better improvement in Tiotropium as compared to Indacaterol group in terms of FEV1 . Although this difference was not statistically significant. Conclusion: Indacaterol 150 mcg/day is equally effective as Tiotropium in dose of 18 mcg /day patients of moderate COPD (stage-2 GOLD criteria).

Cardiac safety of tiotropium in patients with cardiac events: a retrospective analysis of the UPLIFT® trial.

BackgroundTiotropium is an anticholinergic bronchodilator for symptom relief and reducing exacerbations with an established safety profile in patients with chronic obstructive pulmonary disease (COPD). Using data from the 4-year Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT®) study, we re-evaluated the safety of tiotropium HandiHaler® in patients who experienced recent myocardial infarction (MI), heart failure or unstable rhythm disorder during the study.MethodsA post-hoc analysis of all-cause mortality and serious cardiac adverse events (cardiac SAEs), including cardiac deaths and death unknown, was conducted in patients who had experienced cardiac arrhythmia, MI or cardiac failure during UPLIFT® and who completed the study. Descriptive analyses were performed.ResultsMost patients experiencing cardiac events, for which they would have been excluded at baseline, remained in the trial. Kaplan-Meier analyses revealed a trend to later occurrence of cardiac SAEs with tiotropium HandiHaler® versus placebo. Patients who experienced a cardiac event and continued in UPLIFT® were not found to be at subsequently increased risk of all-cause mortality or cardiac SAEs with tiotropium treatment. Evaluation of deaths by major adverse cardiac events composite endpoints also showed that patients treated with tiotropium were not at increased risk of mortality or cardiac SAEs compared with placebo.ConclusionsRisk of cardiac events, mortality or SAEs was not increased by tiotropium in patients experiencing cardiac events for which they would have been excluded at study baseline. The findings support the cardiac safety of tiotropium HandiHaler® in patients with COPD.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-015-0216-4) contains supplementary material, which is available to authorized users.