SESSION TITLE: Asthma
SESSION TYPE: Original Investigation Slide
PRESENTED ON: Wednesday, October 29, 2014 at 08:45 AM - 10:00 AM
PURPOSE: To evaluate the effect of once-daily tiotropium Respimat® (TioR) 5 µg on severe exacerbations, asthma worsening, and symptom control in patients (pts) with asthma who are symptomatic despite receiving at least ICS+LABA, by degree of airflow limitation.
METHODS: Two replicate, double-blind, placebo-controlled studies (NCT00772538; NCT00776984). Eligible pts had: ≥5-year history of asthma diagnosed before age 40 years; Asthma Control Questionnaire (ACQ)-7 score ≥1.5; experienced ≥1 exacerbation during previous year. Pts were either lifelong non-smokers or ex-smokers (<10 pack-years) who quit smoking ≥1 year before study enrollment. Co-primary endpoint: time to first severe exacerbation in pooled data at 48 weeks (asthma deterioration necessitating initiation or doubling of systemic glucocorticosteroids for ≥3 days). Secondary endpoints in pooled data at 48 weeks included time to first asthma worsening (either progressive increase in ≥1 symptoms, outside usual range, or ≥30% decline in best morning peak expiratory flow [PEF], for ≥2 consecutive days), PEF responses, and ACQ-7 response at 24 weeks. Pre-specified analyses were performed in subgroups defined by <60% and ≥60−<80% of predicted post-bronchodilator forced expiratory volume in 1 second (FEV1) values at screening.
RESULTS: 912 pts were randomized 1:1 to TioR or placebo Respimat® (pboR); TioR <60% n=178, ≥60−<80% n=272; pboR <60% n=182, ≥60−<80% n=263. At Week 48, time to first severe exacerbation and time to asthma worsening were longer with TioR vs pboR in the <60% and ≥60−<80% subgroups (HR 0.79 vs 0.82 [no significant interaction] and HR 0.73 vs 0.68 [no significant interaction], respectively). Significant improvements in PEF response vs pboR were seen for TioR in both the <60% (PEFAM 11.4 L/min, P=0.024; PEFPM 18.8 L/min, P<0.001) and ≥60−<80% subgroups (PEFAM 22.7 L/min, P<0.001; PEFPM 28.8 L/min, P<0.001). At Week 24, ACQ-7 responder rate was significantly higher with TioR vs pboR in the <60% subgroup only (55.1% vs 39.6%, respectively; OR 1.87, P=0.005).
CONCLUSIONS: Once-daily tiotropium Respimat® add-on to ICS+LABA reduced both risk of severe exacerbation and asthma worsening and improved PEF vs pboR, independent of degree of airflow obstruction; pts with a greater level of obstruction also showed improvements in asthma symptom control.
CLINICAL IMPLICATIONS: Once-daily tiotropium Respimat® add-on to ICS+LABA reduces risk of severe exacerbation and asthma worsening in pts with symptomatic asthma, independent of degree of airflow limitation.
DISCLOSURE: Donald Tashkin: Grant monies (from industry related sources): Grant from BIPI to UCLA re UPLIFT trial, Consultant fee, speaker bureau, advisory committee, etc.: Boehringer Ingelheim Speak Bureau Petra Moroni-Zentgraf: Employee: Boehringer Ingelheim Michael Engel: Employee: Boehringer Ingelheim Hendrik Schmidt: Employee: Boehringer Ingelheim Huib Kerstjens: Consultant fee, speaker bureau, advisory committee, etc.: From Boerhringer an d Pfizer, in relation to the work presented. As consultant, advisory baord member, and as principal investigator and recruiter., Consultant fee, speaker bureau, advisory committee, etc.: From Almirall, to my institution for consultancies, Consultant fee, speaker bureau, advisory committee, etc.: From Novartis, to my institution for consultancies
Presenting results from clinical trials in asthma patients of tiotropium delivered via the Respimat inhaler. Tiotropium is not approved for use in asthma. Tiotropiumâs safety and efficacy have not yet been established in asthma.