Mark Vandewalker

Tiotropium improves lung function, exacerbation rate, and asthma control, independent of baseline characteristics including age, degree of airway obstruction, and allergic status

BACKGROUNDnMany patients with asthma remain symptomatic despite treatment with inhaled corticosteroids (ICS) with or without long-acting β2-agonists (LABAs). Tiotropium add-on to ICS plus a LABA has been shown to improve lung function and reduce exacerbation risk in patients with symptomatic asthma.nnnOBJECTIVEnTo determine whether the efficacy of tiotropium add-on therapy is dependent on patients baseline characteristics.nnnMETHODSnTwo randomized, double-blind, parallel-group, twin trials (NCT00772538 and NCT00776984) of once-daily tiotropium Respimat(®) 5xa0μg add-on to ICS plus a LABA were performed in parallel in patients with severe symptomatic asthma. Exploratory subgroup analyses of peak forced expiratory volume in 1xa0s (FEV1), trough FEV1, time to first severe exacerbation, time to first episode of asthma worsening, and seven-question Asthma Control Questionnaire responder rate were performed to determine whether results were influenced by baseline characteristics.nnnRESULTSn912 patients were randomized: 456 received tiotropium and 456 received placebo. Tiotropium improved lung function, reduced the risk of asthma exacerbations and asthma worsening, and improved asthma symptom control, compared with placebo, independent of baseline characteristics including gender, age, body mass index, disease duration, age at asthma onset, and FEV1 % predicted at screening and reversibility.nnnCONCLUSIONnOnce-daily tiotropium 5xa0μg compared with placebo improved lung function, reduced the risk of asthma exacerbations and asthma worsening, and improved asthma symptom control, independent of a broad range of baseline characteristics, as add-on to ICS plus LABAs in patients with severe symptomatic asthma.nnnTRIAL REGISTRYnClinicalTrials.gov; numbers NCT00772538 and NCT00776984 URL: www.clinicaltrials.gov.

Tiotropium Respimat Add-on Is Efficacious in Symptomatic Asthma, Independent of T2 Phenotype

BACKGROUNDnAdding tiotropium to existing inhaled corticosteroid (ICS) maintenance therapy with or without a long-acting β2-agonist (LABA) has been shown to be beneficial in patients with symptomatic asthma.nnnOBJECTIVEnTo assess whether responses to tiotropium Respimat add-on therapy were influenced by patients T2 status.nnnMETHODSnIn this exploratory study, data from 4 phase III trials were analyzed: once-daily tiotropium 5 μg or placebo as add-on to ICSxa0+ LABA (PrimoTinA-asthma; 2 replicate trials; NCT00772538/NCT00776984; nxa0= 912); once-daily tiotropium 5 μg or 2.5 μg, twice-daily salmeterol 50 μg, or placebo as add-on to ICS (MezzoTinA-asthma; 2 replicate trials; NCT01172808/NCT01172821; nxa0= 2100). The prespecified efficacy outcomes of these studies have been reported previously. Here, further exploratory subgroup analyses were performed to study whether these coprimary end points were influenced by serum IgE levels, blood eosinophil counts, and clinician judgment of allergic asthma. In addition, for the continuous parameters, namely, IgE and blood eosinophils, their influence on the treatment effect was modeled over the whole range of values.nnnRESULTSnTiotropium was efficacious in improving peak FEV1 within 3 hours postdose and trough FEV1, independent of T2 status. Tiotropium significantly reduced the risk of severe asthma exacerbations and asthma worsening, independent of T2 phenotype; Cox regression modeling supported a beneficial effect of tiotropium on exacerbations, independent of IgE levels or eosinophil counts. Numerical improvements in the 7-question Asthma Control Questionnaire (ACQ-7) responder rate with tiotropium versus placebo were observed in T2high and T2low patients; logistic regression modeling provided further evidence for improvement in ACQ-7 responder rates with tiotropium, independent of IgE levels or eosinophil counts.nnnCONCLUSIONSnThe results of our exploratory analyses suggest that the improvements seen with tiotropium Respimat as add-on to ICS ± LABA in patients with symptomatic asthma on lung function, exacerbation risk, and symptom control are independent of T2 phenotype.