Dataset Information

Efficacy and safety of the CRTh2 antagonist AZD1981 as add-on therapy to inhaled corticosteroids and long-acting ?2-agonists in patients with atopic asthma.

ABSTRACT: Objectives:To evaluate the efficacy and safety of AZD1981, a potent, specific antagonist of the CRTh2 receptor, as add-on therapy to inhaled corticosteroids (ICS) and long-acting ?2-agonists (LABA), in patients with persistent asthma with an allergic component. Patients and methods:In this placebo-controlled, parallel-group Phase IIb study, patients with persistent atopic asthma on ICS and LABA were randomized to receive 12 weeks of treatment with placebo or AZD1981 (80 mg daily, 200 mg daily, and 10 mg, 40 mg, 100 mg, or 400 mg twice daily [BID]). The primary end point was the mean change from baseline in predose, prebronchodilator forced expiratory volume in 1 second (FEV1) averaged over weeks 2, 4, 8, and 12 in the AZD1981-treatment group vs the placebo group. Secondary end points included other measures of lung function, symptoms, and asthma control, as well as standard measures of safety. Results:In total, 1,140 patients (99.7%) received study treatment. There were improvements in the primary end point across all treatment groups over 12 weeks of treatment. However, the improvement for the highest AZD1981 dose (400 mg BID) vs placebo was not statistically significant (0.02 L, P=0.58), preventing interpretation of statistical testing for the lower doses. AZD1981 was well tolerated, and the incidence of adverse events was comparable across placebo and treatment groups. Conclusion:In patients with allergic asthma receiving ICS and LABA therapy, the addition of AZD1981 at doses up to 400 mg BID failed to produce a clinically relevant improvement in lung function or any other measured end point, but appeared to have an acceptable safety profile. This clinical study is registered with ClinicalTrials.gov (NCT01197794).

SUBMITTER: Bateman ED

PROVIDER: S-EPMC5942163 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Efficacy and safety of the CRTh2 antagonist AZD1981 as add-on therapy to inhaled corticosteroids and long-acting β<sub>2</sub>-agonists in patients with atopic asthma.

Bateman Eric D ED O'Brien Christopher C Rugman Paul P Luke Sally S Ivanov Stefan S Uddin Mohib M

Drug design, development and therapy 20180504

<h4>Objectives</h4>To evaluate the efficacy and safety of AZD1981, a potent, specific antagonist of the CRTh2 receptor, as add-on therapy to inhaled corticosteroids (ICS) and long-acting β<sub>2</sub>-agonists (LABA), in patients with persistent asthma with an allergic component.<h4>Patients and methods</h4>In this placebo-controlled, parallel-group Phase IIb study, patients with persistent atopic asthma on ICS and LABA were randomized to receive 12 weeks of treatment with placebo or AZD1981 (80 ...[more]

PMID: 29765200

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Project description:BackgroundSuboptimal adherence to maintenance medication has been associated with poor outcomes in asthma. This study examined single-inhaler inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) adherence and asthma-related outcomes.MethodsThis retrospective observational study of patients with asthma initiating ICS/LABA used data from IQVIA PharMetrics Plus (1 January 2014-31 March 2019). Patients included were ⩾18 years old and had ⩾12 months continuous eligibility before, and ⩾180 days follow-up after, the index date. Adherence was measured as proportion of days covered ([PDC] adherent ⩾ 0.8; non-adherent <0.8) each quarter, with outcomes measured each subsequent quarter. Endpoints were asthma-related overall and severe (inpatient/emergency department [ED] visit) exacerbations, rescue medication use, and asthma-related healthcare resource utilization and costs. Regression models evaluated associations between adherence and outcomes, controlling for repeated measures and differences in baseline characteristics.ResultsOverall, 50,037 patients were included (mean age 45.3 years; mean follow-up 23.3 months). Adherent patients were less likely to experience asthma-related overall (adjusted odds ratio [aOR] 95% confidence interval [CI]: 0.942 [0.890, 0.998]; p = 0.041), or severe exacerbations (aOR [95% CI]: 0.778 [0.691, 0.877]; p < 0.001) per quarter versus non-adherent patients. Adherent patients had lower severe exacerbation rates (adjusted rate ratio [aRR] [95% CI]: 0.792 [0.702, 0.893]; p < 0.001) but similar overall exacerbation rates (aRR [95% CI]: 0.993 [0.945, 1.044]; p = 0.783) versus non-adherent patients. The odds of rescue medication use were lower per 20% PDC increase (aOR [95% CI] short-acting β2 agonist: 0.991 [0.985, 0.996]; p = 0.001; oral corticosteroid: 0.988 [0.982, 0.995]; p < 0.001). Adherent patients were less likely to visit EDs per quarter (aOR [95% CI]: 0.775 [0.680, 0.883]; p < 0.001) and odds of hospitalization were lower per 20% PDC increase (aOR [95% CI]: 0.930 [0.881, 0.982]; p = 0.009). Across most measures, adherent patients incurred lower costs.ConclusionThis real-world study highlights the short-term clinical and economic benefits of ICS/LABA adherence in asthma, particularly in reducing severe exacerbations.

Project description:BackgroundThe Risk of Bias (RoB) tool is used to assess internal validity of randomized controlled trials (RCTs). Our objectives were to: 1) evaluate inter-rater agreement of the RoB tool; 2) determine the time to access supplemental study information; 3) compare the RoB tool with the Jadad scale and Schulz allocation concealment (AC); and 4) examine the relationship between RoB and effect estimates.MethodsWe conducted a systematic review of long-acting beta agonists (LABA) combined with inhaled corticosteroids (ICS) for adults with persistent asthma. Two reviewers independently assessed 107 trials using RoB, Jadad, and AC. One reviewer searched for study protocols. We assessed inter-rater agreement using weighted Kappa (?) and the correlation between tools using Kendall's Tau (?). Mean differences in effect sizes for RCTs with different RoB were calculated using inverse variance method and random effects model.ResultsTrials had good Jadad scores (median 4, IQR 3-4); however, 85% had unclear AC and 87% high RoB. The factor that most influenced RoB was the potential inappropriate influence of study sponsors (95% industry funded). Agreement on RoB domains was fair (??=?0.40) to almost perfect (??=?0.86), and moderate for overall RoB (??=?0.41). Median time to complete RoB assessments was 21 minutes (IQR 14-27) and 12 minutes (IQR 9-16) to search for protocols. Protocols were identified for 5/42 studies (12%); in 3 cases the assessment of selective outcome reporting changed. There was low correlation between overall RoB vs. Jadad (??=?0.04, p?=?0.3) and AC (??=?-0.02, p?=?0.7). Analyses comparing effect estimates and risk showed no important patterns.ConclusionsInter-rater agreement on RoB assessments was better than previously reported suggesting that review-specific guidelines are important. The correlation between RoB and Jadad was low suggesting measurement of different constructs (risk of bias vs. quality of reporting). The extensive involvement of the pharmaceutical industry in this LABA/ICS research should raise concerns about potential overestimates of treatment effects.

Dataset Information

Efficacy and safety of the CRTh2 antagonist AZD1981 as add-on therapy to inhaled corticosteroids and long-acting ?2-agonists in patients with atopic asthma.

Publications

Efficacy and safety of the CRTh2 antagonist AZD1981 as add-on therapy to inhaled corticosteroids and long-acting β<sub>2</sub>-agonists in patients with atopic asthma.

Similar Datasets

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