Dataset Information

Efficacy and safety of antagonists for chemoattractant receptor-homologous molecule expressed on Th2 cells in adult patients with asthma: a meta-analysis and systematic review.

ABSTRACT:

Background

Chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) antagonists are novel agents for asthma but with controversial efficacies in clinical trials. Therefore, we conducted a meta-analysis to determine the roles of CRTH2 antagonists in asthma.

Methods

We searched in major databases for RCTs comparing CRTH2 antagonists with placebo in asthma. Fixed- or random-effects model was performed to calculate mean differences (MD), risk ratio (RR) or risk difference (RD) and 95% confidence interval (CI).

Results

A total of 14 trails with 4671 participants were included in our final analysis. Instead of add-on treatment of CRTH2 antagonists to corticosteroids, CRTH2 antagonist monotherapy significantly improved pre-bronchodilator FEV₁ (MD = 0.09, 95% CI 0.04 to 0.15, P = 0.0005), FEV₁% predicted (MD = 3.65, 95% CI 1.15 to 6.14, P = 0.004), and AQLQ (MD = 0.25, 95% CI 0.09 to 0.41, P = 0.002), and reduced asthma exacerbations (RR = 0.45, 95% CI 0.23 to 0.85, P = 0.01). Rescue use of SABA was significantly decreased in both CRTH2 antagonist monotherapy (MD = - 0.04, 95% CI -0.05 to - 0.03, P < 0.00001) and as add-on to corticosteroids (MD = - 0.78, 95% CI -1.47 to - 0.09, P = 0.03). Adverse events were similar between the intervention and placebo groups.

Conclusions

CRTH2 antagonist monotherapy can safely improve lung function and quality of life, and reduce asthma exacerbations and SABA use in asthmatics.

SUBMITTER: Yang J

PROVIDER: S-EPMC6230288 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Efficacy and safety of antagonists for chemoattractant receptor-homologous molecule expressed on Th2 cells in adult patients with asthma: a meta-analysis and systematic review.

Yang Jing J Luo Jian J Yang Ling L Yang Dan D Wang Dan D Liu Bicui B Huang Tingxuan T Wang Xiaohu X Liang Binmiao B Liu Chuntao C

Respiratory research 20181109 1

<h4>Background</h4>Chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) antagonists are novel agents for asthma but with controversial efficacies in clinical trials. Therefore, we conducted a meta-analysis to determine the roles of CRTH2 antagonists in asthma.<h4>Methods</h4>We searched in major databases for RCTs comparing CRTH2 antagonists with placebo in asthma. Fixed- or random-effects model was performed to calculate mean differences (MD), risk ratio (RR) or risk diff ...[more]

PMID: 30413187

Similar Datasets

Project description:BackgroundPrevention of IgE-binding to cellular IgE-receptors by anti-IgE (Omalizumab) is clinically effective in allergic asthma, but limited by IgE threshold-levels. To overcome this limitation, we developed a single-use IgE immunoadsorber column (IgEnio). IgEnio is based on a recombinant, IgE-specific antibody fragment and can be used for the specific extracorporeal desorption of IgE.ObjectiveTo study safety and efficacy of IgEnio regarding the selective depletion of IgE in a randomized, open-label, controlled pilot trial in patients with allergic asthma and to investigate if IgEnio can bind IgE-Omalizumab immune complexes.MethodsFifteen subjects were enrolled and randomly assigned to the treatment group (n=10) or to the control group (n=5). Immunoadsorption was done by veno-venous approach, processing the twofold calculated plasma volume during each treatment. A minimum average IgE-depletion of 50% after the last cycle in the intention-to-treat population was defined as primary endpoint. Safety of the treatment was studied as secondary endpoint. In addition, possible changes in allergen-specific sensitivity were investigated, as well as clinical effects by peak flow measurement and symptom-recording. The depletion of IgE-Omalizumab immune complexes was studied in vitro. The study was registered at clinicaltrials.gov (NCT02096237) and conducted from December 2013 to July 2014.ResultsIgE immunoadsorption with IgEnio selectively depleted 86.2% (±5.1% SD) of IgE until the end of the last cycle (p<0.0001). Removal of pollen allergen-specific IgE was associated with a reduction of allergen-specific basophil-sensitivity and prevented increases of allergen-specific skin-sensitivity and clinical symptoms during pollen seasons. IgEnio also depleted IgE-Omalizumab immune complexes in vitro. The therapy under investigation was safe and well-tolerated. During a total of 81 aphereses, 2 severe adverse events (SAE) were recorded, one of which, an episode of acute dyspnea, possibly was related to the treatment and resolved after administration of antihistamines and corticosteroids.ConclusionsThis pilot study indicates that IgE immunoadsorption with IgEnio may be used to treat patients with pollen-induced allergic asthma. Furthermore, the treatment could render allergic patients with highly elevated IgE-levels eligible for the administration of Omalizumab and facilitate the desorption of IgE-Omalizumab complexes. This study was funded by Fresenius Medical Care Deutschland GmbH, Bad Homburg, Germany.

Project description:Patients with severe uncontrolled asthma still experience acute asthma symptoms and exacerbations, particularly those with non-eosinophilic inflammation who take the maximum amount of standard drug therapy. Tezepelumab, a human monoclonal antibody, can improve lung function and enhance control of asthma symptoms in those patients, regardless of the disease's baseline characteristics. This study aims to investigate the safety and efficacy of using tezepelumab in controlling severe symptoms of uncontrolled asthma. We performed a comprehensive literature search in several databases, including PubMed, Scopus, Web of Science, Cochrane Library, and clinicaltrial.gov, using a well-established search strategy to include all relevant publications. According to our inclusion criteria, we searched for randomized controlled trials comparing tezepelumab versus placebo in patients with severe, uncontrolled asthma. We analyzed the data using The Revman 5.4 program software. The search identified 589 potential articles. After excluding studies inconsistent with selection criteria, four studies were included and analyzed qualitatively and quantitatively. The pooled effect demonstrated the better performance of tezepelumab over the placebo regarding the decrease in annualized asthma exacerbation rate (MD = - 0.74, (95% CI [- 1.04, - 0.44], p < 0.00001)), asthma control questionnaire-6 (ACQ-6) Score MD = - 0.32, (95% CI [- 0.43, - 0.21], p < 0.00001)), blood eosinophil count (MD = - 139.38 cells/mcL, (95% CI [- 150.37, - 128.39], p < 0.00001)), feNO (MD = - 10 ppb, (95% CI [- 15.81, - 4.18], p = 0.0008)) and serum total IgE (MD = - 123.51 UI/ml, (95% CI [- 206.52, - 40.50], p = 0.004)). All tezepelumab groups had higher pre-bronchodilator forced expiratory volume in 1 s than the placebo group (MD = 0.16, (95% CI [0.10, 0.21], p < 0.00001)). Higher efficacy and safety profile was detected for tezepelumab to control the exacerbations of severe uncontrolled adult asthmatics.

Project description:BackgroundThis study investigated the efficacy and safety of a new asthma therapy combining fluticasone propionate and formoterol fumarate (fluticasone/formoterol; flutiform®), administered twice daily (b.i.d.) via a single aerosol inhaler, compared with its individual components administered separately and placebo, in patients with mild-to-moderate asthma.MethodsPatients aged ≥ 12 years were evenly randomised to 12 weeks of treatment with fluticasone/formoterol (100/10 μg b.i.d.), fluticasone (100 μg b.i.d.), formoterol (10 μg b.i.d.), or placebo, in this double-blind, parallel group, multicentre study. The three co-primary endpoints were: a) change in forced expiratory volume in the first second (FEV(1)) from morning pre-dose at baseline to pre-dose at week 12 for the comparison with formoterol; b) change in FEV(1) from morning pre-dose at baseline to 2 hours post-dose at week 12 for the comparison with fluticasone, and c) time to discontinuation due to lack of efficacy from baseline to week 12 for the comparison with placebo. Safety was assessed based on adverse events, clinical laboratory tests and vital sign evaluations.ResultsStatistically significant differences were demonstrated for all the three co-primary endpoints. Fluticasone/formoterol combination therapy showed significantly greater improvements from baseline to end of study in the change in pre-dose FEV(1) compared with formoterol (Least Squares (LS) mean treatment difference: 0.101 L; 95% Confidence Interval (CI): 0.002, 0.199; p = 0.045) and the change in pre-dose compared with 2 hours post-dose FEV(1) versus fluticasone (LS mean treatment difference: 0.200 L; 95% CI: 0.109, 0.292; p < 0.001). The time to discontinuation due to lack of efficacy was significantly longer for patients in the combination therapy group compared with those receiving placebo (p = 0.015). Overall, the results from multiple secondary endpoints assessing lung function, asthma symptoms, and rescue medication use supported the superior efficacy of the combination product compared with fluticasone, formoterol, and placebo. The fluticasone/formoterol combination therapy had a good safety and tolerability profile over the 12 week treatment period.ConclusionsFluticasone/formoterol had a good safety and tolerability profile and showed statistically superior efficacy for the three co-primary endpoints compared to fluticasone, formoterol, and placebo, in adolescents and adults with mild-to-moderate asthma. EudraCT number: 2007-002866-36; US NCT number: NCT00393991.

Dataset Information

Efficacy and safety of antagonists for chemoattractant receptor-homologous molecule expressed on Th2 cells in adult patients with asthma: a meta-analysis and systematic review.

Background

Methods

Results

Conclusions

Publications

Efficacy and safety of antagonists for chemoattractant receptor-homologous molecule expressed on Th2 cells in adult patients with asthma: a meta-analysis and systematic review.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets