Heightened response of eosinophilic asthmatic patients to the CRTH2 antagonist OC000459. Issue 9 (14th July 2014)

• Record Type: Journal Article
• Authors: Pettipher, R.; Hunter, M. G.; Perkins, C. M.; Collins, L. P.; Lewis, T.; Baillet, M.; Steiner, J.; Bell, J.; Payton, M. A.
• Is Part Of: Allergy. Volume 69:Issue 9(2014:Sep.)
• Page Start: 1223
• Page End: 1232
• Publication Date: 2014-07-14
• Subjects: Allergy -- Periodicals; 616.97
• DOI: 10.1111/all.12451
• Languages: English
• ISSNs: 0105-4538

Abstract

<abstract abstract-type="main" id="all12451-abs-0001"> <title>Abstract</title> <sec id="all12451-sec-0001" sec-type="section"> <title>Background</title> <p>The CRTH2 antagonist OC000459 has previously been demonstrated to reduce airway inflammation and improve lung function in moderate persistent asthma. A study was conducted to determine the effect of lower once daily doses of OC000459 and to define the phenotype of subjects most responsive to treatment.</p> </sec> <sec id="all12451-sec-0002" sec-type="section"> <title>Methods</title> <p>Adult subjects (percentage of predicted forced expiratory volume in 1 s (FEV<sub>1</sub>) 60–85%) were randomized to OC000459 at three dose levels (25 mg once daily, 200 mg once daily or 100 mg twice daily) or placebo for 12 weeks (<italic>n</italic> = 117–125 per group, full analysis set). The primary endpoint was the change from baseline in prebronchodilator FEV<sub>1</sub>, and secondary endpoints included Asthma Control Questionnaire (ACQ) and Standardised Asthma Quality of Life Questionnaire [AQLQ(S)], and incidence of exacerbations and respiratory tract infections.</p> </sec> <sec id="all12451-sec-0003" sec-type="section"> <title>Results</title> <p>OC459 caused a significant improvement in FEV<sub>1</sub> compared with placebo at a dose of 25 mg once daily (<italic>P</italic> = 0.028). A similar increase was observed in the other dose groups, and the mean change in FEV<sub>1</sub> in the pooled dose groups at endpoint was 95 ml greater than placebo (<italic>P</italic> = 0.024). In a <italic>post hoc</italic> analysis of atopic eosinophilic subjects with uncontrolled asthma, a mean increase in FEV<sub>1</sub> of 220 ml was observed compared with placebo (<italic>P</italic> = 0.005). The mean increase in FEV<sub>1</sub> was more marked in younger subjects in this group: for subjects aged ≤40 years, there was a mean increase of 355 ml compared with placebo (<italic>P</italic> = 0.007). Improvements in ACQ and AQLQ(S) were observed in both the full analysis set and the atopic eosinophilic subgroup. There was a lower incidence of exacerbations and respiratory infections in subjects treated with OC000459. There were no drug‐related serious adverse events.</p> </sec> <sec id="all12451-sec-0004" sec-type="section"> <title>Conclusions</title> <p>OC000459 is a safe and effective oral anti‐inflammatory agent, which achieved clinically meaningful improvements in lung function and asthma control in allergic asthmatics with an eosinophil‐dominant form of the disease. A dose of 25 mg given once daily was as effective as the higher doses studied.</p> </sec> </abstract>