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Abstract: Slide Presentations |

BETA-ADRENERGIC RECEPTOR GLY16ARG VARIATION: EFFECT ON RESPONSE TO BUDESONIDE/FORMOTEROL OR FLUTICASONE PROPIONATE/SALMETEROL IN ASTHMA PATIENTS FREE TO VIEW

Helen Ambrose, PhD; Rachael Lawrance, BSc; Mitchell Goldman, MD PhD*
Author and Funding Information

AstraZeneca LP, Wilmington, DE


Chest


Chest. 2007;132(4_MeetingAbstracts):478a. doi:10.1378/chest.132.4_MeetingAbstracts.478a
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Abstract

PURPOSE: To assess the effect of β2-adrenergic receptor gene (ADRB2) Gly16Arg variation on response to fixed-dose (FD) or adjustable-dose (AD) budesonide/formoterol (BUD/FM) pressurized metered-dose inhaler or FD fluticasone propionate/salmeterol (FP/SM) dry powder inhaler.

METHODS: Gly16Arg genotype was determined in 405 of 1222 patients aged ≥12 years with moderate to severe persistent asthma participating in a 7-month study (D5896C00005) after completion of the clinical study. After 10–14 days (current therapy), patients were randomized 2:1 to BUD/FM FD 160/4.5 μg x 2 inhalations (320/9 μg) bid or FP/SM FD 250/50 μg x 1 inhalation bid. After 1 month, FP/SM FD patients continued therapy, and BUD/FM FD patients were randomized 1:1 to BUD/FM FD or AD (adjustable from 320/9 μg bid to 320/9 μg qd or 640/18 μg bid).

RESULTS: 169 (42%) patients were Gly/Gly, 169 (42%) Gly/Arg, and 67 (16%) Arg/Arg. Genotype groups were similar at baseline with respect to demographics and disease severity characteristics. Across all treatments, similar percentages of patients of each genotype experienced an asthma exacerbation (primary clinical outcome, defined as a worsening of asthma requiring oral corticosteroids): 9%, Gly/Gly; 8%, Gly/Arg; 9%, Arg/Arg. Only 4 subjects (3 Gly/Gly and 1 Arg/Arg) experienced hospitalizations or emergency department visits due to asthma. In all treatments, all genotype groups showed mean improvements from baseline in lung function measures (peak expiratory flow and predose forced expiratory volume in 1 second) and in mean percentage of asthma control days (defined as a 24-hour period with no asthma symptoms and no rescue medication use). All treatments were well tolerated regardless of genotype.

CONCLUSION: There was no evidence for an effect of ADRB2 Gly16Arg variation on response to BUD/FM (AD or FD) or FP/SM FD in this patient population; in particular, there was no evidence that patients with the Arg/Arg genotype had greater incidence of exacerbations than patients with other genotypes.

CLINICAL IMPLICATIONS: The results suggest interindividual variability in response to inhaled corticosteroid/long-acting β2-agonist combination therapy cannot be predicted by ADRB2 Gly16Arg genotype.

DISCLOSURE: Mitchell Goldman, Shareholder All authors hold stock in AstraZeneca, the sponsor company; Employee All authors are employees of AstraZeneca; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. The products discussed in this abstract (budesonide/formoterol pMDI and fluticasone propionate/salmeterol DPI) have been approved for use in patients with asthma. However, this abstract includes off-label discussion of a budesonide/formoterol pMDI dosing regimen (adjustable dosing of budesonide/formoterol pMDI 320/9 mcg). In addition, the analysis of the effect of Gly16Arg variation on patient responses to budesonide/formoterol pMDI would be considered research.

Tuesday, October 23, 2007

2:30 PM - 4:00 PM


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