PURPOSE: To assess the effect of β2-adrenergic receptor Gly16Arg variation on clinical responses in asthma patients maintained on budesonide/formoterol or receiving budesonide after formoterol withdrawal.
METHODS: Gly16Arg genotype was determined in 586 patients aged ≥16 years participating in a 12-week, multicenter, double-blind study (SD-039-0726) after completion of the main clinical study. After a 4–5 week run-in period of asthma control optimization with budesonide/formoterol pMDI 80/4.5 μg x 2 inhalations (160/9 μg) bid, stable patients were equally randomized to receive 2 inhalations of budesonide/formoterol pMDI 160/4.5 μg (320/9 μg) qd, budesonide/formoterol pMDI 80/4.5 μg (160/9 μg) qd, budesonide/formoterol pMDI 80/4.5 μg (160/9 μg) bid, budesonide pMDI 160 μg (320 μg) qd, or placebo.
RESULTS: 242 (41%) patients were Gly/Gly, 251 (43%) Gly/Arg, and 93 (16%) Arg/Arg. There were no clear differences between genotype groups in lung function or asthma control during the budesonide/formoterol run-in period. Patients continuing budesonide/formoterol (qd or bid) demonstrated no differences between genotype groups in changes from baseline in morning and evening peak expiratory flow (PEF), predose forced expiratory volume in 1 second (FEV1), rescue medication use, asthma symptoms, and nighttime awakenings. The budesonide and placebo groups allowed for an assessment of genotype effect after formoterol withdrawal. In these groups, there was no consistent evidence for a difference in clinical outcomes between genotype groups. Overall, few patients experienced a serious adverse event (n=4); no serious adverse event was asthma-related. One patient of each genotype (n=3) discontinued due to an asthma-related event.
CONCLUSION: These data suggest that Gly16Arg β2-adrenergic receptor variation does not affect treatment response to continued budesonide/formoterol treatment (ie, at least 16 weeks of treatment total [run-in and treatment periods combined]). No particular genotype group was at increased risk of worsening asthma after stopping formoterol therapy.
CLINICAL IMPLICATIONS: Clinical response to budesonide/formoterol treatment appears to be unaffected by 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 product discussed in this abstract (budesonide/formoterol pMDI) has been approved for use in patients with asthma. However, this abstract includes off-label discussion of a budesonide/formoterol pMDI dosing regimen (once-daily dosing of budesonide/formoterol pMDI [320/9 mcg and 160/9 mcg]). In addition, the analysis of the effect of Gly16Arg variation on patient responses to budesonide/formoterol pMDI would be considered research.