Genetics plays limited role in predicting COPD exacerbation risk, treatment response

Common genetic variants do not appear to play an important role in predicting acute exacerbations of COPD or treatment response to triple therapy, researchers reported in Respiratory Medicine.

“While COPD genome-wide association studies have been reported, revealing more than 20 genetic loci convincingly associated with COPD risk, the genetics of [acute exacerbation of] COPD specifically has only been explored in relatively small, under-powered studies,” Louise Hosking, BCs, pharmacogenetics consultant at GlaxoSmithKline, Stevenage, Hertfordshire, U.K., and colleagues wrote.

Hosking and colleagues investigated the genetic basis of acute exacerbation of COPD in 19,841 participants (40% women) from 23 clinical studies and two disease cohorts. The researchers examined pharmacogenetic effects in acute exacerbations of COPD in 8,439 patients with moderate-to-severe COPD with exacerbation rate, lung function and quality of life endpoints. They followed up for results in an additional 2,201 participants.

Thirty-five percent of participants did not experience moderate or severe exacerbations, 46% experienced at least one moderate but no severe exacerbations, 12% experienced at least one severe but no moderate exacerbations and 7% experienced both types of exacerbations.

Investigators did not find any significant associations between on-treatment response to triple therapy (Trelegy Ellipta, GlaxoSmithKline) with fluticasone furoate (FF)/umeclidinium bromide (UMEC)/vilanterol (VI) in the acute exacerbation of COPD disease analysis. They did observe a significant association with moderate-to-severe exacerbation rates and mitogen-activated protein kinase 8 (MAPK8) among participants taking FF with baseline blood eosinophils of 150 cells/µL or more in the acute exacerbation of COPD pharmacogenetics analysis.

In the post hoc analysis, Azurocidin 1 was associated with on-treatment moderate-to-severe COPD exacerbation rate when stratified by exacerbation history. In addition, Azurocidin 1 was significantly associated with a decreased annual rate of on-treatment moderate-to-severe COPD exacerbations among participants treated with FF/VI with a history of frequent exacerbations.

No signals were supported in independent follow-up in three additional clinical studies with 52-week on-treatment exacerbation data, according to the researchers..

“Given these observations, we conclude that genetics does not play a major role in [acute exacerbation of] COPD disease or in the prediction of [acute exacerbation of] COPD treatment response to FF/UMEC/VI, UMEC/VI, FF/VI, FF, UMEC, or VI treatment in patients with COPD experiencing moderate to severe exacerbations,” the researchers wrote.