Can Pharmacogenetics Be Used to Predict the Response to Fesoterodine Fumarate?

Pharmacogenetics could address the challenge of predicting an individual's response to anticholinergic medications for urgency urinary incontinence (UUI).

Our objectives were to evaluate whether the metabolizer status of cytochrome p450 2D6 (CYP2D6), the drug metabolizing enzyme for fesoterodine, is associated with effectiveness or moderate/severe adverse events (AEs) from fesoterodine fumarate in women with UUI.

In this pilot pharmacogenetics study, 58 women aged ≥50 with ≥3 UUI episodes on a 3-day bladder diary were treated with fesoterodine. Participants were categorized as normal metabolizers (NM), intermediate (IM), or poor metabolizers (PM) based on their genetic CYP2D6 sequence. Effectiveness was measured by Treatment Benefit Scale (responders were "improved" or "greatly improved" versus nonresponders were "not changed" or "worsened"). Moderate and severe AEs were defined by the National Cancer Institute Common Terminology Criteria for Adverse Events.

Among 58 women, 34 (58.6%) were NM, 22 (37.9%) were IM, and 2 (3.4%) were PM. Given the small proportion of PM, we compared the NM and IM groups. Regarding effectiveness for UUI, there was no significant difference between metabolizer cohorts at 4 weeks (82.8% vs 94.4%, P  = 0.38 for NM vs IM, respectively). Metabolizer status was also not associated with moderate-severe AEs (14.7% vs 13.6% for NM vs IM, P  = 1.0).

In this pilot study with limited sample size, CYP2D6 normal and IM metabolizer status was not associated with effectiveness or moderate-severe AEs to fesoterodine fumarate. The proportion of poor metabolizers was low; thus, further investigation in this population is warranted.