Overactive bladder (OAB) is a common condition affecting the quality of life of many people. Antimuscarinics, the current first-line treatments for OAB are associated with adverse events which are more likely to occur in patients with either multimorbidity or polypharmacy [1], however, clinicians could benefit from a clearer understanding of the benefit/risk ratio of antimuscarinics in order to manage patient expectations and, where possible, improve adherence to medication. This study examined the efficacy and safety information from patients in fesoterodine trials to explore the relationship between Treatment Emergent Adverse Events (TEAE)  and clinical response defined according to resolution of OAB symptoms.

This study used pooled data from 6 fixed dose studies of fesoterodine (A0221008, A0221012, A0221013, A0221046, A0221094, A0221095) each a published, parallel, 12-week, double blind RCT.  For each treatment arm, patients were categorized according to whether they achieved either a 50% or 100% decrease in urgency episodes/24h (UUE) at 12 weeks. Analysis was based on the full analysis set (FAS) which included all subjects who took at least one dose of assigned study drug and contributed data to at least one baseline and post-baseline efficacy assessment with the baseline value of the outcome variable > 0. AE occurring up to 7 days post exposure to study drug were included. CNS and cognitive AE were specifically included according to MEDRA accepted terms.

Of the 6689 included patients, (fesoterodine 4mg, 1373, fesoterodine 8mg 3263, placebo 2053, mean age 58.4y) the most frequent TEAE in the fesoterodine groups were dry mouth and constipation. Responders tended to have similar or numerically lower rates of TEAEs compared to the whole study population (Table 1). CNS and cognitive adverse events were few across all treatment arms and categories of response to urgency symptoms.

The most frequent TEAE were dry mouth and constipation. Fewer than 3% of TEAEs were serious or led to treatment discontinuation. With the exception of dry mouth, resolution in urgency symptoms appeared to be associated with a lower likelihood of adverse events compared to TEAE in all patients. Whether this reflected a "tolerance" on behalf of individual patients who balanced benefit against adverse effects or a true drug effect remains speculative. An association between cognitive TEAE and fesoterodine dose or the resolution of urgency symptoms was not observed. However, the incidence of these AE was low across all treatment groups

Compared to all treated patients, resolution of urinary urgency by either 50% or 100% at week 12 appears to be associated with a reduction in TEAE.  The incidence of CNS and cognitive AE was low regardless of fesoterodine dose

Age Ageing. 2017 Jul 1;46(4):620-626.