PARIS—The severity of a patient’s overactive bladder (OAB) symptoms prior to treatment with fixed-dose darifenacin (Enablex) has no effect on treatment response, researchers announced here at the Fourth International Consultation on Incontinence.
Roger R. Dmochowski, MD, professor of urology at Vanderbilt University in Nashville, Tenn., and his colleagues analyzed data pooled from three fixed-dose, phase 3 darifenacin studies to determine if patients respond differently according to baseline symptom severity. The analysis included 1,053 patients randomized to receive darifenacin 7.5 mg or 15 mg once daily or matched placebos.
“A significant improvement in symptoms was observed in patients with mild/moderate and severe baseline symptoms,” he said.
OAB was considered mild/moderate if patients had fewer than 21 incontinence episodes (IEs) per week and severe if patients had 21 or more weekly episodes.
Improvement occurred within two weeks and was maintained throughout the 12-week observation period, data showed.
“As OAB symptoms and symptom severity vary between patients, OAB therapy may be optimized by individualizing treatment,” Dr. Dmochowski wrote in his poster presentation. “Symptom severity may also influence response to therapy. Furthermore, individual response to antimuscarinic therapy, the mainstay of OAB therapy, is highly variable.”
While darifenacin significantly improved OAB symptoms in the three studies included in the analysis (as indicated by a decrease in weekly urinary IEs and daily urgency episodes), patients had different degrees of OAB severity at enrollment, and the effect of baseline severity on treatment response was not evaluated in the individual trials.
All three studies were preceded by a screening visit, two-week washout if required, and a two-week treatment-free or placebo run-in period. Afterward, patients were randomized to 12 weeks of double-blind treatment with the study medication. Patients’ visits occurred at two, six, and 12 weeks. Efficacy was determined by daily diaries patients used to record IEs.
Among subjects with mild/moderate OAB, the median number of IEs per week in the 7.5- and 15-mg groups decreased by 7.0 and 9.0, respectively, from baseline to week 12, the study showed. The median number of IEs per week declined by 6.0 and 6.3 in the corresponding placebo groups.
In the cohort with severe OAB, the median number of IEs per week decreased by 15.0 and 18.5 among patients in the darifenacin 7.5-mg and 15-mg groups, respectively, compared with a median decline of 11.0 and 13.7 IEs in the corresponding placebo groups.
The lower dose of darifenacin was sufficient to achieve a significant effect in patients with mild/moderate OAB, while the higher dose was needed to achieve a significant effect in patients with severe symptoms.
The results confirm the importance of dose titration according to an individual patient’s needs and disease severity, Dr. Dmochowski said.