Hypothesis / aims of study
Muscarinic receptor antagonists are the mainstay of pharmacological treatment of the overactive bladder syndrome (OAB) but long-term adherence is poor. Other than issues of tolerability, unmet expectations on treatment outcomes are one of the key reasons for limited adherence. Two reasons make evidence-based counseling of patients on realistic treatment outcomes of randomized controlled trials troublesome. Firstly, their formal inclusion and exclusion criteria as well as the knowledge to be a participant of a study make it difficult to extrapolate findings to a routine treatment setting. Secondly, randomized studies typically report group means for outcomes that provide little information on the probability to become free of a given symptom. Therefore, we have analyzed two large non-interventional studies to explore the probability of becoming symptom-free.
Study design, materials and methods
Two non-interventional studies of similar design were analyzed. Neither had specified inclusion or exclusion criteria other than the recommendations from the prescribing information. Patients were invited to participate if they started treatment with propiverine ER (30-45 mg/day; dose adjustment during the study was permitted) at the recommendation of their physician. Diary parameters of urgency, frequency, nocturia and incontinence were analyzed at baseline and after 12 weeks of treatment.
Patients were included in the analysis if they had a pathological value for a given symptom at baseline (at least 1 episode of urgency, nocturia or urinary incontinence or at least 8 micturitions per 24 h) and a recorded value after 12 weeks. Moreover, these analyses were repeated in subgroups with smaller and greater symptom intensity at baseline. Symptom-free was defined as no episodes at week 12 for urgency, nocturia and incontinence and ≤7 voids (all per 24 h). Due to the exploratory and post-hoc character of the evaluation, no statistical analysis was performed. Instead, we used the data from two studies to test robustness of the results.
Results
Studies 1 and 2 included 1335 (median age: 68 years, 66% female, treatment naïve: 32%) and 745 (median age: 69 years, 63% female, treatment naïve: 36%) patients, respectively. Median episode frequency in both studies was 10 for urgency, 13 for frequency, 3 for nocturia and 4 and 5 for incontinence in studies 1 and 2, respectively. Median reduction after 12 weeks in both studies was 6 for urgency (-60%), 2 for nocturia (- 67%), 3 for incontinence (-60 to -75%) and 6 and 5 for frequency in studies 1 and 2 (-54 to -62%), respectively. The probability to become free of a given symptom after 12 weeks of treatment is shown in Table 1.
Interpretation of results
The probability to become free of a given symptom was greatest for frequency and incontinence, smallest for nocturia and intermediate for urgency. Patients with a lower symptom incidence at baseline had a greater chance of becoming symptom-free, but even those with at least 14 voids or 4 incontinence episodes had a considerable chance of becoming symptom-free.
Of note, becoming free of one given symptom did not necessarily predict becoming free of the other symptoms. Moreover, this analysis only applies to those who stayed on treatment for 12 weeks.
Although the two non-interventional studies used for this analysis have been based on propiverine ER, we have no reason to believe that very different results would be obtained with other muscarinic antagonists. Nonetheless, analysis of similar datasets obtained with other OAB drugs appears desirable.