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SYMPTOM-SPECIFIC EFFICACY OF TOLTERODINE EXTENDED RELEASE IN PRIMARY CARE PATIENTS WITH OVERACTIVE BLADDER
373
374
PREVALENCE OF INCONTINENCE AND OVERACTIVE BLADDER: EUROPEAN RESULTS FROM THE EPIC STUDY
EPIDEMIOLOGICAL STUDY OF RISK FACTORS FOR URINARY INCONTINENCE AND OVERACTIVE BLADDER IN A PRIMARY CARE POPULATION
Reilly K.1, Milsom I.2, Irwin D.3, Hunskaar S.4, Kopp Z.1, Herschorn S.5, Kelleher C.6, Hampel C.7, Artibani W.8, Abrams P.9 Pfizer, Inc, Outcomes Research, New York, United States, 2Sahlgrenska Academy At Goteborg University, Obstetrics and Gynecology, Goteborg, Sweden, 3University of North Carolina - Chapel Hill, Epidemiology, Chapel Hill, United States, 4University of Bergen, Norway, Public Health and Primary Health Care, Bergen, Norway, 5University of Toronto, Urology, Toronto, Canada, 6St. Thomas’ Hospital, London, Urology, London, United Kingdom, 7Johannes-Gutenberg-Universität, Urology, Mainz, Germany, 8University of Padua, Urology, Padua, Italy, 9Southmead Hospital, Bristol Urological Institute, Urology, Bristol, United Kingdom 1
INTRODUCTION & OBJECTIVES: To determine the prevalence of incontinence in the general and overactive bladder (OAB) populations, and the extent to which different subtypes of incontinence coexist with OAB. MATERIAL & METHODS: This was a cross-sectional population-based survey of people aged ≥18 years in Germany, Italy, Sweden, and the United Kingdom (N=14,666). Telephone interviews were conducted with a geographically stratified random sample of the population. OAB and incontinence types (urgency [UUI], stress [SUI], mixed [MUI] and other) were classified according to the 2002 International Continence Society definitions. Prevalence rates were calculated by adjusting for the age and gender distributions within each country at the time of the survey. RESULTS: The prevalence of incontinence in the general population aged ≥18 years was 5.1% in men and 12.5% in women (9.0% overall). The overall prevalence of OAB was 12.2%, and with and without incontinence, it was 4.6% (3.0% men; 6.0% women) and 7.6% (8.1% men; 7.2% women), respectively. Among those who reported OAB symptoms, approximately one third was incontinent (37.7%). The most prevalent type of incontinence was UUI in men and MUI in women. Overall, UUI (11.5%) and MUI (11.5%) were the most common types of incontinence within the OAB population (Table). Table. Prevalence (%) of Incontinence Within the OAB Population Men
Women
OAB with any incontinence
26.0
45.5
OAB with UUI only
11.7
11.4
OAB with SUI only
2.7
12.1
OAB with MUI
3.6
16.7
OAB with other incontinence only
9.0
5.3
CONCLUSIONS: Symptoms of OAB are more prevalent than all types of incontinence combined. Among the OAB population reporting incontinence, the majority has UUI and/or MUI. These data highlight the heterogeneity of the OAB population and suggest the need for appropriate diagnosis, management, and treatment of individuals with OAB, even in the absence of incontinence.
Mendive J.M.1, Armengol S.2 1 La Mina Primary Care Centre, Urology, Barcelona, Spain, 2Laboratorios Almirall, Departamento Médica, Barcelona, Spain
INTRODUCTION & OBJECTIVES: To study the prevalence of risk factors (RF) for urinary incontinence/overactive bladder (UI/OAB) in primary care patients with at least two symptoms of UI/OAB. MATERIAL & METHODS: Epidemiological, cross-sectional, multicentre, nonprobabilistic study. Patients over 18 years of age and presenting at least 2 symptoms of UI/OAB were included consecutively by 2,276 primary care physicians. RESULTS: The study included 4,674 patients. 72.6% were women, mean age was 64.7 years (SD 10.4), and mean BMI was 27.6 kg/m3 (SD 3.7). The most frequent symptoms of UI/OAB were: frequency (88.6%), urgency (82.9%), nocturia (79.7%) and urge incontinence (71.6%). Over half of the patients studied presented 3 (25.3%) or 4 (32.9%) symptoms of UI /OAB. 23.4% of patients with 2 or more symptoms of UI/OAB had not consulted previously for this reason. RFs were grouped into 5 categories: habits - 32.3% of respondents reported excessive intake (³3 cups/day) of coffee or tea and 29.9% reported intake of ³6 glasses/ day of water, juices or caffeine-free soft-drinks; treatments - 33.5% of patients were on benzodiazepines/hypnotics; 26.6% were taking antidepressants, and 21.3% were taking calcium antagonists; the most frequent risk pathologies were urinary infections in 34.6% of cases and diabetes in 23.1%; and the most frequent gender specific RFs were pregnancies (52.5% of women included had 3 or more pregnancies), and prostate disease (61.7% of men included affected of benign prostatic hypertrophy- BPH-). CONCLUSIONS: The most prevalent symptoms of UI/OAB were frequency and urgency. Almost one third of UI/OAB patients do not limit their intake of liquids. Over half of the women included had carried to term 3 or more pregnancies and over 60% of the men included had antecedents of BPH.
375
376
TOLTERODINE EXTENDED RELEASE (TER) FOR OVERACTIVE BLADDER (OAB): IMPROVEMENT IN OBJECTIVE SYMPTOMS IS CORRELATED WITH REDUCTIONS IN SYMPTOM BOTHER AND IMPROVEMENT IN HEALTH-RELATED QUALITY OF LIFE
SYMPTOM-SPECIFIC EFFICACY OF TOLTERODINE EXTENDED RELEASE IN PRIMARY CARE PATIENTS WITH OVERACTIVE BLADDER
Brodsky M.1, Glasser D.B.1, Coyne K.S.2, Jumadilova Z.3, Carlsson M.4 1
Pfizer, Inc, Medical - Urology, New York, United States, 2The Medtap Institute At Unitedbiosource, Health Outcomes, Bethesda, United States, 3Pfizer, Inc, Outcomes Research, New York, United States, 4Pfizer, Inc, Statistics, New York, United States INTRODUCTION & OBJECTIVES: We assessed the relationships among TER-related improvements in OAB symptoms and changes in Patient Perception of Bladder Condition (PPBC) and health-related quality of life (HRQL) as measured by the Overactive Bladder Questionnaire (OAB-q).
MATERIAL & METHODS: This was a 12-week, open-label trial of TER in a primary care setting. Patients (aged ≥18 y) had ≥2 episodes/3 d of urgency or urgency urinary incontinence (UUI), ≥8 micturitions/24 h, and were at least “moderately” bothered by their most bothersome symptom at baseline (BL). 3-day bladder diaries, PPBC, and OAB-q were completed at BL, week 4, and week 12. On the PPBC, patients rated their perception of bladder problems on a 6-point scale. Median % change in diary variables was analysed using a Wilcoxon signed rank test. A change ≥ the median absolute week 12 change was classified as major improvement, a change >0 but < the median as some improvement, and no change/deterioration as no improvement. For the OAB-q, a minimally important difference (MID) of 10 points was used. Spearman’s coefficients were used to correlate week-12 changes in symptoms, PPBC, and OAB-q domains. RESULTS: 863 patients were included. TER was associated with marked reductions in median % change for urgency (–78%), UUI (–80%), daytime frequency (–30%), and night time frequency (–40%); median changes were –1.2, –0.7, –2.7, and –1.0, respectively. 79% of patients had ≥1-point improvement in PPBC. There were improvements ≥ a MID of 10 points in Symptom Bother, Coping, Concern, Sleep, and Social Interaction domains and total HRQL in 90%, 81%, 85%, 78%, 55%, and 82% of patients, respectively. Symptom Bother scores decreased 63%, and HRQL scores improved 52%. Week-12 changes in symptoms correlated with changes in PPBC (r=0.26–0.36, p<0.001) and OAB-q domains (r=0.24–0.51; p<0.001). Week-12 changes in PPBC and OAB-q are presented in the Table by levels of improvement in diary variables. CONCLUSIONS: TER-treated patients showed statistically significant improvements in OAB symptoms and in PPBC and OAB-q scores. Patients who had larger reductions in symptoms also had marked improvements in PPBC, OAB Symptom Bother, and HRQL, confirming the relevance of these patient-reported outcomes in OAB.
Diary Variable Urgency
UUI
Daytime frequency
Night time frequency
OAB-q Domains (Mean Δ)
Symptom Improvement (n)
PPBC (Mean Δ)
Total HRQL
Major (452)
–2.0
39
–47
Some (281)
–1.3
25
–31
Symptom Bother
None (130)
–0.7
15
–18
Major (332)
–1.8
41
–48
Some (194)
–1.4
28
–36
None (120)
–1.2
17
–22
Major (332)
–1.9
37
–43
Some (208)
–1.4
28
–35
None (106)
–0.8
20
–25
Major (332)
–1.9
38
–43
Some (139)
–1.5
28
–38
None (175)
–1.0
21
–26
Eur Urol Suppl 2006;5(2):116
Glasser D.B.1, Elinoff V.2, Bavendam T.1, Carlsson M.3, Eyland N.4, Roberts R.G.5 Pfizer, Inc, Medical - Urology, New York, United States, 2Regional Clinical Research, Inc., Research, Endwell, United States, 3Pfizer, Inc, Statistics, New York, United States, 4Pfizer, Inc, Clinical Studies, New York, United States, 5University of Wisconsin Medical School, Family Medicine, Madison, United States INTRODUCTION & OBJECTIVES: Overactive bladder (OAB) is defined by symptoms of urgency, with or without urgency urinary incontinence (UUI), often with frequency and nocturia. Outcomes related to specific OAB symptoms are important because patients do not necessarily experience all symptoms and are not bothered by each symptom to the same degree. Obtaining outcomes in a “real-world” patient population provides physicians with information reflective of patients in their own practice. Our objective was to determine, in a primary care setting, the efficacy of tolterodine extended release (ER) for patients’ most bothersome OAB symptom. MATERIAL & METHODS: This open-label study was conducted at primary care and gynecology practices in the United States. Patients (aged ≥18 y) were eligible if they had OAB symptoms for ≥3 months and were at least “moderately” bothered by their most bothersome OAB symptom as indicated on the patient-completed OAB Bother Rating Scale. Patients were treated with tolterodine ER (4 mg QD) for 12 weeks. The primary efficacy endpoint was the percent change from baseline to week 12, using the last observation carried forward technique, in the most bothersome OAB symptom as determined by entries in a 3-day diary; secondary enpoints included changes on the Overactive Bladder Questionnaire (OAB-q) and the Patient Perception of Bladder Condition (PPBC) questionnaire. RESULTS: The most bothersome OAB symptom among the 896 patients enrolled was daytime frequency (30%), nocturnal frequency (28%), UUI (24%), and urgency (18%). Most patients (69%) had ≥1 clinically significant comorbid condition. By week 12, there were significant decreases in the median percent change in all of the most bothersome OAB symptoms in the intent-to-treat population: –80.0 (95% confidence interval [CI], –85.7 to –69.2) for UUI, –78.4 (95% CI, –83.3 to –72.2) for urgency, –40.0 (95% CI, –42.9 to –33.3) for nocturnal frequency, and –30.4 (95% CI, –33.3 to –27.3) for daytime frequency (P<0.0001). The median numeric improvement on the OAB-q symptom bother score, total health-related quality of life (HRQL) score, and the HRQL domains of coping, concern, sleep, and social interaction were all statistically significant (P<0.0001). At week 12, some improvement in overall bladder condition as measured by the PPBC was experienced by 86% of the urgency group, 79% of the nocturnal frequency group, 78% of the daytime frequency group, and 75% of the UUI group. Overall, 50% of patients reported major improvement in bladder condition. The most common adverse events were dry mouth (10%) and constipation (4%). CONCLUSIONS: In primary care patients, tolterodine ER was effective for all OAB symptoms and produced significant reductions in the patients’ most bothersome symptom, whether it was urgency, daytime frequency, nocturnal frequency, or UUI. Even in patients with comorbid conditions, tolterodine was effective and well tolerated. 1
374
PREVALENCE OF INCONTINENCE AND OVERACTIVE BLADDER: EUROPEAN RESULTS FROM THE EPIC STUDY
EPIDEMIOLOGICAL STUDY OF RISK FACTORS FOR URINARY INCONTINENCE AND OVERACTIVE BLADDER IN A PRIMARY CARE POPULATION
Reilly K.1, Milsom I.2, Irwin D.3, Hunskaar S.4, Kopp Z.1, Herschorn S.5, Kelleher C.6, Hampel C.7, Artibani W.8, Abrams P.9 Pfizer, Inc, Outcomes Research, New York, United States, 2Sahlgrenska Academy At Goteborg University, Obstetrics and Gynecology, Goteborg, Sweden, 3University of North Carolina - Chapel Hill, Epidemiology, Chapel Hill, United States, 4University of Bergen, Norway, Public Health and Primary Health Care, Bergen, Norway, 5University of Toronto, Urology, Toronto, Canada, 6St. Thomas’ Hospital, London, Urology, London, United Kingdom, 7Johannes-Gutenberg-Universität, Urology, Mainz, Germany, 8University of Padua, Urology, Padua, Italy, 9Southmead Hospital, Bristol Urological Institute, Urology, Bristol, United Kingdom 1
INTRODUCTION & OBJECTIVES: To determine the prevalence of incontinence in the general and overactive bladder (OAB) populations, and the extent to which different subtypes of incontinence coexist with OAB. MATERIAL & METHODS: This was a cross-sectional population-based survey of people aged ≥18 years in Germany, Italy, Sweden, and the United Kingdom (N=14,666). Telephone interviews were conducted with a geographically stratified random sample of the population. OAB and incontinence types (urgency [UUI], stress [SUI], mixed [MUI] and other) were classified according to the 2002 International Continence Society definitions. Prevalence rates were calculated by adjusting for the age and gender distributions within each country at the time of the survey. RESULTS: The prevalence of incontinence in the general population aged ≥18 years was 5.1% in men and 12.5% in women (9.0% overall). The overall prevalence of OAB was 12.2%, and with and without incontinence, it was 4.6% (3.0% men; 6.0% women) and 7.6% (8.1% men; 7.2% women), respectively. Among those who reported OAB symptoms, approximately one third was incontinent (37.7%). The most prevalent type of incontinence was UUI in men and MUI in women. Overall, UUI (11.5%) and MUI (11.5%) were the most common types of incontinence within the OAB population (Table). Table. Prevalence (%) of Incontinence Within the OAB Population Men
Women
OAB with any incontinence
26.0
45.5
OAB with UUI only
11.7
11.4
OAB with SUI only
2.7
12.1
OAB with MUI
3.6
16.7
OAB with other incontinence only
9.0
5.3
CONCLUSIONS: Symptoms of OAB are more prevalent than all types of incontinence combined. Among the OAB population reporting incontinence, the majority has UUI and/or MUI. These data highlight the heterogeneity of the OAB population and suggest the need for appropriate diagnosis, management, and treatment of individuals with OAB, even in the absence of incontinence.
Mendive J.M.1, Armengol S.2 1 La Mina Primary Care Centre, Urology, Barcelona, Spain, 2Laboratorios Almirall, Departamento Médica, Barcelona, Spain
INTRODUCTION & OBJECTIVES: To study the prevalence of risk factors (RF) for urinary incontinence/overactive bladder (UI/OAB) in primary care patients with at least two symptoms of UI/OAB. MATERIAL & METHODS: Epidemiological, cross-sectional, multicentre, nonprobabilistic study. Patients over 18 years of age and presenting at least 2 symptoms of UI/OAB were included consecutively by 2,276 primary care physicians. RESULTS: The study included 4,674 patients. 72.6% were women, mean age was 64.7 years (SD 10.4), and mean BMI was 27.6 kg/m3 (SD 3.7). The most frequent symptoms of UI/OAB were: frequency (88.6%), urgency (82.9%), nocturia (79.7%) and urge incontinence (71.6%). Over half of the patients studied presented 3 (25.3%) or 4 (32.9%) symptoms of UI /OAB. 23.4% of patients with 2 or more symptoms of UI/OAB had not consulted previously for this reason. RFs were grouped into 5 categories: habits - 32.3% of respondents reported excessive intake (³3 cups/day) of coffee or tea and 29.9% reported intake of ³6 glasses/ day of water, juices or caffeine-free soft-drinks; treatments - 33.5% of patients were on benzodiazepines/hypnotics; 26.6% were taking antidepressants, and 21.3% were taking calcium antagonists; the most frequent risk pathologies were urinary infections in 34.6% of cases and diabetes in 23.1%; and the most frequent gender specific RFs were pregnancies (52.5% of women included had 3 or more pregnancies), and prostate disease (61.7% of men included affected of benign prostatic hypertrophy- BPH-). CONCLUSIONS: The most prevalent symptoms of UI/OAB were frequency and urgency. Almost one third of UI/OAB patients do not limit their intake of liquids. Over half of the women included had carried to term 3 or more pregnancies and over 60% of the men included had antecedents of BPH.
375
376
TOLTERODINE EXTENDED RELEASE (TER) FOR OVERACTIVE BLADDER (OAB): IMPROVEMENT IN OBJECTIVE SYMPTOMS IS CORRELATED WITH REDUCTIONS IN SYMPTOM BOTHER AND IMPROVEMENT IN HEALTH-RELATED QUALITY OF LIFE
SYMPTOM-SPECIFIC EFFICACY OF TOLTERODINE EXTENDED RELEASE IN PRIMARY CARE PATIENTS WITH OVERACTIVE BLADDER
Brodsky M.1, Glasser D.B.1, Coyne K.S.2, Jumadilova Z.3, Carlsson M.4 1
Pfizer, Inc, Medical - Urology, New York, United States, 2The Medtap Institute At Unitedbiosource, Health Outcomes, Bethesda, United States, 3Pfizer, Inc, Outcomes Research, New York, United States, 4Pfizer, Inc, Statistics, New York, United States INTRODUCTION & OBJECTIVES: We assessed the relationships among TER-related improvements in OAB symptoms and changes in Patient Perception of Bladder Condition (PPBC) and health-related quality of life (HRQL) as measured by the Overactive Bladder Questionnaire (OAB-q).
MATERIAL & METHODS: This was a 12-week, open-label trial of TER in a primary care setting. Patients (aged ≥18 y) had ≥2 episodes/3 d of urgency or urgency urinary incontinence (UUI), ≥8 micturitions/24 h, and were at least “moderately” bothered by their most bothersome symptom at baseline (BL). 3-day bladder diaries, PPBC, and OAB-q were completed at BL, week 4, and week 12. On the PPBC, patients rated their perception of bladder problems on a 6-point scale. Median % change in diary variables was analysed using a Wilcoxon signed rank test. A change ≥ the median absolute week 12 change was classified as major improvement, a change >0 but < the median as some improvement, and no change/deterioration as no improvement. For the OAB-q, a minimally important difference (MID) of 10 points was used. Spearman’s coefficients were used to correlate week-12 changes in symptoms, PPBC, and OAB-q domains. RESULTS: 863 patients were included. TER was associated with marked reductions in median % change for urgency (–78%), UUI (–80%), daytime frequency (–30%), and night time frequency (–40%); median changes were –1.2, –0.7, –2.7, and –1.0, respectively. 79% of patients had ≥1-point improvement in PPBC. There were improvements ≥ a MID of 10 points in Symptom Bother, Coping, Concern, Sleep, and Social Interaction domains and total HRQL in 90%, 81%, 85%, 78%, 55%, and 82% of patients, respectively. Symptom Bother scores decreased 63%, and HRQL scores improved 52%. Week-12 changes in symptoms correlated with changes in PPBC (r=0.26–0.36, p<0.001) and OAB-q domains (r=0.24–0.51; p<0.001). Week-12 changes in PPBC and OAB-q are presented in the Table by levels of improvement in diary variables. CONCLUSIONS: TER-treated patients showed statistically significant improvements in OAB symptoms and in PPBC and OAB-q scores. Patients who had larger reductions in symptoms also had marked improvements in PPBC, OAB Symptom Bother, and HRQL, confirming the relevance of these patient-reported outcomes in OAB.
Diary Variable Urgency
UUI
Daytime frequency
Night time frequency
OAB-q Domains (Mean Δ)
Symptom Improvement (n)
PPBC (Mean Δ)
Total HRQL
Major (452)
–2.0
39
–47
Some (281)
–1.3
25
–31
Symptom Bother
None (130)
–0.7
15
–18
Major (332)
–1.8
41
–48
Some (194)
–1.4
28
–36
None (120)
–1.2
17
–22
Major (332)
–1.9
37
–43
Some (208)
–1.4
28
–35
None (106)
–0.8
20
–25
Major (332)
–1.9
38
–43
Some (139)
–1.5
28
–38
None (175)
–1.0
21
–26
Eur Urol Suppl 2006;5(2):116
Glasser D.B.1, Elinoff V.2, Bavendam T.1, Carlsson M.3, Eyland N.4, Roberts R.G.5 Pfizer, Inc, Medical - Urology, New York, United States, 2Regional Clinical Research, Inc., Research, Endwell, United States, 3Pfizer, Inc, Statistics, New York, United States, 4Pfizer, Inc, Clinical Studies, New York, United States, 5University of Wisconsin Medical School, Family Medicine, Madison, United States INTRODUCTION & OBJECTIVES: Overactive bladder (OAB) is defined by symptoms of urgency, with or without urgency urinary incontinence (UUI), often with frequency and nocturia. Outcomes related to specific OAB symptoms are important because patients do not necessarily experience all symptoms and are not bothered by each symptom to the same degree. Obtaining outcomes in a “real-world” patient population provides physicians with information reflective of patients in their own practice. Our objective was to determine, in a primary care setting, the efficacy of tolterodine extended release (ER) for patients’ most bothersome OAB symptom. MATERIAL & METHODS: This open-label study was conducted at primary care and gynecology practices in the United States. Patients (aged ≥18 y) were eligible if they had OAB symptoms for ≥3 months and were at least “moderately” bothered by their most bothersome OAB symptom as indicated on the patient-completed OAB Bother Rating Scale. Patients were treated with tolterodine ER (4 mg QD) for 12 weeks. The primary efficacy endpoint was the percent change from baseline to week 12, using the last observation carried forward technique, in the most bothersome OAB symptom as determined by entries in a 3-day diary; secondary enpoints included changes on the Overactive Bladder Questionnaire (OAB-q) and the Patient Perception of Bladder Condition (PPBC) questionnaire. RESULTS: The most bothersome OAB symptom among the 896 patients enrolled was daytime frequency (30%), nocturnal frequency (28%), UUI (24%), and urgency (18%). Most patients (69%) had ≥1 clinically significant comorbid condition. By week 12, there were significant decreases in the median percent change in all of the most bothersome OAB symptoms in the intent-to-treat population: –80.0 (95% confidence interval [CI], –85.7 to –69.2) for UUI, –78.4 (95% CI, –83.3 to –72.2) for urgency, –40.0 (95% CI, –42.9 to –33.3) for nocturnal frequency, and –30.4 (95% CI, –33.3 to –27.3) for daytime frequency (P<0.0001). The median numeric improvement on the OAB-q symptom bother score, total health-related quality of life (HRQL) score, and the HRQL domains of coping, concern, sleep, and social interaction were all statistically significant (P<0.0001). At week 12, some improvement in overall bladder condition as measured by the PPBC was experienced by 86% of the urgency group, 79% of the nocturnal frequency group, 78% of the daytime frequency group, and 75% of the UUI group. Overall, 50% of patients reported major improvement in bladder condition. The most common adverse events were dry mouth (10%) and constipation (4%). CONCLUSIONS: In primary care patients, tolterodine ER was effective for all OAB symptoms and produced significant reductions in the patients’ most bothersome symptom, whether it was urgency, daytime frequency, nocturnal frequency, or UUI. Even in patients with comorbid conditions, tolterodine was effective and well tolerated. 1