今日の臨床サポート

過活動膀胱

著者: 吉田正貴 国立長寿医療研究センター 泌尿器外科

監修: 松田公志 関西医科大学 泌尿器科学教室

著者校正/監修レビュー済:2021/02/17
参考ガイドライン:
  1. 日本排尿機能学会:過活動膀胱診療ガイドライン第2版(2015)
  1. 日本泌尿器科学会男性下部尿路症状・前立腺肥大症診療ガイドライン(2017)
  1. 日本泌尿器科学会:女性下部尿路症状診療ガイドライン第2版(2019)
  1. 日本排尿機能学会:夜間頻尿診療ガイドライン第2版(2020)
患者向け説明資料

概要・推奨   

  1. 過活動膀胱の治療薬として、以下の薬剤は推奨される(推奨度2)。
  1. 抗コリン薬:バップフォー、ベシケア、ステーブラ、ウリトス、デトルシトール、トビエース
  1. β3受容体作動薬:ベタニス、ベオーバ
  1. 閲覧にはご契約が必要となります
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要とな
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約
  1. 男性の過活動膀胱に対して、α1遮断薬と抗コリン薬の併用療法は、それぞれの単独療法より優れている(推奨度2)。
  1. α1遮断薬単独治療で過活動膀胱の症状が残存する男性患者に対して、抗コリン薬の併用は推奨される(推奨度2)。
  1. β3受容体作動薬と抗コリン薬の併用療法は過活動膀胱に対する2次薬物療法として推奨される(推奨度2)。
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
吉田正貴 : 講演料(アステラス製薬,キッセイ薬品)[2021年]
監修:松田公志 : 講演料(アステラス製薬株式会社),奨学(奨励)寄付など(小野薬品工業株式会社)[2021年]

改訂のポイント:
  1. 定期レビューを行い、難治性過活動膀胱の治療として「膀胱鏡下ボツリヌス毒素注入療法」と「仙骨神経刺激療法」について追記した。

病態・疫学・診察

疾患情報  
  1. 過活動膀胱とは、尿意切迫感を主症状とし、通常はこれに頻尿、夜間頻尿を伴い、場合によっては切迫性尿失禁を合併する状態を総称して過活動膀胱と呼ぶ。過活動膀胱(OAB)では、蓄尿中の膀胱平滑筋の不随意収縮(排尿筋過活動)をしばしば伴う。
  1. 国内の疫学調査では、40歳以上の成人の12.4%に過活動膀胱を認める。
 
過活動膀胱(OAB)の有病率

2002~2003年に全国で実施された排尿に関する調査によると、OABの条件を「排尿回数が1日8回以上」かつ「尿意切迫感が週1回以上」と定義した場合、40歳以上の男女の12.4%にOABの症状がみられるという結果になった。この有病率は加齢とともに上昇し、80歳以上になると35%以上の男女にOABの症状がみられる。
また、女性に比べて男性のOAB患者が多いことから、OABと前立腺疾患との関連が疑われている。

 
  1. なお、下部尿路症状とは、蓄尿症状、排尿症状(排尿中断、尿勢低下、腹圧排尿など)、排尿後症状(残尿感など)の総称である。
  1. 蓄尿症状には、尿意切迫感以外に、頻尿、夜間頻尿、切迫性尿失禁が含まれる。
  1. 尿の貯留に伴い膀胱壁が伸展すると、これが尿意となって大脳に伝達される。この膀胱壁から大脳に至る求心性情報伝達が機能的に亢進すると、尿意切迫感という病的感覚の出現につながる。
  1. 原因として、さまざまな神経疾患、前立腺肥大症に代表される下部尿路閉塞、女性における骨盤底の脆弱化、加齢などが挙げられるが、原因不明の特発性も少なくない。
  1. 同様の症状を呈し得る他疾患(尿路感染症、膀胱結石、膀胱癌など)を鑑別する必要があり、このためには尿検査が必須である。
  1. 適切な治療により過活動膀胱の症状改善が可能である。
問診・診察のポイント  
  1. 尿意切迫感の有無を適切に聞き出す。尿意切迫感とは急に起こる強い尿意で、それを抑えるのが困難な病的知覚である。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

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文献 

著者: Momokazu Gotoh, Osamu Yokoyama, Osamu Nishizawa, Japanese Propiverine Study Group
雑誌名: Int J Urol. 2011 May;18(5):365-73. doi: 10.1111/j.1442-2042.2011.02732.x. Epub 2011 Feb 20.
Abstract/Text OBJECTIVES: The aim of this study was to investigate the efficacy and safety of propiverine for overactive bladder (OAB) in Japanese patients.
METHODS: In this multicentre, randomized, double-blind study, patients ≥ 20 years old with symptoms of OAB for ≥ 12 weeks were allocated to either propiverine (20 mg once daily) or placebo for 12 weeks. Efficacy and quality of life were assessed using a 7-day bladder diary, the OAB symptom score, and King's Health Questionnaire. Safety was mainly assessed by adverse events and the QTc interval.
RESULTS: A total of 567 patients were allocated. Change in number of micturitions/24 h was significantly greater in the propiverine group than in the placebo group (-1.86 vs-1.36, P = 0.001). Compared to placebo, propiverine produced significant improvements in urgency, urgency incontinence, urine volume/micturition, and the OAB symptom score. Significant improvements in urgency, urgency incontinence, and micturition frequency were observed at the first 4 weeks of treatment. All nine domains of King's Health Questionnaire were improved more with propiverine than with placebo. Adverse effects with propiverine were mostly mild, and no patient developed QTc interval prolongation exceeding 500 ms.
CONCLUSION: Propiverine is effective for Japanese OAB patients by improving their symptoms and quality of life with a predictable side-effect profile.

© 2011 The Japanese Urological Association.
PMID 21332825  Int J Urol. 2011 May;18(5):365-73. doi: 10.1111/j.1442-・・・
著者: Osamu Yamaguchi, Eiji Marui, Hidehiro Kakizaki, Naoki Itoh, Takashi Yokota, Hiroshi Okada, Osamu Ishizuka, Seiichiro Ozono, Momokazu Gotoh, Takahide Sugiyama, Narihito Seki, Masaki Yoshida, Japanese Solifenacin Study Group
雑誌名: BJU Int. 2007 Sep;100(3):579-87. doi: 10.1111/j.1464-410X.2007.07031.x.
Abstract/Text OBJECTIVES: To compare solifenacin succinate (5 and 10 mg once-daily) to placebo and propiverine hydrochloride (20 mg once-daily), respectively, in Japanese patients with overactive bladder syndrome (OAB).
PATIENTS AND METHODS: A multicentre, 12-week, double-blind phase III trial randomized men and women aged > or = 20 years with OAB to solifenacin 5 or 10 mg, propiverine 20 mg, or placebo. Changes at endpoint in number of voids/24 h, urgency, incontinence, urgency incontinence and nocturia episodes, volume voided/void, restoration of continence and quality of life (QoL) were examined.
RESULTS: Of 1593 patients randomized, 1584 were treated; at the endpoint there were greater reductions in mean (sd) voids/24 h with solifenacin 5 mg, at -1.93 (1.97), and 10 mg, at -2.19 (2.09), and propiverine 20 mg, at -1.87 (2.70), than with placebo, at -0.94 (2.29) (P < 0.001 for all). Solifenacin (5 and 10 mg) was superior to placebo, and no worse than propiverine 20 mg, for this variable. There were significantly fewer mean (sd) urgency, incontinence and urgency incontinence episodes with solifenacin and propiverine than with placebo, with respective changes on placebo of - 1.28 (2.90), - 0.72 (1.95) and - 0.69 (2.00); solifenacin 5 mg, - 2.41 (2.88), -1.59 (2.12) and -1.45 (1.89) (P < 0.001 for all), and 10 mg, -2.78 (2.82), - 1.60 (1.81) and - 1.52 (1.77) (P < 0.001 for all), and propiverine 20 mg, -2.30 (3.08), -1.25 (2.79) and - 1.19 (2.20) (P < 0.001, = 0.002 and = 0.002 respectively). All active treatments vs placebo improved the volume voided (P < 0.001 for all) and QoL; solifenacin 10 mg reduced nocturia episodes (P = 0.021) and significantly improved urgency episodes (P = 0.012) and volume voided (P = 0.009) vs propiverine 20 mg, and solifenacin 5 mg caused less dry mouth (P = 0.003). Solifenacin 10 mg caused more dry mouth (P = 0.012) and occurrences of constipation (P = 0.004) than propiverine 20 mg, but discontinuation rates between both treatment groups were similar. Continence was restored at endpoint in more than half of the patients on active treatment.
CONCLUSION: Solifenacin 5 and 10 mg once daily significantly improved the symptoms of OAB compared with placebo. Solifenacin therapy at 5 mg once daily is well-tolerated; 10 mg can be given if additional efficacy is required.

PMID 17669143  BJU Int. 2007 Sep;100(3):579-87. doi: 10.1111/j.1464-41・・・
著者: C R Chapple, R Martinez-Garcia, L Selvaggi, P Toozs-Hobson, W Warnack, T Drogendijk, D M Wright, J Bolodeoku, STAR study group
雑誌名: Eur Urol. 2005 Sep;48(3):464-70. doi: 10.1016/j.eururo.2005.05.015.
Abstract/Text OBJECTIVE: To compare two new generation antimuscarinics at their recommended doses for treatment of overactive bladder syndrome (OAB).
METHODS: A prospective, double blind, double-dummy, two-arm, parallel-group, 12-week study was conducted to compare the efficacy and safety of solifenacin 5 or 10 mg and tolterodine extended release (ER) 4 mg once daily in OAB patients. After 4 weeks of treatment patients had the option to request a dose increase but were dummied throughout as approved product labelling only allowed an increase for those on solifenacin.
RESULTS: Solifenacin, with a flexible dosing regimen, showed greater efficacy to tolterodine in decreasing urgency episodes, incontinence, urge incontinence and pad usage and increasing the volume voided per micturition. More solifenacin treated patients became continent and reported improvements in perception of bladder condition assessments. The majority of side effects were mild to moderate in nature, and discontinuations were comparable and low in both groups.
CONCLUSIONS: Solifenacin, with a flexible dosing regimen, was found to be superior to tolterodine ER with respect to the majority of the efficacy variables.

PMID 15990220  Eur Urol. 2005 Sep;48(3):464-70. doi: 10.1016/j.eururo.・・・
著者: Yukio Homma, Osamu Yamaguchi, Imidafenacin Study Group
雑誌名: Int J Urol. 2009 May;16(5):499-506. doi: 10.1111/j.1442-2042.2009.02286.x. Epub 2009 Mar 29.
Abstract/Text OBJECTIVES: To compare the efficacy and tolerability of imidafenacin, a novel antimuscarinic agent, with propiverine and a placebo in Japanese patients with overactive bladder (OAB).
METHODS: Men and women having OAB symptoms were randomized to double-blind treatment with 0.1 mg of imidafenacin twice daily, 20 mg of propiverine once daily, or a placebo for 12 weeks, and assessed for efficacy and safety.
RESULTS: Overall, 781 patients were randomized to imidafenacin (324), propiverine (310), or a placebo (147). After 12 weeks of treatment, a significantly larger reduction in the mean number of incontinence episodes was observed in the imidafenacin group than in the placebo group (P < 0.0001). The non-inferiority of imidafenacin compared with propiverine was confirmed for the reduction in using incontinence episodes (P = 0.0014, non-inferiority margin: 14.5%). Imidafenacin was well tolerated. The incidence of adverse events with imidafenacin was significantly lower than with propiverine (P = 0.0101). Dry mouth, the most common adverse event, was significantly more common in the propiverine group than in the imidafenacin group (P = 0.0302). There were no significant increases in either the imidafenacin or placebo group in the mean QTc interval, whereas there was a significant increase in the mean QTc interval in the propiverine group (P < 0.0001), but there were no clinical arrhythmia and clinical arrhythmic events in any of the treatment groups.
CONCLUSIONS: The novel antimuscarinic agent imidafenacin at a dose of 0.1 mg twice daily was not inferior to propiverine for the reduction of incontinence episodes, and well tolerated for the treatment of OAB symptoms.

PMID 19389083  Int J Urol. 2009 May;16(5):499-506. doi: 10.1111/j.1442・・・
著者: Y Homma, J S Paick, J G Lee, K Kawabe, Japanese and Korean Tolterodine Study Group
雑誌名: BJU Int. 2003 Nov;92(7):741-7.
Abstract/Text OBJECTIVE: To compare extended-release (ER) tolterodine and immediate-release (IR) oxybutynin with placebo in Japanese and Korean patients with an overactive bladder (OAB).
PATIENTS AND METHODS: Men and women aged >or= 20 years with symptoms of urinary urgency, urinary frequency (>or= 8 micturitions/24 h), urge incontinence (>or= 5 episodes/week) and symptoms of OAB for >or= 6 months were randomized to double-blind treatment with tolterodine ER 4 mg once daily, oxybutynin IR 3 mg three times daily or placebo for 12 weeks. Efficacy assessments included changes from baseline in numbers of incontinence episodes per week, voids/24 h and mean volume voided/void. Patient perceptions of bladder condition, urgency and treatment benefit were also assessed.
RESULTS: In all, 608 patients were randomized to treatment with tolterodine (240), oxybutynin (246) or placebo (122). More patients prematurely withdrew on oxybutynin (23%) than with tolterodine (10.4%) or placebo (16.4%). After 12 weeks of treatment, the median number of incontinence episodes/week was reduced significantly more in the tolterodine (79%; P= 0.0027) and oxybutynin groups (76.5%; P= 0.0168) than on placebo (46.4%). There were also significantly greater improvements in the number of voids/24 h and volume voided/void with tolterodine and oxybutynin than with placebo. More patients in the tolterodine and oxybutynin than in the placebo groups reported improvements in perceived bladder condition, ability to hold urine and treatment benefit. Patients treated with oxybutynin reported more adverse events than those treated with tolterodine or placebo. Dry mouth was significantly more common with oxybutynin than with tolterodine (53.7% vs. 33.5%; P < 0.001), and occurred in 9.8% of placebo patients.
CONCLUSION: Tolterodine ER has similar efficacy but is better tolerated than oxybutynin IR in Japanese and Korean patients with OAB.

PMID 14616458  BJU Int. 2003 Nov;92(7):741-7.
著者: Adrian Wagg, Vik Khullar, Daniela Marschall-Kehrel, Martin C Michel, Matthias Oelke, Amanda Darekar, Caty E Bitoun, David Weinstein, Ian Osterloh
雑誌名: J Am Geriatr Soc. 2013 Feb;61(2):185-93. doi: 10.1111/jgs.12088. Epub 2013 Jan 25.
Abstract/Text OBJECTIVES: To assess the efficacy and safety of flexible-dose fesoterodine in elderly adults with overactive bladder (OAB).
DESIGN: Twelve-week, randomized, double-blind, placebo-controlled trial.
SETTING: Sixty-one outpatient clinics in Europe, Israel, and Turkey.
PARTICIPANTS: Seven hundred ninety-four individuals aged 65 and older (47% male) with OAB symptoms for 3 months or longer, mean of eight or more micturitions and three or more urgency episodes per 24 hours, at least some moderate problems on Patient Perception of Bladder Condition (PPBC), and Mini-Mental State Examination (MMSE) score of 20 or greater.
INTERVENTIONS: Participants were randomized to fesoterodine or placebo for 12 weeks, with stratification according to age (>75 vs ≤ 75) and dosing time (morning vs evening). Participants receiving fesoterodine started on 4 mg and could increase to 8 mg at week 4 or 8 and de-escalate to 4 mg at week 8 (sham escalation for placebo).
MEASUREMENTS: Changes from baseline in bladder-diary variables (primary endpoint, urgency episodes) and patient-reported outcomes including OAB Questionnaire, Treatment Benefit Scale (TBS), PPBC, Urgency Perception Scale (UPS), and OAB Satisfaction Questionnaire (OAB-S); all observed or reported adverse events.
RESULTS: By week 8, 64% of fesoterodine-treated and 71% of placebo-treated participants opted for dose escalation. At week 12, the fesoterodine group had statistically significantly greater improvement than the placebo group in urgency episodes, micturitions, nocturnal micturitions, incontinence pad use, and OAB Questionnaire scores but not urgency urinary incontinence episodes. Responder rates on TBS, PPBC, UPS, and OAB-S were statistically significantly higher with fesoterodine. Improvements in most diary variables and participant-reported outcomes were greater with fesoterodine than placebo in participants in both age groups and when administered in the morning and evening. Rates of dry mouth and constipation were 34% and 9% with fesoterodine and 5% and 3% with placebo, respectively. Rates of adverse events and discontinuations were generally similar in participants in both age groups. There was no change in MMSE score.
CONCLUSION: Fesoterodine was associated with significantly greater improvements in most diary variables and participant-reported outcomes than placebo and was generally well tolerated in older people.

© 2013, Copyright the Authors Journal compilation © 2013, The American Geriatrics Society.
PMID 23350833  J Am Geriatr Soc. 2013 Feb;61(2):185-93. doi: 10.1111/j・・・
著者: P Abrams, C C Schulman, S Vaage
雑誌名: Br J Urol. 1995 Sep;76(3):325-36.
Abstract/Text OBJECTIVE: To evaluate the efficacy and safety of tamsulosin 0.4 mg once daily (as a modified-release formulation) compared with placebo in patients with benign prostatic enlargement, lower urinary tract symptoms and prostatic 'obstruction' (symptomatic benign prostatic hyperplasia [BPH]).
PATIENTS AND METHODS: Of 313 patients with symptomatic BPH enrolled in a 2-week placebo run-in period, 296 were subsequently randomized to receive either placebo (98 patients) or tamsulosin 0.4 mg once daily (198 patients) for 12 weeks. The primary variables assessed to determine efficacy were maximum urinary flow rate (Qmax) from free-flow measurements and the total Boyarsky symptom score.
RESULTS: Tamsulosin produced greater improvements in Qmax (1.4 mL/s, 13.1%) than did placebo (0.4 mL/s, 3.8%) (P = 0.028) and a greater decrease in total symptom score (3.4 points, 35.8% reduction) than did placebo (2.2 points, 23.7% reduction) (P = 0.002). Significantly more tamsulosin-treated patients (67%) than placebo-treated patients (44%) had a > or = 25% decrease in total symptom score after 12 weeks (P < 0.001). Treatment with tamsulosin for 12 weeks also produced significant improvements in average urinary flow rate (P = 0.040), irritative (P = 0.013) and obstructive (P = 0.014) symptom scores and symptoms of nocturia (P = 0.022) and hesitancy (P = 0.004). Tamsulosin was tolerated well by the patients. The incidence of adverse events emerging during treatment was comparable in the tamsulosin- and placebo-treated groups (34% and 24% respectively, P = 0.109), as was the incidence of cardiovascular-related adverse events (5% and 7% respectively; P = 0.596). There were no significant differences in changes in blood pressure or pulse rates between the tamsulosin- and placebo-treated groups.
CONCLUSION: Tamsulosin 0.4 mg once daily is safe, well tolerated and clinically effective in improving symptoms and urinary flow rate in patients with symptomatic BPH.

PMID 7551841  Br J Urol. 1995 Sep;76(3):325-36.
著者: Osamu Yamaguchi, Hidehiro Kakizaki, Yukio Homma, Masayuki Takeda, Osamu Nishizawa, Momokazu Gotoh, Osamu Yokoyama, Narihito Seki, Masaki Yoshida, ASSIST Study Group
雑誌名: Urology. 2011 Jul;78(1):126-33. doi: 10.1016/j.urology.2011.02.055. Epub 2011 May 23.
Abstract/Text OBJECTIVES: To assess the efficacy and safety of solifenacin add-on therapy to tamsulosin in lower urinary tract symptoms (LUTS) men with residual overactive bladder (OAB) symptoms despite tamsulosin monotherapy.
METHODS: In this randomized, multicenter, double-blind study, male LUTS patients aged≥50 years with urgency episodes/24 hours≥2 and micturitions/24 hours≥8 were randomized to 3 groups: 12-weeks tamsulosin plus placebo (TAM+PBO), tamsulosin plus solifenacin 2.5 mg (TAM+SOL), and tamsulosin plus solifenacin 5 mg (TAM+SOL). Changes from baseline to end of treatment in the number of urgency episodes/24 hours (primary endpoint), micturitions, nocturia, urgency incontinence episodes, International Prostate Symptom Scores (IPSS), and Overactive Bladder Symptom Score (OABSS) were compared between the TAM+SOL groups and TAM+PBO. Safety was assessed on adverse events, postvoid residual volume, and maximal urinary flow rate (Qmax.).
RESULTS: Six-hundred thirty-eight men were randomized. Urgency was reduced by 2.2 and 2.4 episodes in the TAM+SOL 2.5 and 5 mg groups, respectively. The TAM+SOL 5 mg group showed significant improvement compared with TAM+PBO (-2.4 vs -1.9, P=.049). The number of micturitions in both TAM+SOL groups were significantly reduced compared with TAM+PBO (both P<.001). IPSS storage symptom score and OABSS significantly improved in both TAM+SOL groups compared with TAM+PBO. Changes in IPSS voiding symptom score and Qmax. were similar in all groups. Four patients (1.9%) in the TAM+SOL 5 mg group had urinary retention, but all recovered after catheterization.
CONCLUSIONS: In male LUTS patients with residual OAB symptoms despite tamsulosin monotherapy, TAM+SOL showed efficacy on urgency, which represents OAB symptoms and was well tolerated.

Copyright © 2011 Elsevier Inc. All rights reserved.
PMID 21601248  Urology. 2011 Jul;78(1):126-33. doi: 10.1016/j.urology.・・・
著者: Osamu Nishizawa, Osamu Yamaguchi, Masayuki Takeda, Osamu Yokoyama, TAABO Study Group
雑誌名: Low Urin Tract Symptoms. 2011 Apr;3(1):29-35. doi: 10.1111/j.1757-5672.2010.00081.x. Epub 2010 Sep 20.
Abstract/Text OBJECTIVES: TAABO was a randomized, controlled trial to evaluate the efficacy and safety of combination therapy of tamsulosin (TAM) with propiverine (PROP) in men with both benign prostatic hyperplasia and overactive bladder.
METHODS: It enrolled men 50 years or older who had an international prostate symptom score (IPSS) of 8 or higher, an urgency item score of 1 or higher, and a quality of life (QOL) score of 2 or higher. After 8 weeks of TAM 0.2 mg/day, patients who met the inclusion criteria (8 micturitions per 24 h and 1 urgency per 24 h, evaluated by bladder diary) and were eligible for 12-weeks of continued Treatment II. Five hundred and fifteen patients were enrolled. Thereafter, 214 patients were assigned randomly to receive either TAM alone (n = 67), TAM plus PROP 10 mg (n = 72), or TAM plus PROP 20 mg (n = 75) in Treatment II. The primary efficacy end point was a change in micturitions per 24 h documented in the bladder diary. The change from baseline in urgency episodes per 24 h, IPSS, IPSS/QOL subscore, urinary flow rate and postvoid residual volume were assessed as secondary efficacy measures.
RESULTS: A total of 141 men (47 TAM, 49 TAM plus PROP 10 mg, and 45 TAM plus PROP 20 mg patients) were assessed by week 12. Compared with the TAM, TAM plus PROP 10 mg patients experienced significantly fewer micturitions (P = 0.0261), urgencies (P = 0.0093) per 24 h, lower IPSS storage (P = 0.0465), and IPSS urgency (P = 0.0252) subscores.
CONCLUSIONS: These results suggest that combining TAM and 10 mg of PROP for 12 weeks provides added benefit for men with both benign prostatic hyperplasia and overactive bladder.

© 2010 Blackwell Publishing Asia Pty Ltd.
PMID 26676349  Low Urin Tract Symptoms. 2011 Apr;3(1):29-35. doi: 10.1・・・
著者: Masayuki Takeda, Osamu Nishizawa, Momokazu Gotoh, Masaki Yoshida, Satoru Takahashi, Naoya Masumori
雑誌名: Urology. 2013 Oct;82(4):887-93. doi: 10.1016/j.urology.2013.05.008. Epub 2013 Aug 14.
Abstract/Text OBJECTIVE: To evaluate the effects of add-on treatment with an anticholinergic (imidafenacin) on persistent overactive bladder (OAB) symptoms despite α-blocker (tamsulosin) treatment in patients with benign prostatic hyperplasia (BPH).
METHODS: Patients with BPH ≥50 years old, with urinary urgency at least once per week and total OAB symptom score (OABSS) ≥3 points after ≥8-week treatment with tamsulosin were enrolled in a multicenter, open-label study (not double-blinded). Patients were randomized to receive tamsulosin (0.2 mg/day) alone or tamsulosin (0.2 mg/day) + imidafenacin (0.1 mg 2 times a day). Primary endpoint was 12-week change in OABSS; secondary endpoints were changes in OABSS, International Prostate Symptom Score (IPSS), micturition time chart (MTC), hours of undisturbed sleep (HUS), and quality of life (IPSS-QOL and BPH impact index [BII]). For statistical analysis, a mixed-effects model and t test were used.
RESULTS: In total, 308 men were enrolled. The change from baseline to 12 weeks in total OABSS was significantly greater with add-on imidafenacin than tamsulosin alone (2.11, 95% confidence interval [CI] 1.47-2.74, P <.0001). Improvements in frequencies of daytime urination, nighttime urination, urinary urgency, urgency incontinence, IPSS, HUS, IPSS-QOL, and BII, were significantly greater from 4 weeks through 12 weeks in the imidafenacin group. Between-group difference in postvoid residual volume at 12 weeks was not significant (-1.74 mL, 95% CI -8.19 to 4.72), and no events of urinary retention were reported.
CONCLUSION: Combined tamsulosin and imidafenacin treatment is effective and safe in patients with BPH with persistent OAB symptoms after tamsulosin monotherapy. Furthermore the combination treatment improved the QOL in BPH patients with OAB.

Copyright © 2013 Elsevier Inc. All rights reserved.
PMID 23953605  Urology. 2013 Oct;82(4):887-93. doi: 10.1016/j.urology.・・・
著者: Osamu Yamaguchi, Eiji Uchida, Naruhito Higo, Hidenao Minami, Shigeo Kobayashi, Hiroyuki Sato, Oxybutynin Patch Study Group
雑誌名: Int J Urol. 2014 Jun;21(6):586-93. doi: 10.1111/iju.12372. Epub 2013 Dec 18.
Abstract/Text OBJECTIVES: To evaluate the efficacy and safety of once-daily oxybutynin patch therapy for overactive bladder.
METHODS: A randomized double-blind trial was carried out in patients with overactive bladder syndrome, who received an oxybutynin patch, propiverine (20 mg) or placebo once daily for 12 weeks. The primary efficacy end-point was the change of the mean daily number of micturitions in week 12.
RESULTS: A total of 1530 patients were randomized to receive the oxybutynin patch (573), propiverine (576) or placebo (381). The change of the mean daily frequency of micturition from baseline in the full analysis set was -1.89 ± 2.04 with the oxybutynin patch, which was significantly higher than with placebo (-1.44 ± 2.23) (P = 0.0015). The difference of the mean change in the mean daily number of micturitions between the oxybutynin patch and propiverine groups showed a 95% confidence interval of -0.28 to 0.21, and the upper limit of this interval was below the predefined non-inferiority margin of 0.37, showing non-inferiority of the oxybutynin patch to propiverine. The incidence of dry mouth and constipation was higher with propiverine than with the oxybutynin patch or placebo. Application site dermatitis was more frequent with the oxybutynin patch (31.8%) than with propiverine (5.9%) or placebo (5.2%), but the dermatitis was generally mild.
CONCLUSION: This trial shows the efficacy of the new once-daily oxybutynin patch for overactive bladder. Despite a higher rate of dermatitis with the oxybutynin patch, dry mouth and constipation occurs less often than during treatment with propiverine.

© 2013 The Japanese Urological Association.
PMID 24350662  Int J Urol. 2014 Jun;21(6):586-93. doi: 10.1111/iju.123・・・
著者: Osamu Yamaguchi, Eiji Marui, Hidehiro Kakizaki, Yukio Homma, Yasuhiko Igawa, Masayuki Takeda, Osamu Nishizawa, Momokazu Gotoh, Masaki Yoshida, Osamu Yokoyama, Narihito Seki, Yasushi Ikeda, Sumito Ohkawa
雑誌名: BJU Int. 2014 Jun;113(6):951-60. doi: 10.1111/bju.12649. Epub 2014 Mar 17.
Abstract/Text OBJECTIVE: To evaluate the efficacy and safety of the β3-adrenoceptor agonist mirabegron, in a Japanese population with overactive bladder (OAB).
PATIENTS AND METHODS: This randomised, double-blind, placebo-controlled phase III study enrolled adult patients experiencing OAB symptoms for ≥24 weeks. Patients with ≥ 8 micturitions/24 h and ≥1 urgency episode/24 h or ≥1 urgency incontinence episode/24 h were randomised to once-daily placebo, mirabegron 50 mg or tolterodine 4 mg (as an active comparator, without testing for non-inferiority of efficacy and safety) for 12 weeks. The primary endpoint was the change in the mean number of micturitions/24 h from baseline to final assessment. Secondary endpoints included micturition variables related to urgency and/or incontinence and quality-of-life domain scores on the King's Health Questionnaire. Safety assessments included adverse events (AEs), post-void residual urine volume, laboratory variables, vital signs and 12-lead electrocardiogram.
RESULTS: A total of 1139 patients were randomised to receive placebo (n = 381), mirabegron 50 mg (n = 380) or tolterodine 4 mg (n = 378). Demographic and baseline characteristics were similar among the treatment groups. At final assessment, mirabegron was significantly superior to placebo in terms of mean [sd] change from baseline in number of micturitions/24 h (-1.67 [2.212] vs -0.86 [2.354]; P < 0.001) and mean [sd] change from baseline in number of urgency episodes/24 h (-1.85 [2.555] vs -1.37 [3.191]; P = 0.025), incontinence episodes/24 h (-1.12 [1.475] vs -0.66 [1.861]; P = 0.003), urgency incontinence episodes/24 h (-1.01 [1.338] vs -0.60 [1.745]; P = 0.008), and volume voided/micturition (24.300 [35.4767] vs 9.715 [29.0864] mL; P < 0.001). The incidence of AEs in the mirabegron group was similar to that in the placebo group. Most AEs were mild and none were severe.
CONCLUSIONS: Mirabegron 50 mg once daily is an effective treatment for OAB symptoms, with a low occurrence of side effects in a Japanese population.

© 2014 The Authors. BJU International © 2014 BJU International.
PMID 24471907  BJU Int. 2014 Jun;113(6):951-60. doi: 10.1111/bju.12649・・・
著者: Masaki Yoshida, Masayuki Takeda, Momokazu Gotoh, Shinji Nagai, Takafumi Kurose
雑誌名: Eur Urol. 2018 May;73(5):783-790. doi: 10.1016/j.eururo.2017.12.022. Epub 2018 Feb 1.
Abstract/Text BACKGROUND: Vibegron is a novel, potent, and selective β3-adrenoreceptor agonist for the treatment of patients with overactive bladder (OAB).
OBJECTIVE: To evaluate the efficacy and safety of vibegron versus placebo in Japanese OAB patients.
DESIGN, SETTING, AND PARTICIPANTS: Patients with OAB entered a 2-wk placebo run-in phase. Once eligibility (≥8 micturition/d and either ≥1 urgency episodes/d or ≥1 urgency incontinence episodes/d) was confirmed, patients entered a 12-wk double-blind treatment phase. The anticholinergic imidafenacin was used as an active reference.
INTERVENTION: A total of 1232 patients were randomly assigned to one of the four 12-wk treatment groups: vibegron (50mg or 100mg once daily), placebo, or imidafenacin (0.1mg twice daily).
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was change in the mean number of micturitions/d at wk 12 from baseline. The secondary endpoints were changes from baselines in OAB symptom variables (daily episodes of urgency, urgency incontinence, incontinence, and nocturia, and voided volume/micturition). Quality of life (QoL) and safety were assessed. A constrained longitudinal data analysis model was used for analysis of efficacy.
RESULTS AND LIMITATIONS: Patients taking vibegron 50mg and 100mg orally for 12 wk had significant improvements over the placebo in the primary and secondary endpoints. The proportions of patients with normalization of micturition, resolution of urgency, urgency incontinence, and incontinence were significantly greater than placebo. Vibegron significantly improved QoL, with high patient satisfaction. Incidences of drug-related adverse events with vibegron 50mg and 100mg were 7.6%, 5.4%, similar to placebo (5.1%), and less than imidafenacin (10.3%). Treatment was for just 12 wk and a long-term study is needed.
CONCLUSIONS: The 12-wk treatment with vibegron is effective and well tolerated in patients with OAB.
PATIENT SUMMARY: This randomized study demonstrated that vibegron is clinically useful for treatment of patients with OAB. Trial registration ​JapicCTI-152936. http://www.clinicaltrials.jp/user/cteDetail.jsp.

Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.
PMID 29366513  Eur Urol. 2018 May;73(5):783-790. doi: 10.1016/j.eururo・・・
著者: Osamu Yamaguchi, Hidehiro Kakizaki, Yukio Homma, Yasuhiko Igawa, Masayuki Takeda, Osamu Nishizawa, Momokazu Gotoh, Masaki Yoshida, Osamu Yokoyama, Narihito Seki, Akira Okitsu, Takuya Hamada, Akiko Kobayashi, Kentaro Kuroishi
雑誌名: Int J Urol. 2019 Mar;26(3):342-352. doi: 10.1111/iju.13868. Epub 2018 Dec 13.
Abstract/Text OBJECTIVES: To evaluate the long-term safety (primary objective) and efficacy (secondary objective) of antimuscarinic add-on therapy in patients receiving mirabegron.
METHODS: During a 2-week screening period, patients (aged ≥20 years, mirabegron treatment for ≥6 weeks, residual overactive bladder symptoms) received mirabegron 50 mg once daily. These patients were subsequently randomized to 52 weeks' treatment with mirabegron 50 mg/day plus an antimuscarinic (solifenacin 5 mg, propiverine 20 mg, imidafenacin 0.2 mg, or tolterodine 4 mg) with the potential to double the antimuscarinic dose (except for tolterodine) at week 8. Safety assessments included treatment-emergent adverse events, vital signs, 12-lead electrocardiograms, post-void residual volume, and laboratory evaluations. Efficacy was assessed using changes from baseline in overactive bladder symptom score total score; overactive bladder questionnaire short form score; micturitions, urgency episodes, urinary incontinence episodes, and urgency urinary incontinence episodes/24 h; mean volume voided per micturition; and number of night-time micturitions.
RESULTS: Overall, 80.2% of patients (88.1% women, mean age 65 years) experienced at least one treatment-emergent adverse event, with similar rates for all treatments. The adverse events most commonly reported were dry mouth, nasopharyngitis, and constipation. No marked change was observed in systolic or diastolic blood pressure for any treatment, although pulse rate increased slightly in the mirabegron and propiverine, and mirabegron and tolterodine groups. For all treatments, significant improvements were observed in all efficacy parameters, including overactive bladder symptom score total and questionnaire short form scores.
CONCLUSIONS: Antimuscarinic add-on therapy is well tolerated and effective after initial treatment with mirabegron in patients with overactive bladder symptoms.

© 2018 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Urological Association.
PMID 30548692  Int J Urol. 2019 Mar;26(3):342-352. doi: 10.1111/iju.13・・・
著者: Osamu Yokoyama, Masashi Honda, Tomonori Yamanishi, Yuki Sekiguchi, Kenji Fujii, Takashi Nakayama, Takao Mogi
雑誌名: Int J Urol. 2020 Mar;27(3):227-234. doi: 10.1111/iju.14176. Epub 2020 Jan 20.
Abstract/Text OBJECTIVE: To evaluate the efficacy and safety of onabotulinumtoxinA (botulinum toxin type A) 100 U in patients with overactive bladder and urinary incontinence.
METHODS: This was a phase III, randomized, double-blind, placebo-controlled trial in Japanese patients who were inadequately managed with overactive bladder medications (anticholinergics and/or β3 -adrenergic receptor agonists). Eligible patients were randomized 1:1 to receive a single dose of either onabotulinumtoxinA or placebo into the detrusor muscle (n = 124 each). The primary end-point was the change in the number of daily urinary incontinence episodes at week 12 from baseline. Secondary end-points included volume voided per micturition, other symptomatic measures (urinary urgency incontinence, micturition, urgency and nocturia) and patient-reported outcomes.
RESULTS: In the onabotulinumtoxinA group, there was a significantly greater decrease from baseline in the mean number of daily urinary incontinence episodes compared with the placebo group (2.16; P < 0.001), and significantly greater improvement for all secondary end-points (P < 0.05). Urinary tract infection, dysuria, urinary retention and post-void residual urine volume increased represented adverse events occurring at a higher rate in the onabotulinumtoxinA group. The majority of these were mild or moderate in severity.
CONCLUSIONS: Statistically significant and clinically relevant improvements in symptoms and patient-reported outcomes, and tolerability were seen in patients with overactive bladder and urinary incontinence who had been inadequately managed with overactive bladder medications after using onabotulinumtoxinA.

© 2020 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Urological Association.
PMID 31957922  Int J Urol. 2020 Mar;27(3):227-234. doi: 10.1111/iju.14・・・
著者: Steven Siegel, Karen Noblett, Jeffrey Mangel, Tomas L Griebling, Suzette E Sutherland, Erin T Bird, Craig Comiter, Daniel Culkin, Jason Bennett, Samuel Zylstra, Kellie Chase Berg, Fangyu Kan, Christopher P Irwin
雑誌名: Neurourol Urodyn. 2015 Mar;34(3):224-30. doi: 10.1002/nau.22544. Epub 2014 Jan 10.
Abstract/Text AIMS: This prospective, randomized, multicenter trial evaluated the 6-month success rate of sacral neuromodulation (SNM) with InterStim® Therapy versus standard medical therapy (SMT) for overactive bladder (OAB).
METHODS: Enrolled subjects discontinued OAB medications prior to and during baseline data collection and were randomized 1:1 to SNM or SMT. Subjects had bothersome symptoms of overactive bladder (OAB) including urinary urge incontinence (≥2 leaks/72 hr) and/or urgency-frequency (≥8 voids/day). Subjects failed at least one anticholinergic medication, and had at least one medication not yet attempted. The primary objective was to compare OAB therapeutic success rate at 6 months between SNM and SMT.
RESULTS: Overall, 147 subjects were randomized (70 to SNM and 77 to SMT); 93% were female and mean age was 58. The primary intent to treat analysis showed OAB therapeutic success was significantly greater in the SNM group (61%) than the SMT group (42%; P = 0.02). In the as treated analysis, OAB therapeutic success was 76% for SNM and 49% for SMT (P = 0.002). The SNM group showed significant improvements in quality of life versus the SMT group (all P < 0.001) and 86% of SNM subjects reported improved or greatly improved urinary symptom interference score at 6 months, compared to 44% for SMT subjects. The device-related adverse event rate was 30.5% and the medication-related adverse event rate was 27.3%.
CONCLUSIONS: This study demonstrates superior objective and subjective success of SNM compared to SMT. SNM is shown to be a safe and effective treatment for OAB patients with mild to moderate symptoms. Neurourol. Urodynam. 34:224-230, 2015. © 2014 Wiley Periodicals, Inc.

© 2014 Wiley Periodicals, Inc.
PMID 24415559  Neurourol Urodyn. 2015 Mar;34(3):224-30. doi: 10.1002/n・・・
著者: Cindy L Amundsen, Holly E Richter, Shawn A Menefee, Yuko M Komesu, Lily A Arya, W Thomas Gregory, Deborah L Myers, Halina M Zyczynski, Sandip Vasavada, Tracy L Nolen, Dennis Wallace, Susan F Meikle
雑誌名: JAMA. 2016 Oct 4;316(13):1366-1374. doi: 10.1001/jama.2016.14617.
Abstract/Text Importance: Women with refractory urgency urinary incontinence are treated with sacral neuromodulation and onabotulinumtoxinA with limited comparative information.
Objective: To assess whether onabotulinumtoxinA is superior to sacral neuromodulation in controlling refractory episodes of urgency urinary incontinence.
Design, Setting, and Participants: Multicenter open-label randomized trial (February 2012-January 2015) at 9 US medical centers involving 381 women with refractory urgency urinary incontinence.
Interventions: Cystoscopic intradetrusor injection of 200 U of onabotulinumtoxinA (n = 192) or sacral neuromodulation (n = 189).
Main Outcomes and Measures: Primary outcome, change from baseline mean number of daily urgency urinary incontinence episodes over 6 months, was measured with monthly 3-day diaries. Secondary outcomes included change from baseline in urinary symptom scores in the Overactive Bladder Questionnaire Short Form (SF); range, 0-100, higher scores indicating worse symptoms; Overactive Bladder Satisfaction questionnaire; range, 0-100; includes 5 subscales, higher scores indicating better satisfaction; and adverse events.
Results: Of the 364 women (mean [SD] age, 63.0 [11.6] years) in the intention-to-treat population, 190 women in the onabotulinumtoxinA group had a greater reduction in 6-month mean number of episodes of urgency incontinence per day than did the 174 in the sacral neuromodulation group (-3.9 vs -3.3 episodes per day; mean difference, 0.63; 95% CI, 0.13 to 1.14; P = .01). Participants treated with onabotulinumtoxinA showed greater improvement in the Overactive Bladder Questionnaire SF for symptom bother (-46.7 vs -38.6; mean difference, 8.1; 95% CI, 3.0 to 13.3; P = .002); treatment satisfaction (67.7 vs 59.8; mean difference, 7.8; 95% CI, 1.6 to 14.1; P = .01) and treatment endorsement (78.1 vs 67.6; mean difference; 10.4, 95% CI, 4.3 to 16.5; P < .001) than treatment with sacral neuromodulation. There were no differences in convenience (67.6 vs 70.2; mean difference, -2.5; 95% CI, -8.1 to 3.0; P = .36), adverse effects (88.4 vs 85.1; mean difference, 3.3; 95% CI, -1.9 to 8.5; P = .22), and treatment preference (92.% vs 89%; risk difference, -3%; 95% CI, -16% to 10%; P = .49). Urinary tract infections were more frequent in the onabotulinumtoxinA group (35% vs 11%; risk difference, -23%; 95% CI, -33% to -13%; P < .001). The need for self-catheterization was 8% and 2% at 1 and 6 months in the onabotulinumtoxinA group. Neuromodulation device revisions and removals occurred in 3%.
Conclusions and Relevance: Among women with refractory urgency urinary incontinence, treatment with onabotulinumtoxinA compared with sacral neuromodulation resulted in a small daily improvement in episodes that although statistically significant is of uncertain clinical importance. In addition, it resulted in a higher risk of urinary tract infections and need for transient self-catheterizations.

PMID 27701661  JAMA. 2016 Oct 4;316(13):1366-1374. doi: 10.1001/jama.2・・・
著者: Cindy L Amundsen, Yuko M Komesu, Christopher Chermansky, W Thomas Gregory, Deborah L Myers, Emily F Honeycutt, Sandip P Vasavada, John N Nguyen, Tracey S Wilson, Heidi S Harvie, Dennis Wallace, Pelvic Floor Disorders Network
雑誌名: Eur Urol. 2018 Jul;74(1):66-73. doi: 10.1016/j.eururo.2018.02.011. Epub 2018 Feb 24.
Abstract/Text BACKGROUND: Urgency urinary incontinence (UUI) is a chronic condition for which sacral neuromodulation (SNM) (InterStim/Medtronic) and onabotulinumtoxinA (BTX) (BotoxA/Allergan) are utilized. These therapies have not been compared over extended time.
OBJECTIVE: To compare UUI episodes (UUIE) over 24 mo following SNM or BTX.
DESIGN, SETTING, AND PARTICIPANTS: Multicenter, open-label, randomized, extension trial (February 2012-July 2016) at nine US medical centers involving 386 women with ≥6 UUIE over 3 d inadequately managed by medications. Participants were clinical responders to treatment: ≥50% reduction in UUIEs after SNM placement or 1 mo post BTX.
INTERVENTION: SNM (n=194) versus 200 U BTX (n=192). SNM reprogrammings occurred throughout the 24 mo. After 6 mo, two additional BTX injections were allowed.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome: change in mean daily UUIE over 24 mo.
SECONDARY OUTCOMES: no UUIE, ≥75% and ≥50% UUIE reduction; Overactive Bladder Questionnaire Short Form; Urinary Distress Inventory short form; Incontinence Impact Questionnaire; Patient Global Impression of Improvement; Overactive Bladder Satisfaction of Treatment Questionnaire; and adverse events (AEs). Primary analysis used a linear mixed model.
RESULTS AND LIMITATIONS: Outcome data were available for 260/298 (87%) clinical responders. No difference in decreased mean UUIE was found over 24 mo (-3.88 vs -3.50 episodes/d,95% confidence interval [CI]=-0.14-0.89; p=0.15), with no differences in UUI resolution, ≥75% or ≥50% UUIE reduction. BTX group maintained higher satisfaction (mean difference=-9.14, 95% CI=-14.38--3.90; p<0.001), treatment endorsement (mean difference=-12.16, 95% CI=-17.7--6.63; p<0.001) through 24 mo. Other secondary measures did not differ. Recurrent urinary tract infections (UTIs) were higher after BTX (24% vs 10%; p<0.01), 6% required intermittent catheterization post second injection. SNM revision and removals occurred in 3% and 9% patients, respectively.
CONCLUSIONS: Both treatments offered sustainable UUI improvement, and higher BTX dosing had low clean intermittent catheterization rates, but with UTI risk. SNM revision/removal rates were low due to standardized lead placement with strict treatment response definitions.
PATIENT SUMMARY: We compared a large group of US women with severe urgency urinary incontinence (UUI) who received sacral neuromodulation (InterStim) or onabotulinumtoxinA (Botox A) therapy during a 2-yr period. We found that both therapies had similar success in reducing UUI symptoms, and adverse events were low. However, women in the BotoxA group had higher satisfaction and endorsement with their treatment, but with a higher chance of a urinary tract infection. We conclude that both therapies offer sustained reduction in daily incontinence over 2 yr.

Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.
PMID 29482936  Eur Urol. 2018 Jul;74(1):66-73. doi: 10.1016/j.eururo.2・・・

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