- 學位論文
膀胱內藥物治療間質性膀胱炎—系統性回顧及網絡統合分析
Intravesical Therapy for Interstitial Cystitis – A Systematic Review and Network Meta-analysis
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摘要
研究背景與目的： 間質性膀胱炎/膀胱疼痛症候群是一類與膀胱不適疼痛、頻尿急尿等下泌尿道症狀相關的臨床症狀組合統稱。目前病因仍不明，醫界對於什麼是最好的治療方式也尚未達成共識。膀胱內灌注藥物是一種可以緩解臨床症狀並且增加膀胱容量的治療方式，目前用於膀胱內治療的藥物有很多種，本篇系統性回顧將聚焦於比較各種膀胱內的藥物治療，希望收集完整的文獻證據，以網絡統合分析的方式來提供臨床上治療間質性膀胱炎/膀胱疼痛症候群的建議及指引。 研究方法： 本研究採用系統性文獻回顧，在PubMed、Embase及Cochrane Library等資料庫搜尋比較各種膀胱內灌注藥物用於治療間質性膀胱炎/膀胱疼痛症候群的隨機分派研究。我們使用隨機效應模型的網絡統合分析去比較各種膀胱內灌注藥物包含卡介苗、肉毒桿菌、硫酸軟骨素、肝素、玻尿酸、二甲基亞碸、利多卡因及辣椒素個別使用或合併使用的臨床效果。統計的一致性是使用sidesplitting方式。另外，我們使用SUCRA方式分析及排序各種藥物的療效；漏斗圖被用來分析有無出版性偏誤。 研究結果： 本研究收錄了20個隨機分派研究共1395個病人，其中包含了九種膀胱內灌注藥物和安慰劑對照組的比較。網絡統合分析的結果顯示在病人主觀的治療反應這項結果中，「肝素+利多卡因」有最高的可能是最好的治療選擇(可能性91.8%)；而在降低病人疼痛這項結果中，玻尿酸最可能是最佳的治療(可能性90.2%)。比較「肝素+利多卡因」及玻尿酸之間的治療效果並沒有顯著差異，而這兩種治療方式能顯著改善病人主觀的治療反應、降低疼痛指數(玻尿酸平均降低3.6分；「肝素+利多卡因」平均降低3.2分)以及增加膀胱容量(「肝素+利多卡因」平均增加55.5毫升；玻尿酸平均增加57.5 毫升)。另外，肉毒桿菌可以顯著改善整體病人主觀的治療反應、減少間質性膀胱炎症狀指數、減少間質性膀胱炎問題指數、減少頻尿及急尿感次數，以及降低疼痛指數(平均降低1.88分)。 結論： 「肝素+利多卡因」及玻尿酸這兩種治療方式是目前治療間質性膀胱炎/膀胱疼痛症候群最佳的膀胱內灌注藥物選擇，膀胱灌注這兩種藥物組合，可以顯著改善病人主觀的治療效果、減輕疼痛指數以及增加膀胱容量。另外，肉毒桿菌也是一種有效的治療方式，可以改善病人主觀的治療效果、頻尿、急尿感及減輕病人的疼痛。未來仍需要更多標準化的臨床試驗，才能更好地評估比較各種間質性膀胱炎/膀胱疼痛症候群的治療方式及其療效。
並列摘要
Purpose： Interstitial cystitis/bladder pain syndrome (IC/BPS) was an unpleasant sensation related to the urinary bladder, associated with lower urinary tract symptoms. The etiology of IC/BPS remains uncertain and there is no consensus regarding the optimal treatment. Intravesical therapy is one of the treatments that can relieve the clinical symptoms of IC/BPS and restore bladder function. The present systematic review will focus on the intravesical therapy with different agents. The goal of this network meta-analysis is to incorporate all available evidence into a general statistical framework to compare the efficacy of intravesical therapies and wish to give some guidance for future treatment choices. Material and methods： A systematic literature search was conducted using electronic databases PubMed, Embase, and the Cochrane Library up to and including April, 2018. We did random effects network meta-analysis (NMA) to compare clinical outcomes for different intravesical medications, including Bacillus Calmette-Guerin (BCG), Botulinum neurotoxin A (BoNTA), chondroitin sulfate (CS), heparin, hyaluronic acid (HA), Dimethyl sulfoxide (DMSO), lidocaine, and resiniferatoxin (RTX). The assumption of consistency was assessed by sidesplitting approach. We used the surface under the cumulative ranking (SUCRA) probabilities to rank the outcomes of the treatment. A funnel plot was used to assess the presence of small-study bias in the network meta-analysis. Results： Twenty randomized controlled trials with nine intravesical interventions (BCG, BoNTA, CS, DMSO, “HA+CS”, lidocaine, RTX, HA and “heparin + lidocaine”) compared with placebo or non-placebo on a total of 1395 patients, who were mostly female (92%), were included in our analysis. Network meta-analysis indicated that “Heparin + Lidocaine” had the highest probability to be the best therapy (SUCRA probability: 91.8%) and the second place was HA (SUCRA probability: 75.2%) in the assessment of global response assessment (GRA). Besides, HA had the highest probability to be the best therapy (SUCRA probability: 90.2%), followed by “HA+CS” (SUCRA probability: 84.5%) and “Heparin + Lidocaine” (SUCRA probability: 82.2%). “Heparin + Lidocaine” and HA both had significant treatment effects than placebo in GRA (“Heparin + Lidocaine”: OR: 55.23, 95%CI: 1.50, 2032.91; HA: OR: 8.3, 95%CI:1.05, 65.53), visual analogue scale for pain (VAS) (“Heparin + Lidocaine”: WMD: -3.2, 95%CI: -4.55 to -1.85; HA: WMD: -3.6, 95%CI: -4.89 to -2.31) and functional bladder capacity (FBC) (“Heparin + Lidocaine”: WMD: 55.5, 95%CI: -43.44 to 67.56; HA: WMD: 57.5, 95%CI: 46.9 to 68.1). However, there was no statistically significant difference between these two treatments according to the network meta-analysis results. Furthermore, BoNTA treatment significantly improved GRA (OR: 4.18, 95%CI: 1.25, 14.17), ICSI (WMD: -1.18, 95%CI: -1.69 to -0.66), ICPI (WMD: -2.58, 95%CI: -3.04 to -2.11), frequency (WMD: -3.34, 95%CI: -6.55, -0.14), urgency (WMD: -2.48, 95% CI: -3.31, -1.66) and VAS (WMD: -1.88, 95% CI: -2.8, -0.96). Conclusion: We recommended that “Heparin + Lidocaine” and HA are both the best treatment choices for IC/BPS patients currently, according to the GRA assessment and VAS results. BoNTA is also an effective and reasonable treatment for it significantly improves GRA, ICSI, ICPI, frequency, urgency and VAS. Future researches would be essential to use a standardized design of clinical trials to allow later comparison or combination of data across trials.
參考文獻
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