肉毒桿菌對於膀胱過動症的神經調節效果可能最好


  【24drs.com】根據發表於10月4日JAMA期刊的一篇隨機試驗,約6個月的研究期間,相較於薦骨神經調節,單次注射200單位的A型肉毒桿菌毒素(onabotulinumtoxinA),對於每天的緊急尿失禁發生次數,可以有小幅但達統計顯著意義的減少。
  
  對於這項獲得美國食品藥物管理局核准的神經毒素,這篇研究使用的劑量是核准劑量的2倍,於膀胱過動簡短版問卷的症狀困擾、以及治療滿意度和支持度次量表方面,患者也有較大幅度的改善報告。
  
  不過,這項治療和泌尿道感染風險比較高有關,也增加了間歇性自我導尿之需求,這些會造成與薦骨神經調節比較整體治療價值時的疑慮。
  
  北卡羅萊納州杜克大學婦產科、泌尿科婦科和重建骨盆外科Cindy L. Amundsen醫師等人寫道,整體而言,這些研究結果使得A型肉毒桿菌毒素與薦骨神經調節相較時,不確定是否提供具臨床重要意義的淨效益。
  
  Amundsen醫師表示,不過,在注射200單位的botulinum toxin之後,我們並未發現如之前報告所指出的,使用這個劑量會造成尿滯留率高(亦即使用導管之需求)。至於注射導致發生尿道感染風險方面,令我們驚訝的是,我們注射200單位的風險並沒有高於使用100單位之研究發表的風險。此外,在不良反應或治療便利性的生活品質調查方面,我們的研究發現,不同療法之間並無差異。
  
  Amundsen醫師等人在2012年2月至2015年1月間,於國家健康研究院贊助的骨盆腔底部疾病網絡計畫的9個城市進行了開放標籤試驗,他們隨機指派平均年齡63.0歲的364名難治型尿失禁婦女接受膀胱鏡膀胱內注射200單位(n = 190人)或植入神經調節裝置(n = 174人)。
  
  在6個月的試驗中,A型肉毒桿菌毒素治療使每天的尿失禁次數減少平均3.9次,薦骨神經調節組則是平均減少3.3次,尿失禁次數之檢測是本研究的初級終點(平均差異為0.63;95%信賴區間[CI], 0.13 - 1.14;P = .01)。
  
  其他研究結果方面,完成至少4個月日記的研究對象中,注射組有20%、神經調節組有4%表示他們的尿失禁完全緩解,差異為 -16% (95% CI, -26% 至 -5%;P < .001)。注射組中有46%、神經調節組有26%的尿失禁發生次數減少至少75%,治療差異為-20% (95% CI, -30% 至-9%;P < .001)。
  
  就不良反應方面,薦骨神經調節組有6名婦女(3%)在這6個月期間內有調整或移除她們的裝置。A型肉毒桿菌毒素組中,需要間歇性自我導尿的比率分別是:1個月時為8%、3個月時為4%、6個月時為2%。到6個月時,A型肉毒桿菌毒素組的尿道感染累積發生率為35%,高於另一組的11% (差異為-23%;95% CI, -33% 至 -13%;P < .001)。
  
  Amundsen醫師表示,根據這篇對嚴重症狀婦女進行的隨機研究,屬於第三線治療的botulinum toxin和薦骨神經調節,兩者都可減少緊急尿失禁發生。我們希望這篇研究在醫師與患者針對這兩種治療方式的潛在不良反應與效果差異方面做出決定時,能有所幫助。
  
  紐約市紐約大學Langone醫學中心、教授、泌尿科婦科醫師Victor W. Nitti受邀發表評論時表示,我認為這些資料需仔細衡量,且應瞭解兩種療法的相關知識,事實上,他們使用了Botox核准劑量的2倍,這點在我看來有缺陷。副作用-特別是需要導尿這點,會隨著劑量從100單位增加到200單位而增加。
  
  不過,Nitti醫師表示,在尿失禁發生次數方面,注射組確實與神經調節組有顯著差異。雖然看起來是每天只有減少0.6次的尿失禁次數,當你深入探究且根據統計模式時,它是有效的,所以,我認為這研究對Botox是正面的。
  
  他指出,使用這些第三線治療之前,醫師應建議第一線治療,如行為調整、骨盆底運動、物理治療,之後,如果有需要再使用藥物進行第二線治療。
  
  在選擇第三線治療時,患者與醫師需根據患者的特徵、治療目標、副作用耐受程度等,而決定哪種療法最佳。Nitti醫師表示,舉例來說,絕對反對導尿的患者就不適合使用Botox,可能因為某些因素需進行MRI檢查的患者就不適合植入薦骨神經調節裝置。這些治療應被視為互補性,而不是競爭性。
  
  Amundsen醫師指出,雖然薦骨神經調節治療的初始費用比較高,接受botulinum toxin的患者可能在持續治療上需要額外注射。我們的研究追蹤了患者2年的費用資料,也會在2年療效分析時予以評估。
  
  研究者5月時在美國泌尿科協會(AUA)2016年會報告試驗結果。
  
  資料來源:http://www.24drs.com/
  
  Native link:Botox May Top Neuromodulation in Overactive Bladder

Botox May Top Neuromodulation in Overactive Bladder

By Diana Swift
Medscape Medical News

Over the course of 6 months, a single injection of 200 units of onabotulinumtoxinA resulted in a small but statistically significant greater reduction in daily episodes of urgency urinary incontinence than sacral neuromodulation, according to a randomized study published in the October 4 issue of JAMA.

Use of twice the dose of the neurotoxin approved by the US Food and Drug Administration also led to greater patient-reported improvements on the Overactive Bladder Questionnaire Short Form questionnaire for symptom bother, as well as in treatment satisfaction and endorsement subscales.

However, the treatment was associated with higher risk for urinary tract infections and increased need for transient self-catheterizations, which raises questions about overall value of the treatment compared with sacral neuromodulation.

"Overall, these findings make it uncertain whether onabotulinumtoxinA provides a clinically important net benefit compared with sacral neuromodulation," write Cindy L. Amundsen, MD, a professor of obstetrics and gynecology urogynecology and reconstructive pelvic surgery at Duke University in Durham, North Carolina, and colleagues.

"But our study did not find the high urinary retention rates (that is, the need for catheterization) after injecting 200 units of botulinum toxin, as have been reported in previous studies using this dose. And while there is the risk of developing a [urinary tract infection] with injections, we were surprised that our rate using 200 units was no greater than studies using 100 units," Dr Amundsen told Medscape Medical News. "In addition, our study found no differences between the therapies in quality-of-life measures for adverse events or treatment convenience."

Dr Amundsen and associates conducted the open-label trial between February 2012 and January 2015 at nine sites in the National Institutes of Health–sponsored Pelvic Floor Disorders Network. They randomly assigned 364 women with refractory incontinence and a mean age of 63.0 years to cystoscopic intradetrusor injection at 200 units (n = 190) or implantation of a neuromodulator (n = 174).

Treatments Should Be Viewed as Complimentary, Expert Says

During the 6-month trial, onabotulinumtoxinA treatment resulted in an average of 3.9 fewer episodes of urgency incontinence per day compared with an average reduction of 3.3 episodes with sacral neuromodulation, which was the primary endpoint (mean difference, 0.63; 95% confidence interval [CI], 0.13 - 1.14; P = .01).

In other findings, among participants who completed at least four monthly diaries, 20% in the injection arm vs 4% in the neuromodulation group reported complete resolution of their incontinence, for a difference of ?16% (95% CI, ?26% to ?5%; P < .001). In the injection group, 46% vs 26% in the neuromodulation group had at least a 75% reduction in the number of incontinence episodes, for a treatment difference of ?20% (95% CI, ?30% to ?9%; P < .001).

In terms of adverse events, six women (3%) in the sacral neuromodulation group underwent revision or removal of their devices over the course of 6 months. In the onabotulinumtoxinA group, 8% required intermittent self-catheterization at month 1, 4% at month 3, and 2% at month 6. By 6 months, the cumulative incidence of urinary tract infections was higher with onabotulinumtoxinA, at 35% vs 11% (difference, ?23%; 95% CI, ?33% to ?13%; P < .001).

"Based on this randomized study of severely affected women, in third-line therapies botulinum toxin and sacral neuromodulation, both reduced urgency urinary incontinent episodes," Dr Amundsen said. "We hope this study will help inform physicians and patients who are trying to make a decision between these two therapies, aligning the potential adverse events with differences in efficacy."

Commenting on the study, Victor W. Nitti, MD, a urogynecologist and professor at New York University Langone Medical Center in New York City, told Medscape Medical News, "I believe the data here need to be weighed with some caution and knowledge about the two treatments. The fact that they used twice the approved dose of Botox makes the study somewhat flawed in my opinion. Side effects, and in particular the need to catheterize, go up considerably when going from 100 to 200 units."

Still, Dr Nitti said, the injections did produce a significant difference vs neuromodulation in urinary incontinence episodes. "While it may not seem like 0.6 incontinence episodes per day is a big difference, when you look at it and a statistical model, it is. So I would say that's a positive for Botox."

He added that before these third-line therapies are used, physicians should recommend first-line treatments with behavioral modification, pelvic floor exercises, and physical therapy, followed, if necessary, by second-line treatment with medication.

In selecting a third-line therapy, the patient and her physician need to decide which treatment is best, on the basis of her specific characteristics, goals, and adverse effect tolerance level. "For example, the patient who is absolutely averse to catheterization would not be the best candidate for Botox," Dr Nitti said. "The patient who needs to have MRI studies for one reason or another would not be a good candidate for the implantation of a sacral neuromodulation device. These treatments should be viewed as complementary, not competitive."

Dr Amundsen added that although the initial costs for neuromodulation therapy are higher, patients who receive botulinum toxin may require additional injections for continuing treatment. "Our trial is following participants for 2 years in which cost analysis information will be evaluated as well as 2-year efficacy outcomes," she said.

The researchers reported the results of the trial at the American Urological Association (AUA) 2016 Annual Meeting in May.

This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and by the Office of Research on Women's Health at the National Institutes of Health. One coauthor is the project scientist for the Pelvic Floor Disorders Network at the Eunice Kennedy Shriver National Institute of Child Health and Human Development and was involved in all aspects of the study. One coauthor reported receiving grant funds from Pfizer; another coauthor reported serving as a consultant for Medtronic, Allergan, and Axonics. Dr Nitti has performed research for Allergan.

JAMA. 2016;316:1366-1374.

    
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