Goldstein Andrew, Rubin Rachel, Dahir Melissa, Goldstein Irwin, Faught Brooke M, Bohm-Starke Nina, Krapf Jill, Caetano Peter, Volteau Magali, Silva Robert
The Centers for Vulvovaginal Disorders, Washington, DC 20037, United States.
Georgetown University, Department of Urology Washington, DC 20057, United States.
J Sex Med. 2025 Apr 15;22(4):588-596. doi: 10.1093/jsxmed/qdaf022.
Hypertonicity of the pelvic floor muscles is commonly associated with provoked vestibulodynia (PVD); therefore, patients may benefit from treatments that relax the pelvic floor.
To define optimal (safe and efficacious) doses of abobotulinumtoxinA (aboBoNT-A) for the treatment of PVD associated with hypertonic pelvic floor muscle dysfunction and to explore use of a novel endpoint for pain assessment for PVD.
This phase 2, randomized, placebo-controlled study comprised two steps: dose escalation (Stage 1) and dose expansion (Stage 2). Stage 1 included up to four treatment cycles; Cycle 1 was double blind, Cycles 2-4 open label. Patients were assessed for retreatment every 6 weeks. Stage 2 was not conducted because of early study termination by the sponsor, unrelated to observed safety signals. Enrolled patients-premenopausal women with PVD with associated pelvic-floor hypertonia-were randomized (n = 60) 4:1 to receive aboBoNT-A (doses: 100, 300, 400, or 500 units [U]) or placebo.
The primary endpoint was safety. Additionally, a novel composite endpoint, dilator maximum tested size was evaluated. This endpoint combined assessment of vaginal-dilator tolerability with patient-reported pain assessment on an 11-point numeric rating scale, used as a surrogate measure of sexual activity in this study.
All treatment-emergent adverse events (AEs) were mild or moderate in intensity, with no serious AEs or AEs leading to withdrawal reported in the double-blind period. AEs of special interest (urinary incontinence, anal sphincter atonia) were observed at low incidence and predominantly with higher aboBoNT-A doses. The dilator test composite score might be a useful endpoint for pain assessment, with a greater reduction in pain score noted for the 300 U dose group compared with other dose groups and placebo.
aboBoNT-A was well tolerated in patients with PVD and a novel method for assessing dilator-induced pain was introduced.
The study provided valuable data on use of aboBoNT-A in women with primary or secondary PVD and introduced a novel composite endpoint for assessing dilator-induced pain. Study limitations included the small sample size, limiting formal statistical analysis.
aboBoNT-A was well tolerated in patients with PVD with no safety signals reported. Further studies are warranted to demonstrate clinically meaningful benefits with repeated treatment.
NCT03598777.
盆底肌肉张力亢进通常与激发性前庭疼痛障碍（PVD）相关；因此，患者可能会从使盆底放松的治疗中获益。
确定用于治疗与高张性盆底肌肉功能障碍相关的PVD的阿柏西普肉毒毒素A（aboBoNT - A）的最佳（安全且有效）剂量，并探索一种用于PVD疼痛评估的新终点指标。
这项2期随机、安慰剂对照研究包括两个阶段：剂量递增（第1阶段）和剂量扩展（第2阶段）。第1阶段包括多达四个治疗周期；第1周期为双盲，第2 - 4周期为开放标签。每6周对患者进行再治疗评估。由于申办方提前终止研究（与观察到的安全信号无关），第2阶段未进行。纳入的患者为患有PVD且伴有盆底高张的绝经前女性，随机分组（n = 60），比例为4:1，分别接受aboBoNT - A（剂量：100、300、400或500单位[U]）或安慰剂。
所有治疗中出现的不良事件（AE）强度均为轻度或中度，双盲期未报告严重AE或导致停药的AE。观察到特别关注的AE（尿失禁、肛门括约肌无力）发生率较低，且主要出现在aboBoNT - A剂量较高时。扩张器测试综合评分可能是疼痛评估的一个有用终点指标，与其他剂量组和安慰剂相比，300 U剂量组的疼痛评分降低幅度更大。
aboBoNT - A在PVD患者中耐受性良好，并引入了一种评估扩张器诱发疼痛的新方法。
该研究提供了关于aboBoNT - A在原发性或继发性PVD女性中应用的有价值数据，并引入了一种用于评估扩张器诱发疼痛的新综合终点指标。研究局限性包括样本量小，限制了正式的统计分析。
aboBoNT - A在PVD患者中耐受性良好，未报告安全信号。有必要进行进一步研究以证明重复治疗具有临床意义的益处。
NCT03598777。
