Botulinum toxin for endometriosis-associated chronic pelvic pain: a randomised, double-masked, parallel, phase 2 trial.

Background: Chronic pelvic pain affects one in four women. Botulinum toxin, approved for chronic migraine and cervical dystonia pain, is an emerging treatment for other pain conditions. We evaluated intramuscular pelvic floor botulinum toxin injection in women with endometriosis-associated chronic pelvic pain and pelvic floor muscle spasm, hypothesising that botulinum toxin might reduce both spasm and pain. Methods: In this a randomised, double-masked, parallel, phase 2 trial, women with pelvic floor spasm and pain despite standard endometriosis-specific and pain treatment were randomily assigned 1:1 to injection of 100 Units onabotulinumtoxinA (15 participants) or saline placebo (14 participants) into pelvic floor muscles. The primary outcome was patient report of benefit or no benefit assessed 1 month after masked injection. Patients could choose an open injection from 1 to 12 months after masked injection. Secondary outcomes (pain rating, pain medication usage, effect duration, and other participant-reported measures) were compared to baseline ratings. This study is registered with ClinicalTrials.gov, NCT01553201. Findings: 29 participants were recruited between July 24, 2014 and May 8, 2018. All enrolled women completed the study. At 1 month, significantly more women in the toxin group reported benefit (11 (73%) of 15 vs 4 (29%) of 14; p = 0.027). Women receiving toxin attained a greater percent benefit (p = 0.034) and longer duration (p = 0.023) of pain relief. Those with at least moderate baseline pain had lower pain scores after toxin (p = 0.028). Benefit was present at 1 year in 16 of those requesting open injection (7 of 14 receiving placebo; 9 of 13 receiving toxin). 20 (77%) of 26 patients used less pain medication at 1-year (p < 0.0001), with 12 (92%) of 13 in the BoNT group and eight (62%) of 13 in the placebo group using less medication (p = 0.061). Adverse events were non-serious with no grade 3 or 4 adverse events or deaths, and were similar in both cohorts following masked and open injections. Interpretation: This study demonstrates the efficacy and safety of pelvic floor botulinum toxin injection for women with endometriosis-associated chronic pelvic pain and pelvic floor spasm. Funding: The study was supported by the Intramural Research Program of the U.S. National Institutes of Health (NIH). Allergan, Inc. provided study drug and independent monitoring funds under a Clinical Trial Agreement with NIH and had no other role in the study.