Outcomes of a single trigone-only vs. 20 trigone-sparing injections of OnabotulinumtoxinA for refractory overactive bladder (OAB)

AimsIn studies utilizing a 20‐injection‐site paradigm of onabotulinumtoxinA treatment for overactive bladder (OAB), some patients performed clean intermittent catheterization (CIC). An alternative injection paradigm of fewer injections targeting the lower bladder may reduce the need for CIC by maintaining upper bladder function. This study evaluated the efficacy and safety of an unapproved alternative 10‐injection‐site paradigm targeting the lower bladder.MethodsIn this phase 4, double‐blind, parallel‐group study, patients with OAB and urinary incontinence (UI) for ≥6 months with ≥3 episodes of urinary urgency incontinence (no more than 1 UI‐free day) and ≥8 micturitions per day over 3 days during screening were randomized 2:1 to onabotulinumtoxinA 100 U or placebo injected at 10 sites in the lower bladder.ResultsOf 120 patients, 78 in the onabotulinumtoxinA group and 39 in the placebo group had efficacy assessments. In the double‐blind phase, mean change from baseline at week 12 in daily frequency of UI episodes was greater with onabotulinumtoxinA (−2.9) versus placebo (−0.3) (least squares mean difference [LSMD]: −2.99, p < 0.0001). Achievement of 100% (odds ratio [OR]: 6.15 [95% confidence interval, CI: 0.75–50.37]), ≥75% (OR: 7.25 [2.00–26.29]), and ≥50% improvement (OR: 4.79 [1.87–12.28]) from baseline in UI episodes was greater with onabotulinumtoxinA versus placebo. Reductions from baseline in the daily average number of micturitions (LSMD: −2.24, p < 0.0001), nocturia (LSMD: −0.71, p = 0.0004), and urgency (LSMD: −2.56, p < 0.0001) were greater with onabotulinumtoxinA than with placebo. Treatment benefit was improved or greatly improved in the onabotulinumtoxinA group (74.0% of patients) versus placebo (17.6%) (OR: 13.03 [95% CI: 3.23–52.57]). Mean change from baseline in Incontinence Quality of Life score was greater with onabotulinumtoxinA versus placebo (LSMD: 24.2, p = 0.0012). Two of 78 (2.6%) patients in the onabotulinumtoxinA group used CIC during the double‐blind period; no females used CIC during the double‐blind period. Commonly reported adverse events (≥5%) were urinary tract infection (UTI), dysuria, and productive cough for both groups; rate of UTI was higher with onabotulinumtoxinA versus placebo.ConclusionIn patients treated with onabotulinumtoxinA for OAB with UI, an unapproved alternative injection paradigm targeting the lower bladder demonstrated efficacy over placebo, with a low incidence of CIC.

Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 98%

Efficacy and safety of an alternative onabotulinumtoxinA injection paradigm for refractory overactive bladder

MacDiarmid,

Glazier,

McCrery

et al. 2023

“…Ton et al 17 compared the safety and efficacy of a single trigone‐only injection versus 20 trigone‐sparing injections of BTN/A for refractory OAB. The trigone‐only group had a single dose of 100 units in 10 mL, whereas the trigone‐sparing injections received the same dose, 100 units in 10 mL, given in 0.5 mL injections.…”

Section: Resultsmentioning

confidence: 99%

“…[14][15][16] A further two studies looked at the inclusion of the trigone and the number of injections and included a retrospective chart review, a prospective pilot study, and evidence from a not yet published RCT. 17,18 The results are summarized in Tables 1-3.…”

Section: Resultsmentioning

confidence: 99%

Anatomical location and number of injection sites of intravesical OnabotulinumtoxinA for females with refractory idiopathic overactive bladder: A scoping review

Kelsey,

Wynn,

Holmes

et al. 2024

AimsThe negative impact on quality of life and the economic‐related burden to the patient and the health care system associated with idiopathic overactive bladder (iOAB) is well‐documented. Intradetrusor OnabotulinumtoxinA (BTN/A) injections are a well‐used treatment modality for the management of overactive detrusor refractory to medical management, with well‐documented efficacy and safety profiles. There is currently no best practice guideline for the administration of BTN/A for this procedure and historically the trigone of the bladder has been excluded from the injection paradigm given the risk of vesicoureteral reflux (VUR).MethodsA scoping review methodology was employed to assess available literature to evaluate current techniques used. There is emerging literature that the inclusion of the trigone may increase the efficacy of the procedure, while maintaining a similar adverse effect profile. Similar results could also be obtained by decreasing the number of injection sites. A scoping review was completed with systematic methodology using the Preferred Systematic Reviews and Meta Analyses extension for Scoping Review checklist. The search strategy looked to evaluate BTN/A and number of injection sites and the inclusion of the trigone in female patients with iOAB. Studies with male or neurogenic bladder only were excluded. Mixed studies were included. A specialist research librarian was engaged, with supervision from a functional urologist using a combination of MeSH and natural language terms. Two investigators independently reviewed the titles and abstracts.ResultsTwelve articles were included and were published between 2005 and 2021. There was no evidence of VUR in any of the results. All but one study reported similar if not improved efficacy of trigone‐inclusion. Lower number of injection sites had similar efficacy profiles to higher numbers of intradetrusor injections.ConclusionsFurther high‐quality randomized control trials of trigone inclusion and reduction of injection sites are required. It is hoped that with further exploration of intraoperative methods for BTN/A injections, the development of universally accepted guidelines may optimize management and experiences for patients with iOAB.

“…5 Uncontrolled 37,38 and randomized [39][40][41][42] clinical trials have documented the efficacy of intradetrusor BTA for IC/BPS. Trigone-only injections of BTA have been shown to be effective in refractory OAB, 43 meanwhile no study has compared trigone-only against trigone-sparing BTA in IC/BPS. Some studies suggest that sequential BTA injections are needed to achieve steady-state efficacy.…”

Section: Botulinum Toxin a (Bta)mentioning

confidence: 99%

Pathophysiology, assessment, and treatment of overactive bladder symptoms in patients with interstitial cystitis/bladder pain syndrome

Dobberfuhl

2022

Introduction Interstitial cystitis/bladder pain syndrome (IC/BPS) is prevalent, difficult to treat, and has close symptom overlap with overactive bladder (OAB). A review of the pathophysiology, assessment, and treatment of IC/BPS patients with overlapping OAB symptoms has not been summarized recently in the published literature. Methods A review of the published literature on the overlap of IC/BPS and OAB was conducted using MeSH terminology (1992–2022). Results The pathophysiology of IC/BPS is not fully understood. Animal research has found the bladder trigone and base are richly populated by afferent fibers, including many small unmyelinated C‐fibers that may be upregulated in IC/BPS. Successful therapies with multimodal effects on OAB symptoms in patients with IC/BPS are likely to exert beneficial effects on both pain and lower urinary tract symptoms. Potentially efficacious therapies for the treatment of OAB in IC/BPS include pelvic floor physical therapy, oral pharmacotherapy (antimuscarinics and beta‐3 agonists), sacral neuromodulation, percutaneous tibial nerve stimulation, and botulinum toxin A (BTA). Antimuscarinics and beta‐3 agonists have yielded partial efficacy in IC/BPS, although may help differentiate symptoms of OAB from those associated with IC/BPS. The transvaginal trigone treatment (T3) intradetrusor injection approach allows for delivery of therapeutics to the bladder without the need for a cystoscope and appears to be feasible. Conclusions Further research is needed to understand the pathophysiology of IC/BPS and symptom overlap with OAB, which in turn should enable the development of more personalized therapeutics.