ABC: Anticholinergic Versus Botulinum Toxin Comparison
ABC was a 10-center, double-blind, double-placebo randomized trial in 249 women with idiopathic urgency urinary incontinence that compared one cystoscopic 100 U onabotulinumtoxinA injection with six months of oral solifenacin, escalated or switched to trospium XR for inadequate control; daily urgency incontinence episodes fell by 3.3 with toxin and 3.4 with the anticholinergic regimen (P = 0.81), and toxin gave more complete resolution but more urinary tract infection and catheterization.[1]
- Design and population
- Multicenter, double-blind, double-placebo randomized superiority trial. 249 randomized women without neurologic disease who had five or more urgency incontinence episodes per 3-day diary, were anticholinergic-naive or had used up to two anticholinergics other than solifenacin, darifenacin or trospium, and had a postvoid residual below 150 mL.
- Arms
- OnabotulinumtoxinA 100 U intradetrusor injection with oral placebo versus oral solifenacin with escalation or a switch to trospium XR, plus saline injection
- Report and follow-up
- 2012 · Mean change over months 1 to 6 of the double-blind phase; off-treatment follow-up to month 12
| Endpoint | Results | Effect | Finding |
|---|---|---|---|
| Adjusted mean reduction in urgency incontinence episodes per day averaged over months 1 to 6 (baseline mean 5.0 per day); 241 women analyzed | 3.3 fewer/day vs 3.4 fewer/day | P 0.81 | Not met |
Harms: Urinary tract infection: 40/120 (33%) vs 16/127 (13%); Dry mouth: 37/120 (31%) vs 58/127 (46%); Intermittent catheterization by study criteria at 2 months: 6/117 (5%) vs 0
Design
The Pelvic Floor Disorders Network conducted the trial from February 2010 through May 2012 in women without neurologic disease. Entry required five or more urgency incontinence episodes on a 3-day diary with urgency-predominant incontinence. Women were anticholinergic-naive or had used up to two anticholinergics other than solifenacin, darifenacin or trospium; those taking an anticholinergic at baseline underwent a 3-week washout. Women with a postvoid residual of 150 mL or more or previous onabotulinumtoxinA for urgency incontinence were excluded, and each woman or a caregiver had to show she could perform bladder catheterization before randomization. Randomization was stratified by previous anticholinergic exposure, baseline severity (5 to 8 versus 9 or more episodes per 3 days) and site; 41% of participants had no previous anticholinergic therapy.[1]
Both arms received a double-dummy regimen. The anticholinergic arm took solifenacin 5 mg daily with a saline injection, and the toxin arm received onabotulinumtoxinA 100 U with placebo pills. At months 2 and 4, women with inadequate control on the Patient Global Symptom Control scale and tolerable side effects moved from solifenacin 5 mg to 10 mg and then to trospium XR 60 mg; placebo pills were escalated on the same schedule. All pills stopped at 6 months, and women with adequate control were followed monthly to 12 months. The authors chose 100 U after an earlier 200 U placebo-controlled trial was stopped early because the urinary retention rate was 43%.[1]
The primary endpoint was the change from baseline in mean urgency incontinence episodes per day, from monthly 3-day diaries over 6 months, analyzed with a linear mixed model in the modified intention-to-treat population. The trial was sized to detect a difference of 0.8 episodes per day with 80% power; one interim analysis did not cross its boundary. Every analysis other than the primary comparison was descriptive and unadjusted for multiple testing.[1]
Results
Of 249 women randomized (127 anticholinergic, 122 toxin), 247 were treated and 241 contributed to the primary analysis. Baseline mean was 5.0 urgency incontinence episodes per day. Mean daily episodes fell by 3.3 with onabotulinumtoxinA and by 3.4 with anticholinergic therapy averaged over months 1 to 6 (P = 0.81), so the primary endpoint did not differ between arms; 9% of monthly diaries were missing, evenly distributed between groups.[1]
Among women returning at least four diaries, complete resolution of urgency incontinence occurred in 30/112 (27%) of the toxin arm and 16/119 (13%) of the anticholinergic arm (P = 0.003), and complete resolution of all incontinence in 26/112 (23%) versus 13/119 (11%) (P = 0.003). A reduction of more than 75% was reported by 61/112 (54%) versus 48/119 (40%) (P = 0.06). Changes in the Overactive Bladder Questionnaire Short Form did not differ: symptom severity −44.08 versus −44.55 (P = 0.87) and quality of life 37.13 versus 37.05 (P = 0.98).[1]
After oral drugs stopped at 6 months, adequate symptom control was reported by 62% of the toxin arm and 50% of the anticholinergic arm at month 7 (P = 0.006), and by 38% and 25% at month 12. Of those analyzed, 85/121 toxin and 89/126 anticholinergic participants entered this off-treatment phase.[1]
In a planned adherence analysis, composite adherence to study pills from pill counts and electronic caps averaged 83.3% (SD 16.8) in the anticholinergic arm and 84.8% (SD 13.8) in the toxin arm taking placebo (P = 0.45); 53% of women were at least 80% adherent in each two-month period.[2] In the trial-based cost analysis of 231 women completing 6 months, mean direct costs per participant were $1,266 with toxin and $1,339 with the anticholinergic regimen (P = 0.06), and annualized quality-adjusted life-year gains were 0.039 and 0.046 (P = 0.19). Modeled through 9 months, cost per month of adequate symptom control was $207 versus $305.[3]
Surgery and treatment delivery
The protocol specified injection through a Wolf injection cystoscope with the bladder filled with 100 to 200 mL. A 10 mL volume containing 100 U onabotulinumtoxinA, or placebo, plus 0.1 mL indigo carmine was injected into about 15 to 20 detrusor sites under direct vision with disposable needles. Sites covered the posterior wall and dome and spared the trigone, ureteral orifices and anterior dome, and a 1 mL saline flush followed. A negative dipstick urinalysis was required before injection.[4]
Intermittent catheterization started for a postvoid residual above 300 mL, or above 150 mL when the woman rated it moderately or quite bothersome. By these criteria, 9% (10/111) of the toxin arm met the threshold at 2 weeks, 5% (6/117) at 2 months and 1% (1/106) at 6 months; no one in the anticholinergic arm did.[1]
Adverse events
Urinary tract infection, defined as a culture above 100,000 colony-forming units per milliliter or any antibiotic course for urinary infection, occurred in 40/120 (33%) of the toxin arm and 16/127 (13%) of the anticholinergic arm (P < 0.001). Dry mouth occurred in 37/120 (31%) versus 58/127 (46%) (P = 0.02). Dry eyes (24% versus 17%) and constipation (21% versus 28%) did not differ significantly.[1]
Residual volume above 150 mL was recorded in 30% (33/111) of the toxin arm and 6% (7/120) of the anticholinergic arm at 2 weeks, and in 7% (7/106) versus 4% (5/114) at 6 months. Women also catheterized outside the protocol criteria: self-catheterization since the previous visit was reported at 1 month by 15% (17/117) of the toxin arm and 1% (1/120) of the anticholinergic arm. Serious adverse events occurred in 4/120 (3%) versus 6/127 (5%), and the investigators attributed none to study treatment.[1]
Limitations
The trial compared two active treatments without a placebo-only group, so the share of improvement due to placebo response is unknown. It tested one dose and formulation of toxin as a single injection, and only solifenacin and trospium XR, in women without neurologic disease; the trial gives no data on repeat injections or on other anticholinergics. Oral drugs were stopped at 6 months while the injection was given once, which shapes the off-treatment comparison. The authors suggested that catheterization outside the protocol criteria, in both arms, may have reflected counseling about retention risk. The trial was registered after enrollment began, with 20 participants randomized before registration and none yet at the primary outcome.[1][3]
In conversation
- Built on by ROSETTA (2016). The earlier 100 U toxin-versus-anticholinergic trial informed ROSETTA's dose and refractory-population rationale.
- Parallel to Nitti OAB Trial (2012). Both tested 100 U onabotulinumtoxinA in idiopathic overactive bladder with urgency incontinence; ABC used an anticholinergic comparator rather than placebo.
ABC enrolled women who were anticholinergic-naive or had used up to two other anticholinergics,[1] so its population is broader than trials of refractory overactive bladder such as ROSETTA, which compared a 200 U toxin dose with staged sacral neuromodulation.[6]
Guidelines and approvals
- AUA/SUFU (2024). The rationale for the statement that minimally invasive therapies may be offered with shared decision-making, without requiring prior behavioral, noninvasive or pharmacologic therapy, cites ABC as showing comparable reductions in daily episodes between antimuscarinics and 100 U onabotulinumtoxinA, with more complete resolution, more urinary tract infection and more short-term catheterization after toxin. The statement reads: "Clinicians may offer patients with OAB, in the context of shared decision-making, minimally invasive therapies without requiring trials of behavioral, non-invasive, or pharmacologic management." [5]
Report history
| Published | Report | Cutoff | Headline results | Citation |
|---|---|---|---|---|
| 2011-10-08 | Published protocol · secondary | — | — | Visco AG, Brubaker L, Richter HE, et al. "Anticholinergic versus Botulinum Toxin A Comparison Trial for the Treatment of Bothersome Urge Urinary Incontinence: ABC Trial." *Contemp Clin Trials.* 2012;33(1):184-196. doi:10.1016/j.cct.2011.09.019 DOI |
| 2012-10-04 | Six-month randomized comparison · primary | — | Adjusted mean reduction in urgency incontinence episodes per day averaged over months 1 to 6 (baseline mean 5.0 per day); 241 women analyzed: 3.3 fewer/day vs 3.4 fewer/day; P 0.81 Not met Complete resolution of urgency incontinence among women returning at least four follow-up diaries: 30/112 (27%) vs 16/119 (13%); P 0.003 Complete resolution of all incontinence among women returning at least four follow-up diaries: 26/112 (23%) vs 13/119 (11%); P 0.003 More than 75% reduction in urgency incontinence episodes among women returning at least four follow-up diaries: 61/112 (54%) vs 48/119 (40%); P 0.06 Change from baseline in Overactive Bladder Questionnaire Short Form symptom-severity score (0 to 100; higher is worse), adjusted mean months 1 to 6: -44.08 vs -44.55; P 0.87 Change from baseline in Overactive Bladder Questionnaire Short Form quality-of-life score (0 to 100; higher is better), adjusted mean months 1 to 6: 37.13 vs 37.05; P 0.98 Adequate symptom control (Patient Global Symptom Control 4 or 5 without off-study treatment) one month after oral study drugs stopped, month 7: 62% vs 50%; P 0.006 Adequate symptom control at month 12 (six months after oral study drugs stopped): 38% vs 25%; P 0.61 | Visco AG, Brubaker L, Richter HE, et al. "Anticholinergic Therapy vs. OnabotulinumtoxinA for Urgency Urinary Incontinence." *N Engl J Med.* 2012;367(19):1803-1813. doi:10.1056/NEJMoa1208872 DOI |
| 2016-01-01 | Adherence analysis · secondary | — | Overall composite adherence (mean percentage of expected doses from pill counts and electronic cap data), toxin arm taking placebo pills versus anticholinergic arm taking active pills: 84.8% (SD 13.8) vs 83.3% (SD 16.8); P 0.45 | Visco AG, Brubaker L, Jelovsek JE, et al. "Adherence to Oral Therapy for Urgency Urinary Incontinence: Results from the Anticholinergic Versus Botox Comparison (ABC) Trial." *Female Pelvic Med Reconstr Surg.* 2016;22(1):24-28. doi:10.1097/SPV.0000000000000215 DOI |
| 2016-09-01 | Trial-based cost-effectiveness · secondary | — | Mean direct medical and nonmedical cost per participant over 6 months, 2012 US dollars, among 231 women completing 6 months (119 anticholinergic, 112 toxin): $1,266 vs $1,339; P 0.06 Annualized quality-adjusted life-year gain from baseline (6-month utility gain times 2), derived from the OABq-SF: 0.039 vs 0.046; P 0.19 Modeled cumulative direct cost per month of adequate symptom control through 9 months (cumulative cost $1,266 toxin versus $1,942 anticholinergic): $207 vs $305; P <0.0001 | Visco AG, Zyczynski H, Brubaker L, et al. "Cost-Effectiveness Analysis of Anticholinergics Versus Botox for Urgency Urinary Incontinence: Results From the Anticholinergic Versus Botox Comparison Randomized Trial." *Female Pelvic Med Reconstr Surg.* 2016;22(5):311-316. doi:10.1097/SPV.0000000000000277 DOI |
References
1. Visco AG, Brubaker L, Richter HE, et al. "Anticholinergic Therapy vs. OnabotulinumtoxinA for Urgency Urinary Incontinence." N Engl J Med. 2012;367(19):1803-1813. doi:10.1056/NEJMoa1208872
2. Visco AG, Brubaker L, Jelovsek JE, et al. "Adherence to Oral Therapy for Urgency Urinary Incontinence: Results from the Anticholinergic Versus Botox Comparison (ABC) Trial." Female Pelvic Med Reconstr Surg. 2016;22(1):24-28. doi:10.1097/SPV.0000000000000215
3. Visco AG, Zyczynski H, Brubaker L, et al. "Cost-Effectiveness Analysis of Anticholinergics Versus Botox for Urgency Urinary Incontinence: Results From the Anticholinergic Versus Botox Comparison Randomized Trial." Female Pelvic Med Reconstr Surg. 2016;22(5):311-316. doi:10.1097/SPV.0000000000000277
4. Visco AG, Brubaker L, Richter HE, et al. "Anticholinergic versus Botulinum Toxin A Comparison Trial for the Treatment of Bothersome Urge Urinary Incontinence: ABC Trial." Contemp Clin Trials. 2012;33(1):184-196. doi:10.1016/j.cct.2011.09.019
5. American Urological Association and Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction. The AUA/SUFU Guideline on the Diagnosis and Treatment of Idiopathic Overactive Bladder. 2024. Statement 24 and supporting text.
6. Amundsen CL, Richter HE, Menefee SA, et al. "OnabotulinumtoxinA vs Sacral Neuromodulation on Refractory Urgency Urinary Incontinence in Women: A Randomized Clinical Trial." JAMA. 2016;316(13):1366-1374. doi:10.1001/jama.2016.14617