A pooled analysis of four trials on Onabotulinum-toxin A vs placebo for women with OAB found decrease of 1.9 in incontinence episodes «Nitti VW, Kohan A, McCammon K, et al. Efficacy and...»1. It translates to about 43% decrease in incontinence episodes.
A network meta-analysis included 10 trials on Onabotulinum-toxin A for OAB (unclear how many were included in the meta-analyses) and suggested superior effect from botulinum-toxin A compared to other medical treatments «Drake MJ, Nitti VW, Ginsberg DA, et al. Comparativ...»2. However, interpretation warrants caution as the trials on botulinum-toxin A included patients with more severe symptoms. A high-quality randomized trial on Onabotulinum-toxin A vs medication (anticholinergic) suggested a similar impact from these treatments in urge urinary incontinence «Visco AG, Brubaker L, Richter HE, et al. Anticholi...»3.
The potential harms are Urinary dysuria (RD 1,9 %) and urinary retention requiring catheterization (2,5 %).
| Reference | Study type | Population | Intervention and comparison | Outcomes | Risk of bias |
|---|---|---|---|---|---|
| RCT=randomized controlled trial; SR=systematic review; MA=meta-analysis | |||||
| «Nitti VW, Kohan A, McCammon K, et al. Efficacy and...»1 | Pooled analysis, 4 RCTs | Idiopatic OAB inadequately managed by at least one anticholinergic agent. | Onabotulinum-toxin A vs placebo | UI episodes per day, proportion of patients achieving 50% reduction in UI episodes per day, TEAEs |
Low |
| «Drake MJ, Nitti VW, Ginsberg DA, et al. Comparativ...»2 | SR and network meta-analysis | Adults with idiopathic OAB, with/without UI | Onabotulinum-toxin A vs placebo or other medications |
number of episodes/day:
|
High |
| Reference | Comments |
|---|---|
| «Nitti VW, Kohan A, McCammon K, et al. Efficacy and...»1 | Since the second reference did not allow calculation of relative effect, we included
this pooled analysis. Inclusion criteria: adults with idiopathic OAB for 6 months who were inadequately managed by at least one anticholinergic agent. At least three urgency UI episodes recorded in the 3day bladder diary, at least eight micturitions per day, a negative urine dipstick reagent strip test and asymptomatic for UTI, and willing and able to use CIC if needed. Exclusion criteria: OAB symptoms caused by a neurologic disease and evidence of urethral and/or bladder outlet obstruction. At least two UTIs within 6 months of randomization/Day 1 or use of prophylactic antibiotics to prevent chronic UTIs, PVR >100 mL at screening, elevated PVR that had been treated with an intervention within 6 months, and previous or current diagnosis of prostate cancer or PSA >10 ng/mL at screeningAdditional outcomes: Incontinence Quality of Life Instrument (I-QOL) total score, and the proportion of patients with positive Treatment Benefit Scale (TBS) response, defined as condition "greatly improved" or "improved". TEAEs of urinary interest, including Incomplete bladder emptying requiring catheterization hematuria, and UTI, were evaluated in treatment Cycles 1 through 4. Urinary retention: incomplete bladder emptying requiring catherization. Risk of bias: Randomization procedure and blinding ok, under 10% loss to follow up. No systematic search could lead to selection bias. Included 2 more large trials compared to the next network meta-analysis. May not have missed any relevant trials as the additional trials in NMA probably did not provide data to the meta-analysis. |
| «Drake MJ, Nitti VW, Ginsberg DA, et al. Comparativ...»2 | Inclusion criteria
Exclusion criteria
Study design
Risk of bias: trials were poorly reported leading to unclear risk of bias considering most domains. loss to follow up were 10-18% in four studies reporting the data, additionally, one study reported no loss to follow up. |
Results
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Mean change from baseline (SD) I | Mean change from baseline (SD) C | Mean difference (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: High | |||||
| «Nitti VW, Kohan A, McCammon K, et al. Efficacy and...»1 | 4 RCTs, n=1370 (women) | 12 weeks | -3.0 | -1.1 | -1.9 (-2.3 to -1.5) relative decrease: -43 % (-51 % to -35 %) |
| «Drake MJ, Nitti VW, Ginsberg DA, et al. Comparativ...»2 | 10 RCTs | -1.55 (-2.01 to -1.10) | |||
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Mean change from baseline (SD) I | Mean change from baseline (SD) C | Mean difference (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: moderate The evidence was downgraded due to potential imprecision. |
|||||
| «Nitti VW, Kohan A, McCammon K, et al. Efficacy and...»1 | 4 RCTs, n=1370 (women) | 12 weeks | -24.3 | -7.1 | |
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Relative effect (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: moderate The quality of evidence is downgraded due to imprecision. I=intervention; C=comparison; CI=confidence interval |
|||||
| «Nitti VW, Kohan A, McCammon K, et al. Efficacy and...»1 | 4 RCTs (729/633) | 12 weeks | 13.4% | 12.6% | |
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Relative effect (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: moderate The quality of evidence is downgraded due to imprecision. *not calculated by the study authors |
|||||
| «Nitti VW, Kohan A, McCammon K, et al. Efficacy and...»1 | 4 RCTs (729/633) | 12 weeks | 26 (3.6 %) | 11 (1.7 %) | RR 2.05 (1.02 to 4.1)* |
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Relative effect (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: moderate The quality of evidence is downgraded due to imprecision. *not calculated by the study authors |
|||||
| «Nitti VW, Kohan A, McCammon K, et al. Efficacy and...»1 | 4 RCTs (729/633) | 12 weeks | 44 (6.0 %) | 22 (3.5 %) | RR 1.73 (1.05 to 2.86) |