Table 2.
Summary of efficacy and urodynamic outcomes at Week 6 by NDOI etiology
| Randomized population | SCI | MS | ||||
|---|---|---|---|---|---|---|
| Placebo | AboBoNT‐A | AboBoNT‐A | Placebo | AboBoNT‐A | AboBoNT‐A | |
| (N = 114) | 600 U (N = 114) | 800 U (N = 113) | (N = 49) | 600 U (N = 48) | 800 U (N = 47) | |
| Weekly NDO episodes, change from baseline a | ||||||
| LS mean [SE] (n) | −11.1 [1.6] (99) | −20.9 [1.5] (104) | −19.5 [1.6] (99) | −13.0 [2.3] (41) | −23.4 [2.4] (40) | −29.7 [2.3] (40) |
| Difference to placebo (95% CI) | −9.8 (−14.0, −5.6)*** | −8.4 (−12.6, −4.2)*** | −10.4 (−16.9, −3.9)* | −16.8 (−23.2, −10.3)*** | ||
| Weekly NDO episodes, threshold of improvement from baseline b | ||||||
| 50% reduction, n (%) | 30 (30) | 75 (72) | 60 (61) | 18 (44) | 31 (78) | 34 (85) |
| Odds ratio versus placebo (95% CI) | 5.8 (3.2, 10.7)*** | 3.8 (2.1, 6.9)*** | 4.6 (1.7, 12.3)** | 7.7 (2.6, 22.4)*** | ||
| ≥75% reduction, n (%) | 11 (11) | 62 (60) | 47 (48) | 10 (24) | 28 (70) | 33 (83) |
| Odds ratio versus placebo (95% CI) | 10.4 (5.1, 21.3)*** | 7.2 (3.5, 14.8)*** | 6.8 (2.6, 17.9)*** | 14.8 (5.0, 43.5)*** | ||
| 100% reduction in UI, n (%) | 3 (3) | 37 (36) | 24 (24) | 1 (2) | 15 (38) | 16 (40) |
| Odds ratio versus placebo (95% CI) | 18.5 (5.5, 61.7)*** | 12.4 (3.7, 42.3)*** | 20.0 (3.1, 131.0)** | 25.5 (3.9, 165.4)*** | ||
| I‐QoL total summary score, change from baseline a | ||||||
| LS mean [SE] (n) | 4.7 [2.1] (101) | 19.9 [2.0] (105) | 18.2 [2.0] (106) | 8.8 [3.0] (48) | 23.2 [2.1] (42) | 27.7 [3.0] (44) |
| Difference to placebo (95% CI) | 15.2 (9.65, 20.67)*** | 13.5 (7.9, 19.0)*** | 14.4 (6.0, 22.8)*** | 18.9 (10.7, 27.2)*** | ||
| I‐QoL domain scores, change from baseline a | ||||||
| Avoidance and limiting behavior | ||||||
| LS mean [SE] (n) | 4.5 [2.1] (101) | 19.7 [2.0] (105) | 17.6 [2.0] (106) | 8.7 [3.0] (48) | 22.6 [3.1] (42) | 30.7 [3.1] (44) |
| Difference to placebo (95% CI) | 15.2 (9.7, 20.8)*** | 13.1 (7.6, 18.7)*** | 13.9 (5.4, 22.3)** | 22.0 (13.7, 30.3)*** | ||
| Psychological impact | ||||||
| LS mean [SE] (n) | 5.1 [2.2] (101) | 19.8 [2.2] (105) | 18.2 [2.2] (106) | 10.1 [3.2] (48) | 21.8 [3.3] (42) | 24.0 [3.2] (44) |
| Difference to placebo (95% CI) | 14.8 (8.9, 20.7)*** | 13.1 (7.2, 19.0)*** | 11.7 (2.7, 20.6)* | 13.9 (5.0, 22.7)** | ||
| Social embarrassment | ||||||
| LS mean [SE] (n) | 4.8 [2.4] (101) | 20.4 [2.3] (105) | 18.5 [2.3] (106) | 7.1 [3.4] (48) | 26.2 [3.6] (42) | 29.7 [3.5] (44) |
| Difference to placebo (95% CI) | 15.7 (9.3, 22.0)*** | 13.7 (7.4, 20.1)*** | 19.1 (9.5, 28.8)*** | 22.7 (13.1, 32.2)*** | ||
| I‐QoL total summary score, ≥11‐point increase from baseline b | ||||||
| n (%) | 28 (28) | 67 (64) | 61 (58) | 19 (40) | 28 (67) | 33 (75) |
| Odds ratio versus placebo (95% CI) | 4.4 (2.4, 8.0)*** | 3.1 (1.7, 5.6)*** | 2.8 (1.2, 6.8)* | 4.5 (1.8, 11.2)** | ||
| Time to retreatment, weeks | ||||||
| Median (95% CI) | 19.3 (16.7, 24.1) | 43.7 (36.3, 53.0) | 39.4 (29.1, 43.7) | 24.4 (19.0, 36.9) | 61.9 (26.0, NE) | 48.3 (34.0, 62.7) |
| Urodynamic population | n = 106 | n = 108 | n = 102 | n = 42 | n = 45 | n = 44 |
| MCC (mL), change from baseline c | ||||||
| LS mean [SE] (n) | −8.0 [16.2] (89) | 160.8 [15.5] (98) | 174.9 [16.0] (92) | 1.5 [24.2] (39) | 169.7 [24.4] (38) | 174.4 [23.5] (41) |
| Difference to placebo (95% CI) | 168.8 (125.8, 211.8)*** | 182.8 (139.1, 226.6)*** | 168.3 (101.0, 235.5)*** | 173.0 (107.3, 238.6)*** | ||
| MDFP (cm H 2 O), change from baseline c | ||||||
| LS mean [SE] (n) | −0.9 [2.6] (81) | −30.5 [2.5] (92) | −33.3 [2.5] (86) | −10.9 [4.2] (31) | −35.1 [4.0] (33) | −36.4 [3.9] (36) |
| Difference to placebo (95% CI) | −29.6 (−36.5, −22.8)*** | −32.4 (−39.3, −25.4)*** | −24.2 (−35.5, −12.9)*** | −25.5 (−36.6, −14.5)*** | ||
| V1stIDC (mL), change from baseline c | ||||||
| LS mean [SE] (n) | −9.5 [16.8] (87) | 160.5 [16.4] (92) | 173.7 [16.8] (89) | 44.0 [25.8] (36) | 158.3 [25.6] (36) | 212.8 [26.0] (35) |
| Difference to placebo (95% CI) | 170.0 (125.0, 215.0)*** | 183.1 (137.4, 228.9)*** | 114.4 (43.4, 185.4)** | 168.8 (97.3, 240.4)*** | ||
| DC (mL/cm H 2 O), change from baseline c | ||||||
| LS mean [SE] (n) | −6.4 [7.8] (83) | 18.7 [7.5] (92) | 6.6 [7.7] (86) | 4.5 [12.7] (31) | 33.7 [12.0] (34) | 61.1 [11.6] (37) |
| Difference to placebo (95% CI) | 25.1 (4.4, 45.8)* | 13.0 (−8.1, 34.1) | 29.2 (−5.0, 63.4) | 56.6 (23.3, 89.9)*** | ||
| No IDC during storage d | ||||||
| n (%) | 2 (2) | 41 (42) | 45 (50) | 6 (17) | 18 (50) | 26 (67) |
| Odds ratio versus placebo (95% CI) | 30.6 (7.1, 131.6)*** | 42.9 (9.9, 185.0)*** | 4.8 (1.6, 14.5)** | 10.1 (3.3, 30.7)*** | ||
Note: *p < 0.05; **p < 0.01; ***p < 0.001 vs. placebo.
Abbreviations: AboBoNT‐A, abobotulinumtoxinA; BoNT‐A, botulinum toxin type A; cm H2O, centimeters of water; CI, confidence interval; DBPC, double‐blind placebo‐controlled; DC, detrusor compliance; IDC, involuntary detrusor contraction; GLMM, generalized linear mixed model; I‐QoL, 22‐item incontinence‐related quality of life; LS, least squares; MCC, maximum cystometric capacity; MDFP, maximum detrusor filling pressure; MMRM, mixed model repeated measures; MS, multiple sclerosis; N, number of patients in treatment group; n, number of patients in category; NDO, neurogenic detrusor overactivity; NDOI, neurogenic detrusor overactivity incontinence; NE, not estimated; SCI, spinal cord injury; SE, standard error; U, units; V1stIDC, volume at first IDC.
Based on MMRM with treatment group, visits (Weeks 2, 6, and 12 for weekly NDOI episodes; Weeks 6 and 12 for I‐QoL), treatment by‐visit interaction, treatment‐by‐visit‐by‐etiology group interaction, stratification factors (etiology of NDOI [SCI or MS], prior intradetrusor use [BoNT‐A naïve or non‐naïve]) and study as fixed effects, study baseline value as covariate, and patient as a random effect. Only the results for each aboBoNT‐A dose versus placebo by NDO etiology at Week 6 are presented.
Based on logistic GLMM with treatment group, stratification factors (etiology of NDOI [SCI or MS], prior intradetrusor use [BoNT‐A naïve or non‐naïve]), visit (Weeks 6 and 12 only), treatment‐by‐visit interaction, treatment‐by‐visit‐by‐etiology group interaction, study baseline‐by‐visit interaction, study baseline value and study as fixed effect. The denominator is the number of patients with available data as indicated under “Weekly NDO episodes, change from baseline” or “I‐QoL total summary score, change from baseline,” as relevant. Only the results for each aboBoNT‐A dose versus placebo by NDO etiology at Week 6 are presented.
Based on analysis of covariance model used with treatment group, stratification factors (etiology of NDOI [SCI or MS], prior intradetrusor use[BoNT‐A naïve or non‐naïve]), study baseline value, study and the treatment‐by‐etiology group interaction as fixed effect variables.
Based on logistic regression model with treatment group, stratification factors (etiology of NDOI [SCI or MS], prior intradetrusor use [BoNT‐A naïve or non‐naïve]), study, and treatment‐by‐etiology group interaction as fixed variables. Denominator values for the placebo, aboBoNT‐A 600 and 800 U groups, respectively, were n = 87, 98, 90 for patients with SCI and n = 35, 36, and 39 for patients with MS.