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210 - AUTOLOGOUS MUSCLE DERIVED CELLS FOR URINARY SPHINCTER REPAIR TO TREAT WOMEN WITH RECURRENT OR PERSISTENT STRESS URINARY INCONTINENCE AFTER CONTINENCE SURGERY

210

AUTOLOGOUS MUSCLE DERIVED CELLS FOR URINARY SPHINCTER REPAIR TO TREAT WOMEN WITH RECURRENT OR PERSISTENT STRESS URINARY INCONTINENCE AFTER CONTINENCE SURGERY

K. CARR 1, L. TU 2, M. ROBERT 3, D. QUINLAN4, K. V. CARLSON 5, S. HERSCHORN 1, M. R. KAUFMAN 6, K. PETERS 7, R. J. JANKOWSKI 8, R. DMOCHOWSKI 9, M. CHANCELLOR 10;
1Sunnybrook Hlth.Sci. Ctr., Toronto, Canada, 2Ctr. Hosp.ier Univ.ire de Sherbrooke, Sherbrooke, Canada, 3ob/gyn, Univ. of Calgary, Calgary, Canada, 4Univ. of British Columbia, Victoria, Canada, 5Southern Alberta Inst. of Urology, Calgary, Canada, 6Vanderbilt Univ. Med. Ctr., Nashville, TN, 7Beaumont Hlth.System, Royal Oak, MI, 8Cook MyoSite, Inc., Pittsburgh, PA, 9Vanderbilt, Nashville, TN, 10Oakland Univ. William Beaumont Sch. of Medi, Royal Oak, PA.

Introduction: Recurrent or persistent stress urinary incontinence (SUI) following continence surgery remains a challenging condition for which limited evidence-based treatment guidance exists. Most conventional surgery does not reverse underlying sphincter deficiencies; therefore, patients may benefit from adjuvant treatment with Autologous Muscle Derived Cells for Urinary Sphincter Repair (AMDC-USR), which involves isolation of cells from skeletal muscle biopsies, ex vivo expansion, and subsequent injection into the urethral sphincter.
Objective: To describe the safety and efficacy of AMDC-USR in women with recurrent or persistent SUI after continence surgery.
Methods: This post hoc analysis includes data from women treated in 3 completed AMDC-USR studies (NCT00847535, NCT01008943, NCT01382602) who underwent prior continence surgery and presented with recurrent or persistent SUI as measured by an incontinence episode frequency (IEF) of ≥3 stress leaks over 3 days and ≥3 g 24-hour pad tests. Overall, 38 of 223 study participants met inclusion criteria. Analysis includes 17 women who received 1 or 2 treatments of 150 x 106 AMDC-USR (n=11) or placebo (n=6) in a double-blind, randomized trial (RCT) and 21 women who received 1 treatment of 10 (n=5), 50 (n=2), 100 (n=4), or 200 x 106 (n=10) AMDC-USR in Phase I/II open-label studies. SUI was monitored with 3-day IEF diaries and patient-reported symptom severity (UDI-6 for all studies, ISI for RCT) and quality of life (IIQ-7 for all studies, IQOL for RCT) questionnaires. Patient follow-up occurred at 1, 3, 6, and 12 months for all studies and at 2 years for the RCT. RCT patients were unblinded after their 12-month visits and placebo patients could elect to receive open-label AMDC-USR.
Results: Baseline characteristics are listed in Table 1.

Table 1. Baseline Characteristics

Baseline Characteristic

Open-label Studies AMDC-USR (N=21)

RCT AMDC-USR (N=11)

RCT Placebo (N=6)

Mean age (years) ± std deviation (range)

58 ± 11 (39 - 80)

51 ± 11 (30 - 76)

64 ± 15 (45 - 80)

Mean BMI ± std deviation (range)

28 ± 6 (21 - 44)

27 ± 4 (22 - 33)

26 ± 5 (19 - 32)

Post-menopause (n)

76% (16)

55% (6)

67% (4)

Current stage 1-2 pelvic organ prolapse (n)

24% (5)

9% (1)

67% (4)

Mixed urinary incontinence (n)

57% (12)

36% (4)

50% (3)

Median stress IEF/3 days (range)

12 (3 - 65)

11 (4 - 40)

27.5 (8 - 48)

Median 24-hour pad test (range), g

27.0 (4.5 - 710)

44.8 (6.9 - 153.5)

76.0 (17.8 - 416.4)

Median UDI-6 score (range)

62.5 (29.2 - 91.7)

44.4 (27.8 - 83.3)

44.4 (33.3 - 83.3)

Median ISI (range)

Not available

8 (4 - 12)

10 (4 - 12)

Median IIQ-7 score (range)

44.4 (14.3 - 100)

47.6 (23.8 - 85.7)

47.6 (28.6 - 95.2)

Median IQOL score (range)

Not available

51.1 (18.2 - 70.5)

37.5 (3.4 - 64.8)


Overall, 92% (35/38) of patients completed 12-month diaries. No AMDC-USR safety concerns were identified. Compared to placebo, the AMDC-USR group had a higher responder rate for ≥50% IEF reduction, ≥75% IEF reduction, and ≤1 leak over 3 days throughout the RCT (Figure). Moreover, in both the RCT and open-label studies, AMDC-USR treatment resulted in similar responder rates for IEF reduction at 12 months (Table 2).

Table 2. 12-month Outcomes for Open Label Studies and RCT

12-month Outcome

Open-label Studies AMDC-USR (N=18)

RCT AMDC-USR (N=11)

RCT Placebo (N=6)

≥50% IEF reduction (n)

67% (12)

72% (8)

50% (3)

≥75% IEF reduction (n)

44% (8)

64% (7)

17% (1)

≤1 stress leak/3 days (n)

39% (7)

36% (4)

17% (1)

Median UDI-6 score improvement (range)

25 (-45.8 - 66.7)

16.7 (-27.8 - 44.4)

5.6 (-16.7 - 38.9)

Median ISI score improvement (range)

Not available

4 (-2 - 10)

-2 (-8 - 9)

Median IIQ-7 score improvement (range)

21.4 (-36.5 - 66.7)

23.8 (-38.1 - 76.2)

14.3 (-28.6 - 76.2)

Median IQOL score improvement (range)

Not available

19.3 (-18.2 - 68.2)

10.2 (-23.9 - 83.0)


AMDC-USR treatment also improved patient-reported symptom severity and quality of life. In the RCT, AMDC-USR patients tended to report greater improvement in questionnaire scores than placebo patients (Table 2). Questionnaire score improvement was also observed in open-label studies of AMDC-USR.
All (6/6) RCT placebo patients elected to receive AMDC-USR after unblinding. At final follow-up, about 8 months after AMDC-USR treatment, 3 patients had ≥50% IEF reduction compared to 12-month diaries. Treatment durability from 12 months to 2 years was examined in the RCT. At 2 years, 73% (8/11) of RCT AMDC-USR patients completed 2-year diaries; 100% (6/6) of women with ≥50% IEF reduction at 12 months also met the endpoint at 2 years.
Conclusions: AMDC-USR represents a novel, safe, and durable therapy for women with recurrent or persistent SUI after continence surgery.
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