Quality of life and symptom severity measures in clinical trials of Autologous Muscle Derived Cell therapy for SUI in women with and without prior incontinence surgery.

Kaufman M1, Jankowski R2, Carlson C2, Pruchnic R2, Chen M3, Chancellor M4

Research Type

Clinical

Abstract Category

Female Stress Urinary Incontinence (SUI)

Abstract 48
Urogynaecology 2 - Stress Urinary Incontinence
Scientific Podium Short Oral Session 5
Wednesday 4th September 2019
11:37 - 11:45
Hall H2
Stress Urinary Incontinence Female Quality of Life (QoL) Retrospective Study Clinical Trial
1.Vanderbilt University Medical Center, 2.Cook MyoSite, Inc., 3.Cook Research Incorporated, 4.Oakland University William Beaumont School of Medicine
Presenter
R

Ron Jankowski

Links

Abstract

Hypothesis / aims of study
Hypothesis:  Women with persistent or recurrent Stress Urinary Incontinence (SUI) following prior surgical intervention experience diminished quality of life compared with women with SUI and no prior surgery.

Aim of the study:  To examine the baseline quality of life and symptom severity measures in women with and without prior incontinence surgery enrolling in clinical trials of Autologous Muscle Derived Cells for Urinary Sphincter Repair (AMDC-USR) investigational therapy for SUI.

Background: SUI’s impact on quality of life including psychological, physical and sexual health issues may affect the course of treatment with patients willing to undergo more invasive treatments as symptoms become more severe and quality of life diminishes.

Placement of a synthetic midurethral sling (MUS) is currently recognized as the standard of care for first-line surgical treatment of SUI by multiple international urological and urogynecology organizations. While considered effective for the majority of uncomplicated first-line cases, the MUS procedure is still associated with risks and comorbidities. The failure rate of MUS as first-line surgical management at 12 months is generally reported as approximately 20% for objective measures and as high as 44% for subjective measures [1]. For these women who are refractory to surgical management, there is a further decrease in benefit and an increase in risk with additional surgery. Among the highest independent clinical predictors and risk factors for failure of any MUS procedure is having had a previous incontinence surgery, along with low urethral hypermobility and diagnosed intrinsic sphincter deficiency.  In one of the few published studies, a retrospective analysis comparing women undergoing repeat surgery for SUI with those undergoing primary surgery found that women with in the repeat surgery group reported worse SUI symptoms and significantly lower quality of life at baseline compared with those undergoing primary surgery [2].
Study design, materials and methods
Study Design, materials and methods: We performed a retrospective analysis of baseline quality of life and symptom severity scale scores in women entering investigational clinical studies for AMDC-USR therapy (being developed by Cook MyoSite Inc).  Baseline data from female subjects (N=505) from 3 completed clinical trials (IND1, multiple-dose, open-label, CT.gov ID NCT00847535; CTHM, single-arm, open-label, CT.gov ID NCT01008943; UIAD, double-blind, placebo-controlled, CT.gov ID NCT01382602) and one ongoing phase 3 clinical trial (IND2, double-blind, placebo-controlled, CT.gov ID NCT01893138) of AMDC-USR therapy for SUI were pooled and analyzed. Of those enrolled, 113 (22%) had undergone prior surgical procedures for urinary incontinence (bladder neck suspension, pubovaginal sling or midurethral sling). Stress incontinence episodes were recorded in a 3-day diary, 24-hour pad weight test was conducted at home and validated questionnaires (Incontinence Quality of Life scale (IQOL), Incontinence Impact Questionnaire-7 item short form (IIQ-7), Urogenital Distress Inventory-6 item short form (UDI-6) and Incontinence Severity Index (ISI) scales) were administered. Only subjects with ≥3 stress leaks at baseline were included in the analysis. Results from analysis of individual study data in addition to the pooled data set will be presented.  Comparisons between the prior surgery and no prior surgery groups were made by Wilcoxon rank-sum test.
Results
Results: Subjects who had previously undergone surgery for SUI had a significantly older age and higher BMI and reported significantly worse quality of life scale IQOL, IIQ-7 and UDI-6 scores at baseline compared with subjects with no prior surgery (Table 1). In addition, in comparison with women without prior surgery, women with failed prior surgery had significantly greater number of stress leaks, 24-hour pad test weight and symptom severity scale ISI score at baseline (Table 1).
Interpretation of results
Interpretation of results: Women with recurrent or persistent incontinence after surgery to treat SUI reported poorer quality of life compared to women who had not undergone surgery for SUI, commensurate with increased overall symptom severity. Our data supports contemporary literature indicating greater symptom severity and poorer quality of life in women undergoing repeat surgery for SUI. However, due to the retrospective nature of this analysis of data pooled from several clinical trials, caution is warranted in interpretation of these results.
Concluding message
Concluding Message: Recurrent SUI symptoms following surgical intervention can cause substantial impact on quality of life and women appear to consider less-invasive, alternative approaches to secondary surgical intervention to address their unmet medical need. Assessment of symptom severity objective measures alone are not sufficient to determine the impact of SUI and a complete clinical evaluation should include quality of life measures. Professional societal guidelines indicate that outcomes for secondary surgical intervention have a lower success rate and carry additional risks. AMDC may offer an alternative, minimally invasive therapy that would improve quality of life in addition to treating SUI symptoms that persist after invasive surgical therapies [3], particularly in those women whose refractory symptoms are due to an intrinsic sphincter deficiency with low urethral hypermobility. Further evaluation of AMDC-USR investigational therapy in clinical trials is underway to examine changes in clinical efficacy, quality of life and symptom severity measures in broader SUI populations as well as in women with postsurgical refractory SUI.
Figure 1
References
  1. Richter HE, et al. N Engl J Med 362:2066-76, 2010.
  2. Parden AM, et al. Obstet Gynecol 121:273-278, 2013.
  3. Jankowski R, et al. Int Urol Nephrol 50(12):1-13, 2018.
Disclosures
<span class="text-strong">Funding</span> The studies were funded by Cook MyoSite Inc., Pittsburgh, PA USA <span class="text-strong">Clinical Trial</span> No <span class="text-strong">Subjects</span> Human <span class="text-strong">Ethics Committee</span> Beaumont Hospitals IRB/HIC #1, Vanderbilt Human Research Protection Program Health Sci Comm, Sunnybrook Health Sciences Centre REB, Univ. Calgary Conjoint Health REB, Comité D’Éthique de la Recherche en Santé Chez L'Humain, Trafalgar EB, Vancouver Island Health Authority Clinical REB, Mt Sinai Hospital REB, Ethikkomission der Medizinischen Fakultät der Universität Duisburg-Essen NRES Committee SE Coast-Brighton and Sussex, Queen’s Univ. Health Sciences REB. No room for Study IND2 ERB/IRBs <span class="text-strong">Helsinki</span> Yes <span class="text-strong">Informed Consent</span> Yes