Efficacy of Fesoterodine fumarate in Neurogenic Detrusor Overactivity due to Spinal Cord Lesion (SCL) or Multiple Sclerosis (MS) – a prospective study

Konstantinidis C1, Samarinas M2, Kratiras Z1, Tzitzika M1, Panagiotakopoulos G3, Giannitsas K4, Athanasopoulos A4

Research Type

Clinical

Abstract Category

Neurourology

Abstract 443
OAB: Medication and Sensation
Scientific Podium Short Oral Session 29
On-Demand
Multiple Sclerosis Spinal Cord Injury Pharmacology Quality of Life (QoL) Prospective Study
1. Urology & Neuro-urology Unit, National Rehabilitation Center, Athens, Greece, 2. Urology Department, General Hospital “Koutlibanio”, Larisa, Greece, 3. Department of General Pharmacology, School of Medicine, University of Patras, Greece, 4. Urology Department, School of Medicine, University of Patras, Greece
Presenter
C

Charalampos Konstantinidis

Links

Abstract

Hypothesis / aims of study
According to the International Continence Society (ICS) Overactive Bladder (OAB) is defined as “the presence of urinary urgency, usually accompanied by frequency and nocturia, with or without urgency incontinence, in the absence of a causative infection or obvious pathological conditions”. OAB is by definition idiopathic. On the other hand, Neurogenic Detrusor Overactivity (NDO) is an urodynamically confirmed bladder dysfunction secondary to an underlying neurological pathology (i.e. SCL, MS, stroke), that causes symptoms similar to OAB. NDO is characterized by involuntary contractions, spontaneous or provoked, during filling cystometry of the UroDynamic Study (UDS) accompanied usually by low bladder compliance and capacity, and high detrusor pressure.
Patients with NDO usually suffer from recurrent urinary tract infections (UTI’s), chronic bladder retention with increased residual volumes, hydronephrosis and eventually renal failure. The primary aims for the treatment of patients with NDO are the protection of the Upper Urinary Tract (UUT) and prevention of renal damage, the achievement of urinary continence, restoration of (parts of) the lower urinary tract (LUT) function and improvement of patients’ Quality of Life (QoL). In patients with high detrusor pressure during the filling phase, treatment’s aim is the “conversion of an active, aggressive high-pressure bladder into a passive low-pressure reservoir” despite the resulting residual urine. The reduction of the detrusor pressure contributes to urinary continence and improvement in QoL, preventing simultaneously UTI.
Antimuscarinic drugs are the first-line choice in the treatment of patients with NDO. By blocking the cholinergic/muscarinic receptors of the bladder, they promote inhibition of the parasympathetic pathways resulting in increased bladder capacity and compliance and reduced episodes of urgency and incontinence. Nevertheless, the literature for the use of anticholinergics in Neurogenic Lower Urinary Tract Dysfunction (NLUTD) is still limited and sparse and the response of individual patients to the treatment is variable. Hence, there is only one published meta-analysis about the efficacy of anticholinergics in the treatment of patients with NLUTD.
Fesoterodine fumarate is the newest anticholinergic drug. It is actually a prodrug that is broken down, by plasma esterases, into its active metabolite, 5-hydro-methyl tolterodine. The use of Fesoterodine fumarate has been approved, in many countries, for the treatment of OAB. To the best of our knowledge, no study has been yet published about the use of Fesoterodine fumarate in patients suffering from NLUTD. The aim of our study is to determine the efficacy of Fesoterodine fumarate for the treatment of patients with NDO.
Study design, materials and methods
Eligible subjects for enrollment were considered patients between 18-80 years old suffering from NDO, confirmed by UDS, secondary to MS or SCL of at least 6 months before their enrollment. Exclusion criteria were a recent or during the study UTI, history of urothelial cancer, urolithiasis, stress incontinence, interstitial cystitis, pelvic organ prolapse (≥ III grade), prior pelvic surgery or pelvic radiation treatment, uncontrolled narrow-angle glaucoma, pregnancy and dementia. Furthermore, patients suffering from MS should have been clinically stable for at least 3 months before their enrollment, according to the Expanded Disability Status Scale (EDSS).
The study was designed as an open-label prospective interventional trial without a control group. All participants provided an inform consent and the study was approved by the scientific and ethics committees of our institution. It was considered as unethical to include a placebo (or a non-therapy) control group as the increased detrusor pressure could harm the UUT of the patients. On the other hand, previous studies on other antimuscarinics proved that the placebo effect is rather “limited” in such a cohort of neurological patients.
A 2-week wash-out period was requested, before enrollment for patients under drug medication for the treatment of NDO. All patients underwent a first confirmatory baseline UDS and filled the SF-Qualiveen as a QoL questionnaire. Afterwards, all subjects received a treatment of 8 mg Fesoterodine daily for 3 months. After this period, they repeated the UDS and SF-Qualiveen. Each UDS was performed with the same equipment at the same environment from the same clinician, unaware of the study hypothesis, according to ICS’ good urodynamic practices and terms.
The primary endpoint of the study was the change from baseline to end of treatment in maximum detrusor pressure (Pdetmax) during the filling phase of the UDS and whether the use of Fesoterodine fumarate would decrease it. Secondary endpoints included changes from baseline to end of treatment in other urodynamic variables, particularly bladder capacity and bladder compliance. By analyzing the questionnaires, QoL, pre and post-treatment, was evaluated.
This was a pilot study since Fesoterodine fumarate has never been used in patients with NDO. Statistical analysis has been performed with the use of SPSS v.26.
Results
One hundred thirty-seven patients were recruited and 124 of them, 68 males and 56 females, completed the study. Of included patients, 95 had SCL (60 paraplegics, 35 tetraplegics) and 29 MS. There was no statistical difference at baseline among the tested urodynamic parameters throughout the groups (p> 0.05). The urodynamic parameters Pdetmax, bladder capacity and compliance, were estimated for the whole group before and after treatment and were proved to be statistically different when compared to the baseline (p< 0.001 for all variables), according to Wilcoxon test for a non-parametric sample. Changes in urodynamics parameters were also significant in each of the paraplegic, tetraplegic and MS groups (p< 0.001).
According to all the domains of SF-Qualiveen, QoL also improved. There was a significant difference in SF Qualiveen score after treatment with Fesoterodine in all patients independently of the diagnosis (Table I).
Interpretation of results
According to our knowledge, this is the first study that evaluated the efficacy of Fesoterodine fumarate in neurogenic patients. The results of our study suggest that this treatment can improve crucial urodynamic parameters, which are mirrored in a more acceptable function of the lower urinary tract. Furthermore, this beneficial effect seems to be independent of the underlying neurological disease, as the improvement was statistically significant not only in the whole group but also in each special subgroup analysis.
Concluding message
Fesoterodine fumarate is an efficacious drag in patients with SCL and MS, as it significantly decreases detrusor pressure, increases bladder capacity and compliance, and improves QoL of the patients.
Figure 1 Table I. Differences between SF Qualiveen scores before and after treatment among patients according to their diagnosis
References
  1. Madhuvrata P, Singh M, Hasafa Z, Abdel-Fattah M. Anticholinergic drugs for adult neurogenic detrusor overactivity: a systematic review and meta-analysis. Eur Urol. 2012; 62(5):816-30.
  2. Bonniaud V, Bryant D, Parratte B, Guyatt G. Development and validation of the short form of a urinary quality of life questionnaire: SF-Qualiveen. J Urol. 2008; 180(6):2592-8
  3. Schäfer W, Abrams P, Liao L, Mattiasson A, Pesce F, Spangberg A, et al. Good urodynamic practices: uroflowmetry, filling cystometry, and pressure-flow studies. Neurourol Urodyn. 2002;21(3):261-74
Disclosures
Funding There no Funding or grant for this study Clinical Trial Yes Registration Number ISRCTN 22433402 RCT No Subjects Human Ethics Committee Scientific Committee of National Rehabilitation Center, 30/11/2015, ref: 9/9-12-2015 Helsinki Yes Informed Consent Yes
30/07/2021 01:46:35