ANTICHOLINERGIC DRUGS IN OVERACTIVE BLADDER IN A SERIES OF MULTIPLE SCLEROSIS PATIENTS: LIGHTS AND SHADOWS

Andretta E1, Filocamo T2, Furlan A3, Risi O4, Zuliani C5

Research Type

Clinical

Abstract Category

Neurourology

Abstract 369
E-Poster 2
Scientific Open Discussion Session 18
Thursday 5th September 2019
13:35 - 13:40 (ePoster Station 8)
Exhibition Hall
Multiple Sclerosis Overactive Bladder Conservative Treatment
1.Urology Department - General Hospital DOLO (Venice) ITALY, 2.Urology Department - General Hospital Savigliano (Cuneo) ITALY, 3.Rehabilitation Department - General Hospital Dolo (Venice) ITALY, 4.Neuorurology Unit - General Hospital Treviglio (Bergamo) ITALY, 5.Neurology Department - General Hospital Mirano (Venice) ITALY
Presenter
E

Elena Andretta

Links

Poster

Abstract

Hypothesis / aims of study
Multiple sclerosis (MS) patients (pts) often complain low urinary tract symptoms (LUTS) which are viewed by many pts as their worst symptoms. In case of storage LUTS the first-line treatment are anticholinergics (Ac) but few real-life studies are available in literature regarding their efficacy and tolerability. The purpose of our study was to assess efficacy, tolerability and safety of Ac in MS patients.
Study design, materials and methods
A retrospective analysis of consecutive MS outpatients who began Ac in 2014 was carried out. They were evaluated with a 4-day bladder diary incorporating the Patient's Perception of Intensity of Urgency Scale (PPIUS), the ultrasound measure of the post-void residual (PVR), a single question on improvement of quality of life (QoL) (Yes or No) before and during Ac treatment and the recording of the adverse events (AE)
Results
60 MS -75% women, median age 53 anni±12 years, mean duration of MS 17,6±8,8 years and mean disability status scale (EDSS) 4,7±1,5- were recruited; 43.3% of them were incontinent, the mean PVR was 105 cc (range 0-350 cc) with 24 pts (40%) who voided in average by 3.7 clean intermittent catheterization (CIC)/die (range 1- 8).
The Ac therapy lasted in average 19.9 months (2 days-78 months) and most pts (80%) were treated with oxybutinin immediate release (OxI) at the median dosage of 8.2 mg/die. 
2 pts stopped immediately OxI, 1 for mental confusion and 1 for blurred vision plus severe dry mouth. Storage LUTS improved with Ac in 73.7% of the 58 evaluable pts (15.8% reported the complete recovery) and QoL improved for 57% of them. The mean PPIUS reduction observed was 1.1 (from 3,4 to 2,3), the mean decrease in pads use by day was 0.46 (range 0-4), the mean increase of PVR was 43 cc (range 0-500) with 1 pt who had to start CIC. 
A mean statistically significant reduction of PPIUS was found (p<0.001). 
39 AE were observed in 32/60 pts (53%): 26.6% reported dry mouth (severe in 12.5%), 8.3% constipation, 8.3% voiding LUTS, 6.6% blurred vision, 5% dizziness, 3.3% mental confusion, 3.3% drowsiness and 3.3% gastric pyrosis. 9 serious immediate AE have been reported only with Ox - mental confusion, dizziness, blurred vision –, moreover reported with every Ox formulation in the subsequent Ac treatments. See tab 1
A correlation between occurrence of AE and dosage of OxI was not detected (tab 2).
6 pts stopped definitively Ac for the AE (4 assumed OxI, 1 Ox extended release and 1 trospium), 23 pts changed Ac and 12 increased the dosage of the same Ac.
Interpretation of results
Currently only OxI, and recently also tolterodine, is reimbursed in neurogenic bladder by the Italian Health care system thus many pts (80%) in our survey were treated with OxI. 
LUTS may change over time in MS and therefore their response to treatment. Furthermore MS symptoms can also interact with each other, making their management challenging, with side effects of the coexistent multiple pharmacologic therapies that may be additive. 
Ac tolerability depends mainly on drug selectivity for the bladder over other organs and ability to penetrate the central nervous system (CNS). 
Ac can be either inefficacious or poorly tolerated in many MS pts (1). In our series Ac were inefficacious in 26.3% of pts and only 57% of pts reported the simultaneous improvement of LUTS and QoL. Besides Ac were not tolerated by more than 10% of pts. Some AE, especially the serious neurological ones, were reported only with Ox while constipation and comparison/worsening of voiding LUTS has concerned also trospium.
Considering such data Ac should be used with caution in MS pts, especially Ox, for the high risk of serious AE, probably due to the passage of the blood-brain barrier.
Concluding message
Ac are less effective in MS pts than in other neurological conditions (2). 
OxI can provoke serious AE in up to 10% of MS pts, probably due to its penetration in CNS. Also comparison/worsening of voiding LUTS has been reported in pts treated with Ox and trospium. Therefore MS pts should start Ac therapy at low dosage and should be checked at short intervals.
Figure 1 Tab 1: Distribution of 39 AE in 32/60 pts (53%) for Ac
Figure 2 Tab 2: Correlation between dosage of OxI and AE
References
  1. Nicholas RS, Friede T, Hollis S, Young CA. Anticholinergics for urinary symptoms in multiple sclerosis. Cochrane Database Syst Rev. 2009; 21(1): CD004193
  2. Bennett N, O'Leary M, Patel AS, Xavier M, Erickson JR, Chancellor MB. Can higher doses of oxybutynin improve efficacy inneurogenic bladder?. J Urol. 2004; 171): 749-751.
Disclosures
Funding None Clinical Trial No Subjects Human Ethics not Req'd Clinica observation
28/03/2024 00:04:05