Updates on the Treatments for Female Urinary Incontinence

Updates on the Treatments for Female Urinary Incontinence Courtenay K. Moore, MD Associate Professor, Lerner College of Medicine Fellowship Director, Female Pelvic Medicine & Reconstructive Surgery Glickman Urologic and Kidney Institute, Cleveland Clinic

Objectives To increase the identification of women with bothersome urinary incontinence Differentiate between the various types of incontinence To promote a standardized, evidence based, cost effective approach for management of female incontinence To promote collaboration and coordination of care for women with incontinence between primary care providers and subspecialists

Sally 65 yo die hard Browns fan who wants to be able to sit through a game without peeing (and crying) Voids every 20 minutes and often cannot make it to the bathroom Denies leakage with coughing or exercise Over the last months she has had more accidents & is afraid she might have an accident at the game

Betty Spry 85 yo female with a several year history of worsening leakage associated with activity Reports most severe when she power walks with the gals and has to use 2 3 pads Also leaks with a heavy cough or sneeze Leakage not associated with urgency

So. Why should we be asking about incontinence? What types of incontinence do these women have? What type of work up do Sally and Betty need for their incontinence? Different? Same? What treatments would you offer them?

1/3 women over age 45 and 1/2 women over age 65 have incontinence To Navigate: Use Page Down to move forward, Page Up to move backward and Esc to exit.

Not only common but costly Accounts for 26 BILLION US Health care $$ 1/3 of menstrual pads used for incontinence #2 reason for nursing home admissions Adversely affects quality of life & sexual health ONLY 30% of women with incontinence talk to their doctors about it?????

Women Don t Seek Help I can manage the urine leakage problems myself Urine leakage is a normal part of aging Urine leakage is normal after giving birth Dot know where to seek help Too embarrassed to talk about it Too busy to go to the doctors Treatments don t work Afraid of treatment The treatment is too expensive I do not want to bother my doctor And physicians often don t ask about it #1 reason women finally seek treatment is an accident or near accident in a public place Hagglund Int Urogynecol J (2003) 14: 296 304

Types of Incontinence Stress Urinary Incontinence Involuntary leakage of urine on effort or exertion or on coughing, laughing, sneezing Urgency Incontinence Involuntary leakage of urine associated with urgency Mixed Urinary Incontinence Involuntary loss of urine associated with urgency and also with effort or physical exertion or on coughing, laughing sneezing

Stress Urinary Incontinence Is the Most Common Type in Women Stress 49% Mixed 29% Urge 22%

% Incidence per year Cumulative Incidence of Incontinence in Women According to Age 30 25 20 15 10 5 0 Definition III (ICS)* 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-60 Age (y) *Per International Continence Society; requires objective demonstrability and presence of hygienic or social problem for uncontrolled loss of urine to be acknowledged as UI. Elving LB et al. Scand J Urol Nephrol. 1989;125(suppl):37-43.

Stress Urge It is important to determine type of incontinence and degree of bother because the treatments are different

OAB Syndrome Urinary urgency, usually accompanied by frequency and nocturia, with or without urgency urinary incontinence, in the absence of urinary tract infection or other obvious pathology Overactive bladder (OAB) is NOT a disease, it is a clinical diagnosis characterized by the presence of bothersome urinary symptoms AUA OAB Guidelines, 2014

OAB Symptoms Urgency Sudden, strong desire to urinate Frequency 8+ visits to the toilet per 24 hours 2+ visits to the toilet during sleeping hours (nocturia) (each void is preceded & followed by sleep) Urge Incontinence Sudden & involuntary loss of urine

Nocturia Complaint of interruption of sleep one or more times because of the need to urinate Each void is preceded and followed by sleep Many disorders other than bladder issues lead to nocturia Mobilization of edema/venous insufficiency CHF Sleep apnea Increased sleep interruptions aging

Epidemiology Affects 33 million Americans 500 million worldwide Prevalence 11 19% men and women OAB sx prevalence and severity increase with age OAB wet more common in women Irwin D et al. BJU Int 2011;108:1132 Haab F et al. Neuro Urol 2014;33: S2 Stewart WF et al. World J Urol 2003;20:237

Concerning Statistics Nearly 60% of patients are symptomatic for 2 years before seeking treatment 76% of diagnosed pts remain untreated 50% pts on current treatment regimens say current treatment is not helping their symptoms 73.5% stop medications within 1 yr due to SE or lack of efficacy Abrams P et al. Am J Managed Care. 2000;6:S580 D Souza et al J Manag Care Care Pharm 2008;14:291

Guideline Statement 1 The clinician should engage in a diagnostic process to document symptoms and signs that characterize OAB and exclude other disorders that could be the cause of the patient s symptoms UTI, IC/PBS, Diabetes insipidous, Polydipsia The minimum requirements are a thorough history, physical exam and urinalysis.

History Duration of symptoms Severity of incontinence Inciting events (post op, neurological symptoms) Obstructive voiding symptoms Fluid intake habits Caffeine and alcohol intake Medications Surgeries/radiation/chemo Does it BOTHER the pt enough to warrant treatment?

Co Morbid Conditions: DIAPPERS Diabetes Mellitus Infection Atrophy Psychological disorders Pharmacologic Excessive urine production Restricted mobility Stool impactions

Questions to help differentiate.. Urgency Stress

Physical Exam Vital signs: BP Cognitive function dementia? Mobility/gait/ dexterity Abdominal exam Scars Suprapubic distention Pelvic exam Atrophic vaginitis Urethra SUI/diverticulum Pelvic organ prolapse Levator spasm Perineal skin rash/breakdown Lower extremities edema

Urinalysis UA Rule out UTI Rule out hematuria Microscopic hematuria >3 or more RBC on 1 properly collected specimen in absence of obvious benign cause * Urine Culture NOT indicated unless there are signs of infection on UA PVR: Is it indicated? NO AUA Guidelines 2012

Urinary Diaries Useful to document baseline symptoms & assess treatment efficacy Components # voids Voided volume Fluid intake # of incontinence episodes Helpful in determining if nocturia is secondary to nocturnal polyuria >20 33% 24 hr urine production voided at night

AUA OAB Treatment Guidelines 2014 1 st Line Patient Education Behavioral Therapies -Fluid Management -Bladder Training -PFPT Weight Loss

Treatment First line treatment with behavioral therapy presents essentially no risks and should be offered to all

Fluid Management 25% reduction in fluid intake reduced urinary frequency and urgency daytime frequency 23% urgency 34% nocturia 7% Reducing caffeine urgency & frequency by 37% Hashim H et al. BJU Intl 2008; 102: 62. Bryant et al. Br J Nurs 2002; 11: 560.

Pelvic Floor Muscle Training PFMT via biofeedback, verbal feedback or selfadministered via pamphlet Reduces incontinence by 60% Increased bladder capacity by 40 60cc Burgio KL et al. JAMA 2002; 288: 2293.

Weight Loss 6 mo weight loss program vs education program 8% weight loss in obese women Reduced urgency incontinence episodes: 47% in weight loss group 28% in control group Subak L et al. NEJM 2009; 360: 481.

2nd Line: Pharmacologic Treatment Choice of oral anti muscarinics as second line therapy reflects the fact that these medications reduce symptoms but also can commonly have non life threatening side effects Antimuscarinics Tricyclic antidepressants 2nd Line β3 agonists Antimuscarinics -Oral & Transdermal β3 Agonists

Anti muscarinics Oxybutynin IR Oxybutynin ER Tolterodine ER Trospium Solifenacin (vesicare) Darifenacin (enablex) Fesoterodine (toviaz) Available as generics Oxytrol Gelnique Over the counter

Choice of Anti muscarinic An extensive review of the randomized trials that evaluated pharmacologic therapies for OAB revealed no compelling evidence for differential efficacy across medications Choice of medication should be based on: Prior history of anti muscarinic use Side effect profiles Delivery system Comorbidities Cost/Coverage

Guideline 9 If an immediate release (IR) and an extended release (ER) formulation are available, ER formulations should preferentially be prescribed over IR formulations because of lower rates of dry mouth

Guideline Statement 11 If a patient experiences inadequate symptom control and/or unacceptable adverse drug events with 1 anti muscarinic medication then Dose modification Different anti muscarinic medication β3 adrenoceptor agonist Botox injection

Guideline Statement 12 Clinicians should not use anti muscarinics in patients with narrow angle glaucoma and should used with extreme caution in patients with impaired gastric emptying or a history of urinary retention. Do not use in patients taking solid oral formulations of potassium chloride

Mirabegron β3 adrenergic agonist FDA approved in 2012 β3 receptors in detrusor smooth muscle & urothelium Promotes storage by activating sympathetic nervous system (hypogastric nerve) via norepinephrine Ellsworth et al. J Fam Prac 2014;S63:38

Mirabegron Stimulation results in direct relaxation of detrusor muscle without suppressing amplitude of contraction during voiding Significantly greater decreases in UI and freq than placebo Efficacy similar to anti muscarinics AE NO difference in dry mouth or HTN vs placebo Most common SEs Nasopharingitis HTN Niit et al. Int J Clin Pract 2013;67:619

3 rd Line Medical Therapy: OnabotulinumtoxinA Guideline Statement 17 Clinicians may offer intradetrusor onabotulinumtoxina (100U) as third line treatment in the carefully selected and thoroughly counseled patient who has been refractory to first and secondline OAB treatments. The patient must be able and willing to return for frequent post void residual evaluation and able and willing Botox perform self catheterization if necessary PTNS Interstim 3 rd Line

Onabotulinum Toxin A injection 100 units 20 injection sites 0.5cc/site In office or OR Negative UA 1% lidocaine instilled in bladder Discontinue antiplatelet therapy 3 days

Botulinum Toxin Significantly decreases OAB symptoms Increases bladder capacity Decreased daily UUI by 2.65 vs 0.87 (p<0.001) Needs to be repeated roughly every 6 10 months Most common AEs 6.1% pts initiated ISC Increased risk of UTI (15% vs 6%)

PTNS: Percutaneous Tibial Nerve Stimulation Needle electrode inserted medial/above medial malleolus Impulses travel from the ankle along the tibial nerve to the sacral nerves (S2 4) Weekly x 12 weeks Maintenance Therapy varies 1 session/month

PTNS PTNS vs Tolterodine LA Patient Global Assessment showed greater improvement in PTNS group PTNS vs Sham At 12 months statistically significant reduction in frequency, UUI & nocturia At 36 months daytime frequency, nighttime voids, UUI & QOL all markedly improved from baseline Peters KM, et al. J Urol. 2009 Peters KM, et al, J Urol, 2010 Peters KM, et al, J Urol, 2013

SNS FDA approval 1997: Refractory urgency frequency and urgency incontinence

World Wide Long Term 5 year Results 58% reduction in UUI (p<0.001) 56% reduction in urgency 56% experienced a 50% or more increase in the average volume/void 71% continued success & efficacy Van Kerrebroeck Ph et al. J Urol 178:2029-34, 2007

Now what about Betty? What can we do to keep Betty power walking with the girls?

Weight Loss 5 10% reduction in total body weight results in 50 70% reduction in SUI Subak et al, NEJM, 2009: 360:481-90

In appropriately selected women, Pelvic Floor PT Reduced SUI by 33% Pelvic Floor PT

Devices Pessary 60% of women with stress incontinence were dry Knob sits under urethra to increase urethral support Noblett et al, AJOG 2008, 592.e1-e5

Injectable Therapy for SUI Injectable therapy all current agents are permanent bulking agents Macroplastique Coaptite Durasphere Office procedure 50% dry rate at 2 yrs

History of Surgery for Stress Urinary Incontinence 1913 1949 1959 1961 1973 1978 1981 1987 1991 1995 2001 2008 2013 Kelly Plication MMK Burch Stamey Pereya Needle suspension PVS Raz GittesLap Burch TVT TOT Mini-slings

MUS Retropubic Slings Introduced in 1995 & rapidly became most commonly performed procedure for SUI Transobturator Introduced in 2001 and created to prevent common complications associates with retropubic sling Mini Sling Pubovaginal fascial sling

FDA October 2008 Public Health Notification: Serious Complications Associated with Transvaginal Placement of Surgical Mesh in Repair of Pelvic Organ Prolapse and Stress Urinary Incontinence To alert physicians of complications associated with transvaginal placement of surgical mesh to treat Pelvic Organ Prolapse (POP) and Stress Urinary Incontinence (SUI)

FDA 2013 The safety and effectiveness of multi incision slings is wellestablished in clinical trials that followed patients for up to one year. The safety and effectiveness of mini slings for female SUI have not been adequately demonstrated. Mesh sling surgeries for SUI have been reported to be successful in approximately 70 to 80 % of women at 1 year. Erosion of mesh slings through the vagina is the most commonly reported mesh specific complication from SUI surgeries with mesh. The average reported rate of mesh erosion at 1year is 2%.

MUS Treatment success decreases over time At 5 yr follow up 51% of retropubic & 43% transobturator slings were dry Surgical success rates were higher for retropubic Objective success rates remained high 79 85% with no difference between type of sling Kenton, J Urol, 193:203-10

Autologous Muscle Derived Stem Cells for the Treatment of SUI

Female Incontinence Ask your patients about it they probably won t ask you Treatment is based on degree of bother 1 st Line Therapy should be offered to all pts In pts with OAB Anticholinergics & β 3 agonists should be offered as 2 nd Line Therapy 3 rd Line Therapies should be offered to carefully selected pts In pts with SUI MUS remain safe and effective and are the gold standard of surgery for SUI