PBS/IC (Painful Bladder Syndrome/Interstitial Cystitis) Unravelling the Enigma PMR-MAY-2009-0239 Date of preparation: May 2009 Slides prepared by Galen

PBS/IC (Painful Bladder Syndrome/Interstitial Cystitis)

Unravelling the Enigma

PMR-MAY-2009-0239Date of preparation: May 2009

Slides prepared by Galen Limited as a service to medicine

Uracyst® (Chonroitin Sulfate, 2%) Prescribing Information is available on the last slide of this presentation

What is PBS/IC?

Symptoms and impact of PBS/IC

Management of PBS/IC

Causes and diagnosis of PBS/IC

Uracyst

Agenda

What is PBS/IC?




Uracyst

Agenda

Definition of PBS/IC*

Suprapubic pain related to bladder filling

Increased daytime and night-time frequency

Absence of infection or other pathology

*The ICS reserves the term interstitial cystitis as being a ‘specific diagnosis and requires confirmation by typical cystoscopic features’.

Nomenclature

Interstitial cystitis

Painful Bladder syndrome

Bladder Pain Syndrome

Hypersensitive Bladder Syndrome

Chronic Pelvic Pain Syndrome

PBS/IC

Prevalence of PBS/IC

Females

All patients

Males

0-19 20-29 30-39 40-49 50-59 60-69 70-79

0

2

4

6

8

10

Incidence/100 000

Age group, years

Age-specific incidence rates for males, females and all patients with interstitial cystitis1

What is PBS/IC?




Uracyst

Agenda

Cardinal Symptoms of PBS/IC

Pain

Frequency

Urgency

Patient quote

“IC affects your family life so much. Even with the simple basic things like taking a shopping trip, you have to realise that you can no longer

do what you like, when you like, as you have to plan on finding toilets. My children know that wherever we are ‘Mummy will have to

find a toilet soon’.”

GALEN WOULD LIKE TO THANK MEMBERS OF THE CYSTITIS AND OVERACTIVE BLADDER FOUNDATION FOR SUPPLYING THESE QUOTES .

Patient quote

“Having IC has completely changed my working life. I went from working in a full-time, well paid job to being forced to work

part-time, local to my home, as I couldn’t travel on public transport anymore.”


Patient quote

“IC alters your intimate relationships. It’s very difficult to continue to have a fulfilling relationship when you are suffering with so much pain

and discomfort.You really do need to have a very understandingpartner who realises what you are going through.”


Impact on Quality of Life

Pain, urinary urgency, and urinary frequency

Reduced QoL

Limitations on sexual intimacy

Curtailedactivities

Sleep deprivation

Reduced abilityto work

Economic Impact

More data is required

NHS incurs a considerable cost in treating PBS/IC

Clemens et al (US):1

Direct cost per year per patient = $3,631 Indirect cost to the patient per year = $4,216

What is PBS/IC?




Uracyst

Agenda

Causes of PBS/IC

Irritating solutes

Urothelium

Irritated nerve

GAG layer

Inflammation

Associated conditions

47%

25%23%

13%

9%

13%

8%

15%

19%

11%

1%

10%

6%

18%

3%

11%

15%

23%

Allergy Irritablebow el

syndrome

Sensitiveskin

Vulvodynia Fibromyalgia Migraine Asthma Rheumatoidarthritis

Sjogren'ssyndrome

Diagnosis

Per

cen

tag

e p

reva

len

ce

IC patients

General population

Challenges of diagnosis

Interstitial cystitis

Alone or in different combinations

Nobiologicalmarkers

Restrictiveresearch-based

criteria

Painfulinvasive

techniques

Issues related to the diagnosis of PBS/IC

NIDDK inclusion criteria

Bladder pain or urinary urgency

Glomerulations or Hunner’s ulcer on cystoscopy

Specific findings after hydrodistention

Differential diagnosis

Overactive Bladder

Bladder Carcinoma

Endometriosis

Medication

Urinary Tract

Infection

PBS/IC

What is PBS/IC?




Uracyst

Agenda

Components of basic assessment

Medical History

Physical Examination

Urine cultures

Voiding diary

Symptom scales


Diet

Oral therapy

Intravesical therapy

Diet

Pharmacological management

Epithelial insult

Activation of C fibresRelease of

Substance P

Moreinflammation

Mast cellactivation;

histamine release

Epitheliallayer damage

Potassiumleak into

bladder wall

GAG-like therapies

Inhibit neurological activity

AntihistaminesAnti-inflammatory drugs

Oral therapy

Amitriptyline Analgesics Antihistamines Anti-inflammatory agents Anticholinergics

Oral Therapy continued

Anticonvulsants Cimetidine Immunosuppressive agents Pentosan polysulfate sodium

Intravesical therapy

Chondroitin sulfate

Sodium hyaluronate

Dimethyl sulfoxide

Patient perception of intravesical therapy for PBS/IC

AgentTotal no. of

patientsImproved

Made worse

No effect

DMSO159/750 (21.2%)

59

(37.1%)

57

(35.8%)

43

(27.1%)

Cystistat28/750 (3.7%)

15

(53.6%)

3

(10.7%)

10

(35.7%)

Heparin sodium

25/750 (3.3%)

16

(64%)

5

(20%)

4

(16%)

Surgery

Usually last resort

Bladder augmentation

Urinary diversion

Cystectomy Pelvic pain may continue even after the bladder is removed

What is PBS/IC?




Uracyst

Agenda

The role of GAGs

Uracyst

2% solution of sodium chondroitin sulfate

Medical device

Physically restores the GAG layer

Alleviates symptoms, significantly improving patient quality of life

Uracyst may provide the optimum dose of chondroitin sulfate1

Nickel et al 20081

Aim To assess the efficacy and safety of intravesical chondroitin

sulfate (Uracyst) in the treatment of patients with a clinical diagnosis of IC

Method Fifty-three patients with IC were enrolled in a multicentre,

community-based, open-label study, and received intravesical instillations of Uracyst once a week for six weeks, then once a month for 16 weeks

Endpoints The primary endpoint - the percentage of responders to

treatment at week 10*

* assessed by a Global Response Assessment (GRA) scale

Uracyst - 47% response rate after 6 treatments1

53 patients were treated with Uracyst via urinary catheter • Weekly for 6 weeks • Then monthly for 16 weeks*Responders to treatment are indicated by a marked or moderate improvement on a seven-point Global Response Assessment (GRA) scale.

47%

60%

Pe

rce

nta

ge

of

pa

tie

nts

wh

o r

es

po

nd

ed

* to

Ura

cy

st

6 treatments

10 treatments

Uracyst – effectively relieves the symptoms of PBS/IC1

Pain, urgency and frequency were measured using a 0-10cm visual analogue pain scale

0

1

2

3

4

5

6

7

8

9

Pain Urgency Frequency

Mea

n (

SD

) S

core

s

Baseline

6 treatments

10 treatments

n = 53p<0.001

Uracyst – significantly improves patient quality of life1

Symptom and bother scores were measured using the O’Leary-Sant Symptom/Problem Index

0

2

4

6

8

10

12

14

16

Symptom Bother

Mea

n (

SD

) S

core

s

Baseline

6 treatments

10 treatments

n = 53p<0.001

Instillation of Uracyst

Catheter

Uracyst in bladder

Suggested Uracyst treatment plan

Weekly instillations for 4-6 weeks, then monthly thereafter

Optimum response in 4-6 months Revert back to weekly treatment in cases of

symptom flare-up More frequent therapy may be required in patients

with severe PBS/IC No adverse effects are expected with Uracyst2

Pain/discomfort/infection associated with the catheter are possible

Supporting the patient1

Be understanding of the challenges facing the patient

Reassure the patient

Explore treatment options

Support self-care

Uracyst Prescribing Information

The full Prescribing Information should be consulted prior to use.Uracyst® Abbreviated Prescribing Information. Description: Each ml of Uracyst contains 20mg sodium chondroitin sulfate (400mg of chondroitin sulfate per 20ml vial). Chondroitin sulfate is an acidic mucopolysaccharide and is one of the glycosaminoglycans (GAGs). The luminal surface of the bladder is coated with a layer of GAGs that provide a protective impermeable barrier to the bladder. Damage to this GAG layer may result in deficiencies to its protective barrier, inducing irritations in the bladder wall. Chondroitin sulfate is an important component of the bladder GAGs that can replenish the deficient GAG layer on the bladder epithelium. Indications: For replenishment of the glycosaminoglycan (GAG) layer in the bladder, for patients with damaged or GAG deficient bladder epithelium. Dosage and administration: Instil 20ml into the bladder after any residual urine has been removed. For optimum results, Uracyst should be used full strength without dilution, and retained in the bladder as long as possible (not less than 30 minutes). Repeat the instillation of 20ml weekly for 4 to 6 weeks, then, monthly thereafter until symptoms are relieved. Most patients benefit from 6 weekly 20ml instillations, then monthly instillations thereafter depending on their symptomatic response. Contraindications: Do not administer to patients with known hypersensitivity to the solution. Warnings: For Bladder Instillation only. Uracyst contains neither preservatives nor antimicrobials; therefore, any unused portion must be discarded. Precautions: Bring the contents of vial to room temperature before use. Adverse effects: No known adverse effects. Short-term discomfort may be caused by the catheterisation process. Legal category: Medical device. CE Number: CE 0473. CE Mark Holder: Stellar Pharmaceuticals Inc, 544 Egerton Street, London, Ontario, Canada N5W 3Z8. Package quantities and price: Single-dose glass vial of 20ml. Packages of four: £260 (UK), €300 (Ireland). Storage: Store 2 to 25oC. Do not freeze. Discard unused portions. Distributed by: Galen Limited. Date of preparation: May 2009.

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Adverse incidents should be reported. Reporting forms and information can be found at www.mhra.gov.uk or www.imb.ie. Adverse incidents should also be reported to Galen Limited on +44 (0)28 3833 4974 and select the customer services option, or e-mail [email protected]. Medical information enquiries should also be directed to Galen Limited.

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Documents

PBS/IC (Painful Bladder Syndrome/Interstitial Cystitis) Unravelling the Enigma PMR-MAY-2009-0239 Date of preparation: May 2009 Slides prepared by Galen