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Top Clinical Tips for Inflammatory Bowel Disease Dr Ayesha Akbar Consultant Gastroenterologist Honorary Senior Lecturer Job bag number: UK/AS/0165/07-13 Date of preparation: July 2013

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Page 1: Top Clinical Tips for Inflammatory Bowel Diseasehillingdongp.org.uk/documents/SPK 20148 A Akbar presentation Fina…Top Clinical Tips for Inflammatory Bowel Disease ... instant enema

Top Clinical Tips for Inflammatory Bowel Disease

Dr Ayesha Akbar Consultant Gastroenterologist Honorary Senior Lecturer

Job bag number: UK/AS/0165/07-13 Date of preparation: July 2013

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Contents-focus on UC

Case study

Tests and history

Background

Treatment in relation to ECCO consensus

Data from 5-ASA studies

Summary

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Case study

24 year old female

Presents with 5 week history of bloody diarrhoea

Mild weight loss

What do you want to ask?

What tests would you do?

What is the differential diagnosis?

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History

Foreign travel

Antibiotic usage

Recurrent diarrhoea

Extra-intestinal manifestations

Family History

Smoking history

NSAIDs

Page 5: Top Clinical Tips for Inflammatory Bowel Diseasehillingdongp.org.uk/documents/SPK 20148 A Akbar presentation Fina…Top Clinical Tips for Inflammatory Bowel Disease ... instant enema

Tests

Bloods

– FBC/haematinics

– CRP

– LFTs and albumin

– U&Es

Stool MC&S including CDT

?Faecal calprotectin

AXR if any tenderness or USS

Flexible sigmoidoscopy

Page 6: Top Clinical Tips for Inflammatory Bowel Diseasehillingdongp.org.uk/documents/SPK 20148 A Akbar presentation Fina…Top Clinical Tips for Inflammatory Bowel Disease ... instant enema

Differential diagnoses

Post infective

Ulcerative colitis (or Crohn’s colitis)

Ischaemic colitis

Diverticulitis

Cancer

Page 7: Top Clinical Tips for Inflammatory Bowel Diseasehillingdongp.org.uk/documents/SPK 20148 A Akbar presentation Fina…Top Clinical Tips for Inflammatory Bowel Disease ... instant enema

The Spectrum of Inflammatory Bowel Disease (IBD)

Ulcerative

colitis

Diarrhea

Abdominal pain

Relapsing course

Anemia

Extraintestinal

manifestations

Adapted from Satsangi J, et al. Inflammatory Bowel Diseases. Churchill Livingstone, 2003.

Crohn’s

disease

Indeterminate

colitis

Stenoses

Fistulae

Granuloma

Deep abscesses

Extracolonic

involvement

ASCA

Bloody

diarrhea

Continuous

involvement

pANCA

Mucosal

inflammation

Page 8: Top Clinical Tips for Inflammatory Bowel Diseasehillingdongp.org.uk/documents/SPK 20148 A Akbar presentation Fina…Top Clinical Tips for Inflammatory Bowel Disease ... instant enema

Pathophysiology of IBD

Shanahan F, et al. Gastroenterology. 2001;120:622-635.

Genetic

Susceptibility

Environment

(microflora)

Host

(immune)

Response Inflammation

UC IL-5, IL-10

Crohn’s IL-1, IL-12,

TNFα, IFN-γ

Page 9: Top Clinical Tips for Inflammatory Bowel Diseasehillingdongp.org.uk/documents/SPK 20148 A Akbar presentation Fina…Top Clinical Tips for Inflammatory Bowel Disease ... instant enema

Epidemiologic Risk Factors

UC CD

Appendectomy1 Negative (protective)

None

Smoking2 Negative Positive

Oral contraceptive use2 Questionable Positive

Breast feeding/adverse perinatal events2

Questionable Questionable

High level of sanitation in childhood2

Questionable Positive

1Koutroubakis I, et al. Inflamm Bowel Dis. 2002;8:277-286; 2Koutroubakis I, et al. Hepatogastroenterology.

1996;43:381-393.

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Ulcerative Colitis Pathology

Confluent disease, beginning above the anus

Limited to mucosa

Never involves small bowel (backwash ileitis)

Rarely involves the anus

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Ulcerative colitis

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Ulcerative Colitis Symptoms

Rectal bleeding

Passage of mucus

Diarrhoea

– frequency

– consistency

Urgency

– incontinence

Abdominal cramping / pain

– usually related to bowel opening

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Ulcerative Colitis Anatomical Extent

Proctitis

40%

Left sided

colitis 5%

Substantial 10%

Extensive

20%

Extends from just above anus

Procto-sigmoiditis

25%

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Ulcerative Colitis Symptoms and Relationship to Extent

Proctitis

Extensive disease

Rectal blood and mucus, urgency

Loose motions, severe pain

Extent may vary with time

Extent defines treatment and cancer risk

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Ulcerative Colitis Diagnosis

Establish diagnosis rigid or flexy sigmoidoscopy

Determine severity rigid or flexy sigmoidoscopy

Determine extent colonoscopy if needed

Caution with colonoscopy in very acute disease

If need to decide extent with severe disease, use

instant enema

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Ulcerative Colitis Natural History

Relapsing - remitting course (90%)

– always exclude infection: stool for CDT

– extent usually constant

– presentation usually similar

Rarely severe colitis or toxic dilatation (10%)

Colectomy rate greatest initially

– first year 10%

– first 10 years 25%

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Extra-Intestinal Manifestations Are Common in IBD Patients

Ocular inflammation 2%–13%

Oral ulceration 20%–30%

Satsangi J, et al. Inflammatory Bowel Diseases. Churchill Livingstone; 2003:669-684.

Ankylosing spondylitis 1%–6%

Peripheral arthritis 10%–20%

Erythema nodosum 6%–15%

Pyoderma gangrenosum 0.5%–2%

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Inflammatory Bowel Disease Extra-intestinal Manifestations - Skin

Pyoderma gangrenosum

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Inflammatory Bowel Disease Extra-intestinal Manifestations - Skin - Erythema nodosum

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Inflammatory Bowel Disease Extra-intestinal Manifestations - Joints Large joint inflammation

– usually only one joint

– disease activity related

Polyarthropathy

– peripheral joints

– independent of disease activity

Sacroiliitis and ankylosing spondylitis

– “stiff back”

– independent of disease activity

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Inflammatory Bowel Disease Extra-intestinal Manifestations - Eyes

Anterior uveitis, episcleritis, conjunctivitis

– independent of disease activity

– all cause painful, gritty red eye

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Inflammatory Bowel Disease Extra-intestinal Manifestations - Liver Minor abnormalities of LFTs in 50%

Fatty liver in severe relapses

Chronic autoimmune hepatitis in 2.5%

Gallstones in 30%

Primary sclerosing cholangitis in 2.5%

– Progressive inflammatory disorder of biliary system

Cholangiocarcinoma in 0.1%

Page 23: Top Clinical Tips for Inflammatory Bowel Diseasehillingdongp.org.uk/documents/SPK 20148 A Akbar presentation Fina…Top Clinical Tips for Inflammatory Bowel Disease ... instant enema

Inflammatory Bowel Disease Extra-intestinal Manifestations - Other

Thrombo-embolic disease

– especially in smokers, bed-bound, septic

– need maximal prophylactic anticoagulation

Amyloidosis

– rare

– terminal event

Osteoporosis...

Page 24: Top Clinical Tips for Inflammatory Bowel Diseasehillingdongp.org.uk/documents/SPK 20148 A Akbar presentation Fina…Top Clinical Tips for Inflammatory Bowel Disease ... instant enema

Osteoporosis in IBD

Disease activity leads to loss of bone density

DEXA scanning osteopaenia T score (healthy controls) >1 s.d.

below mean

Osteoporosis T score >2.5 s.d. below mean

Page 25: Top Clinical Tips for Inflammatory Bowel Diseasehillingdongp.org.uk/documents/SPK 20148 A Akbar presentation Fina…Top Clinical Tips for Inflammatory Bowel Disease ... instant enema

Osteoporosis in IBD Contributory factors

disease activity

steroid treatment

impaired Vitamin D and calcium absorption (especially Asians)

smoking (especially women)

sex hormone deficiency

malnutrition

genetic factors

Page 26: Top Clinical Tips for Inflammatory Bowel Diseasehillingdongp.org.uk/documents/SPK 20148 A Akbar presentation Fina…Top Clinical Tips for Inflammatory Bowel Disease ... instant enema

Osteoporosis in IBD At-risk Patients

History of fractures

Recurrent courses of steroid

Postmenopausal with > 1 course steroid per year

T score below -1

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Osteoporosis in IBD Treatment

Exclude osteomalacia (blood tests)

Check Calcium and Vit D levels

– if low, best is Calcium and Vit D supplements

– if normal, best is a bisphosphonate

– HRT of little value

Check bone density every 2 years

Prevention

Page 28: Top Clinical Tips for Inflammatory Bowel Diseasehillingdongp.org.uk/documents/SPK 20148 A Akbar presentation Fina…Top Clinical Tips for Inflammatory Bowel Disease ... instant enema

Prognosis Ulcerative Colitis

75% relapsing-remitting

– 10% only one episode

20% chronic active

5% fulminant

Page 29: Top Clinical Tips for Inflammatory Bowel Diseasehillingdongp.org.uk/documents/SPK 20148 A Akbar presentation Fina…Top Clinical Tips for Inflammatory Bowel Disease ... instant enema

Ulcerative Colitis Cancer Risk

Site of disease Risk vs generalpopulation

Distal X 1.5

Left-sided X 4

Total X 19

All patients X1.5

Population risk 1 in 30 for colorectal cancer

Page 30: Top Clinical Tips for Inflammatory Bowel Diseasehillingdongp.org.uk/documents/SPK 20148 A Akbar presentation Fina…Top Clinical Tips for Inflammatory Bowel Disease ... instant enema

Ulcerative Colitis Cancer Risk

Risk greatest if

– disease more than 8 years

– disease greater than left-sided

– coexisting sclerosing cholangitis

– coexisting bowel polyps

– family history of colorectal cancer

Surveillance

– after 8 years if extensive disease or any of the above with less disease

– if find high-grade dysplasia, consider colectomy

Page 31: Top Clinical Tips for Inflammatory Bowel Diseasehillingdongp.org.uk/documents/SPK 20148 A Akbar presentation Fina…Top Clinical Tips for Inflammatory Bowel Disease ... instant enema

Surveillance

BSG:

UC-pancolitis after 8 years; left sided

After 10 years

Annual if high risk e.g. PSC

3 years moderate risk

5 years in low risk

Page 32: Top Clinical Tips for Inflammatory Bowel Diseasehillingdongp.org.uk/documents/SPK 20148 A Akbar presentation Fina…Top Clinical Tips for Inflammatory Bowel Disease ... instant enema

Corticosteroids have serious side effects (long-term)

Osteoporosis

Cataracts/glaucoma

Higher risk of infections

Growth retardation

Oedema/Cushing syndrome

Behavioral changes

Striae

Diabetes

Page 33: Top Clinical Tips for Inflammatory Bowel Diseasehillingdongp.org.uk/documents/SPK 20148 A Akbar presentation Fina…Top Clinical Tips for Inflammatory Bowel Disease ... instant enema

Mild to moderate UC

Treat with 5-ASA-in flare escalate dose

Rule out infection-stool MC&S

Consider topical therapy

Lack of response at 14 days, consider steroids-use reducing regime. 30mg/day for 1 week; reduce by 5mg/day to zero

Concomitant Calcichew D3 (calcium carbonate, colecalciferol) with steroids

Page 34: Top Clinical Tips for Inflammatory Bowel Diseasehillingdongp.org.uk/documents/SPK 20148 A Akbar presentation Fina…Top Clinical Tips for Inflammatory Bowel Disease ... instant enema

Benefits of St Mark’s hospital

Diagnosis

Patient education

Patient support-3 excellent IBD nurses at St Mark’s

Fast access if flare

Complex cases-weekly IBD MDM

Clinical trials-refractory patients

Multi disciplinary team-nutrition/surgeons

Page 35: Top Clinical Tips for Inflammatory Bowel Diseasehillingdongp.org.uk/documents/SPK 20148 A Akbar presentation Fina…Top Clinical Tips for Inflammatory Bowel Disease ... instant enema

Weekly IBD MDM

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Patient pathway Established diagnosis

Treat in community with increased 5-ASA dose (IBD

nurse support)

Mild to moderate flare

Resolution of symptoms

Failure of resolution after 10-14 days or worsening

symptoms

Hospital review

Page 37: Top Clinical Tips for Inflammatory Bowel Diseasehillingdongp.org.uk/documents/SPK 20148 A Akbar presentation Fina…Top Clinical Tips for Inflammatory Bowel Disease ... instant enema

Job Number: UK/AS/0192/11-11. Date of preparation: January 2012. Job Number: UK/AS/0027/02-13. Date of preparation: February 2013. .

Management of moderately active ulcerative colitis (UC)

Prescribing information can be found at the end of this presentation.

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Job Number: UK/AS/0027/02-13. Date of preparation: February 2013.

What do patients need from their UC treatment?

• Fast symptom relief, among other attributes, is important to patients.

• Evidence shows that patients consider fast relief, relief from rectal bleeding, constant relief and prevention of flare to be among the most important attributes of treatment.

• In the most recent ECCO1 guidelines, it states that: • 10–14 days is a suitable time-point at which to assess

improvement in rectal bleeding, in line with one of the key treatment goals for patients.

• If rectal bleeding persists beyond 10–14 days, then the response can be said to be slow and therapy augmented.

1. Dignass A et al. J Crohn's Colitis 2012, http://dx.doi.org/10.1016/j.crohns.2012.09.002

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Job Number: UK/AS/0027/02-13. Date of preparation: February 2013.

What do patients want from their UC treatment?

• Overall, efficacy and safety-related attributes were more important to patients than those related to dosing regimen, cost and formulary coverage.1

Patient preference survey: treatment-related attributes rated by importance* (n=100)1

1. Gray et al. Aliment Pharmacol Ther 2009; 29: 1114-1120. 2. Data on file.

0

20

40

60

80

100

Patient preference survey attribute

Pa

tien

ts (

%)

Provides relief of

rectal bleeding

94%

Provides

consistent relief

94%

Prevents a

flare of UC

93%

Provides

fast relief

89%

*Percentage of patients rating attributes of 4 or 5 out of 5 on a scale of

importance, with 5 being most important

Page 40: Top Clinical Tips for Inflammatory Bowel Diseasehillingdongp.org.uk/documents/SPK 20148 A Akbar presentation Fina…Top Clinical Tips for Inflammatory Bowel Disease ... instant enema

Job Number: UK/AS/0027/02-13. Date of preparation: February 2013.

The ASCEND trials evaluated Asacol® (mesalazine) in patients with moderately active UC

• The ASCEND clinical trials (ASCEND I, II and III) are the only trials that have specifically evaluated Asacol® (mesalazine) in patients with moderately active UC1-3

• Other studies investigating the treatment of mesalazine have

combined mild and moderate UC populations4,5

1. Hanaeur SB et al. Can J Gastroenterol 2007; 21: 827–834. 2. Hanaeur SB et al. Am J Gastroenterol 2005; 100: 2478–2485.

3. Sandborn WJ et al. Gastroenterol 2009; 137: 1934–1943 e1931–1933. 4. Marteau P et al. Gut 2005; 54: 960–965.

5. Sandborn WJ et al. Aliment Pharmacol Ther 2007; 26: 205–215.

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Job Number: UK/AS/0027/02-13. Date of preparation: February 2013.

Time at which 50% of patients (median time) achieve symptom improvement* with Asacol® 800 mg MR tablets at 4.8 g/day

Symptom improvement

*Symptom improvement: a decrease of at least 1 point for rectal bleeding and stool frequency symptom score from

baseline

7

4

4

0 2 4 6

Both

Improvement of

stool frequency

Improvement of

rectal bleeding

Median time to symptom improvement (days)

n=161

n=160

n=133

Adapted from Orchard TR et al. Alim Pharmacol Ther 2011: 33(9); 1028-1035.

8

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Job Number: UK/AS/0027/02-13. Date of preparation: February 2013.

Time at which 50% of patients (median time) achieve symptom resolution* with Asacol® 800 mg MR tablets at 4.8 g/day

*Symptom resolution: cessation of rectal bleeding and normalisation of stool frequency

Symptom resolution

19

12

9

0 5 10 15 20

Both

Normalisation of

stool frequency

Absence of

rectal bleeding

Median time to symptom resolution (days)

n=161

n=160

n=133

Adapted from Orchard TR et al. Alim Pharmacol Ther 2011: 33(9); 1028-1035.

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Job Number: UK/AS/0027/02-13. Date of preparation: February 2013.

In the PINCE trial, 37% of patients responded to oral treatment alone within 2 weeks1

• Remission included patients who had some UC symptoms

(UC-DAI scores <2)2

1. Marteau P et al. ECCO, Feb 2010, Prague 2010; Abstract P122. 2. Marteau P et al. Gut 2005; 54 :960–965.

Pro

po

rtio

n o

f p

atie

nts

(%

)

0

20

40

60

80

30%

33%

37%

63%

Remission Improvement

P=0.842

P=0.032

100

Data from a post hoc analysis of efficacy at 2 weeks of the PINCE trial; patients with extensive mild to moderately active UC, N=127. The Intent to Treat (ITT) population consisted of 116 patients, who received at least one dose of study drug and had at least one efficacy evaluation after baseline.1,2

4 g/day oral Pentasa® (mesalazine) sachets plus 1 g mesalazine enema (n=63)

4 g/day oral Pentasa® (mesalazine) sachets plus placebo enema (n=53)

Remission = UC-DAI score of < 2

Improvement = a decrease in

UC-DAI of ≥ 2 points from

baseline

UC-DAI, ulcerative colitis

disease activity index

Page 44: Top Clinical Tips for Inflammatory Bowel Diseasehillingdongp.org.uk/documents/SPK 20148 A Akbar presentation Fina…Top Clinical Tips for Inflammatory Bowel Disease ... instant enema

Job Number: UK/AS/0192/11-11. Date of preparation: January 2012. Job Number: UK/AS/0027/02-13. Date of preparation: February 2013. .

Mucosal healing

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Job Number: UK/AS/0027/02-13. Date of preparation: February 2013.

UC therapy should restore/maintain the bowel mucosa integrity as well as control symptoms1

• Published peer-reviewed papers recommend incorporating mucosal healing (along with symptom resolution) into the primary endpoints of therapeutic studies in mild to moderately active UC2,3

• The UC-DAI and the Mayo Score of Endoscopic Disease include clinical measures of UC as well as endoscopic measures3

1. Lichtenstein GR et al. Aliment Pharmacol Ther 2011; 33: 672–678. 2. D’Haens G et al. Gastroenterol 2007; 132: 763–786.

3. Lichtenstein GR et al. Inflamm Bowel Dis 2010; 16: 338–346. 4. Sutherland LR et al. Gastroenterol 1987; 92: 1894–1898.

5. Schroeder KW et al. N Eng J Med 1987; 317:1625–1629.

Score UC-DAI endoscopy score4 Mayo Score of Endoscopic Disease5

0 Normal Normal or inactive disease

1

Mild disease Mild friability

Erythema, decreased vascular pattern, mild friability

2

Moderate disease Moderate friability

Marked erythema, absent vascular pattern, friability and erosions

3

Severe disease Spontaneous bleeding and exudation Spontaneous bleeding, ulceration

UC-DAI, ulcerative colitis disease activity index

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Job Number: UK/AS/0027/02-13. Date of preparation: February 2013.

In ASCEND I and II, Asacol® demonstrated mucosal healing in 80% of patients by week 6

n=156

1. Lichtenstein GR et al. Aliment Pharmacol Ther 2011; 33: 672–678.

Defined by the Mayo Score of

Endoscopic Disease:

Mucosal healing = endoscopy

score of 0 or 1

Complete mucosal healing =

endoscopy score of 0

4.8 g/day Asacol® 800 mg MR tablet

• Mucosal healing was apparent across all disease extents (proctitis, proctosigmoiditis,

left-sided colitis and pancolitis; 73–86%)

Mucosal healing

80%

Pro

po

rtio

n o

f p

atie

nts

(%

)

0

20

40

80

60

100

Data from a post hoc analysis of combined ASCEND I and II data in patients with moderately active UC receiving 4.8 g/day Asacol® 800 mg MR tablets, N=213. This analysis included patients with an endoscopy subscore of ≥2 at baseline (N=182).

32%

Complete mucosal healing

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Job Number: UK/AS/0027/02-13. Date of preparation: February 2013.

Mucosal healing demonstrated across all disease extent

• Mucosal healing is becoming an objective marker for stable disease response1

1. Lichtenstein GR et al. Aliment Pharmacol Ther 2011; 33: 672–678.

73% (n=37)

79% (n=24)

Pancolitis Left-sided colitis Proctosigmoiditis Proctitis

86% (n=35)

82% (n=57)

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Job Number: UK/AS/0027/02-13. Date of preparation: February 2013.

Mezavant XL® (mesalazine) treatment for up to 8 weeks led to complete mucosal healing in 32% of patients

1. Kamm MA et al. Gastroenterol 2007; 132: 66–75. 2. Sandborn WJ et al. Aliment Pharmacol Ther 2007; 26: 205–215.

Complete

mucosal healing =

Modified UC-DAI

sigmoidoscopy

score of 0

• Patients with ulcerative proctitis (extent of inflammation 15 cm or less from the anus) were

excluded from these studies2

Data from a post hoc analysis of two 8-week randomised, double-blind, placebo-controlled trials of Mezavant XL®

in mild to moderately active UC, N=1742

4.8 g/day Mezavant XL® 1.2 g tablet

4.8 g/day Mezavant XL® 1.2 g tablet

Complete Mucosal Healing

32%

Pro

po

rtio

n o

f p

atie

nts

(%

)

0

20

40

80

60

100

UC-DAI, ulcerative

colitis disease

activity index

Data from an 8-week randomised, double-blind, placebo-controlled trial of Mezavant XL® in mild to moderately active UC, N=851

Pro

po

rtio

n o

f p

atie

nts

(%

)

0

20

40

80

60

100

Endoscopic

Remission =

Modified UC-DAI

sigmoidoscopy

score of ≤1 (with a

≥1-point decrease

from baseline) and

no mucosal

friability

UC-DAI, ulcerative

colitis disease

activity index

78%

36%

Endoscopic remission

(all patients; n=85)

Clinical & Endoscopic remission

(patients with moderately active disease; n=50)

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Job Number: UK/AS/0192/11-11. Date of preparation: January 2012. Job Number: UK/AS/0027/02-13. Date of preparation: February 2013. .

Maintenance of Remission

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Job Number: UK/AS/0027/02-13. Date of preparation: February 2013.

The majority of patients with quiescent UC remain in remission at 12 months with Asacol® 800 mg MR tablets at

2.4 g/day in divided doses1,2

1. Hawthorne AB et al. Inflamm Bowel Dis 2012; 18: 1885–93.

2. Hawthorne AB et al. Poster presented at the British Society of Gastroenterology, Glasgow, UK. June 2013 (PTU-058)

Maintenance of remission at 1 year (per protocol population)

64%

80%

0%

20%

40%

60%

80%

100%

Once daily Three times daily

Pro

po

rtio

n (

%)

of

pat

ien

ts

46/72 63/79

p=0.03

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Job Number: UK/AS/0027/02-13. Date of preparation: February 2013.

Summary

• The majority of UC patients experience moderate to highly active disease within the first year of diagnosis.1

• Moderate disease should be distinguished from mild disease.2

• ECCO suggests that escalation of therapy should be considered for patients

in whom rectal bleeding persists beyond 10–14 days of treatment initiation.3

• In patients with moderately active disease, high-dose Asacol® (4.8 g/day)

provides: – Symptom improvement at 2 weeks in 73% of cases4

– Mucosal healing at 6 weeks in 80% of cases overall, across all disease extents (proctitis to pancolitis)5

1. Langholz E et al. Scand J Gastroenterol 1991; 26: 1247–1256. 2. Stange EF et al. J Crohn’s Colitis 2008; 2: 1–23.

3. Travis SPL et al. J Crohn’s Colitis 2008; 2: 24–62. 4. Orchard TR et al. Aliment Pharmacol Ther 2011; 33: 1028–1035.

5. Lichtenstein GR et al. Aliment Pharmacol Ther 2011; 33: 672–678.

ECCO, European Crohn's and Colitis Organisation

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Job Number: UK/AS/0027/02-13. Date of preparation: February 2013.

Summary

• Complex patients- surgical/medical discussion; IBD MDM

• Always involve patient

• Nutrition

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Job Number: UK/AS/0027/02-13. Date of preparation: February 2013.

Combined Abbreviated Prescribing Information: Asacol 400mg MR Tablet, Asacol 800mg MR Tablet, Asacol 250mg and 500mg Suppositories and Asacol Foam Enema

Presentation: Asacol 400mg MR Tablets, PL 10947/0011; each modified release tablet contains 400mg mesalazine (5-aminosalicylic acid). Bottles of 120, £39.21. Bottles of 90, £29.41. Asacol 800mg MR Tablets, PL 10947/0012; each modified release tablet contains 800mg mesalazine (5-aminosalicylic acid). Bottles of 180, £117.62. Asacol 250mg Suppositories, PL 10947/0013, each containing 250mg mesalazine. Packs of 20, £4.82. Asacol 500mg Suppositories, PL 10947/0014, each containing 500mg mesalazine. Packs of 10, £4.82. Asacol Foam Enema, PL 10947/0015, 1g mesalazine per metered dose. Carton containing can of 14 metered doses, 14 disposable applicators and 14 disposable plastic bags, £26.72.

Indications: Ulcerative colitis: Treatment of mild to moderate acute exacerbations. Maintenance of remission. Suppositories particularly appropriate for distal disease, Foam Enema for distal colon disease only. 400mg Tablets, 800mg Tablets, Suppositories: Maintenance of remission. 400mg Tablets and 800mg Tablets only: Crohn's ileo-colitis: Maintenance of remission.

Dosage and administration: ADULTS: 400mg Tablets: Acute disease: 6 tablets a day, in divided doses, with concomitant corticosteroid therapy where clinically indicated. Maintenance therapy: 3 to 6 tablets a day, in divided doses. 800mg Tablets: Mild acute exacerbations of ulcerative colitis: 3 tablets a day in divided doses. Moderate acute exacerbations of ulcerative colitis: 6 tablets a day in divided doses. Maintenance of remission of ulcerative colitis: Up to 3 tablets a day, once daily or in divided doses. Maintenance of remission of Crohn’s ileocolitis: Up to 3 tablets a day in divided doses. Suppositories: 250mg: 3 to 6 a day, in divided doses, with the last dose at bedtime. 500mg: A maximum of 3 a day, in divided doses, with the last dose at bedtime. Foam Enema: 1 (disease of rectosigmoid region) or 2 (disease of descending colon) metered doses as single daily dose for 4-6 weeks. ELDERLY: The normal adult dosage may be used unless renal function is impaired. CHILDREN: 800mg Tablets: Not recommended. 400mg Tablets, Suppositories, Foam Enema: No dosage recommendation.

Contra-indications: A history of sensitivity to salicylates or renal sensitivity to sulfasalazine. Confirmed severe renal impairment (GFR <20ml/min). 400mg Tablets, Suppositories and Foam Enema only: Children under 2 years of age. 800mg Tablets only: Hypersensitivity to any of the ingredients. Severe hepatic impairment. Gastric or duodenal ulcer, haemorrhagic tendency.

Precautions: Use in the elderly should be cautious and subject to patients having a normal renal function. Asacol should be used with extreme caution in patients with confirmed mild to moderate renal impairment. Renal function should be monitored (with serum creatinine levels measured) prior to start of treatment, and periodically during treatment, taking into account individual history & risk factors. Mesalazine should be discontinued if renal function deteriorates. If dehydration develops, normal fluid & electrolyte balance should be restored as soon as possible. Serious blood dyscrasias (some with fatal outcome) have been very rarely reported with mesalazine.

Haematological investigations including a complete blood count may be performed prior to therapy initiation, during therapy, and are required immediately if the patient develops unexplained bleeding, bruising, purpura, anaemia, fever or sore throat. Stop treatment if suspicion or evidence of blood dyscrasia. Concurrent use of other known nephrotoxic agents, e.g. NSAIDs & azathioprine, may increase risk of renal reactions. 400mg Tablets and 800mg Tablets: Lactulose or similar preparations which lower stool pH should not be concomitantly administered. 400mg tablets, Suppositories, Foam Enema: Only use during pregnancy if benefits outweigh the risk. Avoid during lactation unless essential. 800mg Tablets only: Mesalazine should be used with caution during pregnancy and lactation when the potential benefit outweighs the possible hazards in the opinion of the physician. If neonate develops suspected adverse reactions consideration should be given to discontinuation of breast-feeding or discontinuation of treatment of the mother. Discontinue treatment immediately if acute symptoms of intolerance occur including vomiting, abdominal pain or rash. Patients with the rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine because of the presence of lactose monohydrate. Standard haematological indices (including the white cell count) should be monitored repeatedly in patients taking azathioprine, especially at the beginning of such combination therapy, whether or not mesalazine is prescribed.

Undesirable Effects: Common: Nausea, diarrhoea, abdominal pain, headache. Rare reports of leucopenia, neutropenia, agranulocytosis, aplastic anaemia, thrombocytopenia, peripheral neuropathy, pancreatitis, abnormalities of hepatic function and hepatitis, myocarditis, pericarditis, alopecia, lupus erythematosus-like reactions and rash (inc. urticaria), drug fever, interstitial nephritis and nephrotic syndrome with oral mesalazine treatment, usually reversible on withdrawal. Renal failure has been reported. Suspect nephrotoxicity in patients developing renal dysfunction. Very rarely, mesalazine may be associated with exacerbation of the symptoms of colitis, Stevens Johnson syndrome & erythema multiforme. 400mg Tablets, Suppositories, Foam Enema: Rare reports of allergic and fibrotic lung reactions. 800mg Tablets only: Common: vomiting, arthralgia / myalgia. Rare reports of vertigo, bronchospasm, eosinophilic pneumonia, bullous skin reactions. Very rarely, interstitial pneumonitis. Suppositories, Foam Enema: Rarely, local irritation may occur after use of rectal dosage forms of mesalazine.

Legal category: POM. Marketing Authorisation Holder: Warner Chilcott UK Ltd, Old Belfast Road, Millbrook, Larne, County Antrim, BT40 2SH, UK. Asacol is a trademark. Refer to Summary of Product Characteristics before prescribing.

Date of preparation April 2013

Job Bag Number: UK/AS/0095/04-13

Please refer to the SPC before prescribing, particularly in relation to side effects, precautions and contraindications

Adverse events should be reported

Reporting forms and information can be found at www.mhra.gov.uk/yellowcard

Adverse events should also be reported to Warner Chilcott UK Ltd on 0800 0328701

Combined Abbreviated Prescribing Information