Module 4.1.2 (Management of IBD)

Question 1

What is IBD?

Answer 1

• Inflammation of the intestine

Include

• Crohn’s disease
• Ulcerative colitis

> chronic, relapsing, remitting immune-mediated inflammation at various sites of the gastrointestinal tract

Question 2

What are the signs and symptoms of IBD?

Answer 2

• abdominal cramps and pain „
• frequent, watery diarrhea (may be bloody) „
• severe urgency to have a bowel movement „
• fever during active stages of the disease „
• loss of appetite and weight loss „
• tiredness and fatigue „
• anaemia (due to blood loss)

Question 3

What is the difference between UC and CD

Answer 3

Chrons Disease

• Chronic inflammation that may affect any part of the GI tract from mouth to anus „
• Inflammation may extend to of all layers of the GI mucosa „
• The pattern of inflammation is segmental rather than continuous (skip lesions)

Ulcerative colitis

• Inflammation only affects the superficial mucosa
• Mainly affects the rectum and distal colon but may extend to involve the entire colonic mucosa
• Inflammation tend to be continuous rather than patchy

Question 4

For CD, define the following terms;

A) Ileitis

B) ileo-colitis

C) Colitis

Answer 4

A)

• (inflammation of the ileum, the final part of the small intestine)

B)

• (inflammation of the last part of the small intestine (ileum) and the first part of the colon)

C)

• (inflammation in all of the colon)

Diarrhoea, abdominal pain and malnutrition shared among the three

Question 5

What is the difference between mild and severe UC

Answer 5

Mild

• Distal colon & rectum. Progression to the remainder of colon in 15% of patients
• Diarrhoea: Intermittent, 3- 5/day often without cramping pain
• Fever: Absent
• Anorexia and weight loss: absent
• Systemic sx: absent

Severe

• Usually involves the whole colon (pan colitis)
• Diarrhoea: Profuse or constant liquid stools with blood
• Fever: Present 38⁰C to 40⁰C
• Anorexia and weight loss: severe and persistent
• Systemic sx: extreme fatigue, weaskness, prostration

Question 6

What are the aims of drug treatment in UC and CD?

Answer 6

UC

Inducing remission

• Controls symptoms during active disease „
• Remission achieved within 7-14 days if patient responds to treatment

Maintaining remission

• Prevents symptoms from coming back when in remission

Question 7

What type of drug treatment to use for rectum and distal colon?

Answer 7

Topical preparations

Question 8

What are the SIX medication treatment options in IBD?

Answer 8

1. Corticosteroids (topical, oral, IV)
2. 5-Aminosalicylates (topical, oral)
3. Immunosuppressants (oral, IV)
4. TNF-alpha antagonists (SC, IV)
5. Vedolizumab (IV)
6. Ustekinumab (SC)

Question 9

For corticosteroids;

A) why are they used?

B) what are examples? Include forms.

C) What to use for distal colonic inflammation?

D) What to use for severe cases?

E) What are some adverse effects?

F) What happens if stopped rapidly?

put how to taper doses on word doucment notes

Answer 9

A)

• Inducing remission in acute disease

B)

• Hydrocortisone (rectal foam), prednisolone (oral, supp, enema), budesonide (oral, rectal foam)

C)

Topical formulation for distal colonic inflammation

• Suppositories, foam, enema

D)

• IV methylprednisolone for severe cases for 3-5 days then switch to oral formulation

> 70% of patients improve after 2-4 weeks of 40mg of oral prednisolone/day

E)

• Weight gain
• Infection
• Hypertension
• Dyspepsia
• Diabetes

From porlonged use e.g. more than 12 weeks

F)

• Rapid reduction associated with early relapse and acute adrenal crisis

Question 10

For 5-Aminosalicylates (5-ASA);

A) What is the main role?

B) What are the types of drugs? Which drug to use first

C) What types to use for rectum and distal colon

D) What combination is effective

E) What to monitor for?

Answer 10

A)

1. Inducing remission in UC and CD
2. Maintenance of remission in UC (controversial role in CD)

B)

• Include balsalazide (oral), mesalazine (oral, supp, enema, rectal foam), olsalazine (oral), sulfasalazine (oral)
• sulfasalazine (oral) –> use first

C)

• Supp, enema and rectal foam for disease confined to rectum and distal colon

D)

• Combination of rectal + oral 5-ASA more effective than either alone

E)

• Monitor LFTs, FBP, renal function tests

Question 11

For Immunosuppressants;

A) What are the types of drugs used?

B) Why are they used?

C) What drugs to use if first-line treatment is not tolerated?

D) What is the role of IV cyclosporin?

E) What to monitor?

F) What happens when there is low enzyme or high enzyme activity of TPMT in mercaptopurine metabolism?

Answer 11

A)

• Azathioprine, mercaptopurine, IV ciclosporin, methotrexate

B)

• Main role of Azt & Mercaptopurine: Maintenance of remission in patient requiring continuous steroid for control

C)

• MTX (with folic acid) reserved for patient who could not tolerate above drugs

D)

• Inducing remission in severe UC if sx fail to improve after 3-5 days of IV corticosteroid (methylprednisolone)

E)

• „ Monitor FBC and LFT and renal function (with ciclosporin)

F)

• Low enzyme activity leads to increased risk of myelosuppression
• High enzyme activity lead to reduced efficacy

Question 12

For TNF-alpha antagonists;

A) What is its main role?

B) Examples of drugs

C) What precautions are they?

D) Why is a review done every 3 to 6 months?

Answer 12

A)

To induce remission and maintain remission In severe UC & CD if sx refractory to standard therapy

• Can be used as first line tx if disease is severe and extensive

B)

• Adalimumab (SC), infliximab (IV)

C)

• Infection history „
• TB and hepatitis screening „
• Vaccination status

D)

• To assess the efficacy of therapy and any adverse effects

Question 13

For Vedolizumab and Ustekinumab;

A) What is it’s main role?

B) what is Vedolizumab specifically used for?

C) What is Ustekinumab specifically used for?

Answer 13

A)

• To induce remission and maintain remission in severe UC & CD if sx refractory to TNF-alpha antagonist

B)

• For moderate to severe CD and UC
• Not as effective as anti-TNF agents for patient with extra intestinal manifestations

C)

• New drug
• For moderate to severe CD only

Question 14

Acute severe ulcerative colitis is defined by the presence of 6 or more bloody stools per day, plus at least one of the following. What are some of the other signs?

symptoms are similar to CD

Answer 14

• temperature more than 37.8ºC „
• heart rate more than 90 beats/minute „
• haemoglobin less than 105 g/L „
• erythrocyte sedimentation rate more than 30 mm/hour

Question 15

What are some of the risk factors for a severe acute flare of UC?

Answer 15

• Missing IBD medications or taking the incorrect dose „
• Non-steroidal anti-inflammatory drugs (NSAIDs) „
• Antibiotics „
• Smoking (Crohn’s disease) „
• Stress „
• Food

Question 16

How to treat severe acute flare of UC? What to do when symptoms improve?

Answer 16

Methylprednisolone IV

• If sx improve, switch to oral prednisolone and start therapy to induce remission

>If inadequate response, ciclosporin 2 mg/kg intravenously, daily as a 24-hour continuous infusion

> OR infliximab 5 mg/kg by intravenous infusion over 2 hours, at week 0, 2 and 6.

Question 17

How to treat distal colitis (end of rectum) UC? to induce remission

Answer 17

• Rectal 5-ASA + Oral 5-ASA

–>

• If not effective, use oral 5-ASA with rectal corticosteroid (continue until sx resolves then taper)

–>

• If not effective, add on oral prednisolone (40-50 mg daily until sx resolves then taper over 8-12 weeks)

Question 18

How to treat extensive UC (ie colitis proximal to the splenic flexure)?to induce remission

Answer 18

• Oral 5-ASA

–>

• If not effective, add on oral prednisolone (40- 50 mg daily until sx resolves then taper over 8-12 weeks)

–>

• If not effective, add on TNF-alpha antagonist/ vedolizumab

Question 19

Once acute episodes of UC are under control –> what is used for the following maintenance control?

A) First line?

B) If severe initial disease OR frequent relapse?

C) Chronically active disease that is refractory to the above therapy?

Answer 19

A)

• Oral 5 ASA daily +/- rectal ASA (2-3 x weekly)

B)

• As above + Azathioprine (daily) OR mercaptopurine (daily) OR methotrexate + folic acid (weekly)

C)

• TNF-alpha antagonist OR vedolizumab

Question 20

What is used for the symptomatic management for the treatment of UC?

Answer 20

Anti-diarrhoeal

• Loperamide only in mild disease
• DO NOT USE IN SEVERE DISEASE –> causes toxic megacolon (faecal matter backs up, put pressure on colon, causes damage and ruptures colon)

> avoid antispasmodic (hyoscine butylbromide), anticholinergics, and opioid analgesics in severe disease

> reducing intake of insoluble fibre may provide symptomatic relief of diarrhoea during acute flare for some patients

Question 21

What is the most important factor in maintaining remission in CD?

Answer 21

Smoking cessation is the most important factor in maintaining remission

Question 22

Treatment of CD is similar to the treatment of UC with what difference?

Answer 22

5-aminosalicylates oral and rectal therapy have a limited role in Crohn’s disease

Question 23

What does the following severity classification mean for CD

A) S0

B) S1

C) S2

D) S3

Answer 23

A)

• Clinical remission

B)

• Mild (<4 bowel actions/day, no sign of systemic toxicity)

C)

• Moderate

D)

• Severe (>6 bowel actions/day with sign(s) of systemic toxicity)

Question 24

What treatment to use for mild to moderate CD? Also what to use for ileocaecal disease? to induce remission

Answer 24

Oral prednisolone 40-50mg daily (Taper after clinical response)

• For ileocaecal disease: Oral budesonide 9 mg daily for 8 weeks then gradually taper

Question 25

What treatment to use for severe CD? What to if doesn’t respond to first-line treatment? to induce remission

Answer 25

• Azathioprine OR Mercaptopurine OR Methotrexate + folic acid (methotrexate + folic acid if Aza or Merc dont work)

–>

• If not responding to above: Infliximab, adalimumab, vedolizumab, ustekinumab

Question 26

For maintenance treatment in CD;

A) What is used as first-line?

B) What is used if refractory to answer in question A

Answer 26

A)

• Azathioprine (daily) OR mercaptopurine (daily) OR methotrexate + folic acid (weekly) [reserved for patient intolerant of azathioprine and mercaptopurine]

B)

• TNF-alpha antagonist OR vedolizumab OR ustekinumab

Question 27

What are some extra intestinal manifestations of IBD

Answer 27

Hepatic „

• Chronic active hepatitis, fatty infiltration, sclerosing cholangitis

Arthritis „

• Usually affects large joints, occasionally associated with ankylosing spondylitis

Ocular

• Uveitis, iritis

Dermatological or mucosal

• Erythema nodosum, pyoderma gangrenosum, aphthous ulcers

Osteopenia/ Osteoporosis

„ Iron deficiency anaemia due to blood lose from stool

Question 28

What are some of the complications of Crohn’s disease

Answer 28

• Small bowel stricture and obstruction „
• Fistulae „
• Bleeding „
• Malnutrition „
• An increased risk of colon cancer

from mouth to anus, all layers of GI mucosa

Question 29

What are some of the complications of Ulcerative Colitis?

Answer 29

• Severe bleeding „
• Perforated colon „
• Severe dehydration „
• An increased risk of colon cancer „
• Toxic megacolon –> loss of sm muscle, loss of motility, pressures builds up in colon and faeces build up –> sepsis.

superficial musocsa, rectum +distal colon

Question 30

When is surgery indicated in IBD? What does it involve?

Answer 30

• Medication can no longer control symptoms
• Treatment of complications

> Draining abscesses, repairing fistulas, widening strictures and obstructions

Involves

• Resection - removal of diseased portions „
• Restoring intestinal continuity – performed at time of resection „
• Creating an artificial opening at the surface of the abdominal wall - stoma

Question 31

What are some other treatments used in IBD? Provide THREE.

Answer 31

Antibiotic therapy (metronidazole, ciprofloxacin)

• Treatment of complications (perianal disease, fistulas, inflammatory mass, bacterial overgrowth in the setting of strictures)

Faecal Transplantation

• Increase biodiversity of microbiome

Alternative Medicine

• Peppermint Oil „
• Prebiotic „
• Probiotic

Question 32

Summary of IBD

Answer 32

• IBD is a chronic, relapsing and remitting inflammatory disorder of the digestive tract. The two main forms are UC and CD. „
• UC mainly affects the large colon whereas CD can affect any part of GI tract „
• IBD have local and extra-intestinal complications „
• The aims of treatment are to increase the periods of remission and reduce the number of relapses „
• Treatment of UC and CD is divided into two main areas - inducing remission and maintaining remission „
• Drug treatment of IBD include corticosteroids, 5- aminosalicylates, immunosuppressants, antibiotics and TNF alpha antagonists, vedolizumab, ustekinumab „
• Choice of drug and route of administration is guided by location, severity and complications of disease as well as response to current or previous treatment „
• Corticosteroids are NOT used to maintain remission „
• It is important to monitor disease progression and adverse effects of the medications used in the treatment of IBD