Ulcerative colitis therapeutics Flashcards
Which symptoms would be suggestive of a UC diagnosis?
-Bloody diarrhoea for more than 6 weeks
-Abdominal cramping
-Mucus in stools
-Loss of appetite
-Increased urgency of defection
-Pre-defection pain which is relieved on passing a stool
-Tenesmus (persistent, painful urge to pass stool even when the rectum is empty)
-Nocturnal defaecation
-Anaemia
Which additional symptoms in a patient with suspected IBD indicate more severe disease?
Fatigue
Anorexia
Fever
Malaise
At the point of diagnosis how many patients have severe disease?
15%
At the point of diagnosis how many patients have extensive colitis?
20%
How many patients with UC experience extra-intestinal manifestations?
30%
What percentages of patients with UC will require surgery 10 years after diagnosis?
15-20% of patients
What are the disease characteristics that increase the risk of surgery?
Greater severity of inflammation leads to greater extent of inflammation and hence a greater risk for surgery
What are some of the needs for surgery?
Long-term poor response to drug treatment
Severe acute exacerbations
Emergency problems - toxic megacolon
Strictures
Fistulas
Which conditions if present in the family history may make you further suspect IBD?
Coeliac disease
Colorectal cancer
IBD
Which specific regions and layers of the GI system does UC affect?
Unlike Crohn’s disease, Ulcerative colitis ONLY affects the MUCOSAL membrane in the LARGE intestine and so is characterised by:
‘Continuous mucosal inflammation beginning in the rectum and extending proximally.’
Is the inflammation associated with Ulcerative Colitis described as transmural?
Unlike inflammation associated with Crohn’s disease, inflammation associated with Ulcerative colitis is not transmural meaning that the inflammation does not penetrate to the submucosa, muscularis and serosa.
What is the importance of early diagnosis of UC?
Earlier detection, diagnosis and management of UC reduces the severity of inflammation and hence the extent of the large intestine is damage.
What is the different regions of the colon that can be affected by UC?
Inflammation associated with UC begins at the rectum and extends proximally.
Proctitis - rectum only
Proctosigmoiditis - rectum and sigmoid colon
Left sided colitis - rectum, sigmoid colon and descending colon
Pancolitis - inflammation in the entire colon
At diagnosis which percentage of patients have the different types of colitis?
Proctitis - 30-60%
Left sided colitis - 16-45%
Extensive pancolitis - 14-35%
Does the severity of inflammation in UC always correlate to the extent of location?
What is the purpose of therapy in UC?
To reduce symptoms
Induce remission (no longer active disease)
Maintain remission
Improve and maintain quality of life
Minimise toxicity related to drugs
What are some of the clinical complications associated with UC?
Toxic megacolon
Bowel perforation
Strictures
Fistulas
Colorectal cancer
Why are assessment tools such as Montreal and TrueLove and Witts do not always provide accurate monitoring in UC?
In UC, use of scoring systems such as Montreal and TrueLove and Witts have the disadvantage of not correlating absence of symptoms to absence of inflammation. Therefore there is still research being conducted to assess whether other biomarkers can be used to monitor disease progression in UC such as faecal calprotectin.
What potential disease monitoring parameters could be assessed for inflammation progression in UC?
Surveillance in terms of endoscopy
Faecal calprotectin
CPR
Imaging
What is the purpose of monitoring inflammation in UC?
Induce clinical and symptomatic remission by tight regulation of inflammation
Prevention of complications
Assessing and adjusting appropriate drug therapy
What factors influence choice of drug therapy in UC?
Disease location (affect formulation choice)
Disease severity
Previous response to therapy
Disease pattern - relapse frequency
Presence of complications or risk factors for complications
Patient characteristics
Drug characteristics
Cost
What are the two distinguishable types of treatment for a patient with UC?
Acute treatment - inducing remission after diagnosis or a flare
Maintenance therapy- maintain remission
What is a key distinction between the purpose of controlling remission in UC and in Crohn’s disease?
In UC there is less evidence to suggest that ongoing underlying inflammation leads to permanent bowel damage. Therefore, perhaps in comparison to Crohn’s disease there is potentially less need to have a tight regulation of underlying inflammation, but it is still important and the same rules apply, close drug monitoring etc.
What percentage of patients with UC have progressive disease?
1/5
What is the most appropriate identifiers of induced remission in UC?
Clinical remission (endoscopic) combined with patient reported symptoms (absence of rectal bleeding, return of normal bowel habits)
Describe the purpose of the Montreal classification system as a clinical assessment tool.
Measures both the disease severity and extent
Extent: E1 = proctitis
E2 = left sided
E3 = extensive
Severity: S0 = clinical remission
S1 = mild
S2 = moderate
S3 = severe
Define what symptoms would be present in each of the severity stages in the Montreal classification system.
S0 = asymptomatic
S1 = 4 or less stools +/- blood, no systemic symptoms, normal inflammatory markers
S2 = 4 or more stools, minimal signs of systemic toxicity
S3 = 6 stools, pulse 90bpm, high temperature, low haemoglobin, high ESR
Explain symptoms present in the mild classifications of TrueLove and Witts assessment tool.
Mild:
4 or less stools
Little to no blood
No temperature
No pulse
No anaemia
ESR 30 or less
Explain symptoms present in the moderate classifications of TrueLove and Witts assessment tool.
Moderate:
4-6 bowel movements daily
Mild to severe blood in stools
No temperature
No pulse
No anaemia
ESR 30 or less
Explain symptoms present in the severe classifications of TrueLove and Witts assessment tool.
Severe:
6 plus bowel movements daily, with one systemic upset
Visible blood in stools
High temperature
High pulse
Anaemia present
ESR Above 30
What does the Mayo score include?
Rectal bleeding
Stool frequency
Endoscopic score
Physicians score
What is an advantage of the TrueLove and Witts and the Montreal score for monitoring disease progression?
Do not require invasive procedures
How does the disease location influence the choice of treatments?
Affects choice of formulation (topical treatments)
Release profiles
What is the proximal progression rate of patients with UC at 5 and 10 years?
5 years - 10-19%
10 years - Up to 28%
What is the first line treatment for inducing remission in patients with mild to moderate proctitis?
First line: Topical aminosalicylate (specifically suppositories due to rectum delivery)
Remission not achieved in 4 weeks or decline topical treatment: Add oral aminosalicylate (higher response seen together)
Then oral or topical corticosteroid (time limited)
Aminosalicylate contra-indicated or not tolerated: Oral or topical corticosteroid
Why is topical aminosalicylate used in preference to oral aminosalicylate as first line treatment for inducing remission in mild to moderate UC?
Higher mucosal concentration
Work faster and better than oral aminosalicylates
What is an example of a steroid used to induce remission in mild to moderate UC?
Prednisolone 40mg OD for 6-8 weeks or Prednisolone 5mg suppositories OD
What factors help to improve adherence in topical therapies for UC?
Involve patient in decision making
Single dose before bed time (more practical and better retention)
What is the first line treatment for inducing remission in patients with mild to moderate proctosigmoiditis and left sided colitis?
First line: Topical aminosalicylate (enema due to better retention in sigmoid)
Remission is not achieved within 4 weeks:
Add high dose oral aminosalicylate
Or switch to high dose oral aminosalicylate with time limited topical corticosteroid
If further treatment is required following mild to moderate exacerbation of proctosigmoiditis/left sided colitis, what is required?
Stop topical treatments
Offer an oral aminosalicylate and a time-limited course of an oral corticosteroid
In patients with mild to moderate exacerbation of proctosigmoiditis/left sided colitis and decline topical treatment?
Consider a high-dose oral aminosalicylate alone, and explain that this is not as effective as a topical aminosalicylate
If remission is not achieved within 4 weeks, offer a time-limited course of an oral corticosteroid in addition to the high-dose aminosalicylate
In patients with mild to moderate exacerbation of proctosigmoiditis/left sided colitis and can’t tolerate aminosalicylates?
Consider a time-limited course of a topical or an oral corticosteroid
What is considered to be a high dose oral aminosalicylate?
2-3 grams daily (high doses are more effective in inducing remission)
How effective is the combination of topical and oral aminosalicylate?
More effective than oral or topical monotherapy in inducing remission
What dosing regime is most effective for UC?
Once daily dosing is as effective as divided dosing
What is more effective in mild to moderate disease in inducing remission: corticosteroids or aminosalicylates?
Corticosteroids but due to adverse effects profile they are reserved for patients that have failure to respond, contraindicated to aminosalicylates.
What is the first line treatment for inducing remission in mild to moderate disease in extensive colitis?
First line: Topical aminosalicylate and a high-dose oral aminosalicylate
Remission not achieved within 4 weeks: Stop the topical aminosalicylate and offer a high-dose oral aminosalicylate with a time-limited course of an oral corticosteroid
For people who cannot tolerate aminosalicylates:
Consider a time-limited course of an oral corticosteroid
What is the first line treatment for inducing remission in moderate to severe UC?
First line: Oral corticosteroids (40-60mg daily)
What are some of the counselling points when giving oral corticosteroids?
Single dosing rather than divided doses due to less adrenal suppression and as effective
Dosing over 40mg daily is associated with more side effects
50% of patients experience side effects such as acne, mood and sleep disturbances, dyspepsia, glucose intolerance, oedema
Always time limited, before reducing and stopping
When would you expect to see improvement in symptoms after giving oral corticosteroids?
After 2 weeks of treatment
Give an example of a reducing regime of corticosteroids.
2.5-10mg every week over a period of 6-8 weeks
What are some of the drugs used in inducing remission in moderate to severe active disease?
Infliximab, Adalimumab, Golimumab
- used after failure of conventional therapy
Vedolizumab
- used when there is an inadequate/loss of response to conventional therapy or TNFa antagonist
Tofacitinib
- used when disease are responded inadequately / response has been lost to conventional or biological therapy
What patients with UC will require hospitalisation of an acute severe flare at some point during progression?
15-25%
How is an acute severe exacerbation measured?
Assessed against Truelove and Witts
6 or more bloody stools a day and
Will have at least one of the following:
Pulse above 90 bpm
CRP greater than 30 milligrams per litre
Haemoglobin below 105 grams per litre
Temperature above 37.8
What is the first line management for acute severe exacerbations?
IV corticosteroids
e.g. IV Hydrocortisone 100mg QDS
Expected benefit by Day 3
Or IV Ciclosporin or surgery for those who decline, contra-indicated to Corticosteroids
Minimal response by Day 3: addition of IV Ciclosporin
If Ciclosporin is contra-indicated, use Infliximab
What other supportive therapies should be used in patients with severe acute exacerbation of UC?
Nutritional support
Fluid and electrolyte replacement
Stool cultures
Sigmoidoscopy
VTE prophylaxis (increased risk)
Anti-diarrhoeas, anticholinergics, opioids and NSAIDs can lead to colonic dilatation and hence surgery
What is the first line treatment in maintaining remission in mild to moderate proctitis and proctosigmoiditis?
Topical aminosalicylate alone (daily or intermittent) or
an oral aminosalicylate plus a topical aminosalicylate (daily or intermittent) or
an oral aminosalicylate alone, explaining that this may not be as effective as combined treatment or an intermittent topical aminosalicylate alone
When may therapy only be required intermittently?
If flares are intermittent
Using topical therapies every 3 nights has not shown to reduce maintenance of therapy
What is the first line treatment in maintaining remission in mild to moderate left sided or extensive colitis?
Offer a low maintenance dose of an oral aminosalicylate
If patients are not maintained with salicylates in all areas of disease, what should be considered?
Oral azathioprine or mercaptopurine if:
Remission not reached with aminosalicylate or
After 2 or more inflammatory exacerbations in 12 months that require treatment with systemic corticosteroids
How do you maintain remission after a severe acute exacerbation of UC?
To maintain remission after a single episode of acute severe ulcerative colitis:
Consider oral azathioprine or oral mercaptopurine
Consider oral aminosalicylates if azathioprine and/or mercaptopurine are contraindicated or the person cannot tolerate them.
How do you maintain remission in moderate to severe UC?
Continuation of remission drugs
