Transcript New Developments in Acute Pancreatitis

Medical Management of
Ulcerative Colitis
Alistair Makin
Manchester Royal Infirmary
Treatment Choice
Dependent on
 Acute attack or maintenance of remission
 Assessment of Disease Severity (Truelove & Witts 1950’s)
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Mild - < 4 stools /day, no systemic disturbance, normal ESR
Moderate - > 4 stools/day but with minimal systemic upset
Severe - > 6 stools/day with blood, evidence of systemic
disturbance – fever, tachycardia, anaemia or ESR >30
Toxic dilatation
Extent of disease (topical v systemic)
The Acute Attack
Mild to Moderate Disease
Salicylates
 Sulfasalazine (SASP) first used in 1942
 Response rate of 60%
– 25-30% adverse effects
 Newer 5-ASA fewer side effects ( 10%)
 Topical + systemic dosing more effective
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Cochrane Review 4/1/03
– Newer 5-ASA preparations superior to placebo and trend to
benefit over SASP. Considering relative costs a clinical
advantage of newer 5-ASA v SASP is unlikely
New 5-ASA Preparations
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Balsalazide (azo-bonded prodrug) v mesalamine
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46% v 44% achieved remission
Response rate 68% v 61% in new diagnosis
36% v 25% in relapse
Symptomatic remission 25 v 37 days
Pruitt et al 2002
Balsalazide v sulfasalazine
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Similar response rate
Patient withdrawal 7% v 31%
Green et al 2002
The Acute Attack
Role of Steroids
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First used in 1950’s
Severe attack mortality reduced from 37% to < 1%
Topical for left-sided disease
Oral for more extensive disease or failed local Rx
– 40mg/d more effective than 20mg/d
– 60mg/d > 40mg/d but more side effects
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IV initially in severe disease
Baron et 1962
The Acute Attack – when
Steroids Fail
Predictors of failed medical therapy
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> 8 stools/day
Pulse > 100
Albumin < 30g/l
Temp > 38°C
Mucosal islands on plain AXR
Small bowel dilatation
Colonic dilatation
Failure Rate
33%
36%
42%
56%
75%
73%
75%
Lennard-Jones 1975
Chew et al 1991
Surgery - failure to respond after 5 days
Salvage Therapy
Cyclosporin
– Oxford data
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Initial pilot suggested benefit
Dual centre controlled trial of patients failing to
respond at day 5
IV cyclosporin (4mg/kg) + steroids v conventional Rx
– 9/11 on cyclosporin responded v nil
– 60% still well at 6 months
– New York Data
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Similar benefit
54/111 patients major toxicity (2 deaths, 7 severe
infections)
Cyclosporin
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St Marks Data – low dose 2mg/kg
– 31 patients
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11 cyclosporin + steroids
2(18%) urgent - 5(25%) delayed colectomy
20 cyclosporin
5(25%) urgent – 5(25%) delayed colectomy
– Benefit with concurrent azathioprine
Salvage Therapy
Azathioprine
Slow onset of action
Loading IV onset of action still 4 weeks
Methotrexate
No role
Infliximab
Anecdotal evidence but no convincing trial data
Cuckoo Land ?
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Antibiotics
No established role
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Probiotics – commensal bacterial species
Possible role of VSL#3 (a combination of 4 lactobacillus
species) in mild-moderate disease
Trichuris suis eggs
(Porcine Whipworm)
•86% remission
•85% relapse by 12
weeks
•Remission maintained
with 3/52 repeat doses
Remission
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No role for steroids
Sulfasalazine – reduced relapse rate 4-fold
Newer 5-ASA’s comparable
– What Dose?
– How long for?
Long-term at appropriate
dose for preparation used
Novel Approaches
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Oral 5-ASA + twice weekly enemas v oral alone
Reduction in number and incidence of relapses
Higher chance of no relapse
More costly but decreased relapse & hospital costs
Piodi et al 2004
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Patient-led variable dosing
Balsalazide 1.5g bd with 750mg increments up to 6g for
7 days if symptoms increased
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Stable remission
Newly in remission
– 44% relapse by 3 years
- 59%
Green et al 2004
Azathioprine
Converted to 6-MP in liver and then to thioinosinic acid which
impairs purine biosynthesis
- inhibits cellular proliferation
- slow onset of action as act on newly differentiating cells
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Induction & maintenance of remission in refractory
disease
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66% response rate
Need 3 months of treatment to determine response
10% intolerant
Myelosuppression 5% in first 6 months
Late complications so prolonged monitoring needed
Azathioprine
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Dose 2mg/kg
3 monthly FBC/LFT’s once stable
Stop if WBC <3•5 or neutrophils <1•5
How long for?
– Relapse rates on AZA
11%-1 year
32%-5years
– Relapse rates higher if AZA stopped than if continued up
to year 4 of treatment
– when AZA stopped when in remission but >6months Rx
38%-1 year
75%-5 years
– No increase in relapse rates when Rx > 5 years
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Treat for a minimum of 4 years
Conclusions
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Determine severity of attack and treat
appropriately
Topical v systemic
Limit steroid use (DEXA scan if > 3months of
7.5mg.d)
Consider immunosuppression early
Duration of treatment important
Joint management with surgeons of severe and
refractory cases
The worms are coming!