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Medical Management of Ulcerative Colitis Alistair Makin Manchester Royal Infirmary.

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Presentation on theme: "Medical Management of Ulcerative Colitis Alistair Makin Manchester Royal Infirmary."— Presentation transcript:

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2 Medical Management of Ulcerative Colitis Alistair Makin Manchester Royal Infirmary

3 Treatment Choice Dependent on l Acute attack or maintenance of remission l Assessment of Disease Severity (Truelove & Witts 1950’s) l Mild - < 4 stools /day, no systemic disturbance, normal ESR l Moderate - > 4 stools/day but with minimal systemic upset l Severe - > 6 stools/day with blood, evidence of systemic disturbance – fever, tachycardia, anaemia or ESR >30 l Toxic dilatation l Extent of disease (topical v systemic)

4 The Acute Attack Mild to Moderate Disease Salicylates l Sulfasalazine (SASP) first used in 1942 l Response rate of 60% –25-30% adverse effects l Newer 5-ASA fewer side effects ( 10%) l Topical + systemic dosing more effective l 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

5 New 5-ASA Preparations l Balsalazide (azo-bonded prodrug) v mesalamine l 46% v 44% achieved remission l Response rate 68% v 61% in new diagnosis l 36% v 25% in relapse l Symptomatic remission 25 v 37 days Pruitt et al 2002 l Balsalazide v sulfasalazine l Similar response rate l Patient withdrawal 7% v 31% Green et al 2002

6 The Acute Attack Role of Steroids l First used in 1950’s l Severe attack mortality reduced from 37% to < 1% l Topical for left-sided disease l Oral for more extensive disease or failed local Rx –40mg/d more effective than 20mg/d –60mg/d > 40mg/d but more side effects Baron et 1962 l IV initially in severe disease

7 The Acute Attack – when Steroids Fail Predictors of failed medical therapy Failure Rate l > 8 stools/day33% l Pulse > 10036% l Albumin < 30g/l 42% l Temp > 38°C56% l Mucosal islands on plain AXR75% l Small bowel dilatation 73% l Colonic dilatation75% Lennard-Jones 1975 Chew et al 1991 l Surgery - failure to respond after 5 days

8 Salvage Therapy Cyclosporin –Oxford data l Initial pilot suggested benefit l Dual centre controlled trial of patients failing to respond at day 5 l IV cyclosporin (4mg/kg) + steroids v conventional Rx –9/11 on cyclosporin responded v nil –60% still well at 6 months –New York Data l Similar benefit l 54/111 patients major toxicity (2 deaths, 7 severe infections)

9 Cyclosporin l St Marks Data – low dose 2mg/kg –31 patients l 11 cyclosporin + steroids 2(18%) urgent - 5(25%) delayed colectomy l 20 cyclosporin 5(25%) urgent – 5(25%) delayed colectomy –Benefit with concurrent azathioprine

10 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

11 Cuckoo Land ? l Antibiotics No established role l 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

12 Remission l No role for steroids l Sulfasalazine – reduced relapse rate 4-fold l Newer 5-ASA’s comparable –What Dose? –How long for? Long-term at appropriate dose for preparation used

13 Novel Approaches l 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 l Patient-led variable dosing Balsalazide 1.5g bd with 750mg increments up to 6g for 7 days if symptoms increased l Stable remission – 44% relapse by 3 years l Newly in remission - 59% Green et al 2004

14 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 l Induction & maintenance of remission in refractory disease l 66% response rate l Need 3 months of treatment to determine response l 10% intolerant l Myelosuppression 5% in first 6 months l Late complications so prolonged monitoring needed

15 Azathioprine l Dose 2mg/kg l 3 monthly FBC/LFT’s once stable l Stop if WBC <35 or neutrophils <15 l How long for? –Relapse rates on AZA 11%-1 year32%-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 year75%-5 years –No increase in relapse rates when Rx > 5 years l Treat for a minimum of 4 years

16 Conclusions l Determine severity of attack and treat appropriately l Topical v systemic l Limit steroid use (DEXA scan if > 3months of 7.5mg.d) l Consider immunosuppression early l Duration of treatment important l Joint management with surgeons of severe and refractory cases l The worms are coming!


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