1 / 15

Medical Management of Ulcerative Colitis

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) Mild - < 4 stools /day, no systemic disturbance, normal ESR

lilly
Download Presentation

Medical Management of Ulcerative Colitis

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Medical Management of Ulcerative Colitis Alistair Makin Manchester Royal Infirmary

  2. Treatment Choice Dependent on • Acute attack or maintenance of remission • Assessment of Disease Severity (Truelove & Witts 1950’s) • 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)

  3. 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 • 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

  4. New 5-ASA Preparations • Balsalazide (azo-bonded prodrug) v mesalamine • 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 • Similar response rate • Patient withdrawal 7% v 31% Green et al 2002

  5. The Acute Attack Role of Steroids • 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 Baron et 1962 • IV initially in severe disease

  6. The Acute Attack – when Steroids Fail Predictors of failed medical therapy Failure Rate • > 8 stools/day 33% • Pulse > 100 36% • Albumin < 30g/l 42% • Temp > 38°C 56% • Mucosal islands on plain AXR 75% • Small bowel dilatation 73% • Colonic dilatation 75% Lennard-Jones 1975 Chew et al 1991 • Surgery - failure to respond after 5 days

  7. Salvage Therapy Cyclosporin • Oxford data • 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 • Similar benefit • 54/111 patients major toxicity (2 deaths, 7 severe infections)

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

  9. 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

  10. Cuckoo Land ? • Antibiotics No established role • 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

  11. Remission • 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

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

  13. 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 • Induction & maintenance of remission in refractory disease • 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

  14. Azathioprine • 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 • Treat for a minimum of 4 years

  15. Conclusions • 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!

More Related