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IBD What’s New

IBD What’s New. Shawinder Johal MRCP, PhD Consultant Gastroenterologist Northern General Hospital. When patients are unwell. 52% contact GP (52% inappropriate/delay) 26% contact Consultant Gastroenterologist 20% wait until next clinic visit. UC. ULCERATIVE COLITIS. Epidemiology

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IBD What’s New

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  1. IBD What’s New Shawinder Johal MRCP, PhD Consultant Gastroenterologist Northern General Hospital

  2. When patients are unwell • 52% contact GP (52% inappropriate/delay) • 26% contact Consultant Gastroenterologist • 20% wait until next clinic visit

  3. UC

  4. ULCERATIVE COLITIS Epidemiology • Disease of the West (and immigrants thereof) • Twice as common in Winter • Incidence 7/100, 000 • 10% have an affected relative (UC or Crohns) • Young Pathogenesis Unclear. Familial and environmental factors. Abnormal colonic mucosa, luminal contents and immune response Diagnosis Endoscopy and Histology

  5. ULCERATIVE COLITIS Clinical features • Bloody diarrhoea and lower abdominal pain of gradual onset • Anaemia • Weight loss • Fever • Abdominal pain / tenderness

  6. ULCERATIVE COLITIS Extraintestinal Features Related to disease activity -mouth ulcers -erythema nodosum -episcleritis -arthritis (pyoderma gangrenosum) Unrelated to disease activity -Saro-ileitis -Small joint disease -(Ank spond, liver disease)

  7. UC – Clinical Course Extent of Disease at Diagnosis • Pancolitis 36.7% • Left sided proctocolitis 17.0% • Proctitis 46.2% Extension of Disease over time • 54% 5-28 yr FU • 10-30% 10 yr FU

  8. UC – Clinical Course Relapse Rates • First year after diagnosis 50% • 3-7yrs after diagnosis: In remission 25% Relapse every year 18% Intermittent relapses 57% • At any one time only 50% of patients in remission Colectomy Rates – by extent of disease at presentation • Pancolitis 5 yr 32-44% • Proctosigmoiditis 5yr 4-9 %

  9. Mortality • ?Increase in Mortality • 1950’s – 25% mortality in first severe attack Even now:- • 29% of patients with a severe attack of UC will require a colectomy during the same hospital admission and • further 14% within 1 year of that admission

  10. Case 1 -Dr R. 40 Year old lady Known to have Proctitis • Presents with x6 bloody motions per day • Urgency • Second attack • Smoker What would you do?

  11. Tests 1 • FBC • CRP • Stool culture (C. difficile) • Examination - Abdomen, pulse, temp

  12. Options 1 • Oral 5 ASA • Topical 5 ASA • Topical steroids • Oral 5ASA and topical 5ASA • Steroids • Other

  13. Oral 5-ASA in UC • Efficacy uncontroversial • Reduces frequency of relapse~40% • Modest definite value in acute flare • More effective topically than steroids - acute therapy and maintenance • Avoid switching • Not all 5-ASAs the same

  14. Figure 2 Remission and improvement rates. Percentage of patients achieving remission (ulcerative colitis disease activity index (UCDAI) of 0 or 1) or improvement (decrease in UCDAI >2 points). Rem, remission; Imp, improvement.

  15. Oral and topical • DBRCT n = 127 • 4 g/day oral for eight weeks • initial four weeks also enema • 1 g of mesalazine or placebo Marteau 2005

  16. Oral and topical Remission • 44% v 34% at four weeks (NS) • 64% v 43% at eight weeks (p=0.03) Improvement • 89% v 62% at four weeks (p=0.0008) • 86% v 68% at eight weeks (p=0.026)

  17. Figure 3 Time to cessation of rectal bleeding in patients with frank bleeding at baseline. SDF, survival distribution function from Kaplan-Meier survival analysis (proportion of patients with rectal bleeding). All patients without cessation of rectal bleeding by day 56 or who withdrew prematurely were censored.

  18. Suppository plus enema • Enemas mostly not retained in rectum • Consider suppositories • Disease usually prominent if not maximal in rectum • Combination therapy • Intermittent topical therapy

  19. Oral 5ASA - chemoprotective • Cumulative cancer risk in UC is • 2% at 10 years • 8% at 20 years • 18% by 30 years • Cumulative cancer risk in CD IS 7% • If age of onset below 25 year, risk increased to 18% and 19% (UC and CD respectively) • May reduce Ca risk by up to 81% in UC patients

  20. 5-ASA in post-op Crohn’s • Still somewhat controversial • Post-operative prophylaxis • Clinical relapse rate reduced by ~15% • Endoscopic relapse rate reduced by 18% • 6 best studies – n = 1141 • Positive result if >2g/d

  21. Still not feeling better Worried about toxicity and monitoring What benefit? DEMANDS ANSWERS AND ACTION! Case 1

  22. Resistant proctitis-Options • Poor compliance • Re-assess disease • ?IBS • AXR-Treat proximal constipation • Mesalazine 1gm at night and predsol am (sup vs enema) • Prednisolone +/- azathioprine • Anecdotal lignocaine 2% gel bd, Bismuth or butyrate enemas • Surgery

  23. 5-ASA toxicity • Available for many years • Approved for use in pregnancy • Very safe

  24. Sulfasalazine toxicity • occurs in >20%, dose dependent • headache, nausea, epigastric pain • serious idiosyncratic reactions all rare and less frequent than in RA (<1:10,000) • Stevens Johnson • pancreatitis • agranulocytosis • alveolitis

  25. 5-ASA toxicity • Not common – usually mild • Headache (2%), nausea (2%), rash (1%) and thrombocytopenia (<1%) • Adverse events ~ placebo • Very similar for mesalazine, olsalazine and balsalazide

  26. 5-ASA diarrhoea • Not very common – usually mild - <2% • May mimic active colitis • Confusing – link from rechallenge • Class specific

  27. 5-ASA interstitial nephritis • Probably not dose-related • Very rare – max estimate 1:100,000 • More likely if severe colitis • Highest risk if pre-existing renal impairment • No apparent difference between 5-ASAs

  28. Monitoring

  29. Renal monitoring of 5-ASA • Caution in patients with • pre-treatment abnormality • co-morbidity • other nephrotoxic drugs • Otherwise need not anticipate problems

  30. Renal monitoring of 5-ASA • BSG guidelines are relaxed (2004) • Monitoring not “required” • Wise to check creatinine • Before starting therapy • At 6 months • Annually thereafter • Probably fully reversible if identified early in rare event that renal impairment occurs • ECCO (2006) more cautious than BSG

  31. PROGRESS • Feels better • Re-assured • Monitored 1 yearly • Taking mesalazine (M/WF)

  32. Case 2 64 M 3/12 Unwell • X10 per day (nocturnal) • Lost weight • Abd. Pain OPTIONS

  33. Options • Other topical treatment • Oral steroids • Immunosuppressants • Re-assess • Admit

  34. Severe attack • Admit for intensive treatment • iv steroids • Re-hydration • Topical treatment • Avoid food • DVT prophylaxis • Surgeons

  35. The Natural History of UC • On day 3 if more than 8 stools/d or 3-8 stools/d + CRP > 45 mg/l 85% will need colectomy • 40% in remission day 5, 30%deteriorate and have colectomy, 30% partial response • Surgery toxic dilatation, perforation, haemorrhage, sustained temp of 38C, >8 stools at 24h, d Travis et al 1996

  36. Surgery • Only cure • Does not effect extra GI manifestations • Ileo-anal pouch • Proctocolectomy and ileostomy

  37. Cyclosporin-Long Term Outcomes – Steroid-resistant – 3 Series Centre Pt No Initial Long Term Response % Remiss. % N’ham 22 91% 53% at 3yr Hawkey 98 Oxford 50 56% 40% at 2yr Jewell 98 Dublin 46 69% 26% at 2yr O’Donoghue 02

  38. Cyclosporin A • 2mg/kg infusion over 6h (2-5 days) • Oral 3 months • Azathioprine last month as steroids stopped • 60-70% response rate • Continuing worries over safety/ toxicity Renal dysfunction/superinfection • Deaths reported

  39. Immunomodulators in UC AZATHIOPRINE / 6-MP • 2-2.5mg/kg (or half for 6-MP) • Mechanism of action – unknown • One controlled study – Hawthorne 92 – Aza withdrawal RCT – 79 pts – placebo relapse x2 • 30yr retrospective review - Fraser 02 – effective • Unknown – how long to continue?

  40. Other Immunomodulators • Methotrexate • Tacrolimus • Cyclophosphamide

  41. UC – other THERAPIES • Infliximab • Heparin • Nicotine • Probiotics/antibiotics • Short Chain Fatty Acids • Heavy metals • Miscellaneous • Biologicals • Experimental – Leukocytapheresis

  42. Steroids??? How do you use steroids? • Prednisolone vs budesonide • 30-40 mg • Reduce by 5mg per week to 2 weekly • 30mg 1 week, 20mg 1 month and 5mg/week after to zero • Bone protections

  43. Progress • Improves with steroids • Azathioprine • Bone protection • Clinical remission

  44. Case 3 35 year old lady, stable , pregnant?? • Advice • Azathioprine steroids • Mode of delivery • Risk of IBD

  45. Pregnant • Fertility normal except active disease • Best during a period of sustained remission (>6 months) • Continue maintenance therapy (risk of relapse higher) • Joint decision • Relapse, treat with steroids

  46. Acute colitis Yes No Admit Topical, oral 5ASA Topical steroids Iv steroids 3 days Oral steroids Refer Surgery CyA, AZT,

  47. Shawinder.Johal@sth.nhs.uk(Sweeny)

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