Update on IBD. Dr Richard POLLOK Consultant Gastroenterologist and Honorary Senior Lecturer. Queen Mary s Hospital. St George s Hospital

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1 Update on IBD Dr Richard POLLOK Consultant Gastroenterologist and Honorary Senior Lecturer Queen Mary s Hospital St George s Hospital Parkside Hospital

2 Miss LF, aged 24 Recent diagnosis of distal colitis at FS and confirmed histologically Patient treated elsewhere with prednisolone Presented with BO x5/d with blood and hip pain Cause of hip pain?

3 Avascular necrosis of L femoral head

4 BSG guideline bone protection in IBD All >65: consider bisphosphonate at start of steroid treatment <65 at high risk and steroids >3/12: DEXA and bisphosphonates if T score < 1.5 Give Vit D and Calcium whilst on steroid DEXA scan for those at high risk of osteoporosis: (1) > 10kg wt loss (2) BMI <20 or (3) Age >70

5 UC disease extent Extensive or Pancolitis 37% Left sided ulcerative colitis 37% Distal UC 36% Proctitis

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7 Topical 5-ASA treatment Proctitis: 5-ASA supps Distal colitis: 5-ASA foam enema L sided colitis: 5-ASA liquid enema Extensive/pancolitis: topical Rx PLUS oral Rx

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9 Miss LF has an immediate relapsewhat are the options? Further courses of steroids Further courses of topical treatment Add in a thiopurine (azathioprine or 6- mercaptopurine infliximab

10 Azathioprine pathway

11 TPMT activity

12 azathioprine induced neutropaenia Colombel et al 2007

13 Drug monitoring for azathioprine 6MMP zero low high High/norm 6TG zero low Low/normal high Action Poor Compliance OR increase dose Noncompliant Coprescribe alopurinol Reduce dose

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15 Case Miss JE 22yo female student Pan UC Refractory 2/52 oral pred HR 88, T 37.2 C BO x 12/d bloody Day 1 Hydrocortisone 100 qds Mesalazine 1.2g bd LMW Heparin Hb 13.4 WC 8.9 ESR 45 Alb 40 CRP 39 Stool MC&S NEG AXR mucosal oedema

16 Day 3 Poor clinical response CRP 33 BO x 6/d Options?

17 Day 3 Increase dose of steroids start ciclosporin 2 mg/kg Start infliximab 5mg/kg colectomy

18 Day 6 Symptoms unchanged CRP 102 Needs colectomy? Yes No Clostridium difficile toxin +VE

19 Clostridium difficile annual rates

20 Jen et al 2011

21 Fidaxomicin versus vancomycin Louie 2011

22 Faecal transplant-rct Vanc 500mg qds 5/7 followed by gut lavage then donor faeces duodenal infusion, n=16 Vanc 500mg qds 14/7, n=13 Vanc 500mg qds 14/7 followed by gut lavage, n=13 Van Nood 2013

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24 C difficile and IBD majority community acquired Higher rates of carriage in IBD ~8-10% Usually not associated with antibiotic use Associated with steroids and colonic disease Always test on admission Pseudo-membranes uncommon Co-infection associated with poorer outcomes

25 Case history aged 16 school boy, diagnosed with ileocaecal CD given several # CS over 3 years Strictureplasty, aged 19 Azathioprine initiated post-op Well 6 years, MRE inflammation and mild stenosis noted

26 Case history cont. 1 year later obstructive symptoms and admitted c anorexia and rapid weight loss CT Abdo: ileal stricture and possible entero-enteric fistula Treatment c CS and IFX initiated-good initial response 6/12 later recurrent sub-acute obstuctive symptoms requiring resective

27 Questions What is optimal time to introduce thiopurines-would earlier introduction have avoided surgery? Should anti-tnfs have be introduced before clinical deterioration-would they avoid need for further surgery?

28 Can medical treatment alter disease progression Early treatment Altered progression

29 Kaplan-Meier curve showing time from diagnosis to start of thiopurine therapy in the three gr within 5 years of diagnosis. Group A versus B (p ), Group A versus C (p < ), G Time versus from C (p < diagnosis ) to start of thiopurines Group C ( ) Group B ( ) Group A ( ) Months from diagnosis 5 year cumulative probability increased from 12% (Group A) to 25% (Group C) Number at risk Group A ( ) Group B ( ) Group C ( ) Pollok et al 2012

30 Time from diagnosis to first intestinal surgery 5 year cumulative probability reduced from 14% (Group A) to 9% (Group C) Pollok et al 2012

31 Thiopurines and risk of intestinal surgery in Crohn s diseases Pollok et al 2013 in press

32 Biologics

33 Harvey-Bradshaw score 8 infliximab or adulimimab indicated

34 What Role biologics in altering longterm surgical outcomes? DoH UK 2011

35 Cumulative risk of surgery for IFX patients according to response Combe 2011

36 A midwife with watery diarrhoea 58 yo midwife presented with intermittent watery diarrhoea for 6 months She opens her bowels 3-6/d has had diarrhoea at night. she has lost 3kg. No abnormality was seen at a recent colonoscopy performed elsewhere Options? Colonoscopy with colonic biopsies

37 Collagenous Colitis

38 Microscopic colitis Collagenous colitis Lymphocytic colitis

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40 Mrs SC Aged 72 History of ulcerative colitis > 20 years BO>6/d c nocturnal symptoms Intolerant to AZA, 6MP and methotrexate Maintained on prednisolone long term >18mo by prior Gastroenterologist No recent investigation Options?

41 Colonoscopy #1 Pan colitis with features of chronic inflammation including inflammatory polyps and a villiform appearance to the mucosa Biopsies confirm above, and x1 biopsy:..indeterminate for dysplasia Treated with IFX x 3 induction infusions and repeat colonoscopy

42 Repeat Colonoscopy Repeat biopsies from flat mucosa reveal changes consistent with high grade dysplasia Options?

43 dysplasia in UC High grade dysplasia Colectomy recommended, up to 40% may have occult CRC Low grade dysplasia Controversial need 2 specialist pathologists 10-30% may develop CRC within 1 year Consider colectomy or 3-6 monthly colonoscopy

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45 Miss EW, aged 34 Crohn s disease 5 years in stable remission for 3 years on azathioprine Plans to visit S America Attends IBD clinic prior to departure, mentions incidentally she d had yellow fever vaccination that morning at her GP practice Options?

46 Vaccinations in IBD ECCO guidelines 2010

47 Miss JE 26 yo IT specialist with a history of distal colitis Repeated flare-ups with abdo pain, loose stool and occasional fresh blood on paper Receives several course of prednisolone with short-lived benefit FS is normal, Proctoscopy-haemorrhoids Q. what is your diagnosis and how do you approach the problem

48 Prevalence of IBS-like symptoms in IBD Simrén et al. (2002) 57% (23/40) of CD had IBS-like symptoms 33% (14/43) of UC in remission This is 2-3 times higher than in the general population (IBS prevalence = ~15-20%). Assoc. with depression and visits to GP & Gastroenterologist.

49 low FODMAP diet Fermentable Oligosaccharides Disaccharides Monosaccharides And Polyols

50 Excess Fructose Lactose Fructans & Galactans Polyols Apple Pear Peach Watermelon Mango Sugar snap peas Honey High fructose corn syrup Milk (cow, goat & sheep) Yoghurt Cheeses Bread Pasta Couscous Biscuits Cereals Chickpeas Lentils Kidney beans Baked beans Apricot Cherries Plums Prunes Pears Cauliflower Mushrooms Avocado Large serves of: Dried fruit Fruit juice Brocolli Cabbage Brussel sprouts Onion / garlic Sweeteners e.g. Xylitol Sorbitol

51 The FODMAP Hypothesis Loose stools Bloating Small intestine Colon Pain Flatulence

52 Summary A low FODMAP diet is useful in patients with functional symptoms It is supported by high quality studies that show efficacy and mechanisms Better quality trials are needed in patients with IBD

53 Faecal calprotectin To help distinguish between IBD and IBS To assess laboratory disease activity in IBD To assess responses to treatment To assess disease prognosis Research uses

54 Tibble et al 2002

55 In a population with suspected IBD, n=100 (an overall prevalence of IBD 32%) Adults Children true positive true negative false positive 3 9 false negative 2 5 Meta analysis BMJ, 2010

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57 Dr Richard POLLOK Consultant Gastroenterologist Parkside Hospital SW19 St George s Hospital Queen Mary s Roehampton

58 Calprotectin as a predictor of relapse in IBD U.C < 250 mg/l C.D < 250 mg/l R E M I S S I O N p < C.D > 250 mg/l U.C >250 mg/l Month Gastroenterology 2000;119:15-22

59 Traditional Dietary Recommendations Fibre Manipulation Avoid triggers Fatty Foods Dairy Caffeine Fructose Alcohol Spicy Foods Sweeteners

60 Results 74% (46 patients) reported positive improvements in all abdominal symptoms. However; Retrospective Uncontrolled Regression to the mean? Changes to medication

61 Double-blind, Randomised, Placebo-Controlled Evidence Patients with FM and improved symptoms on LFD (n=25) Runin Wash -out Wash -out Wash -out 14d 14d 14d Fructan Fructose Mix Glucose

62 In summary High level evidence that FODMAPs trigger symptoms in IBS with FM. Symptom severity is dose dependent. 75% of patients improved on the LFD. Improvements are due to restriction of FODMAPs and not placebo alone.

63 Does it work in clinical practice? 62 patients with IBS Educated on a LFD. Telephone interview (2-40 months later). Shepherd & Gibson, 2006

64 Primary Outcome Were your symptoms adequately controlled in this phase? Proportion (%) answering Yes