Medicines Optimisation in IBD Can we base it on evidence?

1. Medicines Optimisation in IBDCan we base it on evidence? AnjaSt.Clair Jones Lead Pharmacist Digestive Diseases Royal Sussex County Hospital Brighton

2. Aims and Objectives Enable medicines optimisation in IBD • Understand Inflammatory Bowel Disease (IBD), • Describe drugs used in treatment of IBD • Develop strategies for medicines optimisation

3. Stomach Duodenum Splenic flexure Hepatic flexure Transverse colon Descending colon (Left sided/distal) Ascending colon (Right sided/ proximal) Jejunum Ileum Caecum Sigmoid colon Terminal ileum Rectum Anus

4. Epidemiology • Disease of YOUNG people (peak 10-25y, 50+y) • Up to 260’000 people affected in UK • UC: 10/100’000 per year • prevalence 146/100’000 (NICE 2013, CG 166) • Incidence stable • Difference in ethnic groups (Ashkenazi Jews) • 50% have relapse in any year • 25% acute sever colitis during lifetime (NICE 2013) • 90% are able to FT work 1year after diagnosis • CD: 5-10/100’00 per year • prevalence 157/100’000 (NICE 2012, CG152) • Incidence increasing • 75% able to work in year after diagnosis • 15-20% disabled by disease within 5 years (NICE 2012) • 50-80% require surgery for strictures (NICE 2012)

5. Anatomic distribution in Crohn’s

6. 80% left sided only

7. Pathogenesis Theories of inflammatory bowel disease etiology -Toxic response to luminal contents-Specific microbial pathogen-Abnormal luminal constituents-Increased absorption of luminal macromolecules-Enhanced immunologic response to normal constituents-Autoimmune response-To epithelial cell or mucus glycoproteins-Molecular mimicry (cross-reactivity of intestinal microflora and epithelia)-To immune cells • Trigger – what? • Genetic involvement

8. Immune dysregulation in Crohn's disease

9. CD or UC?

11. Fistulae in IBD

13. Diagnosis and investigations • History and examination • FBC, LFT, ESR or CRP • Microbiological testing (C. Diff., CMV) • Abdo imaging • Endoscopies +/- biopsies • Barium enema, small bowel studies • Colonoscopy • Assessment of disease extent

15. Figure 1a and 1b: endoscopic views of Crohn’s disease showing mucosal oedema, ulceration and exudates.

17. Crohn's Disease Activity Index • CDAI = 2x1 + 5x2 + 7x3 + 20x4 + 30x5 + 10x6 + 6x7 + (weight factor)8 • 1. Number of liquid or very soft stools in one week • 2. Sum of seven daily abdominal pain ratings:    (0=none, 1=mild, 2=moderate, 3=severe) • 3. Sum of seven daily ratings of general well-being:    (0=well, 1=slightly below par, 2=poor, 3=very poor, 4=terrible) • 4. Symptoms or findings presumed related to Crohn's disease arthritis or arthralgia iritis or uveitis erythema nodosum, pyoderma gangrenosum, apththous stomatitis anal fissure, fistula or perirectal abscess other bowel-related fistula febrile (fever) episode over 100 degrees during past week • 5. Taking Lomotil or opiates for diarrhea • 6. Abnormal mass    0=none; 0.4=questionable; 1=present     • 7. Hematocrit [ (Typical - Current) x 6 ] • 8. 100 x [(standard weight-actual body weight) / standard weight]

18. Harvey–Bradshaw Index for Crohn's disease • Number of liquid stools per day • Abdominal pain, sum of seven daily ratings:(0-none, 1-mild, 2-moderate, 3-severe) • Abdominal mass(0-none, 1-questionable, 2-definite, 3-definite & tender) • General well being(0-very well, 1-slightly below par, 2-poor, 3-very poor, 4-terrible) • Complications (score 1 point per item)Arthritis/arthalgiaSkin/mouth lesionsIritis/uveitisAnal fissure, fistula/perianal abscess

20. UC activity scores

24. Therapeutic aim • Remission • Avoid surgery • CRC (5x) Also: • Smoking cessation • VTE prophylaxis (always!!) • Pain control (no NSAIDs) • Osteoporosis prophylaxis • Opportunistic infections • https://www.ecco-ibd.eu/documents/ECCOconsensusOI.pdf

25. Treatments

26. How to optimise treatment? • Correct dose • Co-prescribing • TDM • Exit strategies • Rescue strategies

27. Steroids • Indication: CD and UC • Moderate to severe relapse • Maximise local effect and limit systemic effect • No role in maintenance • 40mg OD Prednisolone reduced slowly by 5mg/week • ≤ 15mg ineffective in active disease • Budesonide not as effective as Pred but alternative in ileo-ascending colonic disease • Less systemic effect • Osteoporosis

28. Rectal steroids Only for patient not responding to rectal mesalazine • Hydrocortisone (Colifoam) 1 od-bd • High plasma levels after administration • Prednisolone NaPhos (Predsol) 1 bd • Rectal mucosa only • Prednisolone metosulphbenzoate (Predenema1 od) • Poorly absorbed • Increased spread (reached ascending colon in some patient) • Prednisolone metosulphbenzoate (Predfoam1od-bd) • Poorly absorbed • Retained in rectum and sigmoid colon

29. Rectal steroids

30. Optimisation • Correct dose • Start at 40mg and slow reduction • Correct formulation • Know where the disease is located • Prevent osteoporosis • Consider infection risk

31. Rectal reparations: site of action and indication

32. 5-ASA • Dose: • Crohn’s: • higher doses ≥ 4g no evidence (post op only) • UC: • Induction of remissions ≥ 4g/day • Maintenance of remission ≥ 2g/day • Rectal preparations (PINCE) • 15% past splenic flexure:2g bd oral + 1g OD rectal (64% remission at week 8 vs 43% oral) • Compliance at week 8 • (PODIUM: OD vs BD:71% vs 59% remission)

34. Adherence and switching • 39% adherence in maintenance Robinson; APT 2013 • 61% chance of relapse vs 11% • Increased risk of CRC 31% vs 3% • 75% risk reduction in adherers • Cost :14% admission = 49% of cost Kane 2006, Bassi 2004, Hawthorne 2008 • Switch patients had 3.5-fold risk of relapse • Endoscopic healing rate is not equivalent

35. Optimisation • Top and tail in sever flares • Consider switching carefully • Support Adherence • Tailor formulation to patient • Reinforce message of CRC prevention • Consider switch of preparation carefully • Consider impact on endoscopic healing